Newsletter - Regenerative Medicine at the McGowan Institute

The McGowan Institute has opened a new, state-of-the-art histology laboratory in our Bridgeside Point facility. The lab development was funded by a grant from the Health Resources and Services Administration. The ability to examine the morphology of tissues as a result of tissue engineering or regenerative medicine interventions is an essential step in bringing potential new therapies to patients. The laboratory offers standard histology services including frozen and fixed tissue preparation, immunohistochemistry, and a wide variety of special stains. Bridgeside Point is the hub for the Institute’s tissue engineering research, and the close proximity of the histology lab to the research laboratories is a substantial aid in the rapid assessment of our emerging technologies.

The laboratory is under the leadership of Jennifer DeBarr, who joined the Institute in October 2003. Jennifer has over 14 years of experience in histology. The success of the lab and the quality of the services is best judged by the customers. The Wagner Laboratories are significant users of the new histology services. Dr. Wagner observes that “the rapid turn-around and the expert support from the lab have enhanced the research of his group”. Another significant user of the McGowan histology services is Dr. Stephen Badylak and his colleagues; Dr. Badylak notes that “the quality of the services and the flexibility of the staff to easily accommodate special requests ensures that our research studies progress unimpeded”.

Jennifer DeBarr is prepared to train anyone who wants to personally use the histology lab, so that faculty and students can make use of the facilities. Jennifer notes that the most commonly requested histological stains include:

H&E (Hematoxylin and Eosin)
Masson’s Trichrome
PAS (Periodic Acid Schiff)
Silver Stains
Verhoff’s
elastic trichrome
Picro-Sirrus red
Safarin O/Fast Green
Immunohistochemistry

The services in the histology laboratory can be adapted to fit the needs of your research. Contact Jennifer about any special projects, stains or requests from your laboratory; she welcomes any suggestions or comments. Contact information: Jennifer DeBarr Histology Laboratory Manager Room 271-Bridgeside Point 412-235-5215 matalikja@upmc.edu

Dr. Strick Elected to American Academy of Arts and Sciences

The American Academy of Arts and Sciences, one of the world’s most prestigious organizations, has elected to its membership Peter L. Strick, Ph.D., professor of neurobiology and psychiatry and co-director of the Center for the Neural Basis of Cognition. Professor Strick is one among 202 men and women who, according to the Academy, “are world-renowned leaders in scholarship, business, the arts and public affairs.” The Academy has among its members 150 Nobel laureates, 50 Pulitzer Prize winners and numerous influential world leaders.

Dr. Strick’s research is leading to exciting new discoveries in how the human brain works. Among his lab’s most important discoveries are the six “premotor” areas in the frontal lobe through which the brain projects to the spinal cord to generate movement. In addition, Dr. Strick has made progress into defining the complex pattern of neural connections that is the substrate of human behavior.

“Dr. Strick’s work in mapping the brain circuitry involved in behavior and motor function has the potential to impact the lives of millions who have mental illnesses or difficulty with physical tasks due to brain injury,” said Arthur S. Levine, M.D., senior vice chancellor, health sciences and dean of the School of Medicine. “We are pleased that the Academy has recognized these achievements.”

Election to the Academy is one of the highest honors in the United States. Founded in 1780 by John Adams, James Bowdoin, John Hancock and other scholars “to cultivate every art and science which may tend to advance the interest, honor, dignity, and happiness of a free, independent, and virtuous people,” the Academy has as members some of the greatest minds from each generation, including George Washington, Ben Franklin, Daniel Webster, Albert Einstein and Winston Churchill. [More]

Report Suggests that Less Is Better- Novel Approach That Has Lung Recipients Taking Far Fewer Drugs

A lung transplant patient takes six pills a day, a regimen that is intended to safeguard the donor organ from immune system attack. But rejection plagues these patients more often and more vigorously than any other kind of organ recipient, so is it necessary that patients take that many pills? Not according to the experience of UPMC surgeons; some of their lung transplant recipients are getting away with taking just one anti-rejection pill daily, and others just the one pill four or five times a week, with no ill effects.

Results of the novel clinical protocol were presented at the American Transplant Congress (ATC) by Kenneth R. McCurry, M.D., assistant professor of surgery at the School of Medicine. With more than a year of follow-up in many patients, Dr. McCurry found that even those patients who have been able to reduce their medications to one pill a day benefit from the approach, which differs from the conventional twice-a-day triple-drug therapy, said Dr. McCurry.

The rationale is to treat patients with as little immunosuppressive medication as possible following the transplant while preventing injury to the graft by the recipient’s immune system.

Since June of 2002, more than 80 patients have been treated under the protocol. At ATC, Dr. McCurry reported results in many of these patients, including 31 who have been followed for more than a year after transplant, several for nearly two years.

“At this point, I think we can say that the standard multi-drug approach to immunosuppression may be excessive and leads to increased complications. Moreover, our promising early results suggest that altering the approach and reducing immunosuppression is not as risky as some would have guessed. The next step we should consider is a multi-center, randomized trial. Only with that kind of data might the transplant community embrace the notion that radical change is warranted,” noted Dr. McCurry. [More]

DEVICE FOR RAPID DETECTION OF NERVE AGENTS NAMED ONE OF ‘GREATEST ARMY INVENTIONS’ FOR 2003

Pittsburgh-based Agentase, LLC’s Nerve Agent Sensor was named one of the 10 “Greatest Army Inventions” of the past year by the U.S. Army Research, Development and Engineering Command. The Sensor is a hand-held device that rapidly changes color in the presence of a contaminant such as sarin, one of many nerve agents that are feared to be used in chemical warfare or terrorist attack. The Agentase Nerve Agent Sensor is already being used in Iraq.

The invention is based on research performed by Professor Alan J. Russell and was funded by the U.S. Army Research Laboratory and the Defense Threat Reduction Agency (DTRA). The team being recognized includes Dr. Russell, Stephen J. Lee, Ph.D., and Robert Campbell, Ph.D., both of the U.S. Army Research Office, a part of the U.S. Army Research Laboratory; Larry Pollack of DTRA; and Keith LeJeune, Ph.D., a former student of Dr. Russell’s and chief executive officer of Agentase, which he and Dr. Russell co-founded.

Dr. Russell’s research has focused on the interface between enzymes and materials like polymers. As such, the Agentase Nerve Agent Sensor makes use of the pH-dependent catalytic activity of enzymes that have been embedded in a polymer sponge-like material. If contamination is detected, within seconds the sponge changes color from yellow to red.
Beyond its high sensitivity to nerve agents, the Nerve Agent Sensor also is resistant to environmental factors, such as high temperatures, and interference from other compounds. It has a two- to three-year shelf life and is compatible with all testing surfaces. [More]

Congratulations to…

Dr. Michael Sacks on promotion to the rank of Professor of Bioengineering in the School of Engineering: Chancellor Mark Nordenberg, in his letter to Professor Sacks wrote, "This promotion to the highest academic rank recognizes that the promise implicit in the conferral of tenure has been fulfilled. Indeed your record of accomplishments to date clearly suggests that the years ahead will bring further contributions of significance benefiting your discipline, this University and the broader society."
Dr. Sacks, in collaboration with Dr. Gorman (PI), University of Pennsylvania have received a grant from the NIH in the amount of $1,332,862 to study "Mitral Saddle Shape Preservation Improves Valvuloplasty."
During the past thirty years Carpentier has pioneered and standardized surgical techniques that allow reliable repair of mitral valves with all types of leaflet, chordal and annular deformities. Use of these techniques has produced good results at centers all over the world. Although the durability of these repairs has been acceptable there is a 10 to 16% long-term failure rate. Reported modes of failure implicate mechanical stress as an etiologic factor.

Imaging techniques in humans and animals have shown the mitral annulus to have a pronounced saddle shape; this shape is conserved across mammalian species. State-of-the-art mathematical modeling indicates that this saddle shape imparts curvature to the leaflets, minimizing leaflet stress and resulting strain.

Most established mitral valve repair techniques include placement of a flat annuloplasty ring. While a flat ring improves early valve competence by reducing annular area and improving leaflet coaptation, annular flattening may reduce leaflet curvature and produced unnecessary stress and strain on leaflet and annular suture lines.

Dr. Sacks and Dr. Gorman hypothesize that saddle-shape annuloplasty will diminish leaflet stress when compared with standard flat annuloplasty. Three-dimensional echocardiography will be used to assess the effect of annuloplasty ring shape on normal mid-systolic leaflet curvature in an ovine model. In addition, sonomicrometry array localization, a technique for cardiac imaging and strain measurement, will be used to assess the effect of annuloplasty ring shape on mitral valve leaflet strain throughout the cardiac cycle. Data from these two techniques will allow a quantitative assessment of the mechanism linking annular shape, leaflet curvature, and leaflet strain. An understanding of this relationship will allow a more rational design of annuloplasty rings, improving the longevity of currently established valve repair techniques.

Dr. Alan Russell on selection by the Pittsburgh Business Times as a recipient of its “Fast Tracker Award” where they annually recognize 50 business professionals under the age of 45 who are making a difference in their business life and community. Mara Mrvos, Pittsburgh Business Times Special Reports Editor notes that “the individuals selected are all committed to their respective careers and communities. For that, we congratulate them and thank them for making the region a better place to live and do business.”

RheoGene Opens Office of Clinical Applications in Pittsburgh

Under the leadership of J. Mark Braughler, Ph.D., vice president of therapeutics, RheoGene will open a Clinical Applications office and laboratory in Pittsburgh. From the Pittsburgh office, Dr. Braughler will direct RheoGene's preclinical and clinical development programs and oversee RheoGene's academic and institutional research collaborations.

Dr. Braughler comes to RheoGene from Paradigm Genetics, Inc. (Research Triangle Park, N.C.) where he was vice president of business development - healthcare. Dr. Braughler joined Paradigm Genetics following its acquisition of TissueInformatics Inc. (Pittsburgh, Pa.), where he had served as senior vice president of business development and acting COO.

RheoGene Inc., is a wholly owned subsidiary of RheoGene Holdings Inc., a wholly owned affiliate of the University of Pittsburgh Medical Center. The company's operations are located in Norristown, Pa. For more information, visit www.rheogene.com

Faculty Spotlight:

Stephen Francis Badylak, D.V.M., M.D., Ph.D.

Regenerative medicine and tissue engineering were terms that had not been yet defined when Dr. Stephen Badylak was in medical school. The field, in which he is now well respected and world renowned, has grown up around him over the past 20 years and it proved to be natural avenue for successive pathways.

With an inquisitive mind and inventive drive, Dr. Badylak embarked on those pathways to the future. While in Medical School, he never thought he would be involved in research, and provide therapies to patients by discovering and developing them. "I thought I'd be practicing medicine fulltime," he said. But biomedicine, as it was then defined, intrigued him and it became a home to foster collaborations, and avenue for the product of invention. "Call it chance or divine intervention---it worked," Badylak said.

Beginning in 1976 when he received his D.V.M. from Purdue University, Dr. Badylak's career path took many intricate turns. He found the practice of veterinary medicine rewarding, but longed for an additional challenge. "I guess I'm just too restless to practice only veterinary medicine. It's a wonderful field and the education involved is terrific," Badylak stated. He considers the field of veterinary medicine the foundation for his successes. With all that he learned and discovered through his education in veterinary medicine, he found his future endeavors much easier.

A few years into veterinary practice, Badylak questioned whether he would be satisfied in that field for the rest of his career. The answer was apparent and Badylak headed to Purdue University’s graduate school where he obtained a Masters in Science in Clinical Pathology, and completed his studies with a Ph.D. in Anatomic Pathology. Even then he knew that his studies were not yet complete. He had begun working with faculty in the Bioengineering Department who had prompted him to pursue his medical degree. In 1985, he received his MD with highest honors from Indiana University’s School of Medicine. "It was a good decision because it allowed me to practice medicine and then get into the human biomedical research field with both feet," Badylak reflected.

According to Badylak, human and veterinary medicine lend components to each other. "Unless you have been through both curricula and practiced both types of medicine you don't get an in-depth understanding of the connections," he surmised.

During his tenure at Purdue Dr. Badylak held a variety of positions including Postdoctoral Research Assistant, Associate Research Scholar, Director of the Hillenbrand Biomedical Engineering Center, and for 16 years he held dual appointments of Head Team Physician for the Athletic Department and Associate Professor in the Veterinary Physiology and Pharmacology Department.
As an avid sports fan, this dual position status allowed him the opportunity to enjoy the best of both worlds. He was able to stay involved in athletics, albeit from the sidelines, while continuing his research endeavors. The time spent working with Men's basketball head coach Gene Keady, and being part of the basketball teams’ success in winning multiple Big 10 championships, proved a thrilling and rewarding experience for Badylak.

During this time, Dr. Badylak's lab carried out scientific investigations in sports medicine applications. His coordinated research with colleagues resulted in the development of small intestinal submucosa (SIS) and other extracellular matrices (ECMs) as a scaffold for orthopaedic, cardiac, and soft tissue repair.

SIS, derived from porcine small intestines, was used in clinical trials in 1997 to replace injured knee ligaments and tendons. This was one of the main highlight’s for Badylak’s research career. Badylak attributes SIS's healing qualities to the ability of mammals' intestines to heal damaged tissue quickly. This discovery was initially stumbled upon in 1987, when Badylak's group was testing it as a vascular graft in dogs. This SIS scaffold, which looks like a white piece of mesh cloth, has been used in repair of anterior cruciate ligaments as well.

The discovery proved valuable to the sports medicine application. Dr. Badylak credits the collaborative efforts with DePuy Orthopaedics, Inc., of Warsaw, Indiana in helping with the development and commercialization of the ACL replacement therapy. "DePuy remains an excellent industry partner,” Badylak said. This relationship, according to Dr. Badylak, sets the standard for such interaction between academia and industry. "DePuy sets the gold standard of how industry can partner with a university. The field of tissue engineering in orthpediacs really began with DePuy and I was very fortunate to be a part of that." It was a 12-year process, from discovery to application and now there are 17 separate FDA allowances for the use of the material in humans, three for the second generation of ACL scaffold.

Diligence in the laboratory and an inquisitive mind has yielded Dr. Badylak over 40 patents. The majority of his patents involve the use of extra cellular matrix as a bioscaffold for regenerative medicine applications. Many are combination patents for use with synthetic polymers and cells, as well as preparation patents and applications for how the patents are used. These patents, Badylak believes, have attracted many industry partners such as the Cook Group, ACell, CorMatrix, as well as DePuy. These four major corporate entities, in one way or another, helped to develop technologies from Badylak's lab to help the quarter of a million patients who have been treated with therapies from their laboratory.

Dr. Badylak has authored more than 130 scientific publications and six book chapters. He has served on several scientific committees, including the Committee on the Use of Human Research Subjects and as a member of the Joint Faculty Committee of the Biomedical Engineering Graduate Degree Program. While at Purdue, he Chaired the Purdue University Tissue Engineering Advisory Board and the Study Section for the Small Business Innovative Research at the National Institutes of Health. He presently serves as a member of the Surgery and Bioengineering Study Section at NIH. Dr. Badylak has either chaired or been a member of the Scientific Advisory Board to several major medical device companies including DePuy Inc. Cook Biotech, Genesis Orthopaedics, Sentron Medical Ventures, and ACell, Inc.

Badylak and his team are most proud of the fact that their dedication and hard work in the laboratory leads to therapy development, commercialization of a product, and ultimately utilization by patients worldwide. These therapies are used in almost every aspect of the surgical field; cardiovascular, urology, dermatology and orthopediatic. “This is why we are here,” Badylak said. “It's very satisfying to see something happen that may not have happened otherwise. The reward is to know you've made a difference.”

Making a difference goes beyond simply having an idea and working in the laboratory, according to Badylak. Partnerships are key factors in attaining the researcher’s goal. “Collaborations with other scientists, administrations of universities and industry are necessary; and then understanding and working through the regulatory system and learning how things are commercialized helps make the finished product,” Badylak said.

Dr. Badylak joined the faculty at the University of Pittsburgh in January of 2003 as a Research Professor in the Department of Surgery and Director of the Center for Pre-Clinical Tissue Engineering within the McGowan Institute.

Currently Dr. Badylak's group is working on esophageal tissue engineering in conjunction with Dr. James Luketich at the University of Pittsburgh’s Medical Center Surgery Department. Dr. Luketich has particular expertise in the multidisciplinary management (combined chemotherapy/radiation/surgery) of esophagogastric and lung cancer. This collaborative team is interested in the pre-clinical model of Barret's Esophagus, a pre-cancerous condition arising in 10-20% of patients with chronic reflux of stomach contents into the esophagus. "This is a very significant clinical problem with a high incidence of cancer formation in patients with limited treatment options," Badylak said.

This technology will aid as a substitute for damaged or missing esophageal tissue in humans affected with Barrett’s Esophagus and excellent results in pre-clinical studies has the team excited about the latest version of bioscaffold technology.

The University of Pittsburgh Medical Center performs the most procedures for this condition throughout the world. Badylak is hopeful that if the next phase of studies yields successful data, the human application can begin within the next 12 to 18 months. "We already have the FDA allowance, the only limitations now are in patient selection and another set of convincing pre-clinical studies,” Badylak stated.

The success of this study will serve as one example of how collaborative efforts can expedite the delivery of therapies to patients, and demonstrates why the McGowan Institute is the model for regenerative medicine research. Badylak gives credit to Dr. Alan Russell, Director of the McGowan Institute for Regenerative Medicine, for setting up the ideal environment to allow this kind of success to happen. “There are opportunities here, to get your hands on new technologies before anyone else and to apply them,” Badylak said.

The philanthropic contribution to the McGowan Institute was one of the major reasons why Dr. Badylak decided to come to the University of Pittsburgh. “I had options on where I could go. Philanthropy makes the difference between one entity, like McGowan and the next,” he said. Badylak knew that at McGowan, he would have to opportunities to do things that would be more difficult elsewhere without this type of philanthropic funding that comes into the Institute.

Philanthropic dollars provide the flexibility that is not necessarily afforded when using a National Institutes of Health grant. “You’re limited to where you can go because you have to stick to the specific aims. If you have a really wild idea, there is no way you can try unless you have the flexibility in the terms of resources and that's equipment, money and people.” Badylak stated.

Recalling the beginning stages of his SIS discovery, Badylak said it was an idea that he couldn’t get funded through traditional methods. “We took a piece of a dog's small intestines and replaced his aorta with it. That is an absolutely wild idea and if I wrote that in a grant proposal, I'd probably be laughed out of the room,” he surmised. In conclusion as inmost of his "Commercialization of Regenerative Medicine" presentations, Dr. Badylak summarizes his research and the work he loves: “This is not easy; this is fun; this is inevitable.”

Institute Contributions to Recent Scientific Conferences

American Society for Artificial Internal Organs (ASAIO)
June 17-19, 2004: Washington, DC

The following graduate students received Fellowship Awards:

Phil Marascalco, student of Dr. Kameneva
Vikram P. Sundararaman, student of Dr. Borovetz
Joie N. Marhefka, student of Dr. Kameneva

Papers/Presentations/Session Chairs

“A Randomized Trial Of The Effectiveness Of Adult Stem Cell Therapy For The Deteriorated Myocardium”; Patel, A

"On Survival Of Blood Cells In Artificial Organs."; Kameneva, M

"Session Chair: Bridging Of Materials With Cells, Tissues And Organelles." Wagner, W

"Static Mixer To Improve Bound Solute Dialysis (BSD) Performance With Standard Dialysis Equipment."; Patzer, J.

"Development of Ventricular Assist Devices For Infants And Small Children"; Snyder, T.

"Effects of Surface Modifications On In Vivo Biocompatibility In Rotary Blood Pumps"; Snyder, T.

"Further Development of A Drag-Reducing Component For Artificial Blood."; Marhefka, J.

"Effect Of Drag Reducing Polymers (DRPS) On Viscoelastic Properties Of Blood Of Normal And Diabetic Rats."; Marascalco, P.

"Development of A Rat Model For Cardiopulmonary Bypass (CPB) To Study The Effects Of Deep Hypothermic CPB On Cerebral Glucose Consumption And Oxygen Uptake."; Sundararaman, V.

"CFD analysis of hydrodynamic characteristics of a novel paracorporeal pumping artificial lung.”; Svitek, R. and Zinovik, I.

“Evaluation of Local Gas Exchange in an Artificial Lung Catheter”; Eash, H.

“Future of Artificial Lungs, New Inspiration”; Zwischenberger, J. featured prominently the work of the Federspiel Lab

REGENERATE
June 9-12, 2004: Seattle, WA

Papers/Session Chairs

“HIF-1a Decreases Upregulation of Proteoglycan Synthesis in Bovine Articular Cartilage Following Oxygen Exposure”; Brucker, Peter, U., Izzo, Nicholas, J., Vogt, Molly, T., Fu, Freddie, H., Chu, Constance, R.

“Fetal Wound Healing: Overview and Potential Mechanisms of Scarless Wound Regeneration”;
Hebda, Patricia A.

“ECM Scaffold Degradation Products as Chemoattractants for Primary Endothelial Cells”; Stephen F. Badylak, and Mervin C. Yoder

“A Novel Guide for Neuronal Tissue Engineering Applications”; Santiago, Lizzie, Y., Marra, Kacey, G.

“A New Method of Measuring the Flexural Rigidity of Normal and Tissue Engineered Rabbit Vocal Folds”;
Ali Mirnajafi., Michael S. Sacks ,Jeremy Raymer,Joseph E. Dohar, Patricia A Hebda

“Thermoplastic Elastomer Design and Processing for Scaffold Applications”; Wagner, William

“Gene therapy and tissue engineering based on muscle-derived stem cells: Promising applications for tissue regeneration”; Huard, Johnny

“Growth and Development Laboratory Matrix Metalloproteinase Therapy Improves Healing of Injured Skeletal Muscle”; Bedair, Hany, Li, Yong, Huard, Johnny

"Effects of blood-soluble drag-reducing polymers on macro- and micro-hemodynamics; potential applications in regenerative medicine"; Kameneva, M.V.

"Extracorporeal Liver Support -Technologies for the Biological Component"; Gerlach, J.C.

Session Chair: Liver Support; Gerlach, J.

Invited lecture "Strategies for the biologic component of liver support"; Gerlach, J.

Teaching Tissue Engineering – McGowan Contributor: Sfeir, Charles

Poster Presentations

“Targeted Delivery of Microspheres to Vascular Tissue”
Deglau, Timothy E., Villanueva, Flordeliza S., Wagner, William R.

“Self-Assembly of Bioactive Nanotubes”
Lee, Sang Beom, Koepsel, Richard R., and Russell, Alan J.

“Tissue Engineering Show and Educational Partnership: The Scholarship of Integration for Public Outreach”
Pollock, John A., Farkas, Daniel L., Russell, Alan J.

“A Method for the Isolation of Canine Endothelial Progenitor Cells from Peripheral Blood”
Reing, Janet, Irvine, Renae, Badylak, Stephen

“Gradient Scaffolds for Tissue Engineering Applications”
Thangappan, Ravikumar, Wargo, Sara, L., Russell, Alan, J.

“DOPA-containing curable prepolymer as a potential wound healing matrix”
Jianying Zhang, Alan H. Wells, David L. Steed, Eric J. Beckman

Funding Opportunities:

For Individuals Affiliated with McGowan Institute for Regenerative Medicine

Questions : Contact Jo-Anne Drabik at drabikj@upmc.edu or 412-235-5124.

National Institutes of Health Notice

Notice: NOT-OD-04-036

May 2004 Conference on the HIPAA Privacy Rule and Research

Release Date: April 1, 2004

URL:http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-036.html

Continuing its efforts to educate the research community, the NIH is holding a one-day conference on May 26, 2004 entitled, “HIPAA and the Privacy Rule: One Year Into Privacy Rule Implementation.” The conference will examine how research has been affected by the implementation of the HIPAA Privacy Rule. Topics to be covered include: clinical research, repositories and databases, health services research, mental health research, and public health activities. Speakers include officials from NIH, the HHS Office for Civil Rights, the HHS Office for Human Research Protections, the U.S. Food and Drug Administration, the Centers for Disease Control and Prevention, the Centers for Medicare and Medicaid Services, the Agency for Healthcare Research and Quality, and the Substance Abuse and Mental Health Services Administration. There are no fees to attend this meeting, but participants must pay their own travel and lodging costs. You need to register to attend at: http://www.capconcorp.com/hipaa04/

National Institutes of Health

Title: Change in Direct Cost Limitations on Solicited Applications

Release Date: April 30, 2004

Notice: NOT-OD-04-040

URL: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-040.html

NIH announces a revision of its policy on direct cost limitations on solicited applications published after this notice. Applications in response to those Program Announcements (PAs) and Requests for Applications (RFAs) that include a limitation on direct costs are to exclude from that limit the facilities and administrative (F&A) costs requested by consortium participants. The F&A costs requested by the consortium will be reflected in the PHS 398 application according to current instructions, and F&A costs awarded under these programs will continue to be awarded under the current practice. However, these consortium F&A costs will not be counted as a direct cost when determining if an applicant is in compliance with a direct cost limitation on a solicited application.

As stated in NIH’s ROADMAP Research Teams of the Future, initiative, NIH recognizes the increased need for support of interdisciplinary research and research teams. Programs that include a limitation on direct costs without the exclusion of consortium F&A costs create a disincentive to the establishment of consortiums, as the inclusion of a consortium’s associated F&A costs reduce the amounts which can be requested for other direct costs within a cost ceiling. This change will allow applicants for these programs to propose the necessary research teams via consortium arrangement without a negative impact their ability to fully utilize the direct cost limitations of the solicitation.

Please note that this does not change the NIH policy on the acceptance of applications requesting direct costs of $500,000 or more for any one year (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html). If you have questions on this Notice, please contact the Grants Management Specialist listed in the RFA/PA, or the Division of Grants Policy at (301)435-0949.

National Institutes of Health

Title: Collaborative Pediatric Critical Care Research Network

Release Date: April 16, 2004

RFA Number: RFA-HD-04-004

Expiration Date: August 10, 2004

CFDA Number: 93.865

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-04-004.html

Letter of Intent Receipt Date: July 12, 2004

Application Receipt Date: August 9, 2004

Purpose: The National Institute of Child Health and Human Development (NICHD) invites applications from investigators willing to participate with the NICHD under a cooperative agreement (U10) to initiate a multi-center program designed to investigate the safety and efficacy of treatment and management strategies to care for critically ill children, as well as the pathophysiological bases of critical illness and injury in childhood. This network will promote the efficient comparison of novel critical care treatment methods and management strategies of potential benefit for children who are critically ill. The objective of this Request for Applications (RFA) is to establish and maintain the infrastructure required for a network of approximately six clinical centers to perform multiple clinical trials as well as pertinent descriptive and translational research for children who are critically ill. An RFA for a Data Coordinating Center to support the network is separately published (RFA HD-04-015). The established network of academic centers will be able to study the required numbers of patients using rigorous common protocols and can provide answers more rapidly than individual centers acting alone.

National Institutes of Health

Title: Preapplication Meeting for the RFA on Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers (RFA-AR-04-008)

Release Date: April 27, 2004

Notice: NOT-AR-04-002

URL: http://grants.nih.gov/grants/guide/notice-files/NOT-AR-04-002.html

This notice is an addendum to RFA-AR-04-008, "Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers," which was released in the NIH Guide for Grants and Contracts on March 18, 2004.

This gives notice that the NIAMS, NINDS, and NICHD have scheduled an informational pre-application meeting at which Program and review staff will make presentations that explain their goals and objectives for the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers described in RFA-AR-04-008 (http://grants.nih.gov/grants/guide/rfa-files/RFA-AR-04-008.html) and answer questions from the attendees. All interested prospective applicants are invited. Applicants may submit written questions prior to the meeting by contacting staff members listed in the original RFA.

The meeting is scheduled for May 26, 2004, 11:00 A.M. - 3:30 P.M., in Room 803, One Democracy Plaza, 6701 Democracy Boulevard, Bethesda, Maryland. Further questions regarding location may be addressed to Ms. Wendy Pang, (telephone: 301-594-5055 or e-mail: pangw@mail.nih.gov). Those who wish to participate using teleconference facilities may contact the videodesk, (telephone 301-594-8433 or e-mail: videodesk@list.nih.gov and attention Felice Harper and Kevin Roberts).

Additionally, consult the following website, established as an information resource for this RFA: http://www.niams.nih.gov/rtac/funding/grants/muscular_dystrophy_2004.htm

Inquiries:

Richard W. Lymn, Ph.D.
Chief, Muscle Biology Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-5128
FAX: (301) 480-4543
Email: LymnR@mail.nih.gov

National Institutes of Health

Title: Support for Human Specimen Banking in NCI-Supported Cancer Clinical Trials

Release Date: April 29, 2004

RFA Number: RFA-CA-05-017

Expiration Date: July 22, 2004

CFDA Numbers: 93.394, 93.395

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-05-017.html

Letter of Intent Receipt Date: June 21, 2004

Application Receipt Date: July 21, 2004

Purpose: The purpose of this initiative is to support the infrastructure needed to ensure the collection of, storage of, and access to high-quality, well-annotated human specimens collected from and representative of the patient populations entered into NCI-funded, phase III clinical treatment trials. The advent of powerful molecular technologies and the emergence of targeted therapeutics have opened the door to developing more effective and, in some cases, individualized treatment of patients with cancer. Access to specimens with associated high-quality clinical, treatment, recurrence, and outcome data will be critical to developing and validating the tests needed for diagnosis, target identification, and prediction of response to therapy. Developing and effectively using cancer interventions based on the comprehensive analysis of critical pathways of cancer initiation and progression will ultimately require access to specimens from patients treated in prospective randomized trials. High quality banks of uniformly collected specimens with validated clinical and outcome data will be essential for development and delivery of the new diagnostic and predictive tools that are critical to eliminating the suffering and death due to cancer by 2015. Groups organizing and carrying out phase III clinical trials are uniquely positioned to provide the high quality specimens and have the informative clinical data and resources needed to meet this challenging goal.

American Heart Association

Title: National Established Investigator Award

Posted Date: May 05, 2004

Funding Opportunity Number: AHA-GRANTS-050504-001

Due Date for Applications: July 12, 2004 Applications must be received electronically via the AHA's web site by 5:00 p.m. Central Time. Applicants who encounter technical difficulties with the electronic submission must contact the National office prior to the deadline; otherwise their applications will be rejected. Late applications will not be accepted.

URL: http://www.americanheart.org/presenter.jhtml?identifier=3019795

The National Research Program funds research broadly related to cardiovascular function and disease, stroke or to related clinical, basic science, bioengineering or biotechnology, and public health problems.

National investigators are also encouraged to submit applications in the following areas of priority research: To improve population and/or behavioral methods or develop novel methods to advance primary and/or secondary prevention goals of the AHA. To improve the effectiveness of therapy, quality of care and systems of healthcare delivery goals of the AHA. Investigators working in two areas of research are particularly encouraged to submit applications. Proposals in these research areas will compete for funding with those in all other areas.

Objective: To support mid-term investigators with unusual promise and an established record of accomplishments; candidates have a demonstrated commitment to cardiovascular or cerebrovascular science as indicated by prior publication history and scientific accomplishments. A candidate’s career is expected to be in a rapid growth phase.

Science Focus: The American Heart Association funds research broadly related to cardiovascular function and disease, stroke or to related clinical, basic science, bioengineering or biotechnology, and public health problems. National investigators are also encouraged to submit applications in two areas of priority research (see 1 and 2 above).

Disciplines: All basic disciplines as well as epidemiological, community and clinical investigations, and bioengineering/biotechnology investigations that bear on cardiovascular and stroke problems.

Target Audience: M.D., Ph.D., D.O. or equivalent doctoral degree at application. Applicants must be faculty/staff members. At the time of award activation, the investigator is usually four (4) years but no more than nine (9) years since first faculty/staff appointment at the assistant professor level or equivalent (including, but not limited to, research assistant professor, research scientist, staff scientist, etc.). Must meet institutional requirements for grant submission at time of application.

National Institutes of Health

Title: Molecular Libraries Screening Centers Network (MLSCN)

Release Date: April 21, 2004

RFA Number: RFA-RM-04-017 (see NOT-RM-04-011)

Expiration Date: August 25, 2004

CFDA Number: 93.389

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-017.html

This RFA is developed as an NIH Roadmap initiative (http://nihroadmap.nih.gov). All NIH Institutes and Centers participate in Roadmap initiatives. The RFA will be administered by the National Institute of Mental Health (NIMH) on behalf of the NIH.

Letter of Intent Receipt Date: July 26, 2004

Application Receipt Date: August 24, 2004

Purpose: The Institutes and Centers (ICs) of the NIH invite applications from investigators interested in participating in an NIH Roadmap pilot program to establish the Molecular Libraries Screening Centers Network (MLSCN). The MLSCN will be a national resource capable of providing innovative high throughput molecular screening (HTS) approaches for the identification of small organic molecules (compounds) that are active in biological assays, and synthetic chemistry to improve the utility of these molecules as bioactive probes for in vitro, and potentially in vivo, studies of normal and abnormal physiology of cells, organs, model systems, and/or organisms.

The over-arching goal of the MLSCN is to screen large numbers of compounds to identify and subsequently optimize small molecules that selectively interact with specific biological targets so that they may be used as probes to understand the function of newly characterized proteins, and to analyze physiological processes, cellular phenomena, and disease mechanisms. NIH’s primary objective for this new public sector screening effort is to identify compounds that will constitute a new set of research tools for use by scientists in both the public and private sector.

In addition, it is anticipated that some of these compounds will be used by both public and private sector scientists as chemical platforms that may lead to new therapeutics. Accordingly, NIH intends that all of the data and information generated by the MLSCN will be made publicly available in a new database to be known as PubChem. In this regard, NIH recognizes that there are significant issues concerning intellectual property rights with respect to patentable inventions developed during the MLSCN program. This subject is discussed more fully below. Within this context however, it is NIH’s hope that inventors will exercise any intellectual property rights retained on inventions developed as part of the MLSCN program in a way that will promote wide accessibility to and further development of the resources that are generated.

Applications are invited from groups that have the interest and capabilities to develop and/or expand their assay development/optimization, screening, and synthetic chemistry operations as well as groups with established capabilities in these domains.

American Heart Association

Title: National Scientist Development Grant

URL: http://www.americanheart.org/presenter.jhtml?identifier=3004142#SDG

Objective: To support highly promising beginning scientists in their progress toward independence by encouraging and adequately funding research projects that can bridge the gap between completion of research training and readiness for successful competition as an independent investigator.

Disciplines: All basic disciplines as well as epidemiological, community and clinical investigations that bear on cardiovascular and stroke problems.

Target Audience: M.D., Ph.D., D.O., D.V.M. or equivalent doctoral degree at application. Applicants should be faculty/staff member initiating independent research careers, usually at the rank of instructor or assistant professor (or their equivalents). Must have faculty/staff appointment at activation. At the time of award activation, no more than four years will have elapsed since an applicant's first faculty/staff appointment at the assistant professor level or its equivalent. Applications may be submitted for review in the final year of a postdoctoral research fellowship or in the initial years of the first faculty/staff appointment. Must meet institutional requirements for grant submission at time of application. An applicant cannot hold, nor have held, any other national award prior to the activation date of the Scientist Development Grant.

American Heart Association

Title: National Established Investigator Award

Updated: March 15, 2004

Application Deadline: July 12, 2004

URL: http://www.americanheart.org/presenter.jhtml?identifier=3019795

The National Research Program funds research broadly related to CVD and stroke and encourages applications in such areas.

Investigators working in two areas of research (see below) are particularly encouraged to submit applications. Proposals in these research areas will compete for funding with those in all other areas.

To improve population and/or behavioral methods or develop novel methods to advance primary and/or secondary prevention goals of the AHA. more

To improve the effectiveness of therapy, quality of care and systems of healthcare delivery goals of the AHA.

National Institutes of Health

Title: Centers of Excellence in Molecular Hematology

Release Date: May 7, 2004

RFA Number: RFA-DK-04-015

CFDA Number: 93.849

URL: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-041.html

Letter of Intent Receipt Date: October 15, 2004

Application Receipt Date: November 16, 2004

Purpose: The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites grant applications for Centers of Excellence in Molecular Hematology (CEMH). The NIDDK anticipates the award of three competing Core Center Grants (P30) in Fiscal Year 2005.

The Centers of Excellence in Molecular Hematology are part of an integrated program of hematologic diseases-related research support provided by the NIDDK. The Centers currently funded in this program have provided a focus for increasing collaboration and improving the cost-effectiveness of supported research among groups of successful investigators at institutions with an established, comprehensive hematologic diseases research base. An open competition is invited, in order to renew and strengthen this program.

National Institutes of Health

Title: NIH Policy on Sharing of Model Organisms for Biomedical Research

Release Date: May 7, 2004

Notice: NOT-OD-04-042

URL: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html

As a public sponsor of biomedical research, NIH is committed to supporting national and international efforts that encourage the sharing and dissemination of important research resources. NIH is also cognizant of the need to support reasonable incentive structures that facilitate commercial development or translation of basic research findings. Restricted availability of unique research resources, upon which further studies are dependent, can impede the advancement of research. Conversely, sharing biomaterials, reagents and data in a timely manner has been an essential element in the rapid progress that has been made in research on many model organisms for biomedical research. The NIH is interested in continuing to ensure that the research resources developed with NIH funding are made readily available in a timely fashion to the research community for further research, development, and application, in the expectation that this will further the research enterprise and accelerate the development of products and knowledge of benefit to the public. At the same time, NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with federal funding pursuant to the Bayh-Dole Act.

This notice reaffirms NIH support for the concept of timely sharing and distribution of biomedical research resources [See NIH Grants Policy Statement (http://grants.nih.gov/grants/policy/nihgps_2003/index.htm); NIH Research Tools Policy, also referred to as Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources: Final Notice (http://ott.od.nih.gov/NewPages/RTguide_final.html), December 1999], and provides further guidance with particular attention on model organisms for biomedical research. Model organisms include but are not restricted to mammalian models, such as the mouse and rat; and non-mammalian models, such as budding yeast, social amoebae, round worm, fruit fly, zebra fish, and frog. [See NIH Model Organism for Biomedical Research Website at http://www.nih.gov/science/models/ for information about NIH activities related to these resources]. Research resources to be shared include genetically modified or mutant organisms, sperm, embryos, protocols for genetic and phenotypic screens, mutagenesis protocols, and genetic and phenotypic data for all mutant strains. Genetically modified organisms are those in which mutations have been induced by chemicals, irradiation, transposons or transgenesis (e.g., knockouts and injection of DNA into blastocysts) or those in which spontaneous mutations have occurred. By sharing of research resources and, thus, avoiding the duplication of very expensive efforts to generate model organism models, the NIH is able to support more investigators than if these useful models had to be generated in duplicate by more than one NIH funded investigator.

This statement applies to extramural investigators funded by NIH grants, cooperative agreements, and contracts, including SBIR and STTR awards. Guidelines already in place for the intramural research program are consistent with those for the extramural community (for example, see http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/resources.htm).

To further extant NIH resource sharing policies, all investigators submitting an NIH application or contract proposal beginning with the October1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding so that other researchers can benefit from these resources, OR state appropriate reasons for why such sharing is restricted or not possible. Unlike the NIH Data Sharing Policy, the submission of a model organism sharing plan is NOT subject to a cost threshold of $500,000 or more in direct costs in any one year, and is expected to be included in all applications where the development of model organisms is anticipated. (The NIH Final Statement on Data Sharing is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html)

The adequacy of plans for sharing model organisms will be considered by reviewers when a competing application is evaluated. Reviewers will be asked to describe their assessment of the sharing plan in an administrative note and, normally, will not include their assessment in the overall priority score. For some special initiatives, such as Request for Applications (RFA) and Request for Proposals (RFP) specifically directed to the development of model organisms, reviewers may be asked to integrate their evaluation of the plan for sharing with other review criteria and factor their assessment into the overall evaluation of scientific merit.

As the expectations and tools available to facilitate model organism sharing continue to evolve, maximum flexibility is encouraged to allow for renegotiations during the project period at the request of either the Institute/Center (IC) or the funded institution in response to materially new and/or unforeseen information or developments. Applicants/Offerors responding to a RFA or RFP may find additional requirements related to resource or data sharing in the specific announcement. Applicants/Offerors are encouraged to discuss their sharing plans with their NIH program contact, who also can direct them to existing repositories or national coordinating centers. A reasonable time frame for periodic deposition of material and associated data should be specified in the application.

Applicants/Offerors are also expected to address as part of the sharing plan if, or how, they will exercise their intellectual property rights while making model organisms and research resources available to the broader scientific community. At a minimum, the plan should address the following questions in a clear and concise manner:

Will material transfers be made with no more restrictive terms than in a Simple Letter Agreement (SLA)(http://ott.od.nih.gov/NewPages/Rtguide_final.html#sla) for the transfer of materials or the Uniform Biological Material Transfer Agreement (UBMTA) (http://ott.od.nih.gov/NewPages/UBMTA.pdf)?

How would inappropriate “reach-through” requirements (as discussed in the NIH Research Tools Policy) on materials transferred be addressed?

How will technologies remain widely available and accessible to the research community, for example, if any intellectual property rights arise for which a patent application may be filed?

Applicants/Offerors are encouraged to inform and/or confer with their institutional offices of technology transfer and other relevant institutional offices to develop plans for addressing these requirements. Applicants/Offerors are reminded that the research institution is required to submit a report of each subject invention to NIH within two months after the inventor discloses it in writing to institutional personnel responsible for invention matters.

In their evaluation of non-competing continuation applications, NIH program staff may consider, as part of the criteria for continued funding, adequate progress in model organism sharing as well as a demonstrated willingness to make research resources developed during the project widely available to the research community. Failure to comply with NIH research resource sharing policies, guidelines, and the accepted plan may also be carefully considered by NIH staff in future funding decisions for the investigator and the investigator’s institution.

Investigators may request funds in their application/proposal to defray reasonable costs associated with sharing materials or data or transfer of model organisms and associated data to appropriate repositories. Investigators are encouraged to confer with their technology transfer office and/or office of sponsored programs for guidance.

National Institutes of Health

Title: Nanomedicine Center Concept Development Awards

Release Date: May 4, 2004

RFA Number: RFA-RM-04-018

Expiration Date: July 27, 2004

CFDA Number: 93.867

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-018.html

Application Receipt Date: July 26, 2004

This RFA is developed as an NIH roadmap initiative (http://nihroadmap.nih.gov). All NIH Institutes and Centers participate in roadmap initiatives. The RFA will be administered by the National Eye Institute (NEI) on behalf of the NIH.

This RFA has two purposes:

Part 1 – describes a new initiative to support a network of NanomedicineDevelopment Centers. This part of the RFA includes a description of an emerging NIH vision of Nanomedicine and the scientific basis driving this initiative.

Part 2 – presents a solicitation of applications, or more aptly, “white papers,” for applicants to request support for planning the NanomedicineDevelopment Centers.

Part 1 – Nanomedicine Initiative Description and Research Objectives: Nanomedicine, an offshoot of nanotechnology, is a new term whose definition is evolving. In the present context, it refers to highly specific medical intervention at the molecular scale for curing disease or repairing tissue. To stimulate work in this field, the NIH will support a major research effort to obtain the fundamental knowledge required to make nanomedicine a reality. It is at this size scale – about 100 nm or less - that biological molecules form the basis of systems that provide structure, control, signaling, homeostasis, and motility in cells. There have been many scientific and technological advances in both the physical and biological sciences over the past several years that make nanomedicine research particularly attractive at this time. For example, new tools are being developed that permit imaging of structure at this scale, high speed measurement of the dynamic behavior of molecular assemblies, and measurement of forces at the molecular scale. These advances are complemented, on the biological side, by our knowledge of the human genome and a greater understanding of the molecular pathology of some diseases. The future of nanomedicine shows promise for providing us with better control of intracellular machinery, leading to better diagnostic tools and more specific treatments of disease with fewer side effects.

Part 2 – Solicitation of the Concept Development Memo (CDM): The CDM is a brief “white paper” that outlines the applicant’s vision for a Nanomedicine Development Center and the set of problems the center might try to solve. This vision should begin with the concepts described in this RFA, and develop them further based upon the applicant’s understanding of the science, the technology, and the medical needs. The applicant should also propose a structure for the proposed center and include a budget and justification to support activities necessary to prepare a Concept Development Plan (CDP, see below). Concept Development Awards (CDA) will be made by September 30, 2004, and the deadline for CDPs will be February 15, 2005. Therefore, in their CDM, applicants should propose a budget that can be used effectively during this time period to gather key investigators for planning meetings, to organize small workshops with members of other scientific, clinical or engineering communities, or organize any other planning activities that will facilitate the assembly of teams and the production of a CDP. The award notice for the CDA will contain an explicit term, requiring submission of a CDP to the NIH by February 15, 2005.

National Institutes of Health

Title: Characterization, Behavior and Plasticity of Pluripotent Stem Cells

Release Date: May 4, 2004

PA Number: PA-04-101

Expiration Date: July 2, 2007

CFDA Numbers: NINDS 93.853, NIDCD 93.173, NIA 93.866, NICHD 93.929, NCI 93.396, NIDA 93.279, and NIMH 93.242.

URL: http://grants.nih.gov/grants/guide/pa-files/PA-04-101.html

Application Receipt Dates: February 1, June 1 and October 1

Purpose: Stem cells appear to possess great plasticity, but the cellular mechanisms regulating their behavior and fate are not understood. If these mechanisms can be harnessed to obtain cells specifically required for therapy, diagnosis or drug discovery, it may be possible to restore function to tissues and organ systems that have been compromised by congenital disorders, developmental malfunction, age, injury, disease or drug exposure. The National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communication Disorders (NIDCD), the National Institute on Aging (NIA), the National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute of Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH) invite applications for studies on the characterization, behavior and plasticity of human and non-human stem cells, regulation of their replication, differentiation, integration and function in the nervous system, and the identification and characterization of normal and tumor stem cells. An understanding of intrinsic and extrinsic signals, especially those involved in the stem cell niche, age-dependent processes and genetic factors that govern the activities of pluripotent cells is crucial in order to utilize them to develop safe and effective treatments for the restoration of function, or to prevent their transformation into tumor-generating cells. Although animal studies demonstrate that stem or progenitor cells can be derived from a variety of tissues and from hosts of different ages, the requirements and potential for differentiation of each type of pluripotent cell appear to be unique. We lack a clear understanding of the intrinsic properties that distinguish one population from another, and how these populations differ in their response to similar conditions in vitro and in vivo. This Program Announcement, which replaces PA-01-078 (Biology of Non-Human Stem Cells in the Environment of the Nervous System) and PA-02-025 (Plasticity of Human Stem Cells in the Nervous System), encourages applications to study the fundamental properties of all classes of human and non-human stem cells, and to confirm, extend, and compare the behavior of stem cells that are derived from different sources and ages or exposed to different regimes in vitro and in vivo or derived from tumors. Of high priority are studies to develop methods for identifying, isolating and characterizing specific precursor populations at intermediate stages of differentiation into neurons and glia, and their relationship to tumor-generating cells. Projects that address comparisons between different classes of human stem cells and between human and non-human stem cells would also be directly relevant to this PA.

National Institutes of Health

Title: Testing Tobacco Products Promoted to Reduce Harm

Release Date: May 5, 2004

PA Number: PA-04-103

Expiration Date: March 2, 2006

CFDA Numbers: 93.393, 93.399, 93.279

URL: http://grants.nih.gov/grants/guide/pa-files/PA-04-103.html

Application Receipt Dates: February 1, June 1 and October 1

Purpose: The purpose of this Program Announcement (PA) is to stimulate multidisciplinary research on potential reduced-exposure tobacco products, both smoked and smokeless, through the interplay of basic, biological, and behavioral research, surveillance, and epidemiology. The tobacco industry is currently promoting some new products with claims that they are less harmful or less addictive because these products purportedly deliver lower amounts of toxic, carcinogenic, and/or addictive agents to the user compared with conventional products. However, to date, the scientific evidence is insufficient to evaluate whether these new products actually reduce the users’ exposure or risk for tobacco-related diseases. The key research question of this PA is, “Do potential reduced-exposure tobacco products provide a truly, less-harmful alternative to conventional tobacco products, both on the individual and population level?”

National Science Foundation

Title: Cross-Directorate Activities (CDA)

Program Description Number: PD 04-1397

URL: http://www.nsf.gov/pubs/progdesc/2004/sbe/1397.htm

Due Dates: No fixed deadline. Dates vary according to CDA intiative. (See website's related information links.)

Description: This program encompasses a collection ofFoundation-wide activities that provide support for human resource development and infrastructure improvement. The Office of Cross-Directorate Activities (CDA) houses and provides information about various cross-directorate programs in which the Division of Social and Economic Sciences and the Division of Behavioral and Cognitive Sciences participate. CDA administers some programs directly and coordinates other programs aimed at Foundation-wide goals of increasing the participation of women, minorities, and the disabled in science and engineering; encouraging and rewarding promising new faculty; support of undergraduate, graduate, and postdoctoral activities; and improving the infrastructure of the social and behavioral sciences.

The CDA Program also supports special studies, analyses, and workshops on issues affecting social and behavioral science disciplines, including issues that span organizational boundaries and division priorities. The program supports activities that address needs in education, human resources, and the creation of a diverse personnel pool. Investigators should discuss their ideas with the program directors. Proposals may be submitted at any time.

National Institutes of Health/NHLBI

Title: Specialized Centers for Cell-Based Therapy (SCCT) for Heart, Lung, and Blood Diseases and Data and Coordinating Center (DCC)

Release Date: May 10, 2004

RFA Number: RFA-HL-04-017

Expiration Date: September 22, 2004

CFDA Numbers: 93.837, 93.838, 93.839

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-04-017.html

Letter of Intent Receipt Date: August 21, 2004

Application Receipt Date: September 21, 2004

Purpose: The primary objective of the Specialized Centers of Cell-based Therapy (SCCT) programs is to foster multidisciplinary research on clinically relevant questions thereby enabling basic science findings to be more rapidly applied to clinical problems. Recent discoveries provide new and unprecedented opportunities for the therapeutic use of stem, progenitor, and differentiated cells for new treatments. Stem cell research, coupled with regenerative medicine, offers the potential to treat major diseases of interest to the National Heart, Lung, and Blood Institute (NHBLI). The objective of this program is to establish and maintain (1) Specialized Centers for Cell-based Therapy (SCCT) to perform preclinical and clinical studies for cell-based therapy and (2) a Data & Coordinating Center (DCC) for the program. The clinical and basic research supported through this Request for Applications (RFA) will be related to cell-based therapy for the treatment of heart, lung, and blood diseases.

National Science Foundation

Title: Research Experiences for Undergraduates (REU)

Program Solicitation Number: NSF 04-584 (Replaces Document NSF 03-577)

CFDA Numbers: 47.074, 47.070, 47.076, 47.041, 47.050, 47.049, 47.078, 47.075

URL: http://www.nsf.gov/pubs/2004/nsf04584/nsf04584.htm

Full Proposal Deadline(s) (due by 5 p.m. proposer's local time):

Deadline for REU Supplement requests: Varies with the research program.

Deadline for REU Sites proposals: August 17, 2004.

I. Synopsis of Program: The Research Experiences for Undergraduates (REU) program supports active research participation by undergraduate students in any of the areas of research funded by the National Science Foundation. REU projects involve students in meaningful ways in ongoing research programs or in research projects specially designed for the purpose. This solicitation features two mechanisms for support of student research: REU Supplements and REU Sites. REU Supplements may be included in proposals for new or renewal NSF grants or cooperative agreements or as supplements to ongoing NSF-funded projects. REU Sites are based on independent proposals to initiate and conduct undergraduate research participation projects for a number of students. REU Sites projects may be based in a single discipline or academic department or be based on interdisciplinary or multi-department research opportunities with a strong intellectual focus. Proposals with an international dimension are welcomed. A partnership with the Department of Defense supports REU Sites in DoD-relevant research areas. Undergraduate student participants in either Supplements or Sites must be citizens or permanent residents of the United States or its possessions.

II. Program Description: The REU program, through both Supplements and Sites, aims to provide appropriate and valuable educational experiences for undergraduate students through research participation. REU projects involve students in meaningful ways in ongoing research programs or in research projects specially designed for the purpose. REU projects feature high-quality interaction of students with faculty and/or other research mentors and access to appropriate facilities and professional development opportunities. Active research experience is considered one of the most effective ways to attract talented undergraduates to and retain them in careers in science and engineering, including careers in teaching and educational research.
REU opportunities are an excellent way to reach broadly into the student talent pool of our nation. NSF is particularly interested in increasing the participation in research of women, underrepresented minorities, and persons with disabilities. REU projects are strongly encouraged to involve students who are members of these groups. Underrepresented minorities are African Americans, Hispanics, American Indians, Alaska Natives, and Native Hawaiians or Other Pacific Islanders.
Supplement and Site projects may be carried out during the summer months, during the academic year, or both. REU Sites may be proposed for durations of one to five years, with a three-year duration being typical in most NSF directorates. The term of REU Supplements may not exceed that of the underlying research project.

Supplementary Information: Some research programs within NSF provide Web sites with additional information about their REU activities. A directory of these Web sites can be found at http://www.nsf.gov/home/crssprgm/reu/nsfsites.htm.

The National Aeronautics and Space Administration

Title: NASA Research Announcement (NRA): Ground-Based Studies for Human Health in Space

Funding Opportunity Number: NNH04ZUU003N

Posted Date: May 25, 2004

Application Deadline Date: August 31, 2004

CFDA Number: 00.000 -- No Description Available

The National Aeronautics and Space Administration (NASA) Office of Biological and Physical Research (OBPR) solicits proposals for Ground-Based studies in selected areas of Biomedical Model Systems (BMS), Biomedical Research and Countermeasures (BR&C), and the National Space Biomedical Research Institute (NSBRI).

This consolidated NRA supports the following goals and objectives of the OBPR:

1. Understand the physiological mechanisms responsible for space-flight-related biomedical and behavioral changes in humans in support of countermeasure development;

2. Develop countermeasures that allow humans to live and work in microgravity for long durations, minimize the risks in readapting to gravity, and optimize crew safety, well-being, and performance; and

3. Identify, characterize, and mitigate health, environmental, and other operational human medical risks associated with space exploration.

Proposers may apply as an individual NASA investigator, or as an investigator to one of the established research teams of the NSBRI. Investigators may submit more than one proposal in response to this NRA; however, identical proposals may NOT be submitted to multiple programs.

All participants in this solicitation are strongly encouraged to promote general scientific literacy and public understanding of life sciences, the space environment, and the OBPR programs through formal and informal education opportunities. Where appropriate, supported investigators will collaborate with NASA to develop a plan for communicating their work to the public.

Starting on or about May 28, 2004, this solicitation will be available electronically via the Internet at: http://research.hq.nasa.gov/code_u/nra/current/NNH04ZUU003N/index.html.

Please Click on Current (Open) Solicitations where you will see the "Ground-Based Studies for Human Health in Space" listed in the table. Click on the entry NRA NNH04ZUU003N in the column labeled "Announcement Number." It will be open for the period May 28, 2004 through August 31, 2004;
proposals may be submitted at any time throughout the period.

For those who do not have access to the Internet, paper copies of this NRA can be obtained by calling (202) 479-9030, ext. 277. Please leave a voice mail message stating your full name, address with zip code, telephone number with area code, and the NRA number (NNH04ZUU003N).

The technical point of contact for this effort is Dr. Bette Siegel, Code UB, NASA Headquarters, Washington, DC 20546-0001. This notice constitutes a NASA Research Announcement as contemplated in FAR 6.102 (d) (2). Notice of Intent to propose is due June 28, 2004. Proposal due date is August 31, 2004.

Notwithstanding the posting of this opportunity at FedBizOpps.gov, Grants.gov, or at both sites, NASA reserves the right to determine the appropriate award instrument for each proposal selected pursuant to this announcement.

National Institutes of Health/NIDDK

Title: Centers for Polycystic Kidney Disease Research

Release Date: May 27, 2004

RFA Number: RFA-DK-04-011

Expiration Date: March 16, 2005

CFDA Number: 93.849

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-04-011.html

Letter of Intent Receipt Date: February 15, 2005

Application Receipt Date: March 15, 2005

Purpose: The National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) invites applications for Interdisciplinary Centers for Polycystic Kidney Disease Research (ICPKD) to expand the research infrastructure for both the autosomal dominant and autosomal recessive forms of polycystic kidney disease (ADPKD and ARPKD). These Centers are intended to attract a partnership of interdisciplinary research among investigators with scientific expertise who will use complementary and integrated approaches to study polycystic kidney disease.

Background: PKD is the fourth leading cause of chronic kidney disease (CKD) in America, affecting approximately 500,000 people. A striking feature of PKD is the variability with which it affects the patient. Some develop only a modest number of renal cysts during their lifetime and may not be aware of being affected by this disorder. Others develop a massive number of renal cysts and may reach renal failure at an early age. It is not unusual for cysts to develop in the liver and within the systemic vasculature. Evidence also indicates that in addition to documented cyst enlargement and interstitial fibrosis, apoptotic loss of non-cystic nephrons is a significant component of the pathology of PKD and may contribute to the progressive loss of renal function.

Much progress has been made since the initial solicitation for PKD centers in 1999. Examples include: improved animal models of disease due to increased understanding of the underlying molecular processes that result in cyst formation and growth; progress in understanding the role of the primary cilium in kidney tubule cyst formation; progress in understanding aneurysmal development in PKD.

The NIDDK has also funded two complementary multicenter clinical studies. In 1999, the NIDDK funded the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) (RFA-DK-99-003) to determine whether changes in anatomic characteristics of the kidneys of patients with PKD will be useful in providing surrogate measures for disease progression. Preliminary findings from this group over the next several years might inform the designs of clinical trials in patients with PKD in the near future. Then, in 2001, the NIDDK established the PKD Clinical Trials Network to design and implement clinical trials to determine which pharmacologic agents might slow the progressive loss of function in PKD. The first large interventional clinical trial in this network, called HALT-PKD, will be a randomized trial of renin-angiotensin axis blockade in patients with PKD.

Despite the progress noted above, however, many challenges remain in determining the genetic and pathophysiologic mechanisms of PKD.

National Institutes of Health

Title: PKD Research and Translation Core Centers

Release Date: May 28, 2004

RFA Number: RFA-DK-04-012

Expiration Date: March 16, 2005

CFDA Number: 93.849

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-04-012.html

Letter of Intent Receipt Date: February 15, 2005

Application Receipt Date: March 15, 2005

Purpose: The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites applications for Polycystic Kidney Disease (PKD) Research and Translation Core Centers to support both basic and clinical research on PKD. The goal of this program is to improve the lives of patients with polycystic kidney disease by improving therapies for this condition. Core Centers should provide shared institutional and national resources to facilitate basic and clinical research on PKD and improve its effectiveness in translating insights from basic biology to clinical practice. The Centers will also support pilot and feasibility studies to develop and test new approaches to therapy.

Background: PKD is the fourth leading cause of chronic kidney disease (CKD) in America, affecting approximately 500,000 people. A striking feature of PKD is the variability with which it affects the patient. Some develop only a modest number of renal cysts during their lifetime and may not be aware of being affected by this disorder. Others develop a massive number of renal cysts and may reach renal failure at an early age. It is not unusual for cysts to develop in the liver and within the systemic vasculature. Evidence also indicates that in addition to documented cyst enlargement and interstitial fibrosis, apoptotic loss of non-cystic nephrons is a significant component of the pathology of PKD and may contribute to the progressive loss of renal function.

Despite the progress noted above, many challenges remain in determining the genetic and pathophysiologic mechanisms of PKD that could potentially be targeted for therapeutic interventions.

National Institutes of Health

Title: Data Coordinating Center for National Collaborative Pediatric Critical Care Research Network

Release Date: May 27, 2004

RFA Number: RFA-HD-04-015

Expiration Date: August 10, 2004

CFDA Number: 93.865

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-04-015.html

Letter of Intent Receipt Date: July 9, 2004

Application Receipt Date: August 9, 2004

Purpose: The National Institute of Child Health and Human Development (NICHD) is interested in research in pediatric critical care, and has issued a Request for Applications (RFA-HD-04-004 http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-04-004.html) for the Collaborative Pediatric Critical Care Research Network to support approximately six Core Clinical Centers in clinical, translational, and descriptive research to investigate the safety and efficacy of treatment and management strategies in the care of critically ill children. As well, the Network will support research to enhance understanding of the pathophysiology of critical illness in childhood and its relationship to morbidity and disability in childhood. The Network will be funded by Cooperative Agreements, and will include a Data Coordinating Center to provide statistical expertise, assistance in study and protocol design, and analysis for Network trials and studies.

Additionally, the Data Coordinating Center (DCC) will support a registry of pediatric critical illness so that accurate epidemiology and trends in pediatric critical care may be tracked nationally. The resources of the DCC will be used to collect and analyze data, and the professional staff will collaborate in study selection and design with the Network Steering Committee. Data collection from non-Network sites or consortia, as well, will be managed by the DCC upon instruction of the Network Steering Committee. Areas of interest include all major areas of pathophysiology in pediatric critical illness.

Centers for Disease Control and Prevention

Title: Tuberculosis Elimination and Laboratory Cooperative Agreements

Billing Code: 4163-18-P

Program Announcement Number: 05003

Application Deadline: July 26, 2004

CFDA Number: 93.116

URL: http://www.cdc.gov/od/pgo/funding/05003.htm

Purpose: The purpose of the Tuberculosis (TB) Elimination Cooperative Agreement Program is to assist the current efforts of state and local TB programs to prevent, control, and eventually eliminate TB in the United States. Financial assistance is provided to TB programs to ensure that program needs for the core TB prevention and control activities are met. This program addresses the "Healthy People 2010" focus area of Immunization and Infectious Diseases in conjunction with the Government Performance and Results Act of 1993 (GPRA).

Funds are available for recipients to address the core TB prevention and control activities (i.e., completion of therapy, contact investigation, TB surveillance, TB public health laboratory, human resource development, and program evaluation).

Measurable outcomes of program progress will be in alignment with all of the following performance goal(s) for the National Center for HIV,STD, and TB Prevention (NCHSTP):
(1) Increase the percentage of TB patients who complete a course of curative TB treatment within 12 months of initiation of treatment (some patients require more than 12 months).
(2) Increase the percentage of TB patients with initial positive cultures who also are tested for and receive drug susceptibility results.
(3) Increase the percentage of infected contacts of infectious cases that are placed on treatment for latent TB infection (LTBI) and complete a treatment regimen.
(4) Increase the percentage of other high-risk infected persons who are placed on treatment for LTBI and complete a treatment regimen.
(5) Increase the percentage of immigrants and refugees designated as Class A, B1, or B2 who are appropriately evaluated and treated. Refer to the following web link, pages 2-6, for classification descriptions. http://www.cdc.gov/ncidod/dq/pdf/ds-forms-instructions.pdf
(6) For jurisdictions with greater than 50 reported cases of TB occurring annually in U.S.-born African Americans, decrease the case rate.
(7) Increase the proportion of adults with TB who have been tested for HIV.
The highest priority TB prevention and control activities are the following activities: finding all cases of active TB and ensuring, through appropriate case management, completion of therapy; finding and evaluating persons who have had contact with infectious TB patients, identifying those with TB and LTBI, and completing treatment of TB disease and LTBI; conducting program evaluation; ensuring human resource development through internal project training and education; and conducting TB surveillance and TB public health laboratory activities that are essential to addressing these priorities. Each of these activities is essential to effective TB prevention and control, and they are mutually reinforcing. Thus, they constitute a "package" of core activities. These activities should be carried out by all TB prevention and control programs, taking precedence over lower priority activities. Lower priority activities are those such as targeted testing and treatment of LTBI in high risk populations.
State TB programs differ in the level of services and resources they provide to local programs and the amount of authority they have over local program activities. Regardless of these differences, state programs should work closely with their local TB programs to ensure that program activities are carried out appropriately and program objectives are met. States should provide leadership and technical assistance to the local programs in assessing program needs, setting local objectives, measuring performance, identifying problems, and designing interventions. In addition, state TB programs should facilitate resolution of inter-jurisdictional challenges (such as ensuring continuity of case management and treatment of persons with active TB who move between jurisdictions).
Directly funded cities should work closely with the state TB program to facilitate consistency on statewide issues, minimize duplication of efforts, and share all reports that are sent to Centers for Disease Control and Prevention (CDC) with the state TB program.

Centers for Disease Control and Prevention

Title: Initiatives to Educate State Legislatures About Priority Public Health Issues

Billing Code: 4163-18-P

Funding Opportunity Number: 04157

CFDA Number: 93.283

URL: http://www.cdc.gov/od/pgo/funding/04157.htm

Letter of Intent Deadline: June 17, 2004

Application Deadline: July 12, 2004

Purpose: The purposes of this program announcement are to identify and implement national educational initiatives to address the need for accurate, comprehensive, and timely public health information for state legislatures through informational forums and other communication channels to address current and emerging public health concerns of state legislatures including barriers to effective public health.

These activities shall not be intended to support or defeat particular state legislation.
Priority areas for these activities are prevention, early detection, and control of disease, injury, and disability, and the strengthening of state and local public health agencies.
This program addresses "Healthy People 2010" focus areas of birth defects, developmental disabilities and health for people with disabilities; chronic disease and related risk factors; environmental health; Human Immuno Deficiency Virus (HIV), sexually transmitted diseases (STD) and Tuberculosis (TB); infectious disease; injury and violence prevention; immunization; occupational safety and health; public health practice and infrastructure. In addition, this program addresses emergency preparedness and response; genomics; health issues facing older Americans, and health disparities.
Measurable outcomes of the program will be in alignment with one (or more) of the following performance goals for the Centers for Disease Control and Prevention:
Increase Legislators awareness and understanding of current and emerging public health activities and issues. Assist in identifying state specific and national public health initiatives.

Increase understanding and knowledge of public health initiatives among state legislators.
Support understanding the public health missions, objectives, and activities of the Centers, Institutes, and Offices at the Centers for Disease Control and Prevention (CDC).

National Institutes of Health

Title: Myelodysplastic Syndrome (MDS): Seeking Cure Through Discovery on Pathogenesis and Disease Progression

Release Date: May 21, 2004

RFA Number: RFA-HL-04-033

Expiration Date: February 17, 2005

CFDA Number: 93.839

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-04-033.html

Letter of Intent Receipt Date: January 16, 2005

Application Receipt Date: February 16, 2005

Purpose: This Request for Applications solicits applications that seek new discoveries in the etiology and pathophysiology of myelodysplastic syndromes (MDS) with the aim to develop new and curative treatment options in the future. A separate RFA HL-04-034 (please see http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-04-034.html) is directed towards myeloproliferative disorders. Applicants are directed to apply to one or the other but not both RFAs.

Background: The frequency and incidence of MDS is increasing in the US population and is thought to be influenced by factors such as advancing age, the use of cytotoxic and mutagenic therapies for cancer, and greater exposure to environmental toxins. While some patients have an insidious onset of the disease that can even be remitting, others experience dramatic presentations including marrow failure or acute hematologic malignancy, which rapidly becomes fatal. The highly variable nature of MDS creates difficulties in the characterization and study of the syndromes and/or diseases that constitute evolving dysplasia of the hematopoietic system and transformation into malignancy.

The etiology and pathophysiology of myelodysplasia is poorly understood. The conditions may arise or evolve from fundamental defective stem cell biology or later disrupted and/or disordered cell lineage differentiation, maturation and proliferation of the hematopoietic system. In some patients the diagnosis is associated with genetic constitutional abnormalities. The occurrence of these blood disorders is also increasingly identified in patients following successful cancer therapy and/or transplantation procedures and presents as a secondary malignancy.

Myelodysplastic syndromes are considered clonal stem cell diseases that are characterized by peripheral cytopenias in the setting of a normocellular or hypercellular bone marrow that morphologically shows bilineage or trilineage dysplasia. Mechanisms of disease include pluripotent stem cell damage, abnormalities in proliferation, differentiation, and apoptosis leading to an ineffective hematopoiesis. The most common diagnosis include refractory anemia (RA), refractory anemia with ringed sideroblast (RARS), refractory anemia with excess blast (RAEB), and refractory anemia with excess blast in transformation (RAEB-T). MDS has a high propensity for transformation to myeloid leukemia but can transform into acute leukemia of other hematopoietic lineage. Overlapping features of MDS with aplastic anemia, T-cell large granular lymphocyte lymphoproliferative disorder, and paroxysmal nocturnal hemoglobinuria suggest a shared pathophysiologic mechanism of marrow failure. A category of secondary MDS is used when typical biologic characteristics of MDS occur after known constitutional or acquired abnormalities (e.g. association with genetic disorders or anti-neoplastic therapy). In addition, some clinical entities are being reclassified into "mixed" myeloproliferative and myelodysplastic disorders, such as chronic myelomonocytic leukemia, atypical myeloid leukemia, and juvenile myelomonocytic leukemia.

However, diagnostic criteria can be imprecise and treatment empiric until malignant transformation is evident. Other than hematopoietic stem cell transplantation (HSCT), no curative therapies are available. Many patients do not have access to nor are appropriate candidates for intensive HSCT therapy. Furthermore, successful outcome following transplant is limited by associated toxicities and complications. Otherwise, traditional chemotherapy, radiation, immunotherapy, biologic modifiers, growth factors, and transfusion support have been used with limited success and are primarily palliative. Therefore, new and improved therapies that will be acceptable for an older patient population are needed.

National Institutes of Health

Title: Cellular and Genetic Discovery Toward Curative Therapy in Myeloproliferative Disorders (MPD)

Release Date: May 21, 2004

RFA Number: RFA-HL-04-034

Expiration Date: February 17, 2005

CFDA Numbers: 93.839, 93.394

URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-04-034.html

Letter of Intent Receipt Date: January 16, 2005

Application Receipt Date: February 16, 2005

Purpose: This Request for Applications (RFA) solicits applications searching for new cellular and genetic markers associated with the origin and progression of myeloproliferative disorders (MPD) that can be applied to the future development of novel therapeutics with curative intent. A separate RFA HL-04-033 (please see http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-04-033.html) is directed towards myelodysplastic syndromes. Applicants are directed to apply to one or the other but not both RFAs.