McGowan Institute?
July 2009 | VOL.8, NO. 7 | www.McGowan.pitt.edu
Wake Forest Vascular Surgeon and Tissue Engineer Moves to McGowan Institute
The McGowan Institute for Regenerative Medicine is pleased to announce the recent appointment of Bryan Tillman, MD, PhD, to the position of Assistant Professor, Division of Vascular Surgery, University of Pittsburgh Medicine Center. As a clinician-scientist, Dr. Tillman will collaborate with many McGowan Institute faculty members to address some of the needs for engineered tissue he has observed as a surgeon.
Dr. Tillman’s research includes applications of tissue engineering to construct replacement vessels for use in dialysis access and for patients with peripheral vascular disease. Replacement of diseased vessels continues to be an important clinical dilemma. At present, for lack of a suitable alternative, synthetic grafts are currently used in many patients. These synthetic grafts, unfortunately, have a variety of complications that include blockage from blood clots and infection. Those problems substantially reduce long-term outcomes for patients and cost billions of dollars to correct.
Dr. Tillman attended Eastern Washington University in Cheney, WA, where he received Bachelors of Science degrees in Chemistry and Biology in 1994. He received his MD and also completed his PhD in the field of gene therapy using targeted viral vectors, both at the University of Alabama. Dr. Tillman completed his residency training in general surgery at the Ohio State University. From 2006 to mid-2009, he was at Wake Forest Institute for Regenerative Medicine as a Tissue Engineering Postdoctoral Research Fellow and a Vascular and Endovascular Surgery Clinical Fellow. In addition to publications in various journals, Dr. Tillman is a member of the American College of Surgeons, Society of American Gastrointestinal and Endoscopic Surgeons, and the Southern Association for Vascular Surgery.
Welcome, Dr. Tillman!
July marks the eighth anniversary of the McGowan Institute. I would like to take this opportunity to express my thanks and appreciation for the commitment of our team of 235 faculty members who have led the sustained growth in regenerative medicine research and practice at the University of Pittsburgh. Faculty alone can accomplish little. We are fortunate to be joined by a committed and visionary team of outstanding students, fellows and staff.
While it’s clear that multidisciplinary teams are necessary to progress quickly in our field, few organizations are fortunate enough to have the networked critical mass to achieve vertical integration. The McGowan Institute—coupled with UPMC and our industry partners—has the reach to advance medical research, clinical assessment, and quality of life for patients. Our aim is to save lives, reduce the cost of health care, stimulate recruitment of students, faculty, and clinicians, and to contribute to the economic growth of the field and thereby our region.
Real progress has been made in the field of regenerative medicine. Eight years ago the McGowan Institute scientific and clinical teams were excited about the prospects for tissue engineering and cellular therapies. It is interesting to note that the progress that has been made is now creating excitement in wider circles that include military caregivers, clinicians, the public and the investment community.
Partnerships are an important component of the Institute’s success. While the progress of our research is the result of many internal partnerships, we recognized several years ago that partnerships with industry, government agencies, and other academic institutions are equally important, as we do not have a monopoly on creativity.
To formalize and facilitate the development of external partnerships, this year we formed the Center for Industry Relations. The Center bridges our faculty with industry and is a key element in our drive for industry engagement and partnerships in regenerative and rehabilitation medicine. To date, through the Center, five major academic/industrial partnerships have been formed. We have launched a new initiative to develop a cadre of specialists to conduct an in-depth assessment of the alternative strategies of who will pay for regenerative therapies, how much, and when. The program also is establishing a regulatory affairs group that will advise our teams on regulatory pathways throughout their research programs. We see these capabilities as essential components in the movement of these emerging technologies from the lab to wide-spread clinical use. We were delighted to recruit Mr. Patrick Cantini to direct the Center in partnership with UPMC’s International and Commercial Services Division. Patrick was a Deputy Director of the Pittsburgh Tissue Engineering Initiative for many years and then spent a year as the Chief Business Officer at the Wake Forest Institute of Regenerative Medicine before deciding to return home to lead this important endeavor.
During the past year, the Institute in partnership with the UPMC Eye Center established the Louis J. Fox Center for Vision Restoration which is planning a comprehensive, multi-disciplinary research and clinical program dedicated to ocular regenerative medicine and improving quality of life for the vision-impaired. The Fox Center’s main focus is discovery and development of new cures for blindness and visual impairment, especially for those with problems affecting the retina, optic nerve, cornea, and lens. Through basic and clinical research, it will provide vision restoration through the augmentation of existing visual pathways or by providing vision through non-visual means.
At the McGowan Institute, our collective commitment remains to advance the sciences related to regenerative therapies, to educate scientists and engineers to pursue technologies related to regenerative medicine, and to lead a generation of clinicians in the implementation of regenerative therapies. We are sincerely appreciative of the support received from many individuals, foundations, and institutions for their commitment and support to this program.
We can all look forward to another exciting year of advances in science and progress in the movement of our emerging technologies to clinical and commercial use. As noted above, our progress is directly attributable to all of the McGowan Team, and next year we will collectively be able to look back and say that we have made more progress along this road that we are traveling together.
Sincerely,
SCIENTIFIC ADVANCES
Mthe quest for a cure for Type 1 diabetes, McGowan Institute for Regenerative Medicine faculty member Massimo Trucco, MD, Chief of the Division of Immunogenetics at Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, and his colleagues are currently conducting a randomized clinical trial to evaluate the safety of a new diabetes-suppressive cell vaccine. Dr. Tucco’s leukapheresis-based dendritic cell approach, approved by the U.S. Food and Drug Administration (FDA), is being tested in humans at Children’s Hospital.
If the leukapheresis-based approach continues to show exceptional safety, the researchers hope to launch a national clinical trial that will assess the effectiveness of the dendritic cells in pediatric patients to prevent diabetes or reverse the disease right after it is clinically confirmed. The study, “Autologous Dendritic Cell Therapy for Type 1 Diabetes Suppression: A Safety Study,” is currently open for enrollment.
Scientists increasingly hope to control Type 1 diabetes by curbing the rogue immune cells that cause it, before patients become completely dependent on daily insulin injections to survive. "Treating at onset in children is the best chance we have," said Dr. Trucco, whose novel vaccine is a possible immune therapy to control Type 1 diabetes. The research suggests if the therapy preserves enough precious insulin-producing cells before irreversible damage is done, maybe patients would need far less insulin.
The National Institutes of Health (NIH) reports that more than 1 million children and teenagers (age 19 and younger) have Type 1 diabetes. According to the NIH, 5 percent to 10 percent of diagnosed diabetes cases in the United States are Type 1 diabetes.
Read More…
McGowan Institute for Regenerative Medicine faculty member Blair Jobe, MD, associate professor of surgery, Director of Esophageal Research, and Director of Esophageal Diagnostics and Therapeutic Endoscopy, in the Heart, Lung, and Esophageal Surgery Institute at the University of Pittsburgh and UPMC, specializes in the treatment of esophageal cancer, esophageal motility disorders, and complicated gastroesophageal reflux disease (GERD). A possible result of long-term GERD is a condition called Barrett’s esophagus. Barrett’s esophagus is when the tissue lining the esophagus—the muscular tube that connects the mouth to the stomach—is replaced by tissue that is similar to the lining of the intestine. This process is called intestinal metaplasia.
Now there is an easier way to find out if you have Barrett's. It is the transnasal unsedated endoscopy, and it's done in an office. The technique is used to evaluate complications of GERD involving the pharynx, larynx, and esophagus as well as other suspected pathologies of the esophagus and stomach. The scope goes through the nose, down the throat, and into the esophagus.
Dr. Jobe believes that the procedure will help doctors understand why certain people with reflux develop Barrett's, but he said most people with this precancerous condition do not get cancer.
No signs or symptoms are associated with Barrett’s esophagus. The exact causes of Barrett’s Esophagus are not known. Although people who do not have GERD can have Barrett’s Esophagus, the condition is found about three to five times more often in people who also have GERD.
Since Barrett’s Esophagus is more commonly seen in people with GERD, most physicians recommend treating GERD symptoms with acid-reducing drugs. Improvement in GERD symptoms may lower the risk of developing Barrett’s Esophagus. A surgical procedure may be recommended if medications are not effective in treating GERD.
Barrett’s esophagus affects about 1 percent of adults in the United States. The average age at diagnosis is 50, but determining when the problem started is usually difficult. Men develop Barrett’s esophagus twice as often as women, and Caucasian men are affected more frequently than men of other races. Barrett’s esophagus is uncommon in children.
Read more...
McGowan Institute for Regenerative Medicine faculty member Ivet Bahar, PhD, John K. Vries Chair and professor in the Department of Computational Biology, and professor in Molecular Genetics and Biochemistry, along with a team of University of Pittsburgh researchers, have identified and described an enzyme inhibitor that allows them to increase the number of cardiac progenitor cells and therefore influence the size of the developing heart. The scientists used a zebrafish model that has powerful advantages for studying embryonic development.
Through the study of developmental biology the researchers gained a better understanding of the developing heart. Knowing the biologic pathways and signals that formed these organs whole and healthy in the first place will help as they try to create treatments that restore normal function to adult damaged or diseased tissues.
For the current paper, the research team focused on a small molecule called BCI, which hyperactivated FGF signaling. They then figured out how: BCI blocked the activity of an enzyme called Dusp6, a feedback regulator that would otherwise have tamped down the enhanced FGF signal.
Knowing that, BCI could then be used as a tool to find out what effect Dusp6 inhibition would have on heart development. The team reported that zebrafish treated with BCI had a greater number of cardiac progenitor cells and, ultimately, larger hearts.
Also, unraveling the fibroblast growth factor pathway has broad implications for improving wound healing. For example, FGF2 has been used in treatment of chronic skin ulcers and following burn surgery in Japan. Thus, BCI alone or in combination with FGF2 might accelerate the healing process and improve wound repair.
Read more…
AWARDS AND RECOGNITIONS
The McGowan Institute for Regenerative Medicine congratulates its faculty member Rory Cooper, PhD, and the staff of the Human Engineering Research Laboratories (HERL) on their selection by the Department of Veterans Affairs as the VA Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering. As a Research Center of Excellence, HERL will receive 1 million dollars each year for a 5-year cycle of funding before having to submit an application for competitive renewal. This is the third time HERL has received this award.
Directed by Dr. Cooper, this Center for wheelchair technology focuses on the design, development, and evaluation of new technologies to improve the mobility of physically-impaired individuals. In its short history, HERL has become an important contributor in the fields of wheelchair design, seating systems, transportation systems, and novel approaches to the delivery of assistive technology.
VA Rehabilitation Research and Development Service (RR&D) Centers focus on research in high-priority areas relevant to the rehabilitation needs of Veterans, providing cutting-edge solutions to the issues of chronic impairment. VA RR&D Centers serve as a resource primarily for Veterans but also for the rehabilitation community at large. These Centers are expected to:
- Successfully leverage core support funding through nationally competed and scientifically reviewed funding vehicles;
- Mentor and support young investigators, both clinician and non-clinician scientists, through pre- and post-doctoral programs, and recruit them into VA;
- Nurture strong interactive relationships with clinical service providers engaged in rehabilitation, long-term management of impairment, and overall quality of life issues;
- Facilitate effective information dissemination for a broad spectrum of audiences; and
- Foster the integration of research findings into clinical practice.
Stephen Strom, PhD was recently named the president-elect of the Cell Transplantation Society. Dr. Strom has been a member of the society since 1995, and he will serve as president for two years.
The Cell Transplantation Society aims to promote research and collaboration in cellular transplantation. Investigators of cell and tissue transplantation share problems and research targets on topics such as separation techniques, culture methods, and cryopreservation and banking, amongst other issues.
Dr. Strom is a Professor of Division of Cellular and Molecular Pathology in the Department of Pathology at the University of Pittsburgh. His research interests include hepatocyte transplantation as a clinical treatment of liver disease, expression and the regulation of drug metabolizing enzymes and transporters in human liver, regulation of human hepatocyte replication and differentiation, and production of hepatocytes for transplantation from stem or progenitor cells.
Congratulations Dr. Strom!
The University of Pittsburgh School of Medicine announced recently the newest members of its Academy of Master Educators. Mark Roberts, MD, MPP, Ora Weisz, PhD, and James Luketich, MD were among those named. Each has been appointed to the academy for a five-year term.
The Academy of Master Educators aims to recognize and reward excellence in education, advance education through innovation and professional development of faculty, and support and promote educational scholarship. After being nominated, potential candidates
must submit a statement of the applicant's educational philosophy, a current curriculum vitae, vidence of efforts in education, a synopsis of the applicant's teaching evaluations, and a list of awards for teaching and other education-related activities. This information then goes through a rigorous review process before the final decision is made by the Dean of Medicine.
Dr. Roberts is a Professor of Medicine, Health Policy and Management and Industrial Engineering and Chief of the Section of Decision Sciences and Clinical Systems Modeling in the Division of General Medicine; Dr. Weisz is an Associate Professor within the Renal-Electrolyte Division of the Department of Medicine and Department of Cell Biology and Physiology; and Dr. Luketich is the Co-Director of Surgical Affairs at the University of Pittsburgh Cancer Institute and the Sampson Family Endowed Chair in Thoracic Oncology in the School of Medicine.
Read more…
#70 – Robert Kormos, MD
– Regenerative Medicine Today welcomes back Robert Kormos, MD. Dr. Kormos is Director of the Artificial Heart Program, and Co-Director of Heart Transplantation at the University of Pittsburgh Medical Center. With Dr. Kormos is a former patient, Erika Haas. They discuss Erika’s experience with Ventricular Assist Device (VAD) and how VADs were used as a bridge to recovery.#71 – Mr. Patrick Cantini
– Mr. Cantini is the Director of Scientific Collaborations at the McGowan Institute. Mr. Cantini discusses the importance and the process of establishing partnerships between McGowan Institute and commercial enterprises and how this aids the transition of emerging technologies from the laboratory to clinical practice.
Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.
| Authors: | |
| Title: | Cell derived hierarchical assembly of a novel phosphophoryn-based biomaterial. |
| Summary: | Phosphophoryn (PP) is an acidic phosphoprotein belonging to the small integrin-bindingligand N-linked glycoprotein (SIBLING) protein family. PP is highly phosphorylated with approximately 200 phosphates per molecule and has a high affinity for calcium. The aim of this manuscript is to demonstrate that PP has the ability to self-assemble when it is overexpressed in a mammalian cell in the presence of calcium. Our data show that when PP is overexpressed using an adenovirus, the self-assembly occurs in the endoplasmic reticulum (ER) which contains high calcium concentration. We hypothesize that the physicochemical properties of the highly phosphorylated state and acidic nature of PP are playing an important role in its assembly in the ER. It appears that when a critical concentration of PP is reached, the assembly is then favored and facilitated. This self-assembly could be due to several factors. (1) The ER provides an ideal environment for this phenomenon to occur, since the ER environment usually promotes aggregation [Stevens and Argon: Semin Cell Dev Biol 1999;10:443-454]. (2) In addition to PP's physicochemical properties, the unfolded protein response could also be playing a role in this self-assembly [Schroder and Kaufman: Mutat Res 2005;569:29-63]. Unfolded protein response could be activated by a broad spectrum of insults that result in protein misfolding and ultimately blocking of the protein synthesis progression to the Golgi apparatus resulting in an accumulation of the protein in the ER. In summary, our data show that PP has the ability to self-assemble in a hierarchical manner |
| Source: | Cells Tissues Organs. 2009;189(1-4):252-5. |
| PI | |
| Co-Investigators | |
| Title | Mechanobiology and Regenerative Medicine |
| Description | Regenerative medicine approaches for the reconstitution of missing or injured tissues and organs involves the use of scaffolds, cells, and bioactive molecules. The use of biologic scaffolds seeded with cells is a common approach and several applications have been successfully translated to clinical medicine including lower urinary tract, gastrointestinal tract, musculotendinous, and dermal skin regeneration. The principles that guide tissue remodeling and regeneration are only partially understood but the influence of biomechanical loading upon the remodeling process is accepted as an important variable. However, there is an almost complete absence of systematic, quantitative studies to determine the effect of this controllable factor upon tissue remodeling, especially tissues with a smooth muscle wall component. The present proposal seeks support to conduct a quantitative, hypothesis driven study that determines the effects of mechanical loading upon smooth muscle phenotype in vitro and in vivo and the related changes to the architecture of the scaffold upon which they are seeded. A biologic scaffold derived from the extracellular matrix (ECM) of a porcine urinary bladder will be seeded with smooth muscle cells derived from different sources: the vascular wall, urinary bladder, and esophagus. The influence of those organ specific mechanical loading regimens upon the remodeling process and the ability to modulate the remodeling process by changing the mechanical loading pattern will be investigated. Two specific aims are described in which: 1) ECM seeded with the three different types of smooth muscle will be subjected to carefully selected mechanical loading regimens and the effect upon cell phenotype and matrix organization will be quantitatively evaluated and 2) two smooth muscle cells types will be evaluated upon ECM used within an organ culture model (rat bladder wall) to evaluate the effect of cellular and ECM remodeling when adjacent normal tissue cells are present. An experienced interdisciplinary team consisting of biomechanical engineers, tissue engineers, physicians, and pathologists has been assembled to conduct these studies. Two consultants, including a leader in the field of regenerative medicine and a statistician, will support this effort. A timeline for completion of these studies, hypotheses to drive the specific aims, alternative approaches for completion of the work, and quantitative criteria for success are provided. |
| Source | NIH |
| Term | 05/15/09 – 14/30/11 |
| Amount: | $361,332 (Year 1), $723,556 (total for 2 years) |
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