McGowan Institute?
November 2007 | VOL. 6, NO. 11 | www.McGowan.pitt.edu
McGowan Distinguished Lecturer Series To Begin
The McGowan Distinguished Lecturer Series will begin on Thursday, November 29, 2007 with Douglas Lauffenburger, PhD of the Massachusetts Institute of Technology as the first featured speaker. The lecture will take place in Scaife Auditorium 5 at 4:00 pm. Immediately following, there will be a Moleculart Networking Session in BST S100 with the oil paintings of McGowan Institute faculty member Dr. Ruben Zamora on exhibit. All are welcome.
The topic of Dr. Lauffenburger's lecture will be "What Are Cells Thinking?—An Engineering Approach to Understanding Signaling Networks Governing Cell Behavior." Dr. Lauffenburger is the Whitaker Professor of Biological Engineering, Chemical Engineering and Biology at MIT. He was the recipient, earlier this year, of the 2007 Pierre Galletti Award from the American Institute for Medical and Biological Engineering, the Institute's highest honor.
Stay tuned for the Spring lectures in this series that will feature Karen Hirschi, PhD of Baylor Medical College and Irving Weissman, MD of Stanford University. Dates for these lectures are March 27 and April 3, 2008. The Spring lectures will also include exhibits by local artists along with a Moleculart Networking Session.
Dr. Savio L-Y. Woo was presented with the Bay Area Knee Society’s Lifetime Achievement Award this month. The society is an academic organization based in San Francisco that is known for annually recognizing outstanding individuals who have made career contributions to advance the art and science of knee surgery.
Dr. Woo was the 21st recipient of this internationally recognized award that many consider the Nobel Prize of the knee. Most of the prior recipients have been orthopaedic surgeons; Woo is the first PhD to have been accorded this honor. Scott F. Dye, president of the Bay Area Knee Society called Dr. Woo a national treasure due to his extensive contributions to the basic science of sports medicine, particularly, the knee.
Dr. Woo is a University Professor, McGowan Institute faculty member and director of Pitt's Musculoskeletal Research Center. For the last 25 years, Dr. Woo has found new ways to enhance healing of the knee, concentrating on the meniscus, tendons, and most importantly, the MCL and ACL. Recently, Dr. Woo has centered his work on the regenerative medical potential of functional tissue engineering regarding ligament healing. This has involved examining the processes of the knee from a molecular to a cellular tissue level. Robotic technology has also been used to explore the function of the ACL and ACL replacement grafts.
The research efforts of McGowan Institute faculty member and plastic surgeon J. Peter Rubin, MD, were recognized with a Presidential Early Career Award for Science and Engineering (PECASE) during a recent ceremony in Washington D.C. This award is the nation's highest honor for scientists who are early in their research careers.
The PECASE was created by President Clinton and the National Science and Technology Council in 1996 as an award program that would honor and support the extraordinary achievements of young professionals at the outset of their independent research careers. Awardees are nominated by one of eight federal departments, who provide the researchers with up to five years of funding to further their research. Dr. Rubin was nominated by the National Institutes of Health which has supported his research grant, "Injectable Engineered Tissue for Cancer Reconstruction."
Dr. Rubin, who is assistant professor of plastic and reconstructive surgery at the University of Pittsburgh School of Medicine, and co-director of the Adipose Stem Cell Center, was recognized for his groundbreaking research on using fat-derived stem cells to engineer soft tissue. This technology may one day be used to generate replacement tissue for breast cancer survivors.
"The use of stem cells to treat disease or regenerate tissue is believed to hold promise because of their potential to both actively participate in the healing process and develop into different specialized cell types. When exposed to specific conditions in the laboratory, fat-derived stem cells have been shown to transform into the same cell types found in fat, bone, cartilage, nerve, muscle, and blood vessels," said Dr. Rubin, who also is director of the Life After Weight Loss Surgical Body Contouring Program at the University of Pittsburgh Medical Center.
Congratulations, Dr. Rubin!
Read more: UPMC News Bureau
McGowan Institute faculty member Jay Kolls, MD, chief of the Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, is the principal investigator of a $12.8 million National Institutes of Health grant to improve the diagnosis/treatment of chronic lung disease. He is also preparing to introduce environmental approaches to disease management in pediatric clinics. His effort, along with those of several others, helped Children's Hospital receive a 2007 Children's Environmental Health Excellence Award for outstanding commitment to protecting children from environmental health risks. This award is given by the U.S. Environmental Protection Agency's (EPA) Office of Children's Health Protection and Environmental Education. Children's Hospital received the award for its environmental accomplishments and was 1 of only 10 organizations to receive this honor.
Jonathan Weinkle, MD, a resident at Children's spearheaded the overall efforts at the hospital. In addition to Dr. Kolls' initiative, the overall program includes:
- Sponsoring/hosting a Children's Environmental Health Conference, which focused on significant pediatric environmental health matters such as neuro-cognitive issues involving heavy metals exposure; environmental exposures and cancer; and environmental exposures and newborn outcomes.
- Establishing for residents a required, CME-accredited noon lecture series (Lunch ‘n Learn), which focuses on environmental health issues and other timely topics. This series is run with the assistance of the University of Pittsburgh Cancer Institute – Center for Environmental Oncology.
- Collaborating with physicians in Children's General Academic Pediatrics Division to offer families guidance in establishing a safe home environment. One component of this program involves screening patients for environmental toxins.
This program represents the clinical piece of Children's goal of becoming a “green” hospital, a goal actively pursued in both the construction of the new hospital campus in Lawrenceville, and the “greening” of daily operations in the current hospital.
The EPA established the Children's Health Program in May 1997 to make the protection of children's health a fundamental goal of public health and environmental protection in the United States.
The McGowan Institute for Regenerative Medicine's Rory Cooper, PhD, is part of a University of Pittsburgh/Carnegie Mellon University team charged with transforming robotics and related technologies to tools that help those with reduced functional capabilities live independently for as long as possible. A story featuring Dr. Cooper and this research appeared in the November 14, 2007 issue of the Pittsburgh Post-Gazette.
Dr. Cooper and colleagues at Carnegie Mellon received a $15 million, five-year grant from the National Science Foundation a year ago to develop the new QoLT Center. As co-director, Dr. Cooper provides his rehabilitative science and engineering technologies expertise to the Quality of Life Technology Research Center—QoLT, for short.
The QoLT team envisions at least three levels of services available to residents: a monitoring/communication system, a personal monitoring system to help with daily routines, and driving assistance that will even note potentially dangerous habits. Other technologies such as "smart cottages" and other futuristic concepts are already in clinical trials. Eventually, a "Quality of Life Technology Kit" will be available in a box at the local home improvement stores.
QoLT projects that the cost for this technology will add about $10,000 to the cost of each equipped residence, but users will recoup part of that through an energy management feature. In the end, this $10,000 is far less than the assisted living charges that residents may be able to avoid.
In addition, think about this fact: If advances like this could delay all nursing home admissions by a month, the savings to society would be about $1 billion monthly. A shortage of both paid personal attendants and family caregivers is anticipated as the elderly population doubles over the next 30 years.
Photo credit: Bob Donaldson, Post-Gazette
Clinical trials in regenerative medicine and tissue engineering that are required to validate pre-clinical studies and to bring new therapies closer to patients are now possible at the new Clinical Translation Unit (CTU). Formally opened on September 28, 2007, the CTU is a joint project between Research and Development RA SA and Hospital Universitario Austral in Buenos Aires, Argentina, in partnership with the McGowan Institute for Regenerative Medicine.
The main concept of the unit lies in having a state-of-the-art cell culture facility inside the operating room, a first-of-its-kind, to facilitate the translation of bench top technologies to the bedside. Together with a strong regulatory expertise at the Hospital Universitario Austral, the CTU allows validation of pre-clinical studies. This represents a good opportunity for tissue engineering companies and university-based projects to acquire clinical data and move forward in their implementation of innovative clinical protocols.
For the grand opening, Professor Masayuki Yamato from Tokyo Women's University gave a lecture on Cell Sheet Tissue Engineering and recognized the significance of the CTU. He honored all by cutting the ribbon during the inauguration. Also participating in the program in Argentina was Alejandro Nieponice, MD, Director, CTU (pictured above) and via a video presentation, Alan Russell, PhD, Director, McGowan Institute.
Pitt Surgery professor and McGowan faculty member Michael T. Lotze, PhD is part of a team led by a Duke University researcher that may have solved the mystery surrounding the healing properties of gold. The result may be a renewed interest in gold salts as a treatment for rheumatoid arthritis among other inflammatory diseases.
Injections of gold salts were first used in the early 1900s by physicians as an arthritis treatment, but the side effects discouraged use of the mineral. Recently, new treatments like methotrexate and biologically engineered drugs have replaced gold as a widely prescribed therapy. It is commonly thought of as a treatment of last resort.
Previously, scientists did not really understand why gold worked, but recent interest in the molecule HMBG1, which provokes inflammation, provided a clue. HMGB1 is found in a higher concentration in the synovial tissue and fluid around the joints—where arthritis occurs. Because gold inhibits the release of HMGB1, it lessens the amount available to provoke the body’s immune system, weakening the inflammatory response.
In addition to his surgery and his research, Dr. Lotze is also director of clinical and translational research at the Molecular Medicine Institute and co-director of the biologic therapy division at UPCI.
The latest technology in regenerative medicine will facilitate surgery for brain, spine, head and neck injuries with an improved gamma knife device. Douglas Kondziolka, MD, McGowan faculty member and Peter J. Jannetta Professor of Neurological Surgery and Radiation Oncology, was among the team of surgeons who provided input, recommendations, and participation in the design and development of UPMC's new system, known as Leskell Gamma Knife Perfexion®. Dr. Kondziolka is also co-director of the Center for Image Guided Neurosurgery at UPMC Presbyterian.
The new system, 1 of only 5 in the U.S., is estimated to increase the number of patients who can benefit from gamma knife surgery by up to 40 percent, given its effectiveness in treating tumors of the skull base and cervical spine.
Gamma knife brain surgery involves no incisions. Instead, it is a high dose of radiation delivered directly to the diseased area, thereby minimizing the risk of damage to healthy tissue. This is a multidisciplinary technology that relies on the training and experience of neurosurgeons, radiation oncologists, and medical physicists.
In 1987, L. Dade Lunsford, MD, distinguished professor of neurological surgery at the University of Pittsburgh and UPMC, was the first to use the gamma knife clinically in North America. UPMC remains the world leader in radiosurgery with more than 8500 patients treated using three fully functional gamma knife units.
The worlds of regenerative medicine and industrial engineering meet at the University of Pittsburgh. Mark Roberts, MD, MPP, FACP, a McGowan Institute faculty member, a Pitt School of Medicine professor, and a UPMC physician, recently published a paper in the engineering journal Management Science explaining how engineering principles are being used to determine the best timing for a liver transplant. Pitt associate professors of industrial engineering, Andrew Schaefer and Lisa Maillart, are co-authors.
Currently, almost 17,000 people in the U.S. are waiting for a donated liver. The wait time on the list to receive an organ from a deceased donor averages about 2 years. Because many of those in need die waiting on this list, another option is to receive a liver from a live donor—a spouse, family member, close friend. The live donor gives a portion of his/her liver, which will regenerate to full-size in both the donor and the recipient. There is less than a 1% risk that the donor will die in this process.
"If you have a choice, what should you do? That's a real question," Dr. Roberts said. "How long should I wait before placing my loved one or significant other in some danger or some risk? That's a fascinating optimization problem."
For help in solving that problem, Dr. Roberts consulted Andrew Schaefer about how to decide when to remove a patient from the waiting list and accept a living donor's liver. Schaefer recognized it as a Markov decision process—a framework named for a Russian mathematician that makes the best decision about problems and risks that change with time. Together, Schaefer and Lisa Maillart devised a formula that considers things such as: How sick is the person in need of a liver? What are the odds the patient will get a liver from a dead donor? What are the odds of survival for the patient and donor? One impediment of the program is it does not consider a patient's quality of life before or after the transplant.
Dr. Roberts would not estimate when the model would be available to doctors and patients. U.S. Food and Drug Administration approval of the model must also be obtained.
The Regenerative Medicine Podcasts continue to explore pertinent topics. The most recent podcasts are:
#42-SYIS-TERMIS - A discussion with the leadership of the North American Chapter of the Students and Young Investigators Section of the Tissue Engineering & Regenerative Medicine International Society during the 2007 TERMIS North American Meeting in Toronto.
#43-Jennifer Braemar Ogilvie, MD - Dr. Ogilvie visits Regenerative Medicine Today to discuss her current regenerative medicine research interests focusing on the development of tissue-engineered endocrine organs, in particular bioengineered thyroid and adrenal glands.
Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.
Authors: |
Bo Zheng, Baohong Cao, Mihaela Crisan, Bin Sun, Guangheng Li, Alison Logar, Solomon Yap, Jonathan B Pollett, Lauren Drowley, Theresa Cassino, Burhan Gharaibeh, Bridget M Deasy, Johnny Huard & Bruno Péault |
Title: |
Prospective Identification of Myogenic Endothelial Cells in Human Skeletal Muscle |
Summary: |
This manuscript documents anatomic, molecular and developmental relationships between endothelial and myogenic cells within human skeletal muscle. Cells coexpressing myogenic and endothelial cell markers (CD56, CD34, CD144) were identified by immunohistochemistry and flow cytometry. These myoendothelial cells regenerate myofibers in the injured skeletal muscle of severe combined immunodeficiency mice more effectively than CD56+ myogenic progenitors. They proliferate long term, retain a normal karyotype, are not tumorigenic and survive better under oxidative stress than CD56+ myogenic cells. Clonally derived myoendothelial cells differentiate into myogenic, osteogenic and chondrogenic cells in culture. Myoendothelial cells are amenable to biotechnological handling, including purification by flow cytometry and long-term expansion in vitro, and may have potential for the treatment of human muscle disease. |
Source: |
Nature Biotechnology 25, 1025 - 1034 (2007) |
PIs: |
Satdarshan P. Singh Monga, MD |
Title: |
Beta-catenin in the growth of hepatocellular cancer |
Description: |
Hepatocellular cancer (HCC) is a disease of poor prognosis. Identifying novel molecular aberrations might present opportunities to identify new therapeutic targets. Due to the similarities between the processes of development and cancer, we used early developing livers to identify genes that might play a primary role in HCC. Platelet-derived growth factor receptor-alpha (PDGFRalpha) was identified from microarray using early developing mouse livers. Expression of PDGFRalpha and its upstream effectors, PDGF-AA and PDGF-CC, were examined in HCC tissues (n = 43) by Western blot, real-time PCR, and immunohistochemistry. Finally, effect of anti-PDGFRalpha antibody (mAb 3G3, ImClone Systems, Inc.) was examined on human hepatoma cells. A high expression of PDGFRalpha was observed during early liver development. HCCs (17 of 21) revealed cytoplasmic PDGFRalpha and activated PDGFRalpha (phospho-Tyr(754)) by immunohistochemistry. Additional HCCs (14 of 22) showed elevated PDGFRalpha levels when compared with the adjacent normal livers by Western blots. Of these 14 patients, 3 showed increased PDGFRalpha gene expression, 3 showed elevated PDGF-AA, and 4 had higher PDGF-CC levels in the tumors compared with adjacent livers. Multiple hepatoma cell lines, when treated with mAb 3G3, showed significant decreases in cell proliferation and survival (P < 0.05). In conclusion, approximately 70% of HCC tissues had elevated PDGFRalpha levels due to diverse mechanisms. PDGFRalpha inhibition in hepatoma cells led to diminution of tumor cell survival and proliferation and thus might be of therapeutic significance. |
Source: |
National Cancer Institute |
Term: |
3 years |
Amount: |
$1.2 million |
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