McGowan Institute?
September 2009 | VOL.8, NO. 9 | www.McGowan.pitt.edu
Scientific American Features BrainPort Vision Device
The work of researchers involved in a joint program of the McGowan Institute for Regenerative Medicine and the UPMC Eye Center—The Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh—which specializes in the most common diseases associated with vision loss, was recently highlighted in the journal Scientific American. The scientific and clinical team of The Fox Center led by McGowan Institute faculty members Joel Schuman, MD, Eye and Ear Foundation Professor and chairman of Ophthalmology, and director of the UPMC Eye Center, and Major General (Ret.) Gale Pollock, executive director of The Fox Center, is working with Wicab, Inc. to improve the effectiveness of BrainPort, a vision device developed by neuroscientists at the Middleton, Wisconsin-based company. Following this collaborative effort, the device could be approved by the U.S. Food and Drug Administration for market by the end of 2009 at a cost of about $10,000 per device.
For those who are blind, the non-surgical BrainPort vision device is an investigational assistive device for orientation, mobility, object identification, and spot reading. It enables perception of visual information using the tongue and camera system as a paired substitute for the eye. Visual information is collected from a video camera and translated into gentle electrical stimulation patterns on the surface of the tongue. Users describe it as pictures drawn on their tongue with champagne bubbles. With training, users may perceive shape, size, location, and motion of objects in their environment. The BrainPort vision device is intended to augment rather than replace other assistive technology such as the white cane or guide dog.
The BrainPort device was demonstrated by Cpl. Mike Jernigan, a medically retired Marine who lost both eyes after being wounded by a roadside bomb in Iraq in 2004, during the McGowan Institute for Regenerative Medicine First Open Meeting. Additional information about this demonstration can be found here.
SCIENTIFIC ADVANCES
Led by McGowan Institute for Regenerative Medicine faculty member Ivet Bahar, PhD, professor and John K. Vries Chair of the Department of Computational Biology, University of Pittsburgh School of Medicine, computational biologists at the Pitt School of Medicine have shown that proteins have an intrinsic ability to change shape, and this is required for their biological activity. This shape-changing also allows the small molecules that are attracted to a given protein to select the structure that permits the best binding. That premise could help in drug discovery and in designing compounds that will have the most impact on protein function to better treat a host of diseases.
According to the classical view, known as “induced fit,” drug binding causes a change in the target protein structure, explained senior author Dr. Bahar. But it now appears that a protein has many different conformations that are already available even without the presence of a binding molecule, which is called the ligand. The ligand attaches to the protein shape that allows it to fit well, and that close interaction can lead to effective inhibition of protein function.
Gathering information about the array of conformations a target protein might exhibit can be of great use when designing new drugs, Dr. Bahar said. That allows the scientist to better identify the structural pocket into which the drug must fit to cause significant alterations in protein function, such as the inhibition of an enzyme reaction.
For the study, Dr. Bahar and her doctoral student, Ahmet Bakan, focused on three common drug targets, namely enzymes important in HIV, inflammatory response, and the cell division cycle. Using the sets of conformations of protein-ligand complexes stored in the Protein Data Bank, an information repository for the scientific community at Rutgers University, the researchers figured out what structures the enzymes had both alone and when bound to a variety of small molecules.
“It seems there are simple but robust rules that control ligand binding,” Dr. Bahar explained. “If we know the rules, we can make better predictions about which binding sites to target to make more effective drugs.”
McGowan Institute for Regenerative Medicine faculty members Derek Angus, MD (pictured top), professor in Critical Care Medicine as well as Health Policy and Management at the University of Pittsburgh, and Mark Roberts, MD (pictured bottom), 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 at the University of Pittsburgh, are co-authors of a recently published Pitt School of Medicine study on how patient race, gender, and insurance status influence decisions about who will go on to receive liver transplants. The study indicates that women, blacks, and patients with Medicare who are in end-stage liver disease are less likely to be referred and evaluated for liver transplantation.
The study, which followed 144,507 patients hospitalized in Pennsylvania with liver-related conditions, sought to determine whether any potential barriers exist at the referral and listing steps in the transplantation process. The team found that 4,361 of these patients underwent transplant evaluation. Of these, 3,071 were waitlisted and 1,537 went on to transplantation. Patients were significantly less likely to undergo evaluation, waitlisting, and eventual transplantation if they were women, black, or covered by Medicare.
Disparities were especially apparent in the early stages of the process when evaluation and listing occurs – 61 percent of men were evaluated for transplantation compared to 39 percent of women; 73.8 percent of whites were evaluated compared to 8.6 percent of blacks; and 62 percent of patients with commercial insurance were evaluated compared to 4.7 percent with Medicare only.
“While our study was not designed to identify causes for these disparities, current practices for identifying and referring liver disease patients for transplantation should be made more transparent,” said Cindy L. Bryce, Ph.D., study lead author and associate professor of medicine, University of Pittsburgh. “Although we face a worsening gap in the supply and demand for organs for liver transplantation, race, gender and insurance status should not be factors that preclude patients from being evaluated for transplantation.”
McGowan Institute for Regenerative Medicine faculty member Rory Cooper, PhD, is the Co-Director for the National Science Foundation Engineering Research Center Quality of Life Technology (QoLT) Center, a unique partnership between Carnegie Mellon University and the University of Pittsburgh that brings together a cross-disciplinary team of technologists, clinicians, industry partners, end users, and other stakeholders to create revolutionary technologies that will improve and sustain the quality of life for all people. Its mission is to transform lives in a large and growing segment of the population – people with reduced functional capabilities due to aging or disability. Future compassionate intelligent QoLT systems will monitor and communicate with a person, understand his/her daily needs and tasks, and provide reliable and happily-accepted assistance by compensating and substituting for diminished capabilities.
Rapid-prototyping and robotics provide some promising solutions to at least some of the challenges faced by people with severe mobility and manipulation, and offer hope for greater independence. Rapid-prototyping helps engineers to make models and even one-of devices in a cost effective and timely manner. This allows computer models to become physical models within days, and real systems within months rather than years. This accelerates the research and design process, and affords people with disabilities more opportunities to participate in the scientific process.
The new robotic systems to help those who use a wheelchair are developed through a holistic, human-centered design approach. The QoLT Center works with real people in the real world to ensure its technologies are sustainable, acceptable, and support a person's place in their community as well as society at large. The Center’s long-term goals are to:
- increase employability and productivity across the life span;
- expand the range of environments in which people will be independently and safely mobile, increasing community participation; and
- expand the number of people and number of years that they can live independently at home.
AWARDS AND RECOGNITIONS
Because of the quick actions of McGowan Institute for Regenerative Medicine faculty member and Pirates fan Christopher Post, MD, PhD, FACS, a Cincinnati Reds fan is alive today. During a recent baseball game at PNC Park, Dr. Post, Director, Allegheny Pediatric ENT Associates Allegheny General Hospital, noticed a man 40 feet away having difficulty breathing and subsequently slumped over in his seat with his face turning gray. This behavior prompted the physician within Dr. Post, who then immediately rushed over to perform CPR and chest compressions. Soon PNC Park staff members and paramedics arrived with a portable defibrillator, one of more than a dozen in the ballpark.
The man, Charles Trimble, was taken via ambulance to the hospital where he continued to improve and after a few days was discharged home. Through tears and wearing a Pirates hat, Mr. Trimble described how thankful he was to Dr. Post for responding so quickly. "He was a total stranger, and I'm just fortunate that he was in attendance and knew what to do," he said.
Coronary heart disease is the No. 1 cause of death in the United States. That's why it's so important to reduce your risk factors, know the warning signs, and know how to respond quickly and properly if warning signs occur.
- Some heart attacks are sudden and intense — like the "movie heart attack," where no one doubts what's happening. But most heart attacks start slowly, with mild pain or discomfort. Often people affected aren't sure what's wrong and wait too long before getting help.
McGowan Institute for Regenerative Medicine faculty member Ipsita Banerjee, PhD, Assistant Professor in the Department of Chemical and Petroleum Engineering at the University of Pittsburgh, has been awarded the NIH Director’s New Innovator Award. The objective of her project, “Defining regulatory mechanisms controlling stem cell fate during differentiation,” is to develop an insightful mechanistic understanding of the process of differentiation through an integrated experimental and theoretical approach organized around three basic questions:
(1) How do the transcription factors interact in controlling and deciding on a cell lineage?
(2) How do environmental perturbations influence these networks towards desired lineage?
(3) How do gene and protein networks operating at the cellular level govern the tissue functionality at the systems level?
Successful completion of this project will directly impact cellular therapy based regenerative medicine, and will pave way for mechanistic understanding of disease progression and potential therapeutic intervention.
The NIH Director’s New Innovator Awards Program was created in 2007 to support a small number of new investigators of exceptional creativity who propose bold and highly innovative new research approaches that have the potential to produce a major impact on broad, important problems in biomedical and behavioral research. The research proposed need not be in a conventional biomedical or behavioral discipline, but must be relevant to the mission of NIH.
The New Innovator Awards complement ongoing efforts by NIH and its Institutes and Centers to fund new investigators through R01 grants, which continue to be the major source of NIH support for new investigators. The term “award” is used to mean a grant for conducting research, rather than a reward for past achievements. Biomedical and behavioral research is defined broadly as encompassing scientific investigations in the biological, behavioral, clinical, social, physical, chemical, computational, engineering, and mathematical sciences.
NIH Director Dr. Francis S. Collins announced this year’s New Innovator Award recipients at the start of the Fifth Annual NIH Director’s Pioneer Award Symposium on September 24, 2009.
Congratulations, Dr. Banerjee!
McGowan Institute for Regenerative Medicine faculty member William Federspiel, PhD, William Kepler Whiteford Professor of Chemical Engineering, Surgery and Bioengineering, has been named the new graduate coordinator in the Swanson School of Engineering’s Department of Bioengineering. The graduate coordinator is the faculty member responsible for the operation of the department's graduate program. The coordinator supervises the operations of admissions, registration, course scheduling, assignment of advisors, graduation, and academic disciplinary procedures. The graduate coordinator generally is the best source of information and advice when questions arise or problems are encountered during graduate study.
Dr. Federspiel is formally joining the Bioengineering Department as his primary home from the Department of Chemical and Petroleum Engineering, where he previously served as Graduate Coordinator from 2000 to 2006. His research interests are in the development of new medical devices to improve patient treatment in critical care medicine. He is Director of the Medical Devices Laboratory in the McGowan Institute of Regenerative Medicine.
Pitt’s Bioengineering graduate program has moved up in the U.S. News & World Report rankings from 15th last year to 12th this year and among public institutions from 6th to 4th.
Congratulations, Dr. Federspiel!
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#74 – Robert Bowser, PhD |
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| Authors: | Anna C. Balazs and Irving R. Epstein |
| Title: | Emergent or Just Complex? |
| Summary: | Efforts toward creating artificial cells are shedding light on how life may have emerged. The concept of emergence in the physical and biological sciences is an elusive one. The term refers to phenomena in which the complexity of structures or behaviors in systems with many interacting components exceeds that predicted from knowledge of the individual components and the forces between them. |
| Source: | SCIENCE; 25 SEPTEMBER 200; VOL 325; pp 1632-1634 |
| PI | |
| Title | Organogenesis of Ectopic Tissue in Lymph Node |
| Description | Our proposal addresses some of the solutions to the development of complex 3-dimensional tissue models and a new paradigm by using lymph node as in vivo bioreactors to grow tissue or organ substitute. Our initial study and prove of concept will be centered around the generation of ectopic liver in lymph nodes for patients suffering end-stage liver diseases. Hepatocyte transplantation has been reported as a possible therapeutic approach for liver disease. However, transplantation has been directed at the liver itself, limiting efficacy in patients with end-stage liver diseases, when cirrhosis and fibrosis are common. In this proposal we demonstrate that the generation of an ectopic liver within lymph nodes is an efficient method to restore hepatic function, highlighting the novel use of this organ as a site for hepatocyte transplantation. Homeostatic expansion of donor hepatocytes in lymph nodes resulted in the rescue of lethal hepatic failure. These data provide the first definitive evidence that a functional ectopic liver can rescue lethal hepatic diseases. Furthermore, with the efficacy of this approach suggests that lymph nodes have therapeutic potential for cell-based transplantation and tissue engineering. Our new paradigm to generate functional liver tissues in lymph nodes will be further applied to other tissues |
| Source | NIH / NIDDK |
| Term | 09/25/09 – 08/31/14 |
| Amount: | Year 1: $797,697 TC |
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