Older age is a well-known risk factor for IPF, a disease in which the lung tissue becomes progressively fibrotic, or scarred, leading to breathing difficulties and death within 3 to 5 years if a lung transplant isn’t possible, said senior investigator Ana L. Mora, MD, assistant professor in the Division of Pulmonary, Allergy and Critical Care Medicine and a member of the Heart, Lung, Blood and Vascular Medicine Institute (VMI) at Pitt. The cause of the disease is unknown, or “idiopathic.”
Project: Create Global Network to Improve Lives of Wheelchair Users
Of the nearly 70 million people worldwide who require wheelchairs for mobility and function, most lack access to appropriate wheelchairs or services to fix them. Now, a handful of University of Pittsburgh scientists are working with the U.S. Agency for International Development (USAID) under a 2-year, $2.3 million sub-award to develop the new International Society of Wheelchair Professionals, a global network to teach and professionalize device repair, build affiliations to put better equipment in the right hands, and ensure a level of standardization, certification, and oversight.
An Intensive Focus on Care
McGowan Institute for Regenerative Medicine affiliated faculty member Derek Angus, MD, Professor and Chair of Critical Care Medicine, University of Pittsburgh Medical Center, was named by HealthLeaders magazine as one of the “20 People Who Make Healthcare Better—2014.” In its annual HealthLeaders 20, the magazine profiles individuals who are changing healthcare for the better. Some that are named are longtime industry fixtures; others would clearly be considered outsiders. Some are revered; others would not win many popularity contests. All in all, those on the list are making a difference in healthcare.
As reported by HealthLeaders magazine’s Cheryl Clark, Dr. Angus has distinguished himself as an expert in the operations, cost, and efficiency of the intensive care unit, especially as it cares for patients with sepsis and septic shock, which strikes more than a million Americans a year.
Stem Cells Faulty in Duchenne Muscular Dystrophy, Researchers Find
Like human patients, mice with a form of Duchenne muscular dystrophy undergo progressive muscle degeneration and accumulate connective tissue as they age. Now, McGowan Institute for Regenerative Medicine affiliated faculty member Thomas Rando, MD, PhD, professor of neurology and neurological sciences at Stanford University School of Medicine, and Stanford researchers have found that the fault may lie at least partly in the stem cells that surround the muscle fibers.
They’ve found that during the course of the disease, the stem cells become less able to make new muscle and instead begin to express genes involved in the formation of connective tissue. Excess connective tissue — a condition called fibrosis — can accumulate in many organs, including the lungs, liver, and heart, in many different disorders. In the skeletal muscles of people with muscular dystrophy, the fibrotic tissue impairs the function of the muscle fibers and leads to increasing weakness and stiffness, which are hallmarks of the disease.
Dr. Rory Cooper Named an NAI Fellow
In December 2014, the National Academy of Inventors (NAI) named 170 distinguished innovators to NAI Fellow status including McGowan Institute for Regenerative Medicine affiliated faculty member Rory Cooper, Ph.D., the FISA/PVA Endowed Chair and a Distinguished Professor of the Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Sciences, University of Pittsburgh. Those named bring the total number of NAI Fellows to 414, representing more than 150 prestigious research universities and governmental and non-profit research institutions.
Novel Biomedical Device Receives Funding
The University of Pittsburgh’s Center for Medical Innovation (CMI) awarded grants through its 2014 Round-2 Pilot Funding Program for Early Stage Medical Technology Research and Development. McGowan Institute for Regenerative Medicine faculty member Steven Little, PhD, Chairman of the Department of Chemical and Petroleum Engineering and Associate Professor and CNG Faculty Fellow in the Departments of Chemical and Petroleum Engineering, Bioengineering, Immunology, and Ophthalmology, affiliated faculty member Tatum Tarin, MD, Assistant Professor in the Department of Urology at the University of Pittsburgh Medical Center (UPMC) and Director of Urologic Oncology at UPMC Mercy, and Abhinav Acharya, PhD Postdoctoral Associate, Department of Chemical & Petroleum Engineering, received funding for their project entitled, “Diagnosis of Aggressive Prostate Cancer via Detection of MMP9 in Biological Fluids.” The award is to develop a prototype chemical assay device for detection of femtomolar levels of MMP9 in biological fluids.
Patient’s Own Stem Cells Could Clear a Cloudy Cornea
Treating the potentially blinding haze of a scar on the cornea might be as straightforward as growing stem cells from a tiny biopsy of the patient’s undamaged eye and then placing them on the injury site, according to pre-clinical model experiments conducted by McGowan Institute for Regenerative Medicine affiliated faculty members James Funderburgh, PhD, Yiqin Du, MD, PhD, and researchers at the University of Pittsburgh School of Medicine. The findings, published in Science Translational Medicine, could one day rescue vision for millions of people worldwide and decrease the need for corneal transplants.
Wheelchair-Mounted Mobile Robotic-Assisted Transfer System
The Patient Assist Robotic Arm (PARA, pictured) is University of Pittsburgh-developed and -patented technology which is licensed to RE2, Inc., which stands for Robotics Engineering Excellence, a local Pittsburgh-based small business. Since RE2’s inception more than 10 years ago, the company has been developing and improving mobile robots used for dismantling explosive devices in far-off wars or safely clearing a meth lab’s cache of weapons here at home.
Now, along with McGowan Institute for Regenerative Medicine affiliated faculty member Rory Cooper, PhD, the FISA/PVA Endowed Chair and a Distinguished Professor of the Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Sciences, University of Pittsburgh, RE2 is moving its robotic ingenuity into helping people with disabilities better navigate the logistics of a world not designed to accommodate them.
Title Diagnosis of Aggressive Prostate Cancer via Detection of MMP9 in Biological Fluids
Description: Award to develop a prototype chemical assay device for detection of femtomolar levels of MMP9 in biological fluids.
Treating the potentially blinding haze of a scar on the cornea might be as straightforward as growing stem cells from a tiny biopsy of the patient’s undamaged eye and then placing them on the injury site, according to pre-clinical model experiments conducted by McGowan Institute for Regenerative Medicine affiliated faculty members James Funderburgh, PhD, Yiqin Du, MD, PhD, and researchers at the University of Pittsburgh School of Medicine. The findings, published in Science Translational Medicine, could one day rescue vision for millions of people worldwide and decrease the need for corneal transplants.
First-Ever Liver Transplant to Treat AHCY Deficiency Performed
S-Adenosylhomocysteine hydrolase (AHCY) deficiency is a rare congenital disorder affecting <1 in 1,000,000 children worldwide. Currently, there have been 8 diagnosed cases, with 6 individuals living with the disorder. With this illness, a genetic mutation in the liver doesn’t allow the body to process protein.
Pitt Innovation Challenge Awards Prizes to Creative Thinkers
A project to develop a portable sensor that monitors a condition called ketosis was recently awarded a $100,000 prize in the second Pitt Innovation Challenge (PInCh). McGowan Institute for Regenerative Medicine affiliated faculty member David Finegold, MD, professor of pediatrics, medicine, and human genetics at the University of Pittsburgh, is a member of the winning team named Nanoketo.
Title NSF Engineering Research Center for Revolutionizing Metallic Biomaterials
Description: The Engineering Research Center for Revolutionizing Metallic Biomaterials (ERC-RMB) will pursue revolutionary advances in metallic biomaterials and the underlying sciences and technologies, leading to engineered systems that will interface with the human body to prolong and improve quality of life. This research effort is coupled with the development of a vibrant, diverse workforce well-prepared for the global challenges and opportunities of the 21st century. The ERC proposes to develop the fundamental knowledge and technology needed to advance biocompatible and biodegradable metal-based, implantable systems with feedback control for reconstruction and regeneration. The research and technology development will be aided by industrial input and clinical assessments. The ERC’s education program is designed to develop innovative and adaptive engineers. Seamlessly integrated undergraduate and graduate bioengi- neering programs will be established at North Carolina A&T State University (NCAT) to support this goal.
Despite previous indications to the contrary, the esophagus does have its own pool of stem cells, said senior investigator Eric Lagasse, PharmD, PhD, associate professor of pathology, Pitt School of Medicine, and director of the Cancer Stem Cell Center at the McGowan Institute for Regenerative Medicine, and researchers from the University of Pittsburgh School of Medicine in an animal study published online in Cell Reports. The findings could lead to new insights into the development and treatment of esophageal cancer and the precancerous condition known as Barrett’s esophagus.
Despite previous indications to the contrary, the esophagus does have its own pool of stem cells, said senior investigator Eric Lagasse, PharmD, PhD, associate professor of pathology, Pitt School of Medicine, and director of the Cancer Stem Cell Center at the McGowan Institute for Regenerative Medicine, and researchers from the University of Pittsburgh School of Medicine in an animal study published online in Cell Reports. The findings could lead to new insights into the development and treatment of esophageal cancer and the precancerous condition known as Barrett’s esophagus.
Creating Medical Devices with Dissolving Metal
University of Pittsburgh researchers recently received another $1.5 million from the National Science Foundation to continue a combined multi-university, private-industry effort to develop implantable medical devices made from biodegradable metals.
Pitt School of Dental Medicine Team Awarded $2 Million NCI Grant to Study How Cancer Spreads to Bone
With a $2 million, 5-year grant from the National Cancer Institute (NCI), part of the National Institutes of Health, McGowan Institute for Regenerative Medicine affiliated faculty member Hongjiao Ouyang, DDS, PhD, DMD, and researchers at the University of Pittsburgh School of Dental Medicine will examine the molecular mechanisms that allow certain cancers, particularly multiple myeloma, to spread to the bone. The project could lead to new interventions to prevent such metastases and perhaps slow down primary tumor growth.
Pitt Gets $11 Million from NIH to Lead Center of Excellence in National Big Data Research Consortium
The National Institutes of Health has awarded the University of Pittsburgh an $11 million, 4-year grant to lead a Big Data to Knowledge Center of Excellence, an initiative that will help scientists capitalize more fully on large amounts of available data and to make data science a more prominent component of biomedical research. McGowan Institute for Regenerative Medicine affiliated faculty member Ivet Bahar, Ph.D., Distinguished Professor and JK Vries Chair, Department of Computational and Systems Biology, Pitt School of Medicine, is a co-director of the new Center for Causal Modeling and Discovery which will be part of an elite national team addressing the challenges of Big Data in biomedicine.
$1.25 Million Received from Defense Department to Make Whole-Eye Transplantation a Reality
University of Pittsburgh School of Medicine researchers co-led by McGowan Institute for Regenerative Medicine faculty members Vijay Gorantla, MD, PhD, associate professor of surgery in the Department of Plastic Surgery at the University of Pittsburgh and the administrative medical director of the Pittsburgh Reconstructive Transplant Program at UPMC, and Joel Schuman, MD, chair of the Department of Ophthalmology, Pitt School of Medicine, and director of the UPMC Eye Center, have been awarded $1.25 million from the U.S. Department of Defense (DOD) to fund two projects that aim to establish the groundwork for the nation’s first whole-eye transplantation program.
McGowan Institute for Regenerative Medicine faculty member Peter Wearden, MD, PhD, surgical director of Pediatric Heart and Lung Transplantation and director of the Pediatric Mechanical Cardiopulmonary Support Program of the Children’s Hospital of Pittsburgh of UPMC, assistant professor of cardiothoracic surgery at the University of Pittsburgh School of Medicine, and deputy director of pediatrics at the McGowan Institute, is a member of a team of medical professionals at Children’s who are using advanced and innovative technologies to perform life-saving procedures on children in need of cardiac support. Dr. Wearden is the leader in the field of pediatric mechanical cardiopulmonary support and receives numerous clinical patient cases from doctors and hospitals outside the Pittsburgh area. He is widely recognized for his clinical innovations where he has adapted existing technologies and devices to address the needs of these tiny patients.
Title Novel Strategies for Optic Neuroregeneration and Retinal Projection Reintegration after Ocular Trauma
As reported by Ann Lukits of the Wall Street Journal, Pittsburgh scientists led by McGowan Institute for Regenerative Medicine faculty member Steven Little, PhD, chairman of the Department of Chemical and Petroleum Engineering and associate professor and CNG faculty fellow in the Departments of Chemical and Petroleum Engineering, Bioengineering, Immunology, and Ophthalmology, are working to develop new techniques to administer medication for glaucoma patients that replace the usual regimen of twice-daily eye drops, a sometimes unreliable treatment. McGowan Institute for Regenerative Medicine faculty member Joel Schuman, MD, Eye and Ear Foundation professor and chairman of the Department of Ophthalmology, with secondary appointments as professor of bioengineering and of clinical and translational science, and professor at the Center for the Neural Basis of Cognition, a University of Pittsburgh/Carnegie Mellon University collaboration, was a member of the research team as well.
Winner of the Michael G. Wells Student Health Care Entrepreneurship Competition Named
Congratulations are extended to Travis Prest who is a member of the laboratory of McGowan Institute for Regenerative Medicine faculty member Bryan Brown, PhD, research assistant professor with the Department of Bioengineering (BioE) at the University of Pittsburgh with a secondary appointment in Pitt’s Department of Obstetrics, Gynecology and Reproductive Sciences. Mr. Prest won the Michael G. Wells Student Health Care Entrepreneurship Competition for his project “Neurogel.” Neurogel is an injectable product which both improves and speeds recovery of peripheral nerves following injury.
Unraveling Traumatic Brain Injuries
University of Pittsburgh researchers—including McGowan Institute for Regenerative Medicine affiliated faculty members Stephen Wisniewski, PhD, senior associate dean and co-director of the Epidemiology Data Center at the University of Pittsburgh Graduate School of Public Health, and David Okonkwo, MD, PhD, associate professor of neurological surgery and clinical director of the Brain Trauma Research Center at Pitt’s School of Medicine—are key players in a national “dream team” that seeks to identify the best biological and imaging markers of traumatic brain injury (TBI) to improve the ability of clinical trials to find effective treatments for the condition, which annually affects 2.5 million people in the U.S., including athletes and soldiers.
Dr. Andrew Duncan Receives NIH Grant Focused on Obtaining a Better Understanding of Liver Biology
Nearly 25 million Americans are affected by liver dysfunction, and liver diseases are the 10th leading cause of death in the US. There is a clear and urgent need for developing new alternatives to whole organ replacement. A better understanding of liver biology is required to improve existing approaches and to innovate therapies for the treatment of liver diseases, including viral hepatitis and steatohepatitis. McGowan Institute for Regenerative Medicine faculty member Andrew Duncan, PhD, assistant professor in the Department of Pathology at the University of Pittsburgh with a secondary appointment in the Department of Bioengineering of the Swanson School of Engineering, recently received a 5-year, $2,174,309 grant from the National Institute of Health’s National Institute of Diabetes and Digestive and Kidney Diseases. The project title is “Mechanisms of Polyploidy and Aneuploidy in the Liver.”
Pitt, Carnegie Mellon Engineers Develop New Method to Explore Mechanical Communication Between Cells
When the body forms new tissues during the healing process, cells must be able to communicate with each other. For years, scientists believed this communication happened primarily through chemical signaling. Now researchers at Carnegie Mellon University and the University of Pittsburgh have found that another dimension – mechanical communication – is equally if not more crucial. The findings, published in the Proceedings of the National Academy of Sciences, could lead to advancements in treatments for birth defects and therapies for cancer patients.
Dr. Anna Balazs Recognized by Pittsburgh WCC for Excellence in the Chemical Sciences
McGowan Institute for Regenerative Medicine affiliated faculty member Anna Balazs, PhD, was selected as this year’s recipient of the Greater Pittsburgh Area Women Chemists Committee’s (WCC) Award for Excellence in the Chemical Sciences. The award “recognizes the achievements of female chemists and chemical engineers in the greater Pittsburgh area who have a record of accomplishment in their field.” According to the committee’s chair, Dr. Balazs’ packet was “nothing short of extraordinary.” Dr. Balazs was recognized at the Awards Banquet of the 2014 American Chemical Society Central Regional Meeting (CERM 2014) held in Pittsburgh on October 30, 2014.
Dedicated to the evaluation and care of voice disorders, the UPMC Voice Center offers a wide range of services and is a unique resource for both the general public and those who use their voices professionally. Its mission is to prevent injury and rehabilitate patients who have voice problems and to provide cutting edge research. The Voice Center is staffed by a select group of medical experts—including McGowan Institute for Regenerative Medicine affiliated faculty member Clark Rosen, MD, director of the UPMC Voice Center and professor of otolaryngology in the University of Pittsburgh School of Medicine—who utilize state-of-the-art technology, including a voice analysis laboratory, to provide patients with a wide range of medical, surgical, and behavioral treatments for all voice disorders.
Dr. Anna Balazs: A 2014-2015 NSF Distinguished Lecturer in Mathematical and Physical Sciences
Annually, the National Science Foundation’s (NSF) Directorate for Mathematical and Physical Sciences invites media and members of the public to a series of lectures that will help promote a national discussion of issues that scientists expect to shape their research in the coming years. McGowan Institute for Regenerative Medicine affiliated faculty member Anna Balazs, PhD, has been chosen to be a Distinguished Lecturer for the NSF on June 22, 2015. Dr. Balazs’ presentation is entitled, “From Pendulums to Heartbeats: Inspirations for Designing Active, Responsive Materials,” and will be held at the NSF in Arlington, Virginia. Dr. Balazs joins renowned speakers from the University of Colorado/NIST, University of California—Los Angeles, New York University, Cornell University, Harvard University, and the University of Wisconsin in the 2014-2015 series of lectures.
Genetic Discovery Yields Prostate Cancer Test, Promise of Future Therapy
A genetic discovery out of the University of Pittsburgh School of Medicine is leading to a highly accurate test for aggressive prostate cancer and identifies new avenues for treatment. The analysis, published in the American Journal of Pathology, found that prostate cancer patients who carry certain genetic mutations have a 91 percent chance of their cancer recurring. McGowan Institute for Regenerative Medicine affiliated faculty member George Michalopoulos, M.D., Ph.D., professor and chairman of the Department of Pathology at the University of Pittsburgh, was a member of the study’s research team. This research was funded by the National Institutes of Health (NIH), American Cancer Society, and University of Pittsburgh Cancer Institute (UPCI).
Dr. Keith Cook to Develop Artificial Lungs that Can Be Worn at Home
Carnegie Mellon University (CMU) professor Keith Cook, PhD, has received a 4-year, $2.4 million grant from the National Institutes of Health (NIH) to support research and development of artificial lungs that patients may use long term in the comfort of their own homes while waiting for a lung transplant. Dr. Cook, an associate professor in the Department of Biomedical Engineering at CMU and a McGowan Institute for Regenerative Medicine affiliated faculty member, will lead the project and collaborate with researchers from the University of Washington, Columbia University, and Allegheny General Hospital in Pittsburgh.
Dr. John Kellum Helps Develop New Kidney Test
McGowan Institute for Regenerative Medicine affiliated faculty member John Kellum, MD, professor of critical care medicine at the University of Pittsburgh, transplant physician in anesthesiology at the Thomas E. Starzl Transplantation Institute, and co-director at the Mechanisms and Novel Therapies for Resuscitation and Acute Illness (MANTRA) Lab, was the lead investigator of a now FDA-approved lab test that will be used to help determine if critically ill hospitalized patients are at risk of developing moderate to severe acute kidney injury (AKI) in the 12 hours following the administration of the test. Early knowledge that a patient is likely to develop AKI may prompt closer patient monitoring and help prevent permanent kidney damage or death.
Dr. Steven Little Named One of Pittsburgh’s 40 Under 40
Each year, Pittsburgh Magazine and the Pittsburgh Urban Magnet Project (PUMP) sponsor the 40 Under 40 Program with the goal of recognizing 40 people under the age of 40 who are committed to shaping our region and making it a better place for everyone to live, work, and play. This year, McGowan Institute for Regenerative Medicine faculty member Steven Little, PhD, was selected from a nomination pool of more than 225 candidates. Dr. Little and fellow honorees were chosen by an independent panel of judges, comprised of former winners, business professionals, and civic leaders. Winners were chosen based on their passion, commitment, visibility, diversity, and overall impact on the region. Dr. Little was recognized not only for his passion as a teacher, researcher, and entrepreneur, but also for his volunteerism with the nonprofit, EduNations, and its work in Sierra Leone. He also was the only engineer to be recognized.
Dr. Ipsita Banerjee Receives NSF Grant
McGowan Institute for Regenerative Medicine affiliated faculty member Ipsita Banerjee, PhD, Assistant Professor in the Department of Chemical and Petroleum Engineering at the University of Pittsburgh, has been awarded a National Science Foundation (NSF) Early-Concept Grants for Exploratory Research (EAGER) grant entitled: “Systems Analysis of Signaling Pathway towards Robust Differentiation.” This award is for 1 year at $100,000.
Title Mechanisms of Polyploidy and Aneuploidy in the Liver
Description: Nearly 25 million Americans are affected by liver dysfunction, and liver diseases are the 10th leading cause of death in the US. There is a clear and urgent need for developing new alternatives to whole organ replacement. A better understanding of liver biology is required to improve existing approaches and to innovate therapies for the treatment of liver diseases, including viral hepatitis and steatohepatitis. Hepatocytes, the primary functional cell type in the liver, display a range of chromosomal diversity resulting from prevalent physiological polyploidy (>90% in mice and 50% in humans) and aneuploidy (60% in mice and 30-90% in humans). In eukaryotic organisms, cells usually contain a diploid genome comprised of pairs of homologous chromosomes. Polyploidy refers to gains in entire sets of chromosomes, and aneuploidy refers to gains and losses of individual chromosomes. The roles of hepatic polyploidy and aneuploidy represent a major gap in our current understanding of liver biology. We recently found that aneuploidy enhances the regenerative capacity of the mouse liver. In response to Tyrosinemia-induced injury, that is normally toxic to the liver, we identified a subset of aneuploid hepatocytes that was resistant to the disease. The data suggest that aneuploid hepatocytes are endowed with enhanced capacity for adaptation and regeneration. Our central hypothesis is that aneuploidy functions as an adaptive mechanism in response to hepatic injury. The goals of this application are to identify mechanisms regulating hepatic aneuploidy/polyploidy and to unravel how aneuploidy affects liver function. To investigate these questions, we propose in Specific Aim 1 to determine whether polyploid hepatocytes are necessary for development of aneuploid livers. Experiments will characterize hepatic cell divisions, karyotypes and stress response in E2f7/E2f8 knockout mice, which have normal liver function but are depleted of polyploid hepatocytes. In Specific Aim 2, we will dissect the role of a novel regulator of hepatic polyploidy, recently identified in our laboratory, microRNA-122 (miR-122). Experiments will determine how miR-122 alters ploidy and aneuploidy throughout life. We will also identify cellular and molecular mechanisms by which miR-122 regulates hepatic ploidy. Finally, in Specific Aim 3, we will determine how random karyotypes (in aneuploid hepatocytes) affect function in the liver. We will utilize a novel xenotransplantation model to examine clonal nodules of regenerating human hepatocytes. Experiments will measure aneuploidy and determine gene expression profiles in these nodules. Together, these studies will define the extent to which aneuploidy affects liver repair/regeneration as well as the molecular mechanisms that control this process. Understanding how aneuploid hepatocytes arise and function will provide new and crucial insights into liver homeostasis, diseases and treatments.
Several years ago, McGowan Institute for Regenerative Medicine faculty member Eric Beckman, PhD, George M. Bevier Professor of Engineering in the University of Pittsburgh Department of Chemical and Petroleum Engineering, and Michael Buckley, MD, oral and maxillofacial surgeon, invented a novel medical adhesive technology. The new adhesive—now known as TissuGlu®—was designed to meet a market demand for a strong, safe tissue adhesive to improve the wound closure process. The product positions tissues for optimal healing while minimizing fluid accumulation. To move the University of Pittsburgh-developed technology towards clinical use, Cohera Medical, Inc. was formed, and the intellectual property was licensed by the University to Cohera.
New Processes Could Provide Personalized Pain Treatment
As reported by Karen Ferrick-Roman, Duquesne University Fall 2014 Magazine, pain costs Americans up to $635 billion each year for medical treatment and in lost productivity, says the Institute of Medicine of the National Academies. That hefty price tag is equivalent to the first 10 years of spending for homeland security, illustrating a nationwide problem of giant proportions. Today, an estimated 116 million Americans live with chronic pain.
