Gene therapy generally relies on viruses, such as adeno-associated virus (AAV), to deliver genes into a cell. In case of CRISPR-based gene therapies, molecular scissors can then snip out a defective gene, add in a missing sequence or enact a temporary change in its expression, but the body’s immune response to AAV can thwart the whole endeavor.
Every time you flex your bicep or stretch your calf muscle, you put your cells under stress. Every move we make throughout the day causes our cells to stretch and deform. But this cellular deformation can be dangerous and could potentially lead to permanent damage to the DNA in our cells, and even cancer. So how is it that we’re able to keep our bodies moving without constantly destroying our cells? Thanks to a new study by McGowan Institute for Regenerative Medicine affiliated faculty member and Carnegie Mellon University (CMU) Chemical Engineering Professor Kris Dahl, PhD, and Associate Professor Sara Wickström, MD, PhD, of the University of Helsinki, we now know that the answer lies in a humble mineral we consume every day.
LyGenesis, Inc., a biotechnology company focused on regenerative medicine founded by McGowan Institute for Regenerative Medicine faculty member Eric Lagasse, PharmD, PhD, recently announced the publication of four peer-reviewed papers on its organ regeneration technology. Dr. Lagasse is LyGenesis’s Chief Scientific Officer, Associate Professor in the Department of Pathology at the University of Pittsburgh, and Director of the Cancer Stem Cell Center at the McGowan Institute. Dr. Lagasse is a co-author on each of the publications.
Hepatocytes — the chief functional cells of the liver — are natural regenerators, and the lymph nodes serve as a nurturing place where they can multiply. In a new study published in the journal Liver Transplantation, researchers at the University of Pittsburgh School of Medicine showed that large animals with ailing livers can grow a new organ in their lymph nodes from their own hepatocytes. A human clinical trial is next.
The McGowan Institute for Regenerative Medicine welcomes new affiliated faculty member Samira Kiani, MD.
McGowan Institute for Regenerative Medicine affiliated faculty member Sachin Velankar, PhD, Professor, Department of Chemical & Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, recently was awarded a National Science Foundation grant for his proposal entitled “Collaborative Research: Micromechanics of Meniscus-bound Particle Clusters.” Dr. Valenkar shares this grant with Charles Schroeder, PhD, Associate Head and Ray and Beverly Mentzer Professor, Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign. The award is for three years for a total of $510,000 ($292K as the Pitt portion).
The National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases has awarded a grant of $2.59 million to George Gittes, MD, director of the Richard King Mellon Foundation Institute for Pediatric Research, co-scientific director at UPMC Children’s Hospital of Pittsburgh, and affiliated faculty member of the McGowan Institute for Regenerative Medicine, to support continuing development of gene therapy technology that may have the potential to cure Type 1 and Type 2 diabetes, which affects approximately 10% of the U.S. population, or more than 34 million people.
Roughly one in eight women in the United States will develop invasive breast cancer over the course of her lifetime, and HER2-positive (HER2+) breast cancers represent about 25 percent of all breast cancer cases. Though multiple therapies exist, most patients will develop metastatic disease and resistance to current treatments.
Today in the United States there are millions of people suffering from liver disease which makes it the second cause of liver transplant. Only 30-35% of those in need of a liver will receive one. Approximately 30,000 people per year will die from liver disease.
The McGowan Institute for Regenerative Medicine welcomes new affiliated faculty member Tirthadipa Pradhan, PhD.
The McGowan Institute for Regenerative Medicine welcomes new affiliated faculty member Mo Ebrahimkhani, MD.
Researchers from Sechenov University and University of Pittsburgh discovered that the resistance of innate immune cells, macrophages, to ferroptosis – a type of programmed cell death – depends on the type of their activation. It turned out that cells helping tissues to recover from inflammation were more vulnerable. The researchers identified the mechanisms underlying the cells’ resistance and explained how this research would help regulate inflammation in a paper published in Nature Chemical Biology. McGowan Institute for Regenerative Medicine affiliated faculty members Valerian Kagan, PhD, DSc, Professor and Vice-Chairman in the Department of Environmental and Occupational Health as well as a Professor in the Department of Pharmacology and Chemical Biology, the Department of Radiation Oncology, and the Department of Chemistry at the University of Pittsburgh, and Ivet Bahar, PhD, Distinguished Professor, the John K. Vries Chair, and the Founding Chair in the Department of Computational & Systems Biology at the University of Pittsburgh’s School of Medicine, are co-authors on the study.
Using skin cells from human volunteers, researchers at the University of Pittsburgh School of Medicine have created fully functional mini livers, which they then transplanted into rats.
The potential benefits of stem cell therapy have been widely discussed for decades. Potential benefits include reduction of the pain of arthritis and help patients heal faster after surgery. But stem cell therapies can be prohibitively expensive. At the projected costs, these potential life-changing treatments would be far out of range of the vast majority of those who need them. But thanks to Carnegie Mellon University’s Kris Dahl, PhD, professor of chemical engineering, and Veronica Hinman, PhD, head of CMU’s Department of Biological Sciences, stem cell therapy could get a lot less expensive. And the key to this approach lies in the incredible regenerative powers of starfish.
NeuBase Therapeutics, Inc., a biotechnology company developing next-generation antisense oligonucleotide (“ASO”) therapies to address genetic diseases, recently announced positive preclinical data from its pharmacokinetics studies in non-human primates (“NHPs”) and in vitro pharmacodynamics data in patient-derived cell lines. NeuBase believes these data validate the key advantages of the proprietary NeuBase peptide-nucleic acid (“PNA”) antisense oligonucleotide (PATrOL™) platform and support the Company’s decision to advance the development of its Huntington’s disease (“HD”) and myotonic dystrophy type 1 (“DM1”) programs, as well as the potential expansion of its therapeutic pipeline into other indications.
Old human cells return to a more youthful and vigorous state after being induced to briefly express a panel of proteins involved in embryonic development, according to a new study by researchers at the Stanford University School of Medicine. Study co-author Thomas Rando, MD, PhD, professor of neurology and neurological sciences and the director of Stanford’s Glenn Center for the Biology of Aging, is an affiliated faculty member of the McGowan Institute for Regenerative Medicine.
Inspired by a tactic cancer cells use to evade the immune system, University of Pittsburgh researchers have engineered tiny particles that can trick the body into accepting transplanted tissue as its own. McGowan Institute for Regenerative Medicine affiliated faculty members involved in the research team include:
Genprex, Inc., a clinical-stage gene therapy company developing potentially life-changing technologies for patients with cancer and other serious diseases, today announced that it signed an exclusive license agreement with the University of Pittsburgh for a diabetes gene therapy that may have the potential to cure Type 1 and Type 2 diabetes, which together currently affect approximately 30.3 million people in the U.S, or 9 percent of the U.S. population.
Abbott Laboratories, the Abbott Park, Illinois-based health care giant, has won approval from the U.S. Food and Drug Administration (FDA) for a less invasive surgical procedure that allows surgeons to implant the company’s heart pump without a patient undergoing open heart surgery.
The dopamine D2 receptor has a previously unobserved role in modulating Wnt expression and control of cell proliferation, according to a new study from the George Washington University (GW) and the University of Pittsburgh. The research, published in Scientific Reports, could have implications for the development of new therapeutics across multiple disciplines including nephrology, endocrinology, and psychiatry. Zachary Freyberg, MD, PhD, an assistant professor of psychiatry and cell biology at the University of Pittsburgh School of Medicine and an affiliated faculty member of the McGowan Institute for Regenerative Medicine, is a senior author on the study.
Magee-Womens Research Institute (MWRI) has received $112,500 in funding from A Glimmer of Hope Foundation (GOH) to further research of metastatic breast cancer (MBC) and to enhance patient support services at UPMC Magee-Womens Hospital.
To commemorate Hypophosphatasia Awareness Day (October 30), Soft Bones, Inc., an organization dedicated to providing information, education and support to those affected by hypophosphatasia (HPP), awarded its tenth annual Maher Family Grant. In commemoration of its tenth anniversary, Soft Bones awarded two grants for the first time ever. McGowan Institute for Regenerative Medicine affiliated faculty member Dobrawa Napierala, PhD, Associate Professor of Oral Biology at the Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine, is one of this year’s awardees and will study adolescents and adults with HPP.
According to the American Cancer Society, kidney cancer is among the top ten most common cancers in men and women, and clear cell renal cell carcinoma (ccRCC) – the most common subtype of tumor associated with kidney cancer – accounts for more than 75 percent of cases.
The University of Pittsburgh’s Center for Medical Innovation (CMI) awarded grants totaling $70,000 to three research groups through its 2019 Round-1 Pilot Funding Program for Early Stage Medical Technology Research and Development. McGowan Institute for Regenerative Medicine affiliated faculty member Carl Snyderman, MD, MBA, is a co-investigator on one of the selected projects, along with Garrett Coyan, MD, a surgery resident in the lab of William Wagner, PhD:
Researchers of Sechenov University and University of Pittsburgh—including McGowan Institute for Regenerative Medicine affiliated faculty members
A new report highlights the latest advances in cell-based therapies for the treatment of disorders of the musculoskeletal system, such as arthritis and osteoporosis, and it identifies key unanswered questions that should be addressed through ongoing research. The report is published in the Journal of Bone and Mineral Research and concurrently in the Journal of Orthopaedic Research, and was issued by a joint Task Force of the American Society for Bone and Mineral Research and the Orthopaedic Research Society. McGowan Institute for Regenerative Medicine affiliated faculty member Rocky Tuan, PhD, Vice-Chancellor and President of The Chinese University of Hong Kong and the former Associate Director of the McGowan Institute, is the co-chair of the Task Force.
Researchers from Carnegie Mellon University (CMU) and Nanyang Technological University, Singapore (NTU Singapore) have developed an organ-on-an-electronic-chip platform, which uses bioelectrical sensors to measure the electrophysiology of the heart cells in three dimensions. These 3D, self-rolling biosensor arrays coil up over heart cell spheroid tissues to form an “organ-on-e-chip,” thus enabling the researchers to study how cells communicate with each other in multicellular systems such as the heart.
As reported by Forbes contributor Robin Seaton Jefferson, LyGenesis, Inc., hopes to enter human trials in 2020 on a therapy that could potentially give patients with end stage liver disease hope for new livers without having to wait on donated organs. The technology, developed through research from McGowan Institute for Regenerative Medicine faculty member Eric Lagasse, PharmD, PhD, associate professor in the Department of Pathology at the University of Pittsburgh and LyGenesis’ Chief Scientific Officer, uses lymph nodes as bioreactors to regrow functioning organs within a patient’s own body. The research found that a variety of different cells types and tissues, including the liver, could engraft and actually grow within lymph nodes. The company is working on injecting cadaver cells into lymph nodes to grow secondary livers.
Study: In the time it takes you to read this sentence, every cell in your body suffers some form of DNA damage. Without vigilant repair, cancer would run rampant, and now scientists at the University of Pittsburgh have gotten a glimpse of how one protein in particular keeps DNA damage in check.
The McGowan Institute has formed an alliance with the International Space Station (ISS) U.S. National Laboratory to develop and demonstrate how microgravity can improve regenerative medicine-based therapies. The ISS provides a unique platform to conduct studies in a microgravity environment.
Researchers at the University of Pittsburgh School of Medicine—including McGowan Institute for Regenerative Medicine affiliated faculty members Alejandro Soto-Gutierrez, MD, PhD, associate professor of pathology at Pitt’s School of Medicine and faculty member of the Pittsburgh Liver Research Center, and Ira Fox, MD, professor of surgery and pediatric transplantation at UPMC Children’s Hospital of Pittsburgh—are the first to grow genetically modified miniature human livers in the laboratory, to emulate human liver disease progression and test therapeutics.
Two Carnegie Mellon University (CMU) faculty members are changing the way that proteins are made for industry through their startup BioHybrid Solutions. McGowan Institute for Regenerative Medicine affiliated faculty member Krzysztof Matyjaszewski, PhD, is the J.C. Warner University Professor of Natural Sciences in the Department of Chemistry, and Alan Russell, PhD, is the Highmark Distinguished Career Professor of Chemical Engineering and former Director of the McGowan Institute.
Patients at UPMC Salvator Mundi International Hospital in Italy will soon have increased access to innovative methods of tissue regeneration that could improve healing and outcomes with reconstructive or aesthetic plastic surgery.
An international group of scientists in the joint study of the laboratory of the Wistar Institute, University of Pittsburgh, and I.M. Sechenov First Moscow State Medical University discovered the change in activity of one of the immune cells types called neutrophils during cancer development: They begin to prevent other immune cells from fighting tumors, and thus decelerate treatment. The scientists found protein causing such changes and demonstrated that suppressing its activity in the cells delays cancer development. The research details are published in Nature. McGowan Institute for Regenerative Medicine affiliated faculty member Valerian Kagan, PhD, Professor and Vice-Chairman in the Department of Environmental and Occupational Health as well as a Professor in the Department of Pharmacology and Chemical Biology, the Department of Radiation Oncology, and the Department of Chemistry at the University of Pittsburgh, and also the Director of the Center for Free Radical and Antioxidant Health, is a co-author of the study.
The same sources thought to inflict oxidative stress on cells—pollution, diesel exhaust, smoking and obesity—also are associated with shorter telomeres, the protective tips on the ends of the chromosomal shoelace.
Starfish can repair injured arms and reptiles can regrow severed tails; from bacteria to humans, every species is capable of regeneration, albeit to variable extents. These functions help make species more resilient, but how can we apply the knowledge of these regenerative mechanisms to improve human health? The University of Pittsburgh Department of Bioengineering has been collaboratively working to address this question through research efforts in tissue engineering and regenerative medicine.
In a follow-up to the recent McGowan Institute for Regenerative Medicine Scientific Retreat Panel Discussion, “Hope vs. Hype of Stem Cell Therapy,” J. Peter Rubin, MD, Chair of the Department of Plastic Surgery, the UPMC Endowed Professor of Plastic Surgery, Director of UPMC Wound Healing Services, and Professor of Bioengineering at the University of Pittsburgh, was a guest on Pittsburgh’s NPR News Station WESA program, The Confluence.
McGowan Institute for Regenerative Medicine affiliated faculty member Joseph Glorioso III, PhD, Co-founder, CODA Biotherapeutics, and Professor and Emeritus Chair, Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, is working on a gene therapy approach for treating chronic pain. CODA is developing engineered neurotransmitter receptors that are activated exclusively by orally bioavailable drugs to control the activity of hyperexcitable neurons responsible for chronic neuropathic pain. The gene encoding the receptor is delivered to dysfunctional neurons by proprietary viral vectors that are optimized for robust and targeted gene transfer. Standard neurosurgical procedures are used to administer these viral vectors directly to the neurons to be controlled. Once expressed, the engineered receptor can be activated by the drug to modulate neuronal activity. This enables the selective, tunable and reversible regulation of the receptor – and hence cellular activity – based on the dosing regimen of the drug. CODA is engineering receptors to have exquisite sensitivity for the pharmacological activator, which should dramatically limit off-target side effects that plague many pharmaceutical treatments.
Do lymph nodes hold the key to regenerating failed organs?
Our body’s lymph nodes generally go unnoticed, unless they become swollen and painful in the fight against infection. They’re part of a body-wide system that quietly grows immune cells, circulates them to infection sites, and carries away waste.
Our cells sometimes have to squeeze through pretty tight spaces. And when they do, the nuclei inside must go along for the ride. Using super-sensitive microscopic imaging, a team of scientists from the University of Pittsburgh and Carnegie Mellon University have made a fundamental biological discovery that explains the structure of the nuclear envelope and gives tantalizing clues as to how cells squish through narrow openings without springing a leak.
