Cell Biology & Regenerative Medicine

Musculoskeletal disorders are associated with chronic and acute pain, physical disability, and decreased quality of life. In addition, the health care costs and productivity losses associated with musculoskeletal injuries continue to increase. As a result, Thomas Jefferson University has become one of the top institutions in the world studying the molecular basis of musculoskeletal diseases and injuries. In conjunction with clinicians at the Rothman Institute and Jefferson Health, CBRM researchers are focused on several key areas, including intervertebral disc disease, osteoarthritis, musculoskeletal infections, fibrosis, osseous pain, and skeletal adaptation. These research programs are utilizing cutting edge tools and techniques to increase our knowledge of musculoskeletal biology and develop new therapeutic strategies to combat musculoskeletal disorders.

Cardiovascular disease is the leading cause of death worldwide. Heart failure is a lifelong condition in which the heart muscle can't pump enough blood to meet the body's needs for blood and oxygen. Hundreds of millions of adults are afflicted with heart failure and there are no effective therapeutics available to prevent deterioration or reverse a failing heart to a healthy state. Similarly, hypertension is a major chronic disease worldwide; one third of the population in the United States is hypertensive, and alarmingly, nearly half of the individuals using anti-hypertensive medication do not have their blood pressure well controlled. These patients exhibit autonomic dysregulation and are susceptible to heart failure. It is now compelling that neural contributions to hypertension and heart failure are a major cause in the development of essential hypertension and in pathological changes in the heart. In this context, researchers at Jefferson are studying the vagus nerve, a key body-brain axis that mediates the communication between most visceral organs and the brain. The vagus nerve is a crucial regulator of cardiovascular homeostasis, and its activity is linked to heart health. Vagal stimulation is emerging as the next frontier in bioelectronic medicine to modulate peripheral organ health and treat disease.

Research at Jefferson focused on identifying molecular, cellular and neuronal circuit mechanisms that are essential for robust control of blood pressure and cardioprotection to prevent heart failure. Ongoing research projects integrate organismal physiology, neuronal cell biology, molecular biology, and computational modeling to explore microRNA-mediated regulation of inflammation, immune response and signaling processes to interfere with the development and maintenance of hypertension, as well as enhance cardioprotection for preventing heart failure.

Liver regeneration is a clinically important tissue repair process, which involves an interplay of coordinated signals from different cell types integrated with the systemic factors to recover functional tissue mass. Reduction or loss of regenerative capacity underlies nearly every chronic liver disease and is thought to drive the pathological changes driving towards liver failure. The regenerative process is also crucial for the success of liver surgical interventions and in transplantation, which remain the primary therapeutic approaches to treat chronic liver failure. It is recognized that nearly a fourth to a third of the population in the United States has or will be afflicted with chronic liver disease. Obesity and alcohol consumption, which are common and increasing in many parts of the world, have become key liver disease risk factors. Despite decades of research and the recognition of several molecular components that facilitate or impair the regeneration response in rodents, an effective mechanistic understanding of the factors that drive the temporal progression and coordinate the tissue repair responses across different cell types, has remained elusive.

Researchers at Jefferson take a systems biology strategy that combines multiscale network modeling with the functional genomics data sets at the single cell scale to fill this major gap in our knowledge. Ongoing projects are translating the animal experimental findings to the human condition to support clinical decision-making in the liver surgery and transplant scenarios. The research program involves a multidisciplinary collaboration between bench scientists, hepatologists, liver surgeons, transplant coordinators and systems engineers, located at Jefferson as well as at national and international institutions.

Mitochondrial disease is a group of disorders caused by dysfunctional mitochondria, the organelles that generate energy for the cell. The purpose of the MitoCare Center for Imaging Research and Diagnosis is to exploit microscopic imaging and other advanced technologies to delineate the multiple emerging mechanisms by which mitochondria are involved in normal tissue function and human diseases such as heart disease, metabolic diseases, neurodegenerative disorders, cancer and primary mitochondrial disease. MitoCare is committed to training students and post-doctoral fellows in the practice of science at the highest level. 

The vision and neurodegenerative research group is comprised of basic scientists and clinician researchers with expertise in ophthalmology and neurology. Areas of interest include understanding: the genetics of congenital abnormalities of the eye; environmental and genetic basis of diseases like age-related macular degeneration; role of metabolic transporters in maintaining normal visual function, lens development and posterior capsule opacification, impact of Parkinson's on the visual system; molecular basis of cancers in the visual system such as uveal melanoma and retinoblastoma; and molecular pathogenesis of the neurodegenerative diseases such as spinal and bulbar muscular atrophy, Alzheimer’s and Parkinson's disease. Investigators in this group conduct innovative research aimed at identifying the biochemical, physiological and molecular/genetic factors contributing to the cause and progression of ocular and neurodegenerative diseases and are working to develop effective new treatments for these devastating disorders.

Systems Biology research uses computational and experimental techniques focused on quantitative system-wide "omic" datasets to solve problems in pathology, molecular biology, physiology and medicine. The Daniel Baugh Institute (DBI) for Functional Genomics/ Computational Biology provides an interdisciplinary base for research and education in systems biology. Research interests of the group center on the development and use of quantitative system-wide omics datasets towards integrative modeling and computational analysis of the dynamics of biological systems. Ongoing research projects are directed at understanding the operational principles of mammalian tissue plasticity, renewal, repair and regeneration. A key goal is to develop novel clinical interventions and decision-support systems for regenerative medicine. The transdisciplinary systems biology strategy integrates computational modeling, systems engineering, bioinformatics, functional genomics, high-dimensional data analysis, and single cell biology. Ongoing collaborative projects focus on liver repair and regeneration, alcoholic liver disease, brainstem neuroinflammation and neuroimmune processes leading to hypertension and heart failure, cell fate regulation underlying developmental defects, cell-cell interactions in tumor microenvironment and network response to immunotherapy, and network modeling of renewal and regeneration in multiple mammalian tissues. The Computational Medicine Center’s strengths are in the areas of non-coding RNAs and pattern discovery.