NYMC > Departments > Academic Departments > Graduate School of Biomedical Sciences > Physiology > Research


While other basic and clinical sciences analyze the molecular and cellular structure of systems and the effects of biological processes, physiology encompasses all of these, integrating myriad facets and layers of scientific scrutiny in the complex function of living organisms.

Christopher S. Leonard, Ph.D., professor and interim chair, is focused on understanding how neurons communicate. Using sophisticated biophysical recording techniques as well as computer modeling, the group examines how neurons in the brain stem and cerebral cortex generate electrical impulses, and how these neurons and their synaptic interactions are modulated by neurotransmitters. Dr. Leonard aims to correlate current cellular studies with the system-level behavior of neurons—processes that regulate how the brain stays awake, sleeps and generates dreams.

Carol A. Eisenberg, Ph.D., associate professor, Dr. Eisenberg’s research focus is on the signaling mechanisms that underlie how myocardial cell health is maintained in the adult heart. This topic is investigated in her laboratory from three distinct but overlapping vantage points. The first project examines signaling pathways activated in the diseased heart using the tgG6/lacZ mouse model. The tgG6/lacZ transgenic mouse expresses a β-galactosidase (lacZ) reporter driven by a specific enhancer of the GATA-6 gene, and which serves as a marker for the re-emergence of a fetal gene program in the heart under conditions of stress and disease. The second project involves the development of culture conditions that allow for the long-term maintenance of fully differentiated myocardial tissue in culture, as the means for understanding how the cardiac cells continues to sustain their viability and functional activity. The final project looks at the cell and molecular events guiding the differentiation of stem cells for replacement cardiomyocytes. These three areas of study are complementary to the laboratory’s overall goal of understanding how the functional capabilities of the adult heart can be preserved throughout life.

Leonard M. Eisenberg, Ph.D., professor, Dr. Eisenberg’s research program focuses on the generation and maintenance of the myocardium in the embryo and adult, with the specific emphasis on the role that epigenetic regulation and Wnt signal transduction play in promoting cardiac cell differentiation. The laboratory’s recent studies over the past few years have been on the importance of G9a histone methyltransferase (HMTase) in regulating the phenotypic potential of adult stem cells. Specifically, we have shown that inhibition of G9a HMTase-mediated histone methylation can shift the differentiation potential of non-cardiac stem cells, such as bone marrow mesenchymal stem cells, to a cardiac competent phenotype. The suppression of G9a HMTase activity in non-cardiac stem cells allows the cells to respond to cardiogenic differentiation factors and exhibit a gene and protein expression profile similar to nascent cardiomyocytes. Among the most prominent of these cardiac differentiation factors are the WNT family of secreted signaling proteins, which have been shown to play important roles in regulating cell fate decisions of stem cells. WNT regulation is essential for brain, limb, kidney, mammary gland, muscle and heart development and their dysregulation has a major influence on tumor formation. Ongoing investigations in the laboratory examine how combinatorial signaling by distinct classes of WNT proteins promote cardiogenesis and allow non-cardiac stem cells to undergo cardiac differentiation following the inhibition of G9a histone methyltransferase.

Jonathan A. N. Fisher, Ph.D., assistant professor investigates problems in molecular, cellular, and systems neuroscience. Current research is focused on the biophysics and neurophysiology of the auditory system. Research interests also include biomedical optics (particularly the development of new neuroimaging techniques) and auditory processing.

An Huang, M.D., Ph.D., professor, research focused on the regulation of microvascular function via NO/sGC pathway that serves as a key player in a variety of aspects of vascular regulation, and also as a specific target of oxidative species such as superoxide, peroxynitrite and hydrogen peroxide as well. Specifically, during the pathological development of vascular dysfunction, such as in vascular aging, metabolic syndrome, heart failure and pulmonary and systemic hypertension, reduced activation of eNOS and enhanced oxidative stress contribute significantly to the altered vascular NO/sGC signaling. By using isolated arterioles to assess flow-induced dilation and shear stress-induced release of NO, I demonstrated that all pathological change-associated endothelial dysfunction is characterized by an impaired NO bioavailability, as a function of decreased shear stress-induced eNOS phosphorylation, increased superoxide formation a decreased antioxidant capacity, wherein, changes in renin angiotensin system (RAS) play key roles. Novel methods used in my lab include but not limited to 1) a perfusion system containing two serial connected vessel chambers for the study of EDHF bioassay and electrophysiology of single vessels 2) a vessel culture perfusion system containing ten separated chambers, which allows us to synchronically evaluate the function of ten single vessels isolated from different animal models or different sexes in an identical experimental environment 3) a perfusing freshly isolated single vessels to obtain endotheliallysates for detecting specific endothelial mRNA(s) and protein(s), and 4) HPLC-fluorescence detector-based measurements of vascular EETs, mitochondrial/cytosolic superoxide, homocysteine, angiotensin, protoporphyrin, ferrochelatase activity etc. from single isolated and pressurized vessels.

Akos Koller, M.D., Ph.D., professor emeritus, studies blood circulation and the effects of naturally occurring substances such as estrogen, nitric oxide, calcium and prostaglandins on the function of arterioles, capillary veins and lymphatic vessels. By studying the endothelium and smooth muscle of blood vessels and probing cellular mechanisms that govern pressure and flow signals, Dr. Koller and his team may provide new clues to improve treatment of hypertension, arteriosclerosis and diabetes.

Edward J. Messina, Ph.D. '73, professor emeritus, is investigating the influence of hormonal, metabolic, myogenic and flow-dependent responses on the regulation of blood flow in skeletal muscle and fat. The myogenic response is the constriction of a blood vessel brought about by increases in blood pressure; flow-dependent dilation is the opposing influence induced by the flow of blood through the vessel. Using in vivo and in vitro studies of arterioles, the group is exploring ways in which disturbances in regulatory processes contribute to the vascular signs and symptoms associated with diabetes mellitus and hypertension.

Brian B. Ratliff, Ph.D., associate professor, research in my laboratory investigates the mechanisms responsible for acute/chronic kidney failure and associated vascular impairment, including examination of potential therapeutic interventions for prevention of kidney damage/failure. More specifically, my laboratory’s research focuses on four of the following areas: 1) Examination of fetal and developmental (organogenesis) programming that leads to the susceptibility of acute/chronic kidney disease and hypertension in the neonate and adult. This area of research also includes examination of impaired placental formation and function during gestation that leads to impaired fetal development. 2) Investigation of the role of oxidative stress in programming, promoting and progression of acute/chronic kidney disease and vascular impairment. 3) Investigation of pro-damage signaling “alarmins” (such as HMGB1) that are released from kidney cells rapidly after initial cellular stress (i.e., induced by factors such as hypoxia, toxins, oxidative stress, etc.). Such alarmins signal and stimulate local and systemic inflammation that leads to progressively worsening tissue injury. 4) Examination of the therapeutic efficacy of various stem cells (including renal mesenchymal stem cells and endothelial progenitor cells) and pharmacological agents for their ability to prevent and/or regenerate kidney and vascular tissues after injury.

William N. Ross, Ph.D., professor, and his colleagues are studying the detailed interactions between neurons in the hippocampus and the cerebellum. Their primary focus is the complex system of dendrites, branch-like extensions of neurons where inputs from different parts of the brain come together and are integrated. Using a combination of electrophysiological and imaging techniques that allows them to view a wider landscape of dendritic events, the team is studying the role of neurotransmitters and receptors in controlling the release of calcium from neurons.

Dong Sun, M.D., Ph.D., professor, is mainly focusing on the regulation of endothelial function of arterioles. In particular, endothelial compensatory mechanisms in response to an impaired endothelial nitric oxide (NO) signaling and endothelial deformation-induced initiation of NO-dependent vascular protective mechanisms are studied. In recent years, he has focused on endothelial dysfunction of micro vessels in response to vascular aging. Using isolated arterioles to assess flow-induced dilation and shear stress-induced release of NO, I demonstrated that age-associated endothelial dysfunction is characterized by an impaired NO bioavailability, due to a decreased shear stress-induced eNOS phosphorylation, an increased superoxide formation and a decreased antioxidant capacity. The increased superoxide formation in aged vessels is a consequence of eNOS uncoupling and increased expression of NADPH oxidase.

Michael S. Wolin, Ph.D., professor, is exploring how metabolic processes, nitric oxidants and nitric oxide interact with redox regulated signaling systems to control the mechanisms in vascular physiology and pathology. Recent studies have underscored the extensive nature of fundamental role of oxidant-signaling mechanisms in cardiovascular disease. By examining the properties of how oxidant-producing enzymes and metabolic control of redox act as sensors in detecting oxygen levels and biological stresses, our studies are improving understanding of how redox changes affect mechanisms that regulate blood vessel contractile function within a single cell or between neighboring cells of endothelium and vascular smooth muscle, and adaptive interactions seen pathophysiological remodeling. The collaborative environment at NYMC has enabled us to extend studying these types of regulatory processes to many other systems such as systemic and pulmonary hypertension, metabolic diseases, and oxidant processes causing additional aspects of inflammation and tissue dysfunction.