Research & Faculty

Heart & Blood Vessel disease

Diseases of the heart and blood vessels are the number one cause of death and every 30 seconds an individual in the U.S. dies from heart and vascular diseases. The risk of developing heart and vascular diseases is greatly increased by diabetes, obesity, and high blood pressure. The Heart and Blood Vessel Disease Research Group at NEOMED seeks to understand these diseases with an ultimate goal of curing them.

Areas of Study

Studying the growth of tiny blood vessels (capillaries) which deliver nutrients and oxygen to an organ. Too much capillary growth causes diseases such as cancer and blindness. Too little capillary growth can cause heart failure and not enough pumping action of nutrients or oxygen to the heart.

Studying ways to minimize the consequences of a heart attack by maintaining the hearts ability to produce energy. Studying ways to stop the heart from failing and amplify the body’s healing processes to prevent failure.

Studying ways to amplify the body’s own populations of stem cells to facilitate healing of the heart after a heart attack. A clinical trial is taking place and has lead to the creation of an engineered stem cell that can serve as a building block for new blood vessels in the heart.

Studying how to prevent the cause and the consequences of diseases such as obesity and diabetes. Studies also look at proteins affected by substances released by the fat tissues and how they contribute to the development of vascular disease and artery blockages.

Faculty Researchers

Director, Heart & Blood Vessel Disease Research Area
Professor and Chair of Physiology
Phone: 330.325.6426
Email: wchilian@neomed.edu

My interest in the vascular biology has been developing for many years along the lines of acute and chronic adaptations of the coronary circulation to physiological and pathophysiological stresses. With regard to chronic adaptations of the coronary circulation, my laboratory was the first to show that ischemia, rather than shear stress, initiates coronary collateral growth. Shear stress is not precluded from this process; rather this mechanism plays a role in the expansion of the vessel after the ischemic stimulus wanes. More recently my laboratory has studied the role the mitochondrial oxidative stress in coronary collateral development, and we have found that such stress blunts the adaptive growth of coronary collaterals. Moreover, rectification of oxidative stress will restore collateral growth in a preclinical model with a poor growth phenotype. With regard to acute adaptations of the coronary circulation to physiological and pathophysiological stresses, I am proud of the accomplishments of my laboratory: we were the first to document myogenic and flow-dependent control of coronary tone; the distribution of microvascular resistance in the beating heart, the effects of preconditioning extended to the vascular endothelium, the mechanism of alpha-adrenergic coronary constriction involves release of a cardiac myocyte derived vasoconstrictor, coronary metabolic dilation is a feed-forward process involving mitochondrial production of H2O2, metabolic dilation is mediated by redox reactions, and Kv1.5 channels play a critical role in metabolic dilation in the heart.

Distinguished University Professor of Biochemistry and Molecular Pathology
Professor of Integrative Medical Sciences
Email: jchiang@neomed.edu

Dr. Chiang’s research is focused on studying bile acid and cholesterol metabolism in the liver and the role of bile acids and nuclear receptors in regulation of glucose, lipid and energy metabolism in liver diseases, diabetes and obesity. This laboratory first purified cholesterol 7α-hydroxylase (CYP7A1), a microsomal cytochrome P450 with strict substrate specificity for cholesterol, and cloned the gene CYP7A1. CYP7A1 is the first and rate-limiting enzyme in the classic bile acid biosynthetic pathway that converts cholesterol to bile acids.

Associate Professor of Biochemistry/Molecular Biology
Research Associate Professor of Pharmacy Practice
Phone: 330.325.6684

To understand the process of inflammation in human disease and the significance of fatty acid Omega hydroxylase genes (CYP4) in regulating inflammation and fatty acid metabolism.

Assistant Professor of Integrative Medical Sciences
Phone: 330.325.6415
Email: ylee3@neomed.edu

Role of orphan nuclear receptor SHP in diet induced diabetes and obesity.

Associate Professor of Integrative Medical Sciences
Adjunct Associate Professor of Pharmaceutical Sciences
Phone: 330.325.6693
Email: yzhang@neomed.edu

My laboratory is interested in understanding the role of both transcription factors and non-transcription factors in controlling lipid and carbohydrate homeostasis and obesity. We are particularly interested in the nuclear receptors FXR (farnoesoid X receptor) and HNF4α (hepatocyte nuclear factor 4α).

These two nuclear receptors play important roles in regulating bile acid, lipid and glucose metabolism. One of our recent research interests has been to study the role of hepatic non-transcriptional factors (such as carboxylesterase 1) in regulating lipid and carbohydrate metabolism and obesity.

We have been utilizing transgenic and knockout mouse models, together with biochemical, molecular and cellular, and pharmacological approaches, to complete our studies.

Associate Professor of Physiology and Pharmacology
Phone: 330.325.6432
Email: jgmeszar@neomed.edu

Professor of Integrative Medical Sciences
Phone: 330.325.6537
Email: ychen1@neomed.edu

Our research focuses on the molecular mechanisms underlying redox signal pathway in mediating the disease pathogenesis of myocardial infarction. We are interested in the role of mitochondria-derived oxygen free radicals, signals of glutathione and nitric oxide in regulating oxidative post-translational modifications (OPTM) and how these events impact the bioenergetics function of mitochondria in the post-ischemic heart.  One line in our work has established alterations of protein S-glutathionylation in mitochondrial complex I and complex II are linked to mitochondrial dysfunction caused by oxidant stress after myocardial ischemia and reperfusion.  In collaboration with the principle investigators of NEOMED/KSU, we are extending the research of this marker to the animal models of type II diabetics and obesity.

A second area of work in the lab is focused on the redox pathway of GSH in controlling the status of complex I/complex II S-glutathionylation and superoxide generation mediated by electron transport chain during myocardial ischemia and reperfusion.  The mechanism underlying if protein S-glutathionylation as an indicative of overproduction of superoxide in vivo or not is extensively explored.  We employ the pharmacologic approach and genetic modified mouse model to study the mechanism of altering redox modification of mitochondrial proteins.  We employed the technique of electron paramagnetic resonance (EPR) to measure the oxygen free radical(s) and redox status of mitochondria in heart.

A third area of work in the lab is focus on how eNOS signal pathway regulates mitochondrial function in the heart and the OPTM of mitochondrial electron transport chain in the post-ischemic heart.  In collaboration with the investigators from the OSU, we has established that increasing protein tyrosine nitration of complex I and complex II was detected in the post-ischemic heart, and closely related to overproduction of NO by eNOS in the early phase of reperfusion.  Physiologically the signal of NO generated by eNOS can regulate mitochondrial respiration, and further modulates the redox status of mitochondria in myocytes. We employ the genetic modified mouse and generate a new mouse model to investigate how the signal by eNOS regulates complex I/complex II S-glutathionylation, and related mitochondrial dysfunction resulted from post-ischemic injury.

Associate Professor of Molecular Pharmacology
Phone: 330.325.6412
Email: jyun@neomed.edu

Assistant Professor of Integrative Medical Sciences
Phone: 330.325.6530
Email: ibratz@neomed.edu

Having extensive research experience in cardiovascular physiology, I am strongly interested in regulation of vasomotor tone by ion channels expressed in arterial smooth muscle and endothelial cells. Using a varied approach, including patch clamp electrophysiology, molecular biology, laser scanning confocal imaging of intracellular Ca2+ events, and video microscopy recordings of diameter changes in pressurized resistance arteries and antisense-mediated suppression of ion channel expression in intact arteries, my lab examines the role of transient receptor potential (TRP) channels expressed by coronary artery smooth muscle and endothelial cells in vascular function. The TRP channel family is a diverse group of voltage-independent cation channels, ubiquitously expressed that are activated by a broad range of physical, chemical, and environmental stimuli, such as: temperature, pressure, stretch, and fatty acids. Many of its vascular physiological functions remain unclear. The TRPV channels represent one of the six known subfamilies and are characteristically gated by vanilloid compounds (e.g., capsaicin opens TRPV1 channels). Currently, my focus is on elucidating the functional roles of TRPV1 channels in the regulation of coronary vascular tone. Recent studies have implicated various TRPV channels in the regulation of vascular tone, but little is known about the role of TRPV1. Recent data indicate TRPV1 channels are functionally expressed in the coronary circulation and that TRPV1 signaling is disrupted in the metabolic syndrome. Ongoing experiments are focused on elucidating the mechanisms by which TRPV1 channels regulate coronary vascular tone in normal and metabolic syndrome subjects.

Assistant Professor of Integrative Medical Sciences
Phone: 330.325.6423
Email: cthodeti@neomed.edu

Cells within all living tissues encounter mechanical forces continuously within a changing dynamic environment, and increasing evidence suggests that mechanical forces regulate cell growth, differentiation, motility, protein synthesis and gene expression. Importantly, mechanical forces are critical regulators of cardiovascular physiology and pathophysiology. Therefore, understanding how cells sense and convert mechanical signals into biochemical signals, mechanotransduction, could offer novel therapeutic targets for treatment of various cardiovascular diseases and in vitro engineering of organs and tissues such as blood vessels. The long-term goal of my research is to work at the interface between soluble and solid state biochemistry using multidisciplinary approaches to investigate the biophysical, biomechanical and biomechanical mechanisms regulating endothelial cell function and angiogenesis and utilize the knowledge to develop effective vascular normalization therapies for cardiovascular abnormalities such as atherosclerosis, hypertension, diabetes and cancer.

Currently, my laboratory is focused on understanding the role of mechanosensitive TRPV4 ion channels in the regulation of:

Tumor angiogenesis: Tumor vessels are characterized by abnormal morphology and patterning that cause vascular hyperpermeability and inefficient delivery of anti-cancer agents. We recently demonstrated that these vessel malformations may arise from aberrant Rho-mediated mechanosensing exhibited by tumor endothelial cells in response to mechanical strain. We also found that TRPV4 channels are required for endothelial cell reorientation in response to mechanical force. Therefore, we are investigating the role of TRPV4 channels and dependent signaling mechanisms in the regulation of tumor endothelial cell mechanosensitivity in order to identify novel targets that can be potentially used to normalize abnormal tumor vasculature and improve delivery of chemotherapeutic drugs in vivo.

Stem cell differentiation into bone and cartilage: Mechanical forces are critical determinants of tissue morphogenesis including bone which is continuously exposed to mechanical forces. Indeed, local micromechanical forces have been shown to regulate human mesenchymal stem cell commitment to bone forming osteoblast like cells. Our focus in this project is to elucidate the biomechanical mechanisms that regulate stem cell differentiation in to bone and cartilage. To this end, we are collaborating with the Departments of Polymer Engineering, University of Akron and Plastic Surgery, Akron Children’s Hospital to develop tissue engineering scaffolds that are mechanically osteo-inductive for bone regeneration therapy.

Assistant Professor of Integrative Medical Sciences
Phone: 330.325.6425
Email: praman@neomed.edu

Overall research focus in the Raman lab is in the area of Vascular Complications associated with Diabetes and Obesity.  We are interested in understanding the cellular and molecular mechanisms underlying pathogenesis of accelerated atherosclerosis associated with hyperglycemia and hyperleptinemia, characteristics of diabetes, obesity and metabolic syndrome.  Ongoing research projects in the lab include:  1) Role of the extracellular matrix protein, thrombospondin-1 (TSP-1) in vascular dysfunction associated with metabolic syndrome; 2) Role of leptin receptor signaling in hyperleptinemia-induced atherosclerosis complications; 3) Elucidation of mechanisms linking glucose metabolism to atherosclerosis; 4) Vasculoprotective mechanisms of the mineral nutrient trivalent chromium in diabetic vascular disease.  For these studies, we utilize a variety of techniques including biochemical assays, cellular and molecular biology approaches and cell culture studies in conjunction with different in vivo mouse models of diabetes, obesity and atherosclerosis, including transgenic mouse lines and tissue-specific knockouts.

Associate Professor of Integrative Medical Sciences
Phone: 330.325.6521
Email: lyin@neomed.edu

Cardiovascular Biology, Genetics and Cardiovascular Diseases, Metabolism Disorder, Stem Cells and Tissue Regeneration.  Current main focus is to study stem cells in cardiovascular regeneration in metabolic syndrome.  We study the partially reprogrammed vascular progenitor cells, bone marrow derived stem cells, adipose derived stem cells, cardiac stem cells and induced pluoripotent stem cells in the animal models for coronary collateral growth which will prevent the myocardial ischemia injury or deliver the promising stem cells with biomaterial for tissue regeneration in myocardium infarction injury.  We also move forward in clinical translation study in patients with cardiovascular diseases.

Questions? Please contact:

William M. Chilian, Ph.D.
Professor and Chair of Physiology
Director, Heart & Blood Vessel Disease Research Area
Phone: 330.325.6426
Email: wchilian@neomed.edu

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