skip to Main Content


Early Career Investigators

Alexandra M. Binder, Ph.D.
Assistant Professor, Department of Cancer Epidemiology, University of Hawaii Cancer Center
High childhood adiposity is associated with a greater risk of type II diabetes, coronary heart disease, hypertension, and certain types of cancer in adulthood. Prior pediatric studies suggest that insulin resistance (IR) may amplify the influence of childhood adiposity on future cardiometabolic health. There is a critical need to understand predictors of childhood IR and how IR modifies the impact of adiposity on the developmental programming of adult disease. Increasing exposure to endocrine disrupting chemicals (EDCs) during critical windows of structural and functional development may be contributing to growing rates of both childhood obesity and IR. The mechanism mediating the prolonged influence of these exposures on growth patterns is poorly understood. We hypothesize childhood adiposity and IR impact patterns of DNA methylation, and that these associations are partially shaped by EDC exposure. We plan to explore these relationships among a subset of females within the ongoing longitudinal Growth and Obesity Cohort Study based in Santiago, Chile. Our extensive longitudinal data and comprehensive series of analyses will allow us to identify patterns of DNA methylation that may contribute to the early life programming of adult cardiometabolic health.

picture of Kapuaola GellertS. Kapuaola Gellert, Ph.D.
Assistant Professor, Department of Native Hawaiian Health
I am an epidemiologist with expertise in cardiovascular disease (CVD), and the population burden of CVD risk factors. Our research focuses on the effect of sleep deficiencies on CVD and cardiometabolic conditions including diabetes. We use epidemiologic methodologies to characterize the risk factors individually and in combination that are involved in the association between sleep deficiencies and diabetes. Our findings will elucidate important risk factors and biomarkers involved in sleep deficiencies and diabetes in Native Hawaiians thereby informing further research on sleep deficiencies and diabetes.

picture of Nicholas JamesNicholas James, Ph.D.
Assistant Professor, Department of Cell and Molecular Biology
My COBRE-Diabetes research is focused on examining the molecular mechanism of signaling from the endocrine hormone FGF-21 within adipose tissue as a means of establishing FGF-21 as a candidate therapeutic molecule for treatment of metabolic disorders. FGF-21 bioactivity is only observed in metabolic tissues wherein it produces a robust pharmacological effect on metabolism, such as an increase in energy expenditure, improved insulin-sensitivity, and lowered circulating triglycerides and cholesterol concentrations. Paradoxically, previous studies have reported significantly higher circulating levels of FGF-21 among patients with metabolic disorders, including obesity, diabetes, and anorexia, compared to health patients. Researchers have hypothesized that adipocytes, and other metabolic tissues, might become resistant to FGF-21 signaling due to the correlation of reduced FGF-21 signaling molecules and patients with metabolic disorders. We are expanding upon these observations to understand how adipocytes become less sensitive to FGF-21, if reduced FGF-21 signaling within adipocytes correlates with reduced metabolic output from these cells (e.g. mitochondrial respiration), and the possibility of altered FGF-21 sensitivity in metabolic tissues as being an upstream event associated with obesity, insulin-resistance, and diabetes.

picture of Noemi PolgarNoemi Polgar, Ph.D.
Assistant Professor, Department of Anatomy, Biochemistry, and Physiology
Diabetes is a rapidly growing public health issue characterized by insulin resistance. In insulin resistance, trafficking of the insulin-responsive glucose transporter GLUT4 to the cell’s surface is impaired, leading to decreased glucose uptake in major metabolic tissues and increased blood sugar levels. Therefore, finding a target that could be used to trigger GLUT4 trafficking and thereby preserve the patient’s insulin response, would represent a major breakthrough for diabetes therapy. Even though skeletal muscle is responsible for the majority of glucose uptake, the molecular mechanisms involved in GLUT4 trafficking in skeletal muscle are not well understood. Our goal is to identify the skeletal muscle-specific regulators of GLUT4 trafficking and to target these regulators to lessen insulin resistance and improve glucose uptake.

picture of Tyler RayTyler Ray, Ph.D.
Assistant Professor, Department of Mechanical Engineering
Sweat contains a wealth of biomarkers relevant to health status, including electrolytes, metabolites, organic compounds, inflammatory/stress biomarkers, proteins and hormones. Aspects of sweat rate and composition have been used in assessing cystic fibrosis, drug use, physical fatigue, cognitive state, depression, and hypertension, among other conditions. Our group seeks to harness sweat-based analytics to improve outcomes for diabetic patients with an innovative monitoring platform for diabetic-related conditions.

Graduated Early Career Investigators

picture of Michael CorleyMichael Corley, Ph.D. (graduated in 2020)
Identifying the Immunoepigenetic Signature of Type 2 Diabetes

The overall goal of my epigenetics diabetes research program is to increase the understanding of how epigenetic mechanisms within immune cells become dysregulated in type 2 diabetes. Specifically, our research is focused on studying DNA methylation, transcriptional programs, immune inflammation, and immune metabolism in type 2 diabetes.

picure of Viola PomoziViola Pomozi, Ph.D. (graduated in 2018)
Role of ATP binding cassette, subfamily C, member 6 (ABCC6) in diabetes and atherosclerosis

Even when controlled, diabetes is the most common cause of diabetic kidney disease (DKD) and end-stage renal disease. Vascular calcification, a predictor of morbidity and mortality, is commonly associated with these pathologies and is the result of metabolic insults linked to both diabetes and DKD. Multiple lines of evidence suggest that ABCC6, a gene associated with pathological calcification in heritable diseases, is an important determinant of vascular calcification in DM and DKD. ABCC6 is a membrane transporter primarily found in liver and kidneys that mediate the production of inorganic pyrophosphate (PPi), a potent calcification inhibitor. Remarkable, reduced ABCC6 expression also enhances dyslipidemia and may also contribute to development of metabolic syndrome.

picture of Alexander StokesAlexander Stokes, Ph.D. (graduated in 2020)
TRPA1 Physiology in Diabetes, Metabolic Syndrome, and Metabolism

Certain cells in your body produce insulin which help the body regulate the amount of sugar your body uses. Excess nutrients exhaust the body’s ability to produce insulin in sufficient quantities to clear sugar from the blood, a condition known as diabetes. An ion channel found in these cells (TRPA1) contributes to calcium influx into these cells, a step that potentiates insulin release, Dr. Stokes and this laboratory study this channel and how it is regulated by other proteins in the cell, as well as studying whether this ion channel can be used as a therapeutic target in diabetes and metabolic regulation.

Pilot Projects

picture of Stacy BrownStacy Brown, M.D.
Assistant Professor, Department of Medicine
I am a neurointensivist with clinical expertise in the management of neurologic emergencies including acute stroke. My research lies at the intersection of stroke epidemiology, vascular neurology, and population genetics. Motivated by observed population health disparities affecting stroke risk and outcome in the Pacific Islands, my project aims to evaluate how polygenic predispositions to diabetes and other cardiometabolic diseases influence risk of stroke in individuals of Native Hawaiian ancestry. I am also interested in how genetic variation related to cardiovascular disease impacts stroke survival, brain resilience, and functional outcomes after cerebrovascular injury.

picture of Abhijit DateAbhijit Date, Ph.D.
Assistant Professor, Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo
Dr. Date’s research focuses on the improvement of biopharmaceutical properties of drugs indicated for the treatment of cardiometabolic disorders to improve their therapeutic efficacy. Dr. Date is currently involved in the development of strategies to improve biopharmaceutical properties and oral bioavailability of metformin, a front-line antidiabetic drug with poor cell permeability. More specifically, he is focusing on the physicochemical and structural modification of metformin and its subsequent encapsulation into nanoparticles to improve the oral bioavailability and therapeutic efficacy of metformin.

picture of Matthew PittsMatthew Pitts, Ph.D.
Assistant Professor, Department of Cell and Molecular Biology
My current research investigates the role of selenoproteins in two discrete populations of neurons, GABAergic parvalbumin (PV)-expressing interneurons and leptin receptor-expressing hypothalamic neurons. Redox imbalance in these two cell types has been implicated as key factors underlying neurodevelopmental disorders and obesity, respectively. With respect to diabetes, my work has identified selenoprotein M (SELENOM) as a novel factor that promotes hypothalamic leptin signaling and thioredoxin antioxidant activity. Current studies are being conducted to elucidate the molecular function of SELENOM with an emphasis on its influence upon mitochondrial bioenergetics and calcium homeostasis.

picture of Kathryn SchunkeKathryn Schunke, Ph.D.
Assistant Professor, Department of Anatomy, Biochemistry, and Physiology
Disruption of cardiac parasympathetic activity is a common hallmark of a variety of cardiovascular diseases including type 2 diabetes (T2D). T2D is accompanied by a marked autonomic imbalance with sympathetic overactivity and reduced parasympathetic cardiac vagal activity. Reduced vagal drive to the heart is a strong independent risk factor for life-threatening arrhythmias, sudden cardiac death and microangiopathic comorbidities, while several experimental studies have shown that increased cardiac vagal activity exerts cardioprotective effects against these complications. The paraventricular nucleus of the hypothalamus (PVN) is an important site of autonomic control, and there are direct projections from the PVN to parasympathetic cardiac vagal neurons (CVNs) that co-release oxytocin. In an animal model of T2D, we will use an innovative chemogenic approach to selectively restore parasympathetic signaling to the heart by activating OXT neurons in the PVN of rats with viral vectors for oxytocin-driven cre recombinase along with floxed Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). In this project, we will determine the molecular mechanisms of T2D-mediated autonomic dysregulation, and test whether chronic activation of PVN OXT neurons can restore these adverse changes.

picture of Michelle TallquistMichelle Tallquist, Ph.D.
Professor, Department of Medicine
The diabetic heart has localized inflammation that is accompanied by deposition of extracellular matrix (ECM) also known as fibrosis. In the presence of chronic fibrosis, contractile dysfunction occurs, often resulting in dilated cardiomyopathy. During the early phases of inflammation, immune cells and ECM secreting fibroblasts communicate with one another. Current models suggest that immune cells drive fibroblast activation. Few cardiac studies have investigated how fibroblast signaling impacts inflammatory cell behavior. The goal of our studies are two fold. The first is to determine if fibroblast signaling contributes to cardiomyocyte hypertrophy. Second we are investigating if loss of fibroblasts leads to enhanced inflammatory responses. Results from these studies will help to identify if fibroblasts play beneficial or detrimental roles in the progression of diabetic cardiomyopathy.

picture of Yiqiang ZhangYiqiang Zhang, Ph.D.
Assistant Professor, Department of Anatomy, Biochemistry, and Physiology
Diabetic cardiocomplications, such as cardiomyopathy and arrhythmias, are the leading causes of death. Despite the obvious impacts of diabetic cardiocomplications, a better understanding of this multi-factorial problem is lacking, and specific effective treatments remain elusive. With an ultimate goal to develop new therapeutics to treat cardiac dysfunctions in diabetes, I am studying epigenetic regulations underlying the disease remodeling of heart cells and related systems. We use novel stem cells and animal models, and precious patient biopsies, and advanced cell functional and molecular biology platforms in our study to understand the pathophysiology of diabetic heart diseases.

Senior Investigators

picture of Mariana GerschensonMariana Gerschenson, Ph.D.
Associate Dean for Research, John A. Burns School of Medicine
Dr. Gerschenson is the Director for the Diabetes Research Center at the University of Hawaii and the PI of the NIH funded 1P20GM113134, ‘COBRE-Diabetes’. She is the Associate Dean for Research and Professor at the John A. Burns School of Medicine at the University of Hawaii. She is a national/international leader in the field of studying pediatric and adult cardiovascular and metabolic complications for the past 30 years. She is a translational researcher who is studying the mitochondrial etiology of insulin resistance in pediatric HIV and in the elderly. Dr. Gerschenson has shown that insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration ( and that that there is mitochondrial dysfunction and insulin resistance in HIV-infected children receiving antiretroviral therapy (

picture of Olivier Le SauxOlivier Le Saux, Ph.D.
Professor, Department of Cell and Molecular Biology
Pathologic mineralization affects a variety of soft tissues but the skin, kidneys, tendons, and cardiovascular tissues are particularly prone to this pathology. Several genetic disorders share phenotypic similarities with acquired forms of ectopic mineralization and are genetically controlled model systems for studies of pathological mineralization. Pseudoxanthoma elasticum (PXE), a multi-organ disease affecting dermal, ocular, and cardiovascular tissues, is one such model for ectopic mineralization disorders. ABCC6 dysfunction is the primary cause of ectopic calcification in PXE but also in some cases of generalized arterial calcification of infancy (GACI) as well as -thalassemia. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into inorganic pyrophosphate (PPi) and adenosine potent inhibitors of calcification. Since the identification of the first mutations in ABCC6, our studies of the molecular genetics, and pathogenesis of PXE and GACI has been profoundly transformed our understanding of ectopic calcification and provides a context for other pathological mineralization that occurs in more common conditions such as diabetes, atherosclerosis, renal failure and even aging.

picture of Takashi MatsuiTakashi Matsui, M.D., Ph.D.
Professor and Department Chair, Department of Anatomy, Biochemistry, & Physiology
Dr. Matsui has extensive experience in research on the insulin signaling pathway in cardiomyocytes, especially cardioprotective effects against pathological settings such as ischemia. Diabetes is an independent risk factor for both heart failure and ischemic heart disease. Because of the important role of mTOR (mammalian target of rapamycin) in the insulin signaling pathway, Dr. Matsui and his colleagues are working to define the role of mTOR in diabetic hearts, and exploring the mTOR signaling pathway as a novel therapeutic target for treatment of heart failure in diabetes.

picture of Marjorie MauMarjorie Mau, M.D.
Professor,Department of Native Hawaiian Health
Dr. Marjorie K. Leimomi Mala Mau, MD, MS, MACP, FRCP is an ABIM-certified Endocrinologist and has been conducting diabetes and cardiometabolic health and health care disparities research since 1992 when she returned home to join the University of Hawaiʻi. She is the inaugural chair of the Department of Native Hawaiian Health and the Myron “Pinky” Thompson endowed chair for Native Hawaiian Health Research. She is currently the PI of the Diabetes Prevention Program Outcome Study in Hawaiʻi (Clinic #22) and has been continuously funded by NIH for the last 27 years. She is the first Native Hawaiian and the first woman to be selected as a Masters of the American College of Physicians (MACP). In 2018, She was honored as one of only 25 MACP physicians in the USA to be inducted as Fellow of the Royal College of Physicians (FRCP) in London, arguably the oldest physician society celebrating 500 years of existence in 2018.

picture of Ralph ShohetRalph Shohet, M.D.
Professor, Department of Medicine
Diabetes is a major and growing contributor to heart disease. We have previously studied the effects of diabetes on vascular endothelium (PMC2365940), thereby identifying a role for Galectin-3 in gylycemic control (PMC4499178). Now we primarily study the role of the transcription factor Hypoxia Inducible Factor (HIF), in the heart. A principal effect of HIF stabilization in hypoxia is to enhance glycolytic metabolism. This has led us to examine the metabolic remodeling that occurs after infarction and identify HIF-regulated RNA splicing events, including modulation of Pyruvate Kinase, that affect glucose utilization in the ischemic myocardium (PMC6087881). This has direct pertinence to diabetes which can increase the size and morbidity of infarctions, likely through effects on the balance of oxidative and glycolytic metabolism. We also administer the mouse phenotyping Core, providing assessment of cardiac function by echocardiography, and perturbation of function through surgical models of infarction and hypertrophy; these capabilities are useful to the young investigators of the Diabetes COBRE. Other investigators in our Center for Cardiovascular Research study atherosclerosis and cardiac fibrosis, both of which are directly and substantially affected by diabetes.

picture of W. Steven WardW. Steven Ward, Ph.D.
Professor, Department of Anatomy, Biochemistry and Physiology
As the Director of Research in the Department of Obstetrics, Gynecology & Women’s Health, I assist with resident and faculty research throughout the department. We have numerous projects on gestational diabetes, and our diverse population of caucasians, Pacific Islanders, and Asian-Americans brings includes a broad spectrum of obesity related diabetes.
Back To Top