UNIVERSITY OF SOUTH FLORIDA
Signature Interdisciplinary Program in Cardiovascular Research
USF Health

Basic Sciences

Elizabeth Barnett, Ph.D.

Elizabeth Barnett, Ph.D. – Epidemiology and Biostatistics

Research Area: Cardiovascular epidemiology; Racial/ethnic and geographic disparities in heart disease and stroke; Emergency medical services availability and access and cardiovascular outcomes; hospital STEMI care protocols and patient outcomes.

Theresa Beckie, Ph.D.

Theresa Beckie, Ph.D.Nursing

NIH funded study (2003-2008) NIH funded for $1.5 million. We are also working on measuring inflammatory biomarkers in women with heart disease Funded GrantAbstract "A Women's-Only Phase II Cardiac Rehabilitation Program" Women are at-risk and underserved in the area of cardiovascular health. Of the millions of patients with coronary artery disease (CAD) who are candidates for cardiac rehabilitation (CR), only 5% to 22% typically participate, and they are mostly men. The literature calls for novel rehabilitative approaches for women with CAD. The goal of this study is three-fold: to enhance the rehabilitation of women after acute coronary events, to challenge assumptions about women with CAD, and to assist women in reducing risk factors that threaten their health with a stage-matched, gender-sensitive program. The aims of this study are to compare improvements in physical and psychosocial functioning of participants in a 12-week women’s-only phase II CR program with those seen in women attending a traditional, less gender-focused phase II CR program of the same length, and to compare maintenance of these improvements at 37 weeks. A single blind, 2-group longitudinal clinical trial design, employing random assignment, is being used. A sample of 400 women who have experienced a myocardial infarction, coronary revascularization, percutaneous coronary intervention, or angina, and who are referred to a phase II CR program are being randomly assigned to 1 of 2 groups. The experimental group is receiving a 12-week, 36 session program involving gender-sensitive education and counseling. The second group is receiving a traditional CR program. The Transtheoretical Model of Behavior Change is being used to tailor the behavioral intervention to maximize risk factor modification. Regardless of their stage of change and regardless of the risk behavior, each participant is taught the stage-appropriate processes promoting self-efficacy for maximizing risk factor modification. The psychosocial outcomes include perceive health status, quality of life, anxiety, depression, and social support. The physiological outcomes include blood pressure, body mass index, body fat composition, strength, lipid profile, fasting glucose, functional capacity, and exercise activity. Statistical analysis will include descriptive statistics and correlation coefficients to determine the relationship among the variables. MANOVA will be used for hypothesis testing. The study has clinical and public health significance because of its potential to promote healthy behaviors and reduce the burden of CAD in an underserved population who largely do not attend traditional CR programs. The findings have the potential to influence a paradigm shift for clinical practice and lead to important policy changes.


H. James Brownlee, Ph.D.

H. James Brownlee, Ph.D.Chair – Family Medicine

Research Area: metabolic syndrome, prediabetes, Coenzyme Q10 for statin-induced myalgias.

Denise Cooper, Ph.D.

Denise Cooper, Ph.D. – Molecular Medicine

Our research focuses on the molecular mechanisms involved in the post-transcriptional regulation of gene expression at the level of RNA splicing. With the completion of the sequencing of the human genome project, it is now recognized that there are considerably more proteins expressed than genes. One mechanism for deriving protein diversity is through alternative pre-mRNA splicing. It is alo a means of modulating signaling pathways as kinases are often the targets of splicing. The regulation of splicing by hormonally regulated pathways is an emerging field with insulin and growth factors signaling via Akt to regulate splicing factors. Alterations in these pathways by cytokines in disease states alters splicing machines and the balance of proteins expressed.

Karen Corbin

Karen Corbin – Graduate Assistant – Molecular Medicine

We study argininosuccinate synthase-mediated mechanisms of endothelial nitric oxide production

John Dietz, Ph.D.

John Dietz, Ph.D. – Molecular Pharmacology & Physiology

Research Area: Cardiac hormones, hypertension, salt and water balance, renal physiology, heart failure.

Duane Eichler, Ph.D.

Duane Eichler, Ph.D.Director, Basic Sciences, Professor of Molecular Medicine and Pediatrics:

Our laboratory has provided a unique perspective of vascular endothelial health, showing that argininosuccinate synthase, originally identified as a urea cycle enzyme, is a key regulator of endothelial cell behavior. We hypothesized that an important mechanism by which physiologic and pathogenic stimuli affect vascular endothelial function requires the expression and regulation of argininosuccinate synthase, the rate-limiting enzyme of the citrulline-nitric oxide cycle. Overall we have developed a strong evidential case supporting this hypothesis, demonstrating that substrate availability, governed by arginine regeneration, plays an essential role in vascular endothelial nitric oxide production and viability. These findings not only provide a contemporary understanding of the pathology of cardiovascular disease, but also raise the possibility of distinguishing a unique therapeutic target.

Brenda Flam, Ph.D.

Brenda Flam, Ph.D.  - Visiting Postdoctoral Fellow – Internal Medicine

(1) Regulation and localization of enzymes involved in endothelial nitric oxide generation (2) Determination of markers of cardiovascular injury caused by blunt force trauma and /or puncture wounds (test method development).

William Gower, Ph.D.

William Gower, Ph.D. – Professor - Molecular Medicine:

My research centers on understanding the role of natriuretic peptides and their receptors in the regulation of gastrointestinal function. Specifically, we are investigating the role of cardiac hormones, ANP and BNP, in the regulation of gastric acid secretion, and gastric motility. These studies involve both physiological and biochemical approaches to elucidating the role of natriuretic peptides in the regulation of digestive tract physiological and pathophysiological function as well as understanding the molecular mechanisms mediating these effects.

Adam Guyer

Adam Guyer – Pathology & Cell Biology

May current research area as a Masters student is in the Department of Neurosurgery. I am currently looking at the role of human umbilical cord blood cells (HUCBC) as a potential therapy for brain ischemia. Specifically, I am looking at the effect of ischemia on an oligodendrocyte/HUCBC co-culture in vitro. I begin the MD program at USF in August. I hope for a future career in vascular surgery. I plan to continue basic medical research during my time here, and would like to focus future research on cardiovascular physiology/pathology.

Amal Hakki, Ph.D.

Amal Hakki, Ph.D. – Molecular Medicine

Our lab work covers a wide range of research which links basic science with clinical implication. The major goal is to investigate the role of microorganisms, in particular, Chlamydia infection as a risk factor in various pathological conditions, such as atherosclerosis, coronary artery disease, autoimmune diseases, and arthritis, among others. In addition, we are studying the impact of various natural products such as EGCG green tea major ingredient, on immune system. Such study will be geared towards the protective effects which might lead to suppression or amelioration the severity of certain pathological condition. The conducted research will involve cellular, as well as molecular aspects of immune responses.

Lindsey Jackson, Ph.D.

Lindsey Jackson, Ph.D. – Graduate Research Assistant – Molecular Medicine

Thyroid hormone regulation of HMG-CoA reductase.

Kersti Linask, Ph.D.

Kersti Linask, Ph.D. – Professor – Pediatrics

Cardiovascular development: cardiac cell differentiation; development of form and function.

Dayami Lopez, Ph.D.

Dayami Lopez Ph.D., - Assistant Professor – Molecular Medicine

Our research concentrates on determining the regulatory mechanisms that control the expression of proteins involved in cholesterol metabolism. One of these is the sterol carrier protein X (SCPx) which is a peroxisomal protein whose expression is directly associated with the levels of fatty acids and triglycerides in the serum. This protein functions both as a lipid transfer protein due to its C-terminal identity with its close family member SCP2, and as a thiolase required for peroxisomal b-oxidation of branched fatty acids and for bile acid biosynthesis. We are also focusing on the study of the low density lipoprotein (LDL) receptor, the major determinant of plasma LDL-cholesterol levels. The involvement of factors such as the autosomal recessive hypercholesterolemia protein (ARH) and the proprotein convertase subtilisin kexin 9 (PCSK9) in the regulation of the LDL receptor gene is also currently under examination. The last protein that we study is the adenosine triphosphate (ATP)-binding cassette (ABC) type 1 transporter (ABC1 or ABCA1) which is a key player in modulating the levels of plasma HDL and intracellular cholesterol in the liver and macrophages.

Shyam Mohapatra, Ph.D.

Shyam Mohapatra, Ph.D. – Professor – Internal Medicine

Research interests in Nanotechnology application to Cardiovascular Disease

Kendall Morris, Ph. D.

Kendall Morris, Ph.D. – Associate Professor – Molecular Pharmacology and Physiology

Research involves the neural control of cardiorespiratory function. Recent research has focused on the effect of afferent input (chemo- and baro-receptors as well as lung stretch receptors) on distributed brainstem neural networks involved in respiratory and sympathetic nervous system control. Methods include extracellular spike train recording in vivo, computer assisted data entry and analysis (cycle triggered histograms, cross correlograms, spike triggered average histograms, and the gravity method) and computer simulations of neural networks inferred from in vivo data.

Gene Ness, Ph.D.

Gene Ness, Ph.D. – Professor – Molecular Medicine

My research focuses on molecular mechanisms which operate physiologically to regulate the rate of cholesterol biosynthesis. The mechanisms by which hormones and dietary factors operate to regulate rates of transcription and translation of HMG-CoA reductase, the enzyme which catalyzes the rate-limiting step in cholesterol biosynthesis are being investigated in vivo.

Britta Neugaard, Ph.D., M.P.H.

Britta Neugaard, Ph.D. – Health Services Researcher – Department of Veterans Affairs

Research area is focused on population level health, specifically cardiovascular health. My research focus is on quality of care and health outcomes of patients treated for acute coronary syndromes.

Sarah Norring

Sarah Norring, Graduate Student – Molecular Pharmacology and Physiology

Drug – induced arrhythmias, hERG structure and function

Keith Pennypacker, Ph.D.

Keith Pennypacker, Ph.D. Associate Professor- Molecular Pharmacology and Physiology

Our research is concentrated on understanding the physiological mechanisms underlying neurosurvival after injury in order to devise novel therapeutic approaches for neurological disorders, particularly stroke. There are three intertwined ongoing projects, which all relate to brain injury. These are NF-κΒ signal transduction in brain injury, human umbilical cord blood cells (HUCBC) as a treatment for stroke at delayed time points, and sigma receptors as a target for therapeutic intervention for stroke. Currently there is only one FDA-approved drug for stroke therapy with a narrow therapeutic window of three hours. Our focus is to discover novel therapies that broaden the therapeutic window so that more stroke victims are able to receive therapy.

We have found that the NF-κΒ transcription factor is a pivotal signaling protein in neurosurvival signaling after injury. Using NF-κΒ reporter mice, ischemic or neurotoxic insult induces the activity of this transcription factor in neurons in susceptible regions. Neurons from mice lacking the expression of the NF-κΒ p50 subunit are significantly more susceptible to neurodegeneration after injury. This transcription factor is a component of neurosurvival signaling in response to brain injury. Additionally, mice lacking expression of the p50 subunit do not perform active avoidance tasks as well as their non-transgenic brethren. These studies show that this signaling molecule is involved in neuroplastic events and not limited to only injury.
Our studies using systemic administration of HUCBC have shown that the therapeutic window for stroke treatment is broader than is currently believed. Intravenous injection of HUCBC at 48 hours post-middle cerebral artery occlusion (MCAO) reduces infarct volume by 80% in rats. These cells migrate to the injured hemisphere and to the spleen. The spleen reacts to the stroke injury by reducing its size by 50% and by increasing the expression of inflammatory-associated cytokines. HUCBC treatment inhibits the spleens reduction in mass and inhibits the spleen’s expression of inflammatory cytokines. Moreover, splenectomy prior to stroke reduces infarct volume by 90% in MCAO-treated rats. Based on these findings, an effective treatment for stroke at delayed time points requires both anti-inflammatory and neuroprotective properties.

The sigma receptor agonist, DTG, recognizes both sigma 1 and 2 receptors. We have found that subcutaneous administration of this agent 24 hours post-MCAO reduces infarct volume by 85%. Cultured neurons treated with DTG are protected when exposed to hypoxia and during chemical ischemia. Microglia treated with lipopolysaccharide produce the cytotoxins, nitric oxide and TNF-α; DTG is able to completely block the production of both of these cytotoxins. Similar to HUCBC treatment, this pan-sigma receptor ligand provides both neuroprotection and anti-inflammation as a potential treatment to widen the therapeutic window of stroke. Additionally, preliminary studies show that DTG is effective in treating a mouse model of ALS and is neurprotective against compounds related to nerve gas toxins. Thus, these ligands have the potential to have therapeutic efficacy for a broad range of neurological conditions.

Frances Sahebzamani, Ph.D., ARNP

Frances Sahebzamani, Ph.D., ARNP; Assistant Professor; Director; Primary Care Program – College of Nursing; College of Medicine, Dept. Family Medicine

Insulin resistance, obesity, prediabetes, diabetes and preventive cardiology in the primary care setting.

Tara Schwetz

Tara Schwetz, Graduate Student – Molecular Pharmacology and Physiology

I am investigating how glycosylation can modulate the function of 4 specific isoforms of voltage-gated potassium channels involved in repolarization of the cardiac action potential. Alteration of normal functioning of these channels could potentially lead to changes in normal cardiac rhythm and, therefore, arrhythmias.

Andreas Seyfang, Ph.D.

Andreas Seyfang, Ph.D.,  Assistant Professor – Molecular Medicine and Center of Excellence for Aging & Brian Repair

At the Laboratory of Medical Microbiology and Molecular Parasitology, we are studying membrane permeases (transporters) and receptors in opportunistic microbial pathogens including the protozoan parasite Trypanosoma cruzi, which is the causative agent of Chagas myocarditis (American trypanosomiasis), and closely related Leishmania flagellates. My laboratory also studies the fungal and nosocomial pathogen Candida albicans, which is a primary cause for fungal endocarditis. Hence, our studies have been funded by the American Heart Association since 1997 and I am serving as AHA Study Section reviewer since 2004. We use a multi-disciplinary approach of biochemistry, proteomics, molecular pharmacology and genetics to investigate the structure-function relationship, substrate/drug selectivity, protein-protein interaction, and significance for microbial pathogenicity of these membrane proteins at the molecular level in in vitro culture and animal models.

Kelly Stamp, Ph.D., R.N.

Kelly Stamp, Ph.D., R.N. – College of Nursing

Research interests include: Primary Prevention of Coronary Heart Disease and Cardiovascular Disease.

John Tsibris, Ph.D.

John Tsibris, Ph.D., Professor – Obstetrics and Gynecology – Department of Molecular Medicine

Research interests include: Etiology of human uterine leiomyomata using proteomics following target identification by cDNA arrays. Focus on proteins (ionotropic glutamate receptor GluR2, ephrin B2, EphB4, moesin and non-muscle myosin heavy chain) expressed in endothelial cells in the blood vessels of both leiomyoma and myometrium. My guinea pig model for uterine leiomyomata allows an exploration of the effects of troglitazone, estradiol, retinoic acids and vitamin D analogs on tumor growth and tumor vascularization and, possibly, tumor innervation.

Lynn Wecker, Ph.D.

Lynn Wecker, Ph.D. – Professor – Pharmacology & Physiology

Our laboratory seeks to understand how brain chemistry affects or determines behaviors with an emphasis on the etiology and treatment of neuropsychiatric disorders including schizophrenia, depression and addictive behaviors. Multidisciplinary approaches are used to elucidate how age, drugs of abuse, and environmental and genetic factors affect both brain chemistry and behavior. Currently, studies focus on elucidating the effects of sustained nicotine exposure on the function and expression of neuronal nicotinic receptors and transcription factors in the brain. We are particularly interested in the long-term consequences of drug exposure during adolescence. Studies in our laboratory have recently demonstrated that α4β2 neuronal nicotinic receptors are subject to regulation by phosphorylation/dephosphorylation mechanisms, and that sustained nicotine exposure may modify these events. We are currently elucidating the specific kinases and phosphatases involved, as well as the specific amino acids on the receptor that are phosphorylated. Results from these studies will ultimately provide information on the molecular and cellular basis of addictive behaviors, thereby leading to new strategies for the treatment of these disorders.
 

Daniel Yip, Ph.D.

Daniel Yip, Ph.D. – Associate Professor – Molecular Pharmacology and Physiology

The research interests of my laboratory are develops and applies confocal fluorescence microscopy and laser-based video microscopy to study renal cellular function in situ and in vivo. Currently we are investigating the regulation of water channels (aquaporin-2) trafficking in kidney collecting duct by AVP (arg-vasopressin) and ANP ( atrial natriuretic peptide); cellular mechanism of pressure natriuresis and its relationship with the development of hypertension, and role of integrins in mechanical signal transduction in renal vascular smooth muscle.