Trainees Supported by the Multidisciplinary Training Program in Hypertension
Past Doctoral Trainees:
Darren Beck, PhD
Mentor: Randy Braith, PhD
Department of Applied Physiology and Kinesiology
Darren Beck joined the University of Florida (UF) Department of Applied Physiology and Kinesiology (APK) in 2005 as a graduate research assistant. He recently completed his fifth year as a doctoral student at UF where he devoted 100% of his time to research under the direction of Randy W. Braith, PhD. His first four years of doctoral study were supported by an Alumni Fellowship awarded by the College of Health and Human Performance at UF. His research in his final year was supported by a predoctoral fellowship through a T32 grant under the UF Hypertension Center, effective August 2009. He completed all of his course and research credit requirements towards his PhD. in Exercise Physiology and became a candidate for his degree by successfully passing his qualification examinations in August 2009. He performed phlebotomy and subsequent analysis of human blood drawn for biomarker assays (soluble vascular cell adhesion molecule (sVCAM), tumor necrosis factor-a (TNF-a), high sensitivity C-reactive protein (hsCRP), norepinephrine, monocyte chemoattractent protein (MCP-1), and endothelin (ET-1) in preparation for his dissertation research titled “Effects of 8 weeks of exercise training on arterial function in prehypertensives”.
He received approval for his dissertation research protocol and proposal from the Internal Review Board at the University of Florida and his dissertation committee and began enrolling study participants, collecting data, and training his participants for his dissertation research topic in the spring of 2010. He completed the necessary participant enrollment in August 2010. He completed the exercise training of the remaining participants and completed analysis of his research data in October 2010. He successfully defended his dissertation November 2010 and was conferred his Ph.D. December 20, 2011. He is currently in the vetting process for a postdoctoral research associate position.
Mariellen Moore, PharmD
Mentor: Julie Johnson, PharmD, FCCP, BCPS
Department of Pharmacotherapy and Translational Research
Mariellen Moore joined the University of Florida (UF) Department of Pharmacotherapy and Translational Research as a graduate student in 2007. She completed her Doctor of Pharmacy from UF in spring 2007 with honors. She completed her Associate of Arts in spring 2003 with honors. Dr. Moore is currently a fourth year graduate student at UF where she devotes 100% of her time to research under the direction of Julie A. Johnson, PharmD, FCCP, BCPS. The first two years of her studies were supported by a teaching assistanceship under the College of Pharmacy, Department of Pharmacotherapy and Translational Research, and her research is now supported through a T-32 grant under the UF Hypertension Center, effective July 2009. She has taken additional coursework pertaining to her research interests in fall 2009 and 2010. She has completed all required coursework for her graduate studies and has successfully progressed to PhD candidate status.
Dr. Moore’s research involves the adverse metabolic effects of antihypertensive medications. As part of her project, she planned and coordinated a sub-study associated with Dr. Johnson’s active hypertension study. She screened more than 120 patients in three local clinics and attended more than 180 clinic visits between June 2009 and December 2010 (when the main trial ended). A total of 26 patients completed her clinical study to at least midpoint (22 completed all three visits, 4 completed the first two visits) for a total of 76 study visits included in the final data set. Dr. Johnson’s hypertension study and the sub-study closed enrollment in August 2010. She has completed analysis for her clinical study and completed two drafts of that chapter and three drafts of her introduction chapter for her dissertation. Additionally she is investigating whether clinical, genetic and molecular factors are predictive of adverse metabolic effects from antihypertensive medication exposure in Dr. Johnson’s large hypertension trial. Currently she is writing and analyzing for the clinical predictor aim, collaborating with investigators in the department of biostatistics. The final portion of her dissertation, to assess the genes associated with dysglycemia resulting from antihypertensive therapy is not yet underway. It is expected that each major chapter in her dissertation will be published in a timely manner, resulting in three papers. The first will be descriptive and exploratory in nature, evaluating medication-associated dysglycemia through multiple methods. The second will contribute to our knowledge base on clinical predictors associated with medication-associated dysglycemia. The final paper will contribute to the pharmacogenomics literature, evaluating the genetic contribution to antihypertensive-associated dysglycemia. Associated with her research project, Dr. Moore is writing a review paper on what is known to date on the metabolic effects of antihypertensive medications and current clinical controversies, collaborating with a professor within the department.
Dr. Moore has maintained significant interaction with students through her graduate studies. She has mentored pharmacy students in Dr. Johnson’s lab for the previous two summers (2009, 2010), has conducted monthly topic discussions with Dr. Johnson’s advanced pharmacy rotation students for the past few years, has coordinated department journal club (spring 2010 to spring 2011) and also delivered lectures on general Pharmacogenomics (1 hour, fall 2009 and 2010) and Acute Coronary Syndromes (3 hours, fall 2010). As part of the clinical aspect of her graduate studies in clinical pharmaceutical sciences, Dr. Moore strives to maintain clinical excellence. She has maintained professional licensure since summer 2007 and in fall 2010 became a Board Certified Pharmacotherapy Specialist (BCPS).
Dr. Moore has served for the last year as a Member-At-Large on the National Resident Advisory Committee in the American College of Clinical Pharmacy (ACCP) and attended to the College’s Annual Meeting to further committee participation. She is also a member of the American Society for Clinical Pharmacology and Therapeutics (ASCPT), is a member of the Molecular Pharmacology and Pharmacogenetics committee and actively participates in their Mentoring Program. Dr. Moore has presented her research at the both ACCP (2005) and ASCPT (2010) national meetings. She has also presented at a local, College of Pharmacy Research Forum (2006). In addition, she has delivered department seminars pertaining to her research for the past three years.
Benjamin Predmore, PhD
Mentor: David Julian, PhD
Department of Zoology
Benjamin Predmore was a graduate student working in the laboratory of Dr. David Julian, Department of Biology at UF. He previously obtained a BS in Biology from Penn State (2005). Ben has completed the required Integrative Principles courses through the Department of Zoology as well as two semesters of graduate level statistics and the Fundamentals of Cardiovascular Physiology offered through the Department of Physiology and Functional Genomics. His graduate GPA is 4.0. Ben was also a laboratory instructor for Physiology and Molecular Biology of Animals for two semesters in the 2007/2008 academic year. He then focused on his laboratory research entirely. His research broadly investigated hydrogen sulfide signaling in the cardiovascular system, with a specific focus on changes in the hydrogen sulfide signaling system during the aging process and how this is influenced by dietary intervention, namely caloric restriction. Other research interests included the mechanisms behind hydrogen sulfide signaling in vessel rings and potential overlaps with hypoxia induced signaling, as well as interactions of hydrogen sulfide with endothelial nitric oxide synthase. He finished his Ph.D. in the summer of 2009, and has since joined the laboratory of Dr. David Lefer, Cardiothoracic Research Laboratory in the Department of Surgery at Emory School of Medicine. Here he has learned micro-surgical techniques in a mouse model of ischemia-reperfusion injury, hepatic ischemia, and chronic heart failure in addition to learning functional and biochemical assays for heart function and failure in both mice and swine. He has most recently moved into the field of nitric oxide/ nitrite physiology and learned the techniques required to measure the nitric oxide metabolites: nitrite, nitrate, nitrosoproteins.
Robert Regenhardt, MD, PhD
Mentor: Colin Sumners, Ph.D.
Department of Physiology and Functional Genomics
Robert Regenhardt is an MD/PhD student in the UF College of Medicine. He entered UF as an undergraduate in the fall of 2004, and in spring 2006 was accepted into the Junior Honors Medical Program (JHMP), which is a 7 year combined BS/MD program at the UF College of Medicine. Following his junior undergraduate year, he matriculated into the UF medical school in fall 2007, having also been accepted into the MD/PhD program. He began his PhD studies, funded through a pre-doctoral fellowship from the Hypertension T32, at the beginning of July 2009.
PhD Training Program: Research
In the last 2 years since entering Dr. Colin Sumners’ laboratory to pursue his Ph.D work, Mr. Regenhardt has been active in establishing the groundwork for his area of study. The overall plan for Mr. Regenhardt’s PhD work is that he is investigating the protective actions of the heptapeptide Ang-(1-7) against stroke that occurs following prolonged hypertension. The animal model that he began with is the SHRSP (Stroke Prone Spontaneously Hypertensive Rat). These animals become progressively hypertensive with age. Greater than 80% of male SHRSP develop cerebral hemorrhage when they are over 100 days in age, and this effect is exacerbated by feeding the animals a high salt diet. Mr. Regenhardt has established this model in the laboratory and conducted several trials using this strain to determine the effects of central administration of Ang-(1-7) on cerebral hemorrhage in SHRSP. From his efforts, Mr. Regenhardt has demonstrated that Ang-(1-7) increases survival of these rats. He has also shown that these rats show an increased performance on a behavioral exam. In the last year, he has spent more time studying the mechanism of protection. In another model of stroke, he demonstrated that Ang-(1-7) blunts increases in iNOS and proinflammatory cytokines. He is currently working to test if this same mechanism is responsible for the protective effects in the SHRSP model. Additional progress has included:
- Writing and gaining approval for an IACUC protocol for his experiments.
- Learning all of the surgical techniques that are required for his work. These include implantation of blood pressure telemetry transducers to follow the progression of hypertension, and intracerebral cannulae for CNS delivery of Ang-(1-7).
- Mastering the behavioral procedures that will be utilized for determining the behavioral deficits produced by stroke, and the procedures for assessing stroke infarct volume and neuronal damage.
- Establishing a solid background on the literature concerning the actions of angiotensin peptides (both beneficial and deleterious) in cerebrovascular damage.
- Developing another model of hemorrhagic stroke that utilizes intrastriatal collagenase injection to produce a defined, focal intracerebral hemorrhage.
- Developing an oxygen glucose deprivation model of stroke in primary neuron culture to examine the nonvascular effects of Ang-(1-7).
- Investigating mechanisms of cerebroprotection induced by Ang-(1-7) treatment, including altered expression of iNOS and proinflammatory cytokines.
Jacqueline Sayyah, PhD
Mentor: Peter P. Sayeski, PhD
Department Physiology and Functional Genomics
Post-Doctoral Fellow in the Department of Pharmacology at UCSD. She is currently examining the role of sustained Rap1 activation in astrocytoma proliferation and invasion. She previously obtained a BS in Biochemistry from UCLA (1998) and MS from Georgetown University in Biochemistry and Molecular biology (2001). She was a CRTA fellow in the National Cancer Institute (Bethesda, MD) 2003-2004. She has completed all required IDP core course work and advanced courses with A and B+ grades. She successfully defended her dissertation and graduated in May of 2009. Her research involved the development of novel Jak2 tyrosine kinase inhibitors and how these inhibitors may be beneficial to people suffering from Jak2-dependent diseases such as myeloproliferative disorders, cardiovascular disease and diabetes.
Mentor: Barry J. Byrne, MD, PhD
Department of Molecular Genetics and Microbiology
During my first year of receiving T32 funding: I have made progress on each of my proposed specific aims, published in Human Gene Therapy Journal, passed my predoctoral qualifying exam, and received outside funding from the Barth Syndrome Foundation. The first specific aim in my proposal was to characterize the first mouse model of Barth Syndrome. We demonstrated a 95-98% knockdown in skeletal muscle and cardiac tissue, abnormal cardiolipin levels, aberrant mitochondrial morphology, a reduction in skeletal muscle contractility all at two months of age, and a marked decrease in cardiac ejection fraction at 7 and 10 months of age. This data has been published as of November 2010 (PMID: 21091282). My second aim proposes designing and creating an AAV construct to deliver the full-length human Tafazzin cDNA to correct gene expression. We have successfully achieved detectable protein levels using AAV2/1-hTAZ in vitro and in vivo. This data was recently presented at the American Society of Gene and Cell Therapy (ASGCT) conference in Seattle, WA.
Currently underway, we have recognized the need to accelerate progression of the disease in the mouse model. Although we have reported signs of cardiomyopathy at 7 and 10 months of age, there does not seem to be an abnormal cardiac phenotype early on. Therefore, we have chosen an endurance exercise protocol to stress both skeletal muscle and the heart. Mice were swum for 5 weeks, 5 days a week, for 90 minutes a day using a ramp protocol. Measurements include cardiac, oxidative phosphorylation capacity, and mitochondrial assessment. This data has yet to be analyzed. If we do not achieve cardiac overload, we will use transverse aortic constriction (TAC) to elicit a more severe cardiac stress.
Additionally, we have recently repackaged our AAV construct in an AAV9 serotype capsid and delivered it intramuscularly to Tafazzin knockdown mice (TAZKD) and will evaluate cardiolipin profiles post-infection. If we are able to demonstrate correction of cardiolipin levels, we will proceed with a systemic treatment in TAZKD mice and investigate cardiac function and oxidative capacity. If cardiolipin profiles are not fully restored, alternative promoters will be used to drive hTAZ expression to achieve endogenous TAZ levels.
Finally, we have begun collaborating with Dr. Nao Terada in designing future experiments where we will obtain BTHS patient fibroblasts and reprogram them into induced pluripotent stem cells (iPS cells). We then will differentiate these cells into cardiomyocytes to evaluate cellular nutrient metabolism, mitochondrial respiration and membrane potential as well as treating these cells with AAV9-hTAZ. This work in conjunction with other studies being done by Dr. Terada’s group will be submitted for an RO1 in the future.
In addition to my progress in the lab, I have been attending the Hypertension Seminar Series and the Neuromuscular Seminar Series under the direction of Dr. Baylis and Dr. Judge respectively, and in March attended the NIH funded NSMRCC Muscle Physiology Workshop in California. I have had the opportunity to present poster presentations for the Genetics Research Day, Neuromuscular Symposium and at the College of Medicine Research Day here at the University of Florida and have given an oral presentation for the Pediatrics Science Day at UF. Although I have finished my coursework as of Spring 2010, I took “Advances in Hypertension Research,” this past spring and continue to attend the Genetics Journal Club during both the fall and spring semesters.
Past Post-Doctoral Trainees:
Debra Ely, PhD
Mentor: Mohan K. Raizada, PhD
Department of Physiology and Functional Genomics
Debra Ely joined the University of Florida (UF) Department of Physiology and Functional Genomics as a postdoctoral fellow in 2009. She came from the University of Iowa where she received her PhD in Biomedical Engineering in 2008. She received a Masters of Science in Engineering from the University of Michigan in 2003 and Bachelors of Science in Electrical Engineering from Tuskegee University in 1994. In between her undergraduate and graduate education Dr. Ely worked as a hardware development engineer at IBM.
Currently, Dr. Ely is a second year fellow at UF where she devotes 100% of her time to research under the direction of Mohan Raizada, Ph.D. Her research is supported through a T-32 grant under the UF Hypertension Center.
“We investigated the effects of ACE2 on vasculature using an antibacterial and antiprotozoal agent, diminazene aceturate (dize). Dize is similar in structure to a putative ACE2 activator used in our lab, XNT. Our lab has shown that both drugs increase ACE2 but not ACE activity. XNT is commercially unavailable and expensive whereas the opposite holds true for dize. Therefore we chose to investigate the effects of dize on vasculature using a muti-chamber myograph. We have shown in aortic rings preconstricted with phenylephrine that dize causes vasorelaxation when compared to controls. To investigate the mechanism by which dize acts we are looking at reactive oxygen species levels in transthoracic aorta treated with dize.”
Dr. Ely is pursuing a cardiovascular research position in industry once her contract ends this summer.
Dwayne Henry, MD
Mentor: Mark S. Segal, MD, PhD
Department of Nephrology, Hypertension and Renal Transplantation
Dwayne Henry joined the University of Florida (UF), Department of Pediatrics/ Nephrology division as a fellow in 2006. He came from the University of Oklahoma Health Science Center, where he completed a combined internal medicine/pediatrics residency from 2002-2006. He attended medical school at St. Matthews University in Belize, Central America (2002). He received his undergraduate degree from the University of North Texas in 1997. He is currently enrolled in the Advanced Postgraduate Program in Clinical Investigation (APPCI) where he is taking classes to obtain a certificate in clinical investigation. He is also pursuing a Masters in Health Service Administration through Saint Josephs College.
During his fellowship the first year was focused on clinical patient care. The remainder of his second and third years consisted of one half day clinic per week and research under Mark Segal MD/PhD in the division of nephrology, Department of Internal Medicine at UF. His research was supported through a T-32 grant under the UF Hypertension Center. He received the Douglas J. Barrett Fellowship Award in March 2008 from the Children’s Miracle Network for research support.
Dr. Henry has co-authored a chapter on Acute Interstitial Nephritis in Pediatric Nephrology in the Intensive Care Unit, published 2009. He has e-published a case report on “Low viral load post-transplant lymphoproliferative disease localized within the tongue” in the journal Transplant Infectious Disease, July 22, 2008. He has given an oral presentation on March 13, 2008 at UF’s 26th Annual Pediatric Science Days 2008 on “An interesting case of elevated beta HCG in a dialysis patient”.
Dr. Henry’s research involved enumerating circulating endothelial cells from cord blood of infants from healthy mothers and comparing them to mothers with hypertension and diabetes to determine if the maternal disease process has an effect on the infant endothelium.
Dr. Henry completed his pediatric nephrology fellowship in September 2009. Since completing his fellowship he has been an assistant professor in pediatric nephrology at The University of Oklahoma Health Science Center, Children’s Hospital in Oklahoma City, Oklahoma. His primary role is clinical nephrology. He has e-published a case report on ” A patient with an unusual cause of right lower quadrant pain and vomiting: Pyelonephritis of an ectopic right kidney masquerading as acute pyelonephritis” in the journal Case Reports in Medicine, February 4, 2010. He has given Pediatric Grand Rounds titled “Pediatric Hypertension” on November 19, 2009. On this day he gave noon conference to the pediatric residents on chronic kidney disease. He had a poster presented at the 4th Annual Pediatric Research Days at the University of Oklahoma on “Mercury Poisoning: A Treatable Cause of Resistant Hypertension” on April 23, 2010.
Jennifer Sasser, PhD
Mentor: Chris Baylis, PhD
Department of Physiology and Functional Genomics
Jennifer Sasser joined the University of Florida (UF) Department of Physiology and Functional Genomics as a postdoctoral fellow in 2006. She graduated from the Medical College of Georgia Department of Pharmacology and Toxicology where she received her PhD with distinction in 2005. She received her undergraduate degree with highest honors in chemical engineering from the Georgia Institute of Technology in 1999.
Dr. Sasser is currently a sixth year fellow at UF where she devotes 100% of her time to research under the direction of Chris Baylis, PhD. The first two years of her fellowship were supported by a postdoctoral fellowship from the American Heart Association, and her research is now supported through a T-32 grant under the UF Hypertension Center, effective August 2008. Dr. Sasser was recently awarded a Scientist Development Grant from the American Heart Association to continue her studies on the effects of relaxin during hypertension and hypertensive kidney disease. She has completed the UF graduate Advanced Renal Physiology and Current Topics in Hypertension Research courses.
During her postdoctoral fellowship, Dr. Sasser has served on the Trainee Advisory Committee, the Water and Electrolyte Homeostasis Section Steering Committee, and the Strategic Planning Committee for the American Physiological Society and is currently a member of the editorial board for the American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. She was recently nominated to the Women in Physiology Committee of the American Physiological Society. Dr. Sasser received travel awards for the annual meeting of the American Society of Nephrology in 2006 and 2007, the Young Investigator Travel Award to the FASEB Summer Research Conference on Renal Hemodynamics in 2007, the Caroline tum Suden/Francis Hellebrandt Professional Opportunity Award from the American Physiological Society in 2008, and the American Society of Nephrology Basic Science Travel Award in 2008.
In the past year, Dr. Sasser has presented at the 2010 American Society of Nephrology annual meeting (Renal Phosphodiesterase-5 Inhibtion Promotes Natriuresis in both the Virgin and Pregnant Female Rat) and the 2011 Experimental Biology Meeting (Nebivolol does not protect against 5/6 ablation/infarction induced chronic kidney disease in rats) . In addition, she was a co-author on 3 abstracts presented at the EB meeting. She has submitted an abstract to the Fall Conference of the AHA Council for High Blood Pressure Research (Relaxin reduces blood pressure, proteinuria, and asymmetric dimethylarginine during high dose Angiotensin II infusion) and is an invited speaker to the 2011 APS Conference on “Physiology of Cardiovascular Disease:Gender Disparities” this Fall.
Dr. Sasser’s research involves the role of inner medullary phosphodiesterase-5 activity in the volume expansion of pregnancy and the roles of relaxin and asymmetric dimethyl arginine in hypertension and chronic kidney disease.
Hua Yao, PhD
Mentor: Carrie Haskell-Luevano, PhD
Department of Pharmacodynamics
Hua Yao joined the University of Florida (UF) Department of Pharmacodynamics as a postdoctoral fellow in March 2009. She earned her Ph.D. at the University of Florida in the Department of Medicinal Chemistry in 2007.
Dr. Yao is currently a third year postdoctoral fellow at UF where she devotes 100% of her time to research under the direction of Carrie Haskell-Luevano, PhD. Since joining the laboratory in March 2009, she has been supported through this T-32 grant. During the past 6 months Dr. Yao has been learning new techniques and generating preliminary data for her research project studying the role of the melanocortin pathway in the regulation of blood pressure. The melanocortin system is involved in the regulation of obesity and type 2 diabetes, both of which are linked to cardiovascular disease.