Program Faculty
A balanced blend of investigators, female and male, clinical and basic scientists with MD and/or PhD training, and diverse research expertise participate as training faculty in this program to sustain overlapping investigative themes and to foster group mentoring goals and the use of multidisciplinary approaches by our trainees. These general themes in this training program are highly relevant to the pathophysiologic events that occur during the development and/or complications of cardiovascular disease. Training faculty include:
Training Faculty and Investigative Themes
| Training Faculty | Affiliation | Role | Investigative Theme |
|---|---|---|---|
| Ahuja, Sunil Kumar, MD | Medicine, Microbiology, Immunology and Biochemistry | Preceptor | |
| Bai, Yidong, PhD | Cell Systems and Anatomy | Preceptor | |
| Bansal, Shweta, MD | Nephrology & Epidemiology | Preceptor | |
| Bieniek, Kevin, PhD | Pathology & Laboratory Medicine | Preceptor | |
| Bopassa, Jean C., PhD | Physiology | Preceptor | Inflammation, Cell Injury, and Adaptation |
| Chen, Chu, PhD | Physiology | Preceptor | |
| DeFronzo, Ralph A. , MD | Medicine | Preceptor | Inflammation, Cell Injury, and Adaptation |
| Dong, Lily Q., PhD | Medicine/Diabetes | Preceptor | Diabetes |
| Gould, Georgianna G., PhD | Physiology | Preceptor | |
| Han, Hai-Chao, PhD | Biomedical Engineering | Preceptor | Cardiovascular Pathophysiology |
| Hargreaves, Kenneth M., DDS/PhD | Endodontics | Preceptor | |
| Lechleiter, James D., PhD | Cellular and Structural Biology | Preceptor | Cardiovascular Pathophysiology |
| Michalek, Joel, PhD | Population Health Sciences | Preceptor | |
| Muniswamy, Madesh, PhD | Medicine/Cardiology | Preceptor | |
| Paukert, Martin, MD | Physiology | Preceptor | |
| Prasad, Anand, MD | Medicine/Cardiology | Preceptor | |
| Pugh, Jason R., PhD | Physiology | Preceptor | Inflammation, Cell Injury, and Adaptation |
| Rasmussen, Blake B., PhD | Physiology | Preceptor | |
| Reeves, W. Brian, MD | Medicine/Nephrology | Preceptor | Inflammation, Cell Injury, and Adaptation |
| Salehi, Marzieh, MD | Medicine/Diabetes | Preceptor | |
| Satizabal Barrera, Claudia, PhD | Alzheim Neurodegenerative Inst | Preceptor | |
| Sayre, Naomi L., PhD | Neurosurgery | Preceptor | Cardiovascular Pathophysiology |
| Shapiro, Mark S., PhD | Physiology | Preceptor | Cardiovascular Pathophysiology |
| Sharma, Kumar, M.D., FAHA, FASN | Medicine/Division of Nephrology | Preceptor | |
| Sung, Patrick, PhD | Biochemistry & Structural Biology | Preceptor | |
| Venkatachalam, Manjeri, MD | Pathology | Preceptor | Inflammation, Cell Injury, and Adaptation |
Training Faculty Research Profiles.
Jean C. Bopassa, PhD, Novel Mechanisms in Estrogen-Dependent Cardioprotection following Ischemia Reperfusion Injury. Dr. Bopassa’s long term research goal is to investigate the mechanisms involved in sex hormone cardioprotection against ischemia/reperfusion injury. His central hypothesis is that acute post-ischemic activation of estrogen receptors confers cardioprotective effects against ischemia/reperfusion injury by activating pro-survival signaling pathways leading to reduction of post-translational modifications of mitochondrial proteins resulting in the inhibition of the mitochondrial permeability transition pore (mPTP) opening, a key event in cell death after ischemia/reperfusion. Recently, he observed that acute pre-ischemic estrogen-induced cardioprotection against ischemia/reperfusion injury was primarily mediated via G protein-coupled estrogen receptor 1 (GPER1). His present investigations focus on whether acute post-ischemic estrogen treatment can also induce cardioprotective effects viaGPER1 in the intact animal. Male and ovariectomized female mice are subjected to left anterior descending artery occlusion followed by reperfusion. An estrogen bolus is delivered via the femoral vein before reperfusion and a GPER1 antagonist is given before estrogen administration. Myocardial infarct size and mitochondrial Ca2+ retention capacity required to induce mPTP opening are assessed after reperfusion. Expression of ubiquitinylated or acetylated calpains 1 and 10 is measured by Western Blot in mitochondrial and cytosolic fractions. Dr. Bopassa’s research program also allows the postdoctoral trainee an opportunity to interact with a variety of disciplines via active collaborations with Drs. Toney and Aune.
Robert A. Clark, MD, Oxidative Stress Associated Cell Signaling in Host Defense and Disease. Dr. Clark has an extensive background of 30 years in basic research relevant to human diseases. His major focus has been on mechanisms of the inflammatory response and the cell biology and biochemistry of human phagocytic cells, ranging from studies of neutrophil function and clinical disorders to in-depth molecular analyses of cellular components involved in the killing of invading microorganisms and the regulation of their expression and function. Dr. Clark’s laboratory studies neutrophil signal transduction and activation at cellular and molecular levels, focusing particularly on the respiratory burst NADPH oxidase, a multi-component enzyme responsible for much of the microbicidal capability of phagocytic cells through the stimulus-dependent formation of reactive oxygen species (ROS). Recombinant proteins are used to determine the mechanisms of enzyme activation, considering phosphorylation, translocation of cytosolic components to membranes, role of SH3 domains, and the function of the rac GTPases. The overall goal is to understand at a molecular level the cellular responses that result in microbial killing and tissue injury. An area of increasing interest focuses on a family of genes (NOX) that are homologous to the neutrophil oxidase, but are expressed in many non-myeloid cells where they are involved in signaling, cell growth, aging, and host defenses. The lab is exploring the role of these oxidases in transcriptional regulation of genes that are relevant to chronic inflammation, the biology of aging, and to the host response to invading microorganisms. Of rapidly increasing prominence in Dr. Clark’s program are the oxidative stress-associated cellular signaling and injury pathways involved in degenerative diseases of the vascular system. Trainees working in this laboratory will learn a broad range of basic concepts and techniques in biochemistry, molecular biology, and cell biology. They will be engaged in projects dealing with the mechanisms of generation of ROS by the NOX family of NADPH oxidases, as well as the functional roles of these products of oxygen metabolism, emphasizing oxidative stress and degenerative diseases.
Ralph A. DeFronzo, MD, Pathophysiological Alterations in Type 2 Diabetes Mellitus (T2DM). The major focus of Dr. DeFronzo’s research has been (1) examination of the cellular mechanisms by which insulin promotes glucose uptake and metabolism in healthy subjects and (2) definition of metabolic, biochemical, and molecular basis of impaired insulin action in obese nondiabetic and type 2 diabetic individuals, in the normal glucose tolerant offspring of two diabetic parents, in patients with a variety of endocrinopathies, and in subjects with the insulin resistance syndrome, (3) the role of mitochondrial dysfunction in the development of insulin resistance; (4) the relationship between insulin resistance and the development of atherosclerotic cardiovascular disease; (5) the role of lipotoxicity and glucotoxicity in the pathogenesis of type 2 diabetes; (6) elucidation of the genes responsible for type 2 diabetes. These studies have been carried out in both man and animals and have involved a variety of techniques including: (a) muscle biopsy; (b) novel isotopic methodologies developed in his laboratory; (c) forearm and leg catheterization; (d) indirect calorimetry; (e) insulin/hyperglycemic clamps; (e) biochemical, enzymatic, and isotopic determinations on tissue (muscle, adipose, liver) samples; (f) molecular analysis of the glucose transporter and hexokinase genes and their expression/function in muscle; (g) molecular and biochemical analysis of the insulin receptor signal transduction system (IR and IRS-1 phosphorylation; p85 and PI3 kinase activity associated with IRS-1; total PI3-kinase activity); (h) quantitation of muscle/liver/abdominal fat content by MRI/MRS; (i) measurement of muscle ATP synthesis by MRS; (j) measurement of mitochondrial function using confocal laser microscopy and enzymatic activity assays. These techniques allow in vivoand in vitro quantitation of glucose transport, phosphorylation, and oxidation, glycolysis, glycogen synthesis, muscle enzyme activity (hexokinase, glycogen synthase/phosphorylase, pyruvate dehydrogenase), insulin signaling, hepatic glucose production, and gluconeogenesis. By contrasting measurements performed in diabetic and obese patients with those in healthy controls, the specific intracellular disturbances responsible for insulin resistance (both peripheral and hepatic) in these common clinical disorders have been delineated. The specific contributions of chronic hyperglycemia (“glucose toxicity”) and chronic hyperinsulinemia to the observed defects in insulin action and insulin secretion in type 2 diabetes have also been explored; observations in this area have yielded novel and innovative approaches to the treatment of type 2 diabetes. In all of the above, there are ample opportunities for clinically-based postdoctoral research training, an especially relevant issue for physicians who desire a well-founded program in the basic mechanisms of occlusive vascular disease
Lily Q. Dong, PhD, Adiponectin Receptor-Mediated Intracellular Signaling. The major focus of Dr. Dong’s research is on the identification of alterations that contribute to insulin resistance, a primary contributing factor in the pathogenesis of type 2 diabetes. This condition (characterized by the loss of insulin sensitivity in tissues) results in an impairment of glucose uptake in skeletal muscle and fat cells, and an uncontrolled production of glucose in hepatic cells; all of these events contribute to increase glucose levels within the bloodstream. Adiponectin or Acrp30 is secreted by adipose tissue and released into the bloodstream where it serves as an insulin sensitizer. The serum concentration of adiponectin is significantly reduced in type 2 diabetic and obese patients. Since adiponectin enhances insulin sensitivity, it has the potential to be used therapeutically in the treatment of type 2 diabetes and obesity. However, the molecular mechanism governing adiponectin action is largely unknown. Dr. Dong’s group has identified APPL1, an adaptor protein with multiple function domains, as the first signaling molecule with immediate binding to adiponectin receptors, and positively mediating adiponectin signaling in muscle cells in vitro and in vivo. In addition, she has shown that APPL2, an isoform of APPL1, negatively regulates adiponectin signaling. She proposed that APPL1/APPL2 isoforms function as an integrated “Yin-Yang” regulator in adiponectin signaling. Recently, her laboratory has demonstrated that APPL1 mediates the insulin sensitizer role of adiponectin by facilitating the binding of IRS1/2 to the insulin receptor in response to adiponectin stimulation. These findings provide potential mechanisms behind insulin resistance and the development of type 2 diabetes. Dr. Dong’s laboratory provides a rich research training environment for early career scientists to acquire state-of-the art skills relevant to the development of interventions for improved insulin sensitivity in diabetes.
Yogesh Gupta,PhD, Our studies seek to provide a complete and coherent picture of human mRNA modification complexes at the molecular and atomic level with a final goal to develop novel anticancer therapeutics targeting the RNA methylome and other nucleoprotein assemblies. We employ leading-edge structural biology methods such as fX-ray crystallography, NMR, SAXS, EM in combination with an array of other biophysical and chemical biology tools to elucidate structures and mechanisms of macromolecular complexes central to childhood malignancies.
Hai-Chao Han, PhD, Arterial Tortuosity and Diastolic Heart Failure. Dr. Han’s cardiovascular biomechanics laboratory studies vascular wall remodeling in tortuous arteries and diastolic compliance in diastolic heart failure. Tortuous blood vessels are commonly seen in the aorta, carotid, iliac, cerebral, retinal, coronary, and peripheral arteries and veins. They are associated with aging, hypertension, and atherosclerosis but the mechanisms remain unclear. The long term goal of Dr. Han’s laboratory is to elucidate the biomechanical mechanisms of the development of vessel tortuosity and to develop new techniques to treat and prevent these vascular diseases. Another area of research in Dr. Han’s lab focuses on the surgical treatment of left ventricular hypertrophy and diastolic heart failure. Reduced left ventricular diastolic compliance is a feature of heart failure with preserved ejection fraction (HFpEF), which is responsible for half of all heart failure hospitalizations and is increasing in prevalence each year. In collaboration with Dr. Marc Feldman in Cardiology, Dr. Han’s lab strives to develop a surgical technique to increase left ventricular compliance to treat diastolic heart failure. Experimental, computational and theoretical modeling approaches are integrated in these studies. The ultimate goals are to better understand adaptation in the cardiovascular system and to improve treatment of cardiovascular diseases.
James Lechleiter, PhD, Molecular and Cellular Mechanisms of Neuroprotection during Ischemia, Brain Injury, and Neurodegeneration. Research in Dr. Lechleiter’s laboratory is focused on the molecular and cellular mechanisms of neuroprotection that occur in response to ischemic stress, acute brain injury and aging. Sophisticated technologies employ in vitro and in vivo strategies. A major emphasis is on the potential of astrocytes as a novel therapeutic target for the treatment of brain injuries. Astrocytes are known to play a crucial role in supporting and protecting neuronal function and in modulating brain energy metabolism. One research project is an investigation of the underlying protective mechanisms mediated by stimulation of the purinergic P2Y1 receptor. A second major research project is directed towards understanding the neuroprotective efficacy of thyroid hormones via stimulation of fatty acid oxidation. A third area of research is focused on the long-term neurological consequences of repetitive traumatic brain injury (rTBI). Finally, Dr. Lechleiter’s laboratory is investigating the role of ER stress and the unfolded protein response (UPR) immediately after brain injuries as well as in the development of age-associated neurological deficits. Thus, diverse research training opportunities exist within Dr. Lechleiter’s laboratory.
Joel Michalek, PhD, I have 40 years experience in the analysis and reporting of clinical and epidemiological studies and 30 years experience as a consultant to the pharmaceutical industry, I have published papers in statistical methodology, clinical trials, and epidemiology, and my current interests include methods to analyze survival and count data in cross-over studies.
Anand Prasad, MD, Dr. Prasad is the Director of the Cardiac Catheterization Laboratory at University Health System. His clinical interests are centered on the endovascular treatment of peripheral arterial disease including carotid and lower extremity disease, transcatheter aortic valve replacement, percutaneous ventricular support devices and complex high risk percutaneous coronary interventions. Dr. Prasad has a focus on Vascular Medicine, isalso board certified by the American Board of Vascular Medicine, and holds a certification as a Registered Physician in Vascular Interpretation (RPVI). He conducts a monthly Vascular Medicine Clinic and is constructing a vascular imaging and venous ablation program at UT Health.He has served as the Associate Program Director and Program Director for the Cardiovascular Diseases Fellowship Program at UT Health San Antonio. In addition to an active role in Fellow training, Dr. Prasad is involved with clinical research. He is the PI on both investigator initiated and industry sponsored clinical trials. His areas of current interest include novel approaches to therapy for limb salvage and acute kidney injury following endovascular interventions. He is also involved with efforts to understand subclinical vascular disease in minority populations and serves as a co-investigator in the Cameron County Hispanic Cohort Study. The goals of this endeavor are to understand the prevalence, predictors, and outcomes related to subclinical peripheral arterial disease in Mexican Americans. His research career has led to over 90 publications in peer reviewed journals. He is an Associate Editor of Catheterization and Cardiovascular Interventions (CCI), Associate Peripheral Arterial Disease Section Editor for SCAI.org, on the ACC Interventional Section writing committee, ACC NCDR PVI Steering committee,
XLPAD steering committee and on the editorial board for the Journal of Invasive Cardiology and editorial consultant for the Journal of the American College of
Cardiology.The intersection of his research and clinical interests has led to the creation of the largest cardio renal symposium in the United States: Cardio Renal Connections. As cofounder of this meeting, Dr. Prasad has worked to bring together clinicians, nurses, students, researchers, and industry to better address the challenges in management of patients with concomitant heart and kidney disease.
Jason Pugh, PhD, A fundamental question in neuroscience is how neurons receive, process, and transmit signals, transforming sensory input to behavioral output. At the cellular level, neurons transmit signals and store information primarily through synaptic connections between neurons. Synapses are remarkably diverse in the transmitters used, receptors express (both pre- and postsynaptic), kinetics, and ability to undergo short-term and long-term changes in strength. Each of these properties influences how information is transmitted and stored at a particular synapse. We are interested in understanding how synaptic properties are fine-tuned to function within specific circuits and process information.To address these questions, we work on synapses in the cerebellar circuit, a brain region primarily involved in motor learning and motor coordination (though involvement in cognitive functions have also been demonstrated). We study synaptic transmission in the cerebellar circuit because the underlying neural circuity is relatively simple and highly regular throughout the cerebellum, making it possible to correlate synaptic properties with specific circuit functions and even behavioral output. We primarily use patch clamp electrophysiology, to measure postsynaptic currents and potentials, and two-photon calcium imaging, to measure pre- or postsynaptic calcium influx and cell morphology. Our lab is currently focused on two projects:1. Function of presynaptic GABAA and GABAB receptors. Parallel fiber synapses (the primary excitatory synapses in the cerebellum) express GABAA and GABAB receptors in their presynaptic boutons. Previous work has shown that GABAA receptors enhance release of neurotransmitter while GABAB receptors inhibit release of neurotransmitter. However, these two receptors are activated by the same ligand (GABA) and are therefore likely to be co-activated in vivo. Do the opposing effects of these receptors cancel one another out? Does one receptor effect dominate over the other? Or do differences in the kinetics and affinities of these receptors allow them to be selectively activated in some conditions? 2. Role of dystrophin in cerebellar function. Muscular dystrophy is caused by mutations in the gene for dystrophin, a protein highly expressed in muscle tissue that acts as a linker between the intracellular cytoskeleton and the extracellular matrix. Dystrophin is also expressed in the central nervous system and many individuals with muscular dystrophy show cognitive deficits, suggesting dystrophin may also play a role in neuronal function. Dystrophin is most highly expressed in Purkinje cells of the cerebellum, specifically at inhibitory synapses onto these cells. We hypothesize that dystrophin mutations disrupt cerebellar function which contributes to the loss of motor and cognitive function observed in muscular dystrophy. We are addressing these questions using patch-clamp electrophysiology to measure synaptic function and firing in the cerebellar circuit of mouse models of muscular dystrophy and creating a Purkinje cell specific knock-out of dystrophin for behavioral testing.
W. Brian Reeves, MD, Inflammation and Ion Channels in Acute Kidney Injury (AKI), and TNF in Diabetic Nephrophathy. Dr. Reeves’ research focuses on understanding the role of TNF and ion channels in inflammatory renal injury. He is specifically interested in understanding aberrant cell signaling that leads to injury and progression of renal pathology. His program uses a multidisciplinary approach involving human studies, whole animal studies and genetic manipulation, as well as detailed biochemical and molecular biological assessment of injury and cell signaling. Dr. Reeves has demonstrated that TNF is elevated in experimental models of cisplatin nephrotoxicity and that inhibition or deletion of TNF reduced kidney injury. His lab determined that TNF signals primarily via TNFR2 and subsequent p38 MAPK activation to produce toxicity. Moreover, the source of TNF was shown to be parenchymal cells rather than leukocytes, and that TLR4 on renal parenchymal cells was critical for cisplatin-induced TNF production and kidney injury. Using a diphtheria toxin depletion model, Dr. Reeves found that dendritic cells had an anti-inflammatory action and protected against cisplatin AKI; and that production of IL-10 by dendritic cells accounted for some of this anti-inflammatory action. Inflammation is recognized to play a role in diabetic nephropathy, but the mediators of this process are still being defined. Dr. Reeves has performed animal studies to examine the role of TNF as a mediator. He determined that the production of TNF is increased in diabetic mice subjected to ischemic injury and that this exuberant production of TNF is responsible for the increased susceptibility of diabetic mice to ischemic injury. Using TNF deficient mice and TNF neutralizing antibodies, Dr. Reeves demonstrated that TNF is an important mediator of diabetic nephropathy. Moreover, with conditional knockouts of TNF developed in his laboratory, Dr. Reeves determined that macrophages are a key source of TNF within diabetic kidneys. This work forms the basis for proposed studies to examine the effects of TNF antagonists on diabetic nephropathy in humans.
Naomi Sayre PhD, Cholesterol Homeostasis and Neuroprotection during Stroke. Dr. Sayre’s laboratory is interested in the processes that affect brain repair and recovery after injury, with particular emphasis on the role that cholesterol homeostasis plays in these processes after stroke. Astrocytes are the primary supportive cells in the brain and also regulate cholesterol homeostasis, and so have unique potential to affect recovery after brain damage due to stroke. Astrocytes secrete apolipoprotein E (ApoE), and in humans, 3 alleles exist (E2, E3, and E4). ApoE4 is associated with poor recovery after stroke and traumatic brain injury, particularly in the long term after damage. In the brain, the main clearance receptor for ApoE4 is LRP1 (low-density lipoprotein receptor related protein 1). LRP1 promiscuously binds and removes several extracellular ligands and receptors from the plasma membrane via receptor-mediated endocytosis. Dr. Sayre hypothesizes that ApoE4 differentially interacts with LRP1 compared to ApoE3. This differential interaction is expected to result in greater competition for LRP1 function, thereby resulting in a decreased ability of LRP1 to remove extracellular ligands and receptors. Dr. Sayre seeks to determine if ApoE4 increases sensitivity to cell death after stroke by competing for inflammatory receptor clearance by LRP1. In vascular cells, LRP1 has been shown to influence the quantity of the TNFα receptor on the plasma membrane. Dr. Sayre hypothesizes that in the brain, ApoE4 prevents removal of TNFα receptor by LRP1, thereby conferring increased sensitivity to cytokines such as TNFα. Such sensitivity is expected to result in greater-long term damage after stroke or traumatic brain injury. Dr. Sayre will test this hypothesis with a combination of cell-culture models and in vivo mouse models of stroke and traumatic brain injury; she plans to utilize floxed-LRP1 mice to generate astrocyte-specific LRP1 knock outs.
Mark S. Shapiro, PhD, Modulation and Functional Role of Ion Channels in Excitable Cells. The research program of Mark Shapiro spans the physiology, modulation and role in disease of a variety of ion channels in neurons, cardiomyocytes and non-excitable cells, with particular emphasis on voltage-gated K+ and Ca2+ channels. Most of the projects in this laboratory center on “M-type” (KCNQ) K+, and Ca2+ channels, and signaling pathways of Gq/11-coupled receptors, using patch-clamp electrophysiology of native neurons and heterologous systems, biochemistry, confocal and TIRF microscopy, molecular biology and live single-cell and whole-animal imaging. Dr. Shapiro also uses STORM super-resolution nanoscopy to probe the multi-protein complexes underlying modulation of ion channels in a variety of cell types. In addition, he is systematically exploring the role of the scaffolding/regulatory protein, A-kinase anchoring protein (AKAP)79/150 in orchestrating transcriptional and regulatory control of M/KCNQ channels in sympathetic and nodose sensory neurons, in the brain, and in smooth muscle. He has documented the PIP2 sensitivity of many types of channels to the regulatory lipid, phosphatidylinositol 4,5-bisphosphate (PIP2), the mechanisms and structural determinants of receptor-mediated suppression of M currents and Ca2+ currents, the modulation of KCNQ channels by calmodulin, AKAPs and Src kinase, the roles of M channels in airway smooth muscle, and in sensory neurons. Besides these channels, his laboratory is also studying the mechanisms of regulation and organization of pain-sensing TRPV channels, Ca2+-activated TMEM16/Ano channels and other channels critical to sensation, mood, airway and cardiovascular function.
Although Dr. Shapiro’s laboratory is primarily involved in basic-science, he also devotes effort to translational projects. Thus, he is investigating novel strategies to prevent acquired epilepsies and the role of M channel regulation at the acute and transcriptional levels in epileptogenesis. Additionally, he also is exploring novel and provocative roles of M/KCNQ channels as a neuroprotective mechanism to prevent brain damage during cerebrovascular ischemic stroke and traumatic brain injury; the latter studies involve other researchers in San Antonio at three different institutions. Finally, he is engaged in novel molecules to treat asthma and other airway and cardiovascular diseases.
Kumar Sharma, MD, FAHA, FASN, Dr. Sharma is the chief of the Division of Nephrology and vice chair for research in the Department of Medicine. Dr. Sharma was professor of medicine and director of the Center for Renal Translational Medicine and director of the Institute of Metabolomic Medicine at the University of California San Diego. His research explores the mechanisms and treatment of diabetic nephropathy. Dr. Sharma has several National Institutes of Health-funded projects including a DP3: Type 1 diabetes targeted research award of $6 million to identify novel paradigms in diabetic complications, more than $3 million from the JDRF to identify novel biomarkers in an international cohort of studies in Type 1 diabetes and more than $3 million for the Animal Models of Diabetic Complications Consortium and novel clinical trials in diabetic nephropathy from the National Institute of Diabetes and Digestive and Kidney Diseases. He serves on numerous study sections and is a standing member of the NIH Pathology of Kidney Disease study section. He plays a lead role in the NIH Kidney Precision Medicine program, and UT Health San Antonio will be the national hub for analysis of spatial metabolomic profiles of kidney tissues. As vice chair for research, Dr. Sharma will oversee the creation of a mentoring program for young investigators, the implementation of pilot programs and the organization of research themes across the department.
Manjeri Venkatachalam, MD, Cell Injury and Cell Death in Acute Renal Failure. Dr. Venkatachalam’s research career has spanned the gamut of the structural, physiological and biochemical basis for normal kidney function and its breakdown in disease, including in response to high blood pressure and diabetes. This has included a good deal of emphasis on the renal microvasculature: glomerular arterioles, peritubular capillary network and glomeruli. Current work in his laboratory is devoted to understanding how acute kidney injury (AKI) contributes to the progression of chronic kidney disease (CKD), eventuating in end stage renal disease. In his working hypothesis, AKI plays a role either as single incidents (or a limited number of episodes) of acute injury in the setting of CKD, or as multiple, serially occurring microscopically focal acute injury consequent to occlusive arteriolosclerosis and/or arteriolar spasm. Dr. Venkatachalam is testing these possibilities in CKD models with graded reductions of renal mass (mimicking the pathophysiology of CKD) and superimposed AKI, and in hypertensive models of CKD that exhibit occlusive arteriolosclerosis and microscopically focal acute damage. Dr. Venkatachalam believes that incomplete repair of tubule injury and impaired recovery of normal tubule structure results in a pathologically altered persistently undifferentiated tubule phenotype that exhibits phlogistic and profibrotic signaling, causing tubulointerstitial fibrosis. For severe and/or progressive tubulointerstitial fibrosis to occur, kidneys afflicted by CKD must suffer either massive AKI episodes usually caused by ischemia, or serial microscopically focal AKI caused by microvascular pathology. In either case, a hemodynamic/vascular defect is fundamental. He has established reproducible models of hypertensive and non-hypertensive CKD and ischemic AKI, and his studies are ongoing. Thus, kidney research in Dr. Venkatachalam’s laboratory is fundamentally related to vascular pathology and dysfunction, and his research would therefore provide an excellent platform for training in vascular disease.