Medical College of Georgia
Department of Pharmacology and Toxicology
Medical College of Georgia
Department of Anesthesiology and Perioperative Medicine
I am a M.D. and D.Sc. with expertise in: immune mechanisms of renal diseases, diabetes-associated vascular disease, and role of growth hormone releasing hormone (GHRH) receptor on impaired incretin signaling and dyslipidemia.
My teaching goal is to provide the students with a distinctive discipline and responsibility on learning, and to facilitate for them the understanding of the most important concepts of the lecture and at the same time to motivate them to actively participate by means of interactive exchange with the lecturer and/or with fellow students. This takes away a big burden of study time and as such increases the motivation and interest of the students for the course in question.
This can be accomplished by e.g. including a quiz or exercises at the end of the lecture and a subsequent analysis of the correct and incorrect answers. Another possibility is to include short presentations by a group of students in the lecture. I had this experience myself as a medical student, and the interactions and feedbacks from the rest of the students as well as from the professor in the classroom, result in a very productive teaching/learning experience.
Research is my passion and takes most of my work effort. However, I always have the time for teaching, and my teaching accomplishments, most of which performed when I was an Associate Professor at the University of Zulia, Venezuela, include a lecture on “Apoptosis in Renal Disease” during the course of “Actualization in Clinical Investigation”, a Program of Continue Education for the Professional Medical Community, and also being a Teaching Professor of the Periodontal Graduate Course “Microbiology and Immunology” with the following lectures: Major Histocompatibility Complex; T cell Receptor (TCR) and Accessory Molecules; T cell Activation; Complement System; Autotolerance and Autoimmunity; Transplantation Immunology; and Tumor Immunology. Moreover, I served as a Member of the Scientific Committee and Coordinator of Symposia, of the bi-annual Scientific Sessions of University of Zulia, Venezuela.
As a Research Faculty at Augusta University, I have participated as an Invited Professor for Clinical Case Discussion, for Second Year Medical Students of the School of Medicine from 2011 - 2014. Also, I have participated as a member of the Departmental panel for the evaluation of PhD students. Moreover, I have presented Departmental seminars as well as during the weekly Metabolic Meetings. I also participated in the VBIO8130 Modern Drug Discovery and Development course on April 2016 and on March 2017, with a lecture on “Block Buster Drugs in Diabetes” for undergraduate students , and in the VBIO8010 Methods in Cardiovascular Research course on April-November 2020, with a lecture on "Animal and cellular models of acute kidney injury" for graduate students.
I have moreover a vast experience in effectively training under- and post-graduate students in the lab, both at University of Zulia, Venezuela and at Augusta University. This teaching includes not only different laboratory techniques but also critical thinking and solving problems, in order to make the students acquainted with the difficult task of formulating and interpreting data and generating results in a scientific manner, which can only be accomplished when students are closely involved in research and are regularly exposed to the laboratory environment.
I hold a full-time position as a Research Junior Faculty in the Vascular Biology Center, and in the Department of Pharmacology and Toxicology at Augusta University (AU), Medical College of Georgia (MCG).
My work has focused in the past on the understanding of immune and inflammatory mechanisms of renal diseases. Currently, in collaboration with Dr. Rudolf Lucas (Vascular Biology Center, AU, MCG), and Dr. Michael Madaio (Department of Medicine, AU, MCG), I am participating in studies aimed to investigate the therapeutic potential of a peptide mimicking the lectin-like domain of TNF in nephrotoxic nephritis (NIH/NIDDK, Co-Investigator, 10%).
During the last years, I have taken on experimental studies that address the integrity of a critical enzyme, nitric oxide synthase (NOS) that plays an important regulatory role maintaining the normal function of blood vessels at the endothelial-blood interface and in moderating adverse influences. These studies address the competing role of the enzyme arginase, subtype I, with that of endothelial nitric oxide synthase (eNOS) for their common substrate L-arginine, thus reducing the production of nitric oxide (NO), the critical mediator of vascular blood flow and cardiac function, as well as renal vascular and excretory mechanisms, while elevating generation of damaging reactive oxygen species. These effects predispose to vascular dysfunction and contribute to the development of coronary disease and nephropathy, major complications associated with diabetes. I have shown for the first time a crucial role of the enzyme arginase 1 in streptozotocin-induced type 1 diabetes-associated coronary vascular dysfunction in rats and mice. My findings concerning the elevation of oxidative stress, resulting from a dysfunctional eNOS, mediated by increased arginase activity in the vasculature, will potentially have important implications in terms of understanding pathophysiological mechanisms of vascular complications during diabetes, as well as other vascular diseases. I have a productive collaboration with Dr. Lucas, which has resulted in important scientific contributions, and a collaborative study on pneumonia-associated pulmonary barrier dysfunction in type 2 diabetes (ADA, Co-Investigator, 10%). We will investigate why capillary lung endothelial cells are more susceptible to pneumolysin-induced barrier dysfunction in type 2 diabetes, for which I will be evaluating the actions of arginase upregulation in this pathology.
Major research interest:
Dyslipidemia represents an important risk factor for progressive heart and kidney disease in subjects with diabetes mellitus. Patients with improper control of glucose levels have also more difficulties in controlling abnormal lipid levels. Two factors are important for proper handling of glucose: the incretin glucagon like-peptide 1 (GLP-1), which is a hormone released from the gut during digestion, and glucagon, which is a hormone released from the pancreas, and has opposing effects to insulin and GLP-1, thus raises glucose levels. GLP-1 has also been found to control abnormal lipids levels. New drugs known as GLP-1 agonists or DPP4 inhibitors help type 2 diabetes (T2D) patients in controlling glucose levels and body weight. This therapy has not been approved in the U.S. by the Food and Drug Administration for type 1 diabetes (T1D) patients, but has been shown to have some positive effects in these subjects as reported by few studies. Despite these promising findings, achieving proper glycemic control and lipid levels in both T1D and T2D patients is still a challenge, and may be influenced by impaired GLP-1 signaling in target organs. Activation of receptors for the Growth Hormone Releasing Hormone (GHRH) regulates growth hormone (GH) release by the pituitary. However, functional GHRH receptors have also been found in extra-pituitary sites. It has not been studied so far whether the GHRH receptor is expressed in organs associated with lipid and glucose metabolism, and whether its function would contribute to the deficient GLP-1 signaling and hence to the enhanced postprandial lipids and glucose levels in patients with T1D or T2D diabetes. Our experimental studies in a T1D rodent model demonstrate an increase in glucagon secretion, enhanced expression of GHRH receptor in the small intestine, increased levels of plasma lipids in the fed state, as well as impaired vascular and kidney function. These abnormalities were significantly improved in animals receiving an antagonist of the GHRH – MIA-602, developed by Dr. Andrew Schally, University of Miami – at a dose that did not affect plasma growth hormone (GH) levels. These findings unravel a previously unidentified pathway in T1D mediated by GHRH receptor associated with impaired GLP-1 signaling, hyperglucagonemia and dyslipidemia. These results have been recently published in the Proceedings of the National Academy of Sciences of the United States of America (Romero 2016, PNAS), and the studies were supported by a Pilot Study Research Program Intramural Grant, I obtained (PI) from the Office of the Vice President for Research at the Augusta University, Medical College of Georgia.
We now seek further information regarding the expression of the GHRH and its receptor, as well as its functional splice variants, in human tissues from cadaver donors related to lipid and glucose homeostasis, i.e.: small intestine, pancreas and liver. We will correlate our findings with disease condition, lipid profile and glucose or HbA1C levels, as well as GLP-1 receptor expression in the same tissues. We will also perform in vitro studies with commercially available human cell lines from small intestine and pancreas, to determine signaling mechanisms downstream to GHRH receptor associated with impairment of GLP-1 receptor function. We will also continue our experimental studies with different rodent models of T1D and T2D, and with conditional GHRH receptor knockout mice, to determine proof of concept, and also common pathways associated with dyslipidemia and hyperglucagonemia during diabetes. The main goal of these studies is to unravel important information, not explored so far, on expression of GHRH receptor in human tissues associated with glucose and lipid metabolism. The studies can further have an impact on new therapies to improve the outcome of T1D and T2D patients with poor or difficult to manage glycemic control, severe dyslipidemia, or statin intolerance.
