乔治亚医学院药理学和毒理学系
乔治亚医学院麻醉与围手术期医学系
我是一名医学博士和博士，专长于：肾脏疾病的免疫机制，糖尿病相关血管疾病，生长激素释放激素（GHRH）受体在肠促胰岛素信号受损和血脂异常中的作用。
我的教学目标是为学生提供一种独特的学习纪律和责任感，并促进他们对讲座中最立即博概念的理解，同时通过与讲师和/或与同学的互动交流，激励他们积极参与。立即博就减轻了学习时间的负担，从而增加了学生对相关课程的积极性和兴趣。这可以通过在讲座结束时进行小测验或练习以及随后对正确和错误答案的分析来实现。另一种可能性是在讲座中包括一组学生的简短陈述。作为一名医科学生，我自己也有过立即博的经历，从其他学生以及课堂上的教授那里得到的互动和反馈，产生了非常富有成效的教学/学习经历。研究是我的热情所在，占据了我大部分的工作精力。然而，我总是有时间去教学，我的教学成就，大部分是在委内瑞拉苏利亚大学担任副教授期间完成的，包括在“临床研究的实现”课程中讲授“肾脏疾病中的细胞凋亡”，专业医学社区继续教育项目，以及作为牙周研究生课程“微生物学和免疫学”的教学教授，授课内容如下：主要组织相容性复合体；T细胞受体（TCR）及其辅助分子；T细胞活化；补系统;自身耐受性与自身免疫；移植免疫学;肿瘤免疫学。此外，我还担任委内瑞拉苏利亚大学两年一次的科学会议的科学委员会成员和专题讨论会协调员。作为奥古斯塔大学的研究人员，我曾作为特邀教授参加2011 - 2014年医学院二年级医学生的临床病例讨论。此外，我还作为部门评审小组的一员参与了博士生的评估。此外，我还在部门研讨会以及每周的代谢会议上发表演讲。我还参加了2016年4月和2017年3月的VBIO8130现代药物发现与开发课程，为本科生讲授了“糖尿病中的重药”，并参加了2020年4月至11月的VBIO8010心血管研究方法课程，为研究生讲授了“急性肾损伤的动物和细胞模型”。此外，在委内瑞拉苏利亚大学和奥古斯塔大学的实验室中，我在有效培训本科生和研究生方面有着丰富的经验。这种教学不仅包括不同的实验技术，还包括批判性思维和解决问题的能力，以使学生熟悉以科学的方式表述和解释数据并产生结果的艰巨任务，这些任务只有在学生密切参与研究并经常接触实验室环境时才能完成。
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.
