New Research Grants - July 2017
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Daniel Leung, MD, MSc
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Mucosal associated invariant T (MAIT) cells in Vibrio cholerae infection and vaccination Cholera is a diarrheal disease affecting millions of people worldwide each year and current vaccines are less effective in young children than in older persons. How the human immune system protects against cholera is not well known, but it likely involves the development of effective antibody responses. We propose studies looking at how Mucosal-Associated Invariant T (MAIT) cells may play an important role by bridging the innate and adaptive immune responses and helping the body develop antibody responses against cholera. |
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Adam Spivak, MD
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Modulating Immune Function in Chronic HIV Infection via MTOR Inhibition in Peripheral Blood Effector Lymphocytes Despite the ability of antiretroviral drugs to control HIV infection, the immune system does not fully return to normal. The goal of this research proposal is to determine whether blockade of a cellular pathway called mTOR using FDA-approved drugs can reverse the immune dysfunction observed in treated HIV infection. A better understanding of the etiology of immunosenescence in treated HIV-1 infection has implications both for the HIV-1 epidemic and for a wide variety of age-associated conditions. |
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Marcus G. Pezzolesi, PhD
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The role of microRNAs in progressive renal decline in Type 1 diabetes Progressive renal decline is the central manifestation of diabetic nephropathy (DN) that leads to end-stage renal disease (ESRD). In participants of the Joslin Kidney Study (JKS), a longitudinal investigation of the natural history of DN in Type 1 diabetes (T1D), we recently demonstrated that microRNAs (miRNAs) involved in transforming growth factor (TGF)-β1 mediated renal fibrogenesis are deregulated early in patients who are at risk for progression to ESRD. Importantly, this deregulation occurs prior to the initiation of renal function decline, suggesting that these miRNAs have potential utility as novel biomarkers of the risk of progression to ESRD in DN. We hypothesize that additional miRNAs exist that play important roles in renal function decline in patients who are at risk of progression to ESRD but have not yet been studied. The identification of these miRNAs will lead to the discovery of novel factors involved in the pathogenesis of renal function decline. The goal of our research project is to further leverage biobanked specimens from the JKS, along with innovative next-generation sequencing technology and systems biology-based approaches, to i) determine the expression profile of the full complement of miRNAs that are differentially expressed early in T1D patients who are at risk for progression to ESRD and prior to the initiation of renal function decline and ii) to begin to investigate the mechanisms by which these miRNAs contribute to disease pathogenesis. |
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Tianxin Yang, MD, PhD
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Interaction of (pro)renin receptor and PPARy in regulation of plasma volume Appropriate fluid environment is necessary for normal performance of all body chemical reactions, as well as maintenance of tissue perfusion and oxygenation, and elimination of metabolic wastes. Such a vital function largely relies on the ability of the kidney to adjust urinary excretion of water and electrolytes according to the intake. The objective of the grant is to examine the role of PPARgamma/(pro)renin receptor-dependent pathway in the control of fluid balance. PPARgamma is a nuclear receptor critically involved in regulation of energy metabolism as well as fluid homeostasis. The synthetic PPARgamma agonist, thiazolidinedione, is highly effective in managing type 2 diabetes but causes fluid retention that may increase the risk of cardiovascular disease. While the metabolic role of PPARgamma is well studied, the mechanism of how the antidiabetic therapy induces fluid retention has not been resolved. On the other hand, (pro)renin receptor, a new member of the renin-angiotensin system, has recently emerged as a critical mediator of renal control of fluid and electrolyte balance and blood pressure. In the current proposal, we seek to test the hypothesis that PPARgamma directly targets (pro)renin receptor in the kidney to increase fluid reabsorption to expand plasma volume. A better understanding of this pathway will help diagnose and treat fluid disorders such as the side effect of thiazolidinedione, a commonly prescribed antidiabetic medicine. |
