Shilpa Buch,
Professor and Senior Executive Vice Chair for Research,
University of Nebraska Medical Center
I am currently a Professor & Executive Vice Chair for Research and the Director of the Nebraska Center for Substance Abuse research at the University of Nebraska. I received my PhD in 1982 in Microbiology from Maharaja Sayajirao Univ in Baroda, India and moved to Canada for postdoctoral training. I began my independent research career as an Assistant Professor at the Hospital for Sick Kids, Toronto, following which, I moved to Kansas University and embarked on a research area focused on understanding how addictive drugs co-operate with HIV-1 to exacerbate neurological complications. I rose through the ranks at Kansas and in 2007, made a move as a full Professor to University of Nebraska in Omaha. Research approaches used in my lab involve a multipronged approach comprising of a variety of complementary model systems ranging from cell cultures to rodent models to the higher more relevant macaque model of SIV pathogenesis. More recently, my research interest is centered on exploring how exosomes act as conduits to transport key signaling mediators (small noncoding RNAs/microRNAs) to distant recipient cells as a means to regulate gene expression and cellular cross talk. I lead an active research program involving collaborations both nationally and internationally, with over 225 peer-reviewed publications. I have consistently held NIH funding throughout my career and continue to serve on NIH study sections. During my career, I have had the good fortune of being recognized by various national and International societies with the Wybran (2012) and the Distinguished services (2023; 2013) Awards, both of which hold a special meaning for me. I have also been awarded the UNMC Scientist laureate award (2016) in addition to the Kansas City scientist award. Aligning closely with my passion for mentoring, has enabled me to take an active leading role in the Women’s Mentoring Program at UNMC (2015-2017). I have also received the Women in Neuroscience award at the International Society of Neurovirology in 2016. I have played an active role as a Secretary of the Society on Neuroimmune Pharmacology and have been invited as a speaker & as a Chair at various meetings and have also organized several symposia. To further hone my leadership skills, I graduated from the Executive Leadership for Academic Medicine Program that fosters the growth and career trajectories of women leaders nationally.
Astrocytes at the Crossroads of HIV and Alzheimer’s Disease
Wednesday, 26 July 2023 at 20:00
Add to Calendar ▼2023-07-26 20:00:002023-07-26 21:00:00Europe/LondonAstrocytes at the Crossroads of HIV and Alzheimer’s DiseaseExtracellular Vesicles 2023: Technologies, Biomarker Cargo and Diagnostics in Orlando, FloridaOrlando, FloridaSELECTBIOenquiries@selectbiosciences.com
Increased life expectancy of HIV+ patients in the post anti-retroviral therapy era parallels with increased incidence of HIV-associated neurological disorders (HAND) and associated comorbidities such as Alzheimer’s Disease (AD). The persistence of HAND is thought to involve poor penetration of the antiretroviral drugs across the BBB into the CNS, leading to persistent low-level viral replication in the CNS with accumulation of cytotoxic viral proteins including Tat. Interestingly, there have been reports on Tat-mediated production of the toxic neuronal amyloid protein & the interaction with the former, leading to enhanced toxicity. Additionally, opiates have shown to exaggerate HIV mediated neuropathogenesis in different animal models. Abundant glial cells such as the astrocytes have also garnered interest as potential contributors of amyloidosis, & this could translate into a significant added burden to the process of amyloidosis in the context of Tat & Opiates. Present study was aimed at assessing the role of astrocytes in mediating Tat/Morphine induced amyloidosis in the context of HAND & opiate use disorder. Our in vivo data showed that SIV+ macaques/HIV+ patients, exhibited region specific up-regulation of the amyloidogenic components in the brain that co-localized with GFAP positive astrocytes. In vitro findings aimed at dissecting the cell-type specificity involved in amyloidosis revealed up-regulation of AD markers – BACE-1, amyloid precursor protein (APP), ABetamoC64, p-Tau, as well as increased activity of BACE-1 in Tat-exposed human primary astrocytes (HPA). Molecular mechanism(s) underlying this process involved up-regulation of hypoxia inducible factor (HIF-1a) with a concomitant translocation to the nucleus & binding to the lncRNA BACE-1AS resulting in formation of a unique complex as confirmed by RIP and EMSA. Further, ChiP assay showed functional binding of the complex to BACE-1 promoter leading in turn, to increased expression of BACE-1 by transcriptional, post transcriptional and translational mechanisms along with increased activity leading to consequential generation of ABeta-42 protein via cleavage of APP. We next sought to assess whether morphine-stimulated astrocyte extracellular vesicles (ADEV) could shuttle the amyloid cargoes to neurons. Our results showed that morphine exposure up-regulated the release of morphine-ADEVs, carrying amyloids and that silencing HIF-1Alpha in astrocytes not only reduced the numbers of released ADEVs, but also inhibited the packaging of amyloid cargos in ADEVs. These findings were further validated in brain derived EVs (BEVs) isolated from macaques, wherein it was shown that BEVs from morphine-dependent macaques, carried varieties of amyloid cargoes including the cytokine IL-1Beta. Targeting HIF-1Alpha can thus be considered as an adjunctive therapy approach for HAND patients on cART with a comorbidity of opiate misuse.
Add to Calendar ▼2023-07-26 00:00:002023-07-27 00:00:00Europe/LondonExtracellular Vesicles 2023: Technologies, Biomarker Cargo and DiagnosticsExtracellular Vesicles 2023: Technologies, Biomarker Cargo and Diagnostics in Orlando, FloridaOrlando, FloridaSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2023-07-26 20:00:002023-07-26 21:00:00Europe/LondonAstrocytes at the Crossroads of HIV and Alzheimer’s DiseaseExtracellular Vesicles 2023: Technologies, Biomarker Cargo and Diagnostics in Orlando, FloridaOrlando, FloridaSELECTBIOenquiries@selectbiosciences.com
