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The role of antidepressants in central and peripheral myeloid HIV persistence and inflammation

Award Number: K01MH132466
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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The role of antidepressants in central and peripheral myeloid HIV persistence and inflammation - Project Summary/Abstract This is a resubmission application for a Mentored Research Scientist Development Award (K01) to support the career development of Dr. Stephanie Matt to facilitate her transition to an independent academic investigator in the HIV and neuroimmunology research fields. An intense and comprehensive mentoring and research plan has been developed to use high-throughput techniques to assess antidepressant-mediated HIV viral dynamics and inflammatory signaling in human myeloid and co-culture models. Dr. Matt’s training will be supported by a firm institutional commitment to her career development and a strong mentoring team of leaders in the HIV and psychoneuroimmunology research fields, each providing strategic guidance in both the development of this proposal and mentoring as her career progresses. The proposed research plan is a natural extension of the recent studies Dr. Matt has been conducting in her mentor Dr. Peter Gaskill’s laboratory but is distinguished by examination of HIV infection and inflammation in clinical cohorts, biostatistical analyses, as well as neuronal profiling. Neurological complications of HIV infection (neuroHIV) remain prevalent even with antiretroviral therapy (ART). Depression is one of these increasingly common complications that can substantively worsen HIV disease progression. Myeloid cells such as macrophages and microglia are primary HIV targets that can serve as viral reservoirs and drive HIV neuropathogenesis, but their activation also mediates depression-associated inflammation. Inflammatory links between HIV, depression, and the drugs used to treat them are not well understood. However, HIV, depression, and antidepressants act on receptors and transporters that alter neurotransmission, and neurotransmitter receptor activity on immune cells can influence inflammatory signaling and HIV infection. This suggests that changes in neurotransmitter levels by antidepressants could affect the size of myeloid HIV reservoirs, exacerbating neuroHIV and influencing the progression of depression and treatment resistance. Thus, the overarching hypothesis of this proposal is that specific antidepressants can activate both CNS and peripheral myeloid cells that critically contribute to inflammation and HIV persistence. This proposal will test this hypothesis using a multifaceted approach to evaluate the effects of in vivo antidepressants and ART on viral dynamics and inflammation in myeloid cells in association with cognitive function in depressed people living with HIV (Aim 1), effects of antidepressants regulating discrete viral dynamics in HIV-infected, ART-treated iPSC CNS and peripheral myeloid populations (Aim 2), and how antidepressants influence viral dynamics and neuronal function in co-cultures of HIV-infected, ART-treated microglia and distinct neuronal subtypes (Aim 3). These studies will significantly advance our understanding of the cellular mechanisms underlying the role of antidepressants in HIV neuropathogenesis. This opportunity will provide comprehensive training and a solid foundation on which to build a successful and independent research program to investigate mechanisms by which neuropsychiatric drugs could drive inflammation in the context of HIV.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $185,220 )
2025	2025	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	3	5/30/2025	NON-COMPETING CONTINUATION	$185,220
														Subtotal = $185,220

Issue Date FY: 2024 ( Subtotal = $185,220 )
2024	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	2	5/24/2024	NON-COMPETING CONTINUATION	$185,220
														Subtotal = $185,220

Issue Date FY: 2023 ( Subtotal = $185,220 )
2023	2023	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Mental Health Research Grants	000	1	5/15/2023	NEW	$185,220
														Subtotal = $185,220

Grand Total All Awards = $555,660

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The role of antidepressants in central and peripheral myeloid HIV persistence and inflammation

Award Number: K01MH132466

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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