Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation
NIDA - National Institute on Drug Abuse
About This Grant
Abstract People with HIV (PWH) who use methamphetamine (METH) experience disproportionately high rates of neurocognitive impairment and chronic neuroinflammation, even with suppressive antiretroviral therapy. Microglia are central to these CNS complications, yet the molecular mechanisms by which METH exacerbates HIV-induced microglial dysfunction remain poorly understood. A major limitation in the field has been the lack of integrative, systems-level studies capable of identifying key molecular regulators of neuroinflammation and viral persistence in the context of HIV and substance use comorbidity. Our preliminary studies implicate MECOM (MDS1 and EVI1 complex locus protein), a stress-responsive transcriptional regulator, as a potential mediator of METH-induced microglial reprogramming under HIV infection. We observed that METH alters HIV replication and cytokine production in iPSC-derived microglia, with persistent effects following their integration into brain organoids. Bulk transcriptomic analyses revealed MECOM upregulation under HIV/METH co-exposure, suggesting a role in neuroimmune dysregulation. This proposal combines integrated transcriptomic and proteomic (multi-omics) analyses with advanced human-derived models, including iPSC-derived microglia, neuroimmune organoids, and HIV-infected humanized NOG-hIL34 mice, to map and validate MECOM- associated networks. We will first define MECOM-regulated signaling pathways and protein interaction networks in HIV-infected microglia exposed to METH using integrative transcriptomic and proteomic analyses. Building on these findings, we will then determine the functional consequences of MECOM deletion in human-derived in vitro models and in HIV-infected humanized mice. By uncovering how METH alters MECOM-dependent signaling in HIV-infected microglia, this study will provide new mechanistic insight into HIV-associated neuroinflammation and identify candidate molecular targets to mitigate CNS complications in PWH with comorbid substance use.
Grant Summary
Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation is a NIDA - National Institute on Drug Abuse grant providing up to $668K for university, nonprofit, healthcare org. Applications are due 2028-03-31 (open). Check eligibility and apply with FindGrants.
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Eligibility
How to Apply
Up to $668K
2028-03-31
- 1Confirm your organization is eligible for Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation from NIDA - National Institute on Drug Abuse, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIDA - National Institute on Drug Abuse before the deadline.
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Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation: Frequently Asked Questions
Who is eligible for the Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation?
Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation is offered by NIDA - National Institute on Drug Abuse and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation provide?
Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation provides up to $668K per award from NIDA - National Institute on Drug Abuse. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation deadline?
Applications for Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation are due 2028-03-31 (open). Because deadlines can change, verify the date with the funder, NIDA - National Institute on Drug Abuse, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation?
To apply for Integrated Human Neuroimmune Platforms to Define MECOM-Associated Microglial Mechanisms in HIV Persistence and Methamphetamine-Induced Neuroinflammation, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDA - National Institute on Drug Abuse.