Interplay of Autophagy Regulated Cell Death and HIV Pathogenesis in Substance Use Disorders

Funding Opportunity Number: RFA-DA-25-009

Deadline
Letter of Intent: October 14, 2024
Submission: November 14, 2024

Description
The notice of funding opportunity (NOFO) aims to support studies to expand our knowledge of mechanisms driving autophagy and to identify autophagy pathways that can be exploited to control HIV infection and pathogenesis of comorbities in the context of addictive substance use. The NOFO invites mechanistic studies and preclinical studies testing effects of compounds known to interfere with autophagy pathways on HIV infection and immune system. All studies must clearly address the intersection between HIV and substance use.

Research Questions

The NOFO encourages mechanistic pilot studies using in vivo and in vitro models. Research questions aim to address how the autophagy regulated HIV-induced cell death pathway may be part of an approach to target HIV harboring cells in CNS of people living with HIV (PLWH) and SUDs would be of interest.

The research areas that are pertinent to this NOFO include, but are not limited to:

  • Investigations of the interconnection and reciprocal regulation between synaptic autophagy and neurotransmission in the context of SUD and HIV.
  • Understand autophagy regulated innate immune responses induced by HIV infections and addictive substances.
  • Study how autophagy processes are involved in the changes in neuronal excitability, synaptic plasticity, neuron-glia communication, and neural circuit activity that contribute to SUD, HIV infection and viral reservoir persistence.
  • Decipher autophagy machinery in HIV pathogenesis, with and without the presence of addictive substances. Specifically, the trafficking and processing of the core autophagy proteins, how autophagy regulates and coordinates chemotactic cell migration, and the downstream signaling cascades.
  • Explore the role of autophagic regulation in viral and host transcriptional regulation in HIV neuropathogenesis, with and without the presence of addictive substances.
  • Explore the role of autophagy in aging related biological processes under the influence of HIV and SUD.
  • Develop tools and technology to harness autophagy to balance T-cell function to mitigate neuroinflammation induced by HIV and SUD.
  • Delineate autophagic signaling mechanisms that regulate synaptic scaling to leverage pharmacological approaches suitable for restoring synaptic function in chronic neuroinflammatory states under the influence of SUD and HIV.

For more information, please see the opportunity website.