UNMC_Acronym_Vert_sm_4c
University of Nebraska Medical Center

Laboratory of Palsamy Periyasamy, PhD

Research interests

My research is dedicated to exploring the complex world of epigenetic changes triggered by HIV-1/HIV-1 proteins and substance abuse. Specifically, I focus on how these changes activate glial cells like microglia and astrocytes, leading to neuroinflammation. My ultimate goal is to discover potential strategies for treating NeuroHIV. Epigenetics, a captivating field, involves inheritable modifications in gene activity without altering the DNA sequence. DNA methylation, histone alterations, and non-coding RNAs such as lncRNAs and microRNAs regulate this process.

Surprisingly, these epigenetic changes are closely linked to substance abuse and HIV-1 infection. Yet, the complex molecular and epigenetic mechanisms underlying how HIV-1 and substance abuse impact microglial activation and neuroinflammation remain enigmatic. To decode these intricacies, my research focuses on untangling the epigenetic landscape, with a spotlight on promoter DNA methylation and its interaction with neuroinflammatory responses in the context of HIV-1 and substance abuse, including substances like cocaine, morphine, methamphetamine, and alcohol. The knowledge gained from these investigations could lay the groundwork for developing epigenetic targets, offering innovative therapeutic approaches to alleviate the challenges of HIV-associated neurocognitive disorders in the era of combined antiretroviral therapy.

Collaborators

Professor, Department of Neurological Sciences Senior Associate Dean of Research and Development, College of Medicine Director, Center for Integrative and Translational Neuroscience

Howard Fox, MD, PhD
Techniques used in the lab
  • Biochemical and molecular assays
  • RNAscope HiPlex assay
  • In situ hybridization
  • Bisulfite genomic DNA sequencing
  • TOPO-TA cloning
  • Gene arrays
  • microRNA target validation assays
  • RNA immunoprecipitation
  • CHIP assay
  • Dual luciferase assay
  • Confocal microscopy
  • In vitro gene silencing assays
  • Rodent studies
Ongoing Projects
  • Role of epigenetics in HIV, drugs abuse-mediated neuroinflammation
  • Role of HIV/HIV proteins and drug abuse in inflammasome activation
  • Role of alcohol in NLRP6 inflammasome signaling in astrocyte activation and neuroinflammation
  • Role of lncRNA Xist and miR-124 in HIV Tat-mediated microglial activation
  • Epigenetic regulation of PPARG in cocaine-mediated microglial activation and neuroinflammation
  • Investigating the therapeutic potential of N-Acetylcysteine in alleviating cocaine-mediated microglial activation and neuroinflammation

Funding

HIV Tat and morphine-mediated pyroptosis activates astrocytes: Role of NLRP6 inflammasome in HAND

Role: Principal Investigator

Source: DHHS/NIH/NIDA/5R01DA052266
Investigating the therapeutic potential of N-Acetylcysteine in alleviating cocaine-mediated microglial activation and neuroinflammation

Role: Principal Investigator

Source: DHHS/NIH/NIGMS/P20GM130461 (Pilot)
Pharmacokinetic, pharmacodynamic, and toxicological interactions among opioids and cabotegravir

Role: Co-Investigator (MPI: El-Hage; Buch, Fletcher)

Source: DHHS/NIH/NIDA/5R01DA057145
Single cell determinants of brain in the context of viral persistence in SIV/cART/cocaine non-human primates

Role: Co-Investigator (MPI: Buch; Rana)

Source: DHHS/NIH/NIDA/1U01DA058402
Molecular mechanisms underlying HIV & Cocaine-mediated microglial activation: Targeting NLRP3 inflammasome

Role: Co-Investigator (PI: Buch)

Source: DHHS/NIH/NIDA/5R01DA050545
HIV Tat & cocaine-mediated alterations in microglial migration & activation involve epigenetic regulation or miRNAs

Role: Co-Investigator (PI: Buch)

Source: DHHS/NIH/NIDA/5R01DA043138

Cocaine-mediated microglial activation involves epigenetic regulation of PPARG

Role: Principal Investigator

Source: COBRE: DHHS/NIH/NIGMS/P20GM130461 (Pilot)

Role of lncRNA Xist and miR-124 in HIV Tat-mediated microglial activation

Role: Principal Investigator

Source: DHHS/NIH/NIMH/P30MH062261 (UNMC CHAIN Center - Pilot grant)
HIV Tat-mediated astrocyte activation involves NLRP6-mediated pyroptosis: Implications for neuroinflammation in HAND

Role: Principal Investigator

Source: DHHS/NIH/NIMH/R25MH080661 (JHU R25 TRNAMH – Pilot grant)

Role of miR-124 in HIV-1 Tat & cocaine mediated microglial activation

Role: Principal Investigator

Source: DHHS/NIH/NIDA/5R03DA044087

Epigenetic regulation of astrocyte-specific NLRP6 inflammasome and PANoptosis in HIV Tat and methamphetamine-mediated neuroinflammation

Role: Principal Investigator (Contact)/Sil (MPI)

Source: DHHS/NIH/NIDA/1R01DA060753