The focus of Dr. Mohan’s laboratory is to investigate epigenetic mechanisms, in particular, the role of microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and DNA methylation in the molecular pathogenesis of HIV/SIV induced gastrointestinal, neurological and cardiovascular comorbidities. A major driver of these comorbidities is chronic inflammation/immune activation that persists in PLWH despite viral suppression by anti-retroviral therapy (ART). To alleviate chronic inflammation, Dr. Mohan’s lab is currently investigating the combinatorial effect of ART and naturally available low-dose phyto-cannabinoids, namely, delta-9-tetrahydrocannabinol and cannabidiol on T cell and macrophage dynamics, oral and intestinal microbiome (microbiota-gut-brain axis), neuroinflammation, plasma and cerebrospinal fluid metabolome. Through new collaborations, Dr. Mohan’s lab is also exploring the use of novel non-invasive technologies for the delivery of long-acting ART drugs and gene therapy vectors into the brain to reduce viral persistence. Currently, his laboratory is extending the cannabinoid studies to other chronic inflammatory diseases such as Tuberculosis and Alzheimer’s disease using the unique rhesus macaque model of tuberculosis, and the aged Baboon model of Alzheimer’s disease, respectively. Research in his laboratory is currently funded by two NIH R01 and a R21/R33 grant.
Inside the Lab
Despite viral suppression by anti-retroviral drugs, chronic inflammation/immune activation persists in HIV-infected patients and increases their risks of developing non-AIDS illnesses such as cardiovascular diseases, neurological dysfunction, enteropathy etc. Dr. Mohan and his research team have made significant contributions to the understanding of epigenetic mechanisms underlying HIV induced gastrointestinal dysfunction and more importantly, how these changes can be inhibited/reduced using anti-inflammatory cannabinoids. His research focuses on several different aspects of HIV/SIV pathogenesis. His laboratory performs both basic and translational studies using the premier SIV-infected macaque model of HIV/AIDS to:
- Identify receptor mediated and other downstream epigenetic mechanisms associated with the anti-inflammatory effects of cannabinoids using the rhesus macaque model of HIV/SIV infection. Current research efforts are to identify the role of cannabinoid receptor 2 and peroxisome proliferator activated receptor gamma using specific agonists in the in vivo setting. Specific downstream epigenetic mechanisms (molecular) that we are actively exploring include DNA methylation and small and long non-coding RNA
- Investigate the anti-fibrotic effects of cannabinoids and related compounds and identify specific molecular mechanisms underlying the ability of cannabinoids to inhibit collagen deposition in lymph nodes.Identify proinflammatory pathways and networks associated with HIV associated neuroinflammation and explore the potential of both low dose cannabinoids to suppress neuroinflammation in the setting of ART.
- Evaluate the effect of cannabinoids on the secretion and composition of extracellular vesicles in HIV/SIV infection. This is a newly funded study focused on HIV/SIV induced gastrointestinal epithelial dysfunction and lymphoid fibrosis.
- Drugs of abuse including cocaine continue to be a significant co-morbidity of HIV infection. Drug usage is associated with risky behaviors and poor adherence to antiretroviral drugs, which leads to increased incidences of HIV infection and poor long-term prognosis of disease course. In addition to negative behavioral manifestations, drugs of abuse have been shown to directly impact the immune system leading to a neuroinflammatory state in the central nervous system. In a newly funded pilot study we will investigate the effects of cocaine on viral replication, neuroinflammation, immune dysfunction and dysbiosis using the SIV-infected rhesus macaque model.
- Exploring cannabinoids as a viable host directed therapeutic strategy to treat Mtb/HIV coinfection.
Mohan’s lab current collaborators include Dr. Chioma Okeoma (Stonybrook University in New York), Drs. Bapi Pahar and Xavier Alvarez (Tulane University), Drs. Siddappa Byrareddy and Shilpa Buch (University of Nebraska, Omaha) and Dr. Kaushal (Texas Biomed/SNPRC).
Main Technologies and Methods Used
- T and B cell immunology
- Intestinal epithelial cell biology
- Primary Lymph node fibroblast cell culture and biology
- Transcriptomics (microRNA/mRNA/lncRNA) including RNAseq and microarrays
- Gene/microRNA overexpression, knockdown and RT-qPCR.
- Luciferase reporter assays
- Immunofluorescence/Confocal microscopy
- Immunoprecipitation/Western Blotting
- Flow cytometry
- Targeted Bisulfite sequencing