Project 2
Chronic, immune activation is one of the major hallmarks of HIV in the modern era, despite the effectiveness of antiretroviral therapy (ART) in suppressing viral replication. This chronic immune activation is largely mediated by myeloid-lineage cells, including monocytes, macrophages, and microglia. This demonstrates a critical need to develop new anti-inflammatory strategies that are effective in inhibiting myeloid activation in the context of chronic HIV infection and treatment. Cannabinoids, particularly the phytocannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) are among the most promising new anti-inflammatory components in the cannabis plant. However, their impact of HIV associated inflammation remains unclear. Additionally, knowledge is limited on their impact on the brain, particularly with respect to adult neurogenesis. Our lab studies the effect of CBD and THC administration in a virally suppressed rhesus macaque model, focusing on their ability to suppress myeloid-mediated inflammation and neuronal function and viability.
Grants:

- R01 DA052859 from NIDA entitled “Cannabidiol and Macrophage Chronic Inflammation in a Virally Suppressed Rhesus Macaque Model”
- U01 DA058527 from NIDA entitled “Elucidating single cell changes in neurogenic brain regions during HIV and cannabinoid exposure”
- Ament SA, Campbell RR, Lobo MK, Receveur JP, Agrawal K, Borjabad A, Byrareddy SN, Chang L, Clarke D, Emani P, Gabuzda D, Gaulton KJ, Giglio M, Giorgi FM, Gok B, Guda C, Hadas E, Herb BR, Hu W, Huttner A, Ishmam MR, Jacobs MM, Kelschenbach J, Kim DW, Lee C, Liu S, Liu X, Madras BK, Mahurkar AA, Mash DC, Mukamel EA, Niu M, O'Connor RM, Pagan CM, Pang APS, Pillai P, Repunte-Canonigo V, Ruzicka WB, Stanley J, Tickle T, Tsai SA, Wang A, Wills L, Wilson AM, Wright SN, Xu S, Yang J, Zand M, Zhang L, Zhang J, Akbarian S, Buch S, Cheng CS, Corley MJ, Fox HS, Gerstein M, Gummuluru S, Heiman M, Ho YC, Kellis M, Kenny PJ, Kluger Y, Milner TA, Moore DJ, Morgello S, Ndhlovu LC, Rana TM, Sanna PP, Satterlee JS, Sestan N, Spector SA, Spudich S, Tilgner HU, Volsky DJ, White OR, Williams DW, Zeng H. The single-cell opioid responses in the context of HIV (SCORCH) consortium. Mol Psychiatry. 2024 Jun 15;. doi: 10.1038/s41380-024-02620-7. [Epub ahead of print] Review. PubMed PMID: 38879719
- Rosado-Franco JJ, Ellison AL, White CJ, Price AS, Moore CF, Williams RE, Fridman LB, Weerts EM, Williams DW. Roadmap For The Expression Of Canonical and Extended Endocannabinoid System Receptors in Peripheral Organs of Preclinical Animal Models. Physiological Reports. e15947. Pubmed PMID: 38408761.
- White, CJ, Gausepohl, AM, Wilkins, HN, Eberhard, CD, Orsburn, BC, Williams, DW. Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy. Journal of the American Society for Mass Spectrometry. 2024 Jan 30;. doi: 10.1021/jasms.3c00276. PubMed PMID: 38288997.