Gill Center for Biomolecular Science

Phone:

812-855-4518

Email:

adhopesh@indiana.edu

Department:

Psychological and Brain Sciences

Campus:

IU Bloomington

Education:

• Ph.D. in Pharmacology and Toxicology; Simon Fraser University, British Columbia, Canada; 2012
• MSc in Biotechnology; Abertay University, Dundee, UK; 2007
• B.Pharm; University of Pune; Pune, India; 2004

Research interests:

The endocannabinoid system consists of endogenous cannabinoids (endocannabinoids), cannabinoid receptors (primarily CB1 and CB2), and the enzymes that synthesize and degrade endocannabinoids. Δ9-Tetrahydrocannabinol (Δ9-THC), the primary psychoactive component of cannabis, produces many of its psychoactive effects by engaging CB1 cannabinoid receptors. In addition to its psychoactivity, cannabis has been shown (or suggested) to be efficacious for multiple therapeutic indications and maladies. My interest in cannabinoid receptors stems from my graduate studies. My doctoral work was directed towards understanding the actions of certain mammalian low toxicity pesticides and benzophenanthridine alkaloids on cannabinoid receptors. Using various biochemical and functional assays we demonstrated that these agents were antagonists/inverse agonists at cannabinoid receptors at low micromolar concentrations. My continued interest in cannabinoid receptors led me to a postdoctoral position with the Mackie lab, where I developed and executed a range of cell-based functional assays (e.g., adenylyl cyclase, arrestin recruitment, IP1, pERK1/2, etc) to screen different cannabinoid receptor 2 (CB2) ligands. We found that these ligands showed marked functionally selectivity and activated subsets of signaling pathways with varied potencies and efficacies. My fascination with GPR119 (a novel lipid and cannabinoid receptor that has been investigated for the treatment of obesity and type 2 diabetes) began from my earlier preliminary data where I found that GPR119 ligands displayed strong functional selectivity with different potencies and efficacies. I plan to explore the actions of these ligands in in vivo animal models of obesity and diabetes. My long-term research goal is to dissect the complex cellular signaling pathways that are recruited following the activation of GPR119 and other cannabinoid receptors and how this knowledge can be harnessed for therapeutic benefit.

Representative publications:

• Lin X, Dhopeshwarkar AS, Huibregste M, Mackie K and Hohmann A (2018) Slowly signaling G-protein biased CB2 cannabinoid receptor agonist LY2828360 suppresses neuropathic pain with sustained efficacy and attenuates morphine tolerance and dependence. Molecular Pharmacology. 93(2): 49-62.
• Westphal MV, Schafroth MA, Sarott RC, Imhof MA, Bold CP, Leippe P, Dhopeshwarkar A, Grandner JM, Katritch V, Mackie K, Trauner D, Carreira EM, Frank JA.(2017) Synthesis of photoswitchable Δ9-tetrahydrocannabinol derivatives enables optical control of cannabinoid receptor 1 signaling. Journal of American Chemical Society.139 (50): 18206-18212.
• Dhopeshwarkar A.S., Murataeva N., Makriyannis A., Straiker A. and Mackie K. (2017) Two Janus cannabinoids that are both CB2 agonists and CB1 antagonists. Journal of Pharmacology and Experimental Therapeutics. 360(2):300-311.
• Dhopeshwarkar A and Mackie K. (2016) Functional selectivity of CB2 cannabinoid receptor ligands at a canonical and non-canonical pathway. Journal of Pharmacology and Experimental Therapeutics. 358(2):342-351.
• Dhopeshwarkar A.S. and Mackie K. (2014) CB2 cannabinoid receptors as a therapeutic target - What does the future hold? Molecular Pharmacology.86(4):430-437 doi: 10.1124/mol.114.094649.(Invited review)
• Natalia Murataeva, Amey Dhopeshwarkar, Danielle Yin, Jose Mitjavila, Alex Straiker, Ken Mackie (2016) Where’s my entourage? The curious case of 2-OG, 2-LG, and 2-PG.Pharmacological Research. 110(1):173-180.