Biography

James Frank completed his bachelor’s degree in Chemistry at the University of British Columbia in Vancouver, where he worked in the lab of Prof. Stephen G. Withers. There, he developed fluorescent glycosides for the detection of glycosidases in high-throughput screens. Frank then travelled overseas for an industry job at Corden Pharma LLC near Basel, Switzerland, where he developed a large-scale synthesis of a complex glycolipid pharmaceutical. He obtained his Ph.D. in Organic Chemistry at the Ludwig Maximilian University of Munich in Germany in the lab of Prof. Dirk Trauner, where his research focused on the synthesis/evaluation of photo-switchable lipids. In 2017, Frank joined the bioelectronics group of Prof. Polina Anikeeva at Massachusetts Institute of Technology, where he engineered fiber-based implants to apply these photochemical probes to control behavior in freely moving rodents. He joined the Vollum Institute in 2018 as a Vollum Fellow and Research Assistant Professor, where his research interests focus on the roles of lipids on cell physiology. In 2021, Frank was named Assistant Professor in OHSU's Department of Chemical Physiology & Biochemistry, with a joint appointment in the Vollum.

Summary of current research

The Frank lab develops light-sensitive small molecule probes to manipulate neurons with increased spatiotemporal precision. In particular, we focus on developing photo-switchable and photo-caged ligands which permit remote control over cannabinoid receptor (CBR) activity.

The CBRs are widely distributed across the human nervous system and are important to a number of neuropsychological conditions including drug addiction. CB1 and CB2 are inhibitory GPCRs that respond to lipophilic endocannabinoids such as anandamide. They remain infamous due to their activation by Δ⁹-tetrahydrocannabinol (Δ⁹-THC), a component of Cannabis sativa believed to exert its psychoactive effects primarily via CB1 in the brain. As consumption of cannabinoids for medicinal or recreational use becomes more widespread, it is critical we investigate their potential to modulate reward processing and addictive behavior. Importantly, we must also understand their interactions with other narcotics like opioids, the abuse of which presents an increasing health epidemic across North America.

Our lab uses a multidisciplinary approach involving organic chemical synthesis, whole-cell electrophysiology, fluorescence imaging and immunohistochemistry to develop and assess the ability of our technology to interface with brain tissue at subcellular precision. After chemical synthesis of the probes, we evaluate their activity in cultured rodent neurons and acute brain slices. These tools are designed to illuminate the roles of CBRs in modulating rewarding stimuli in the mesolimbic dopamine system and will be used probe the interactions between cannabinoid and opiate receptors in models of addiction.

Selected publications

♦ Top three important research papers
* Corresponding author           ^# Co-first author            Frank lab trainees (OHSU)

Garza, S.J.#; Tobias, J.A.#; Ni, J.; Frank, J.A.* Photorelease of Anandamide at the Cell Plasma Membrane with Optically-Cleavable Targeted Ligands. ChemRxiv. DOI: 10.26434/chemrxiv.15005963/v1

Viray, A.E.G.; Frank, J.A.* (2025) The photoswitchable cannabinoid azo-HU308 enables optical control of Ca²⁺ dynamics in INS-1 b-cells via off-target effects on TRPC channels. FEBS Open Bio. DOI: 10.1002/2211-5463.70146

Garza, S.^#; Kicin, B.^#; Sarott, R.C.; Pfaff, P.; Kosar, M.; Weishaar, T.; Schnacke, P.; Lobingier, B.; Carreira, E.M.*; Frank, J.A.* (2025) Real-Time Optical Control of CB1 Receptor Signaling In Vitro with Tethered Photoswitchable (-)-trans-D⁹-Tetrahydrocannabinol Derivatives. Journal of the American Chemical Society, 147 (27), 23482-23491. DOI: 10.1021/jacs.4c18379

Howe, C.A.; Icka-Araki, D.; Viray, A.E.G.; Garza, S.; Frank, J.A.* (2024) Optical control of TRPV1 channels in vitro with tethered photopharmacology. ACS Chemical Biology, 19 (7), 1466-1473. DOI: 10.1021/acschembio.4c00052

Kosar, M.; Sarott R.C.; Sykes, D.A.; Viray, A.E.G.; Vitale, RM.; Tomašević, N.; Li. X.; Ganzoni, R.L.Z.; Kicin, B.; Reichert, L.; Patej, K.J.; Gómez-Bouzó, U.; Guba, W.; McCormick, P.J.; Hua, T.; Gruber, C.W.; Veprintsev, D.B.; Frank, J.A.*: Grether, U.*; Carreira, E.M.* (2024) Flipping the GPCR Switch: Structure-Based Development of Selective Cannabinoid Receptor 2 Inverse Agonists. ACS Central Science, 10 (5), 956-968. DOI: 10.1021/acscentsci.3c01461

Kosar, M.; Sykes, D.A.; Viray, A.E.G.; Vitale, R.M.; Sarott, R.C.; Ganzoni, R.L.; Onion, D.; Tobias, J.A.; Leippe, P.; Ullmer, C.; Zirwes, E.A.; Guba, W.; Grether, U.*; Frank, J.A.*; Veprintsev, D.*; Carreira, E.M.* (2023) Platform Reagents Enable Synthesis of Ligand-Directed Covalent Probes: Study of Cannabinoid Receptor 2 in Live Cells. Journal of the American Chemical Society, 145 (28), 15094-15108. DOI: 10.11.463883

Tobias, J.A.; Rajic, G.; Viray, A.E.G.; Icka-Araki, D.; Frank, J.A.* (2021) Genetically-targeted endocannabinoid uncaging enables optical control of GPR55 in pancreatic β-cells. Chemical Science, 12, 13506-13512. DOI: 10.1039/D1SC02527A

♦ Sarott, R.C.; Viray, A.E.G.; Pfaff, P.; Sadybekov, A.; Rajic, G.; Katrich, V.; Carreira, E.M.*; Frank, J.A.* (2021) Optical Control of Cannabinoid Receptor 2-Mediated Ca²⁺ Release Enabled By Synthesis of Photoswitchable Probes. Journal of the American Chemical Society, 143 (2), 746-743. DOI: 10.1021/jacs.0c08926

♦ Frank, J.A.^#*; Antonini, M-J.^#; Chiang, P-H.; Canales, A.; Konrad, D.; Garwood, I.; Rajic, G.; Koehler, F.; Fink, Y.; Anikeeva, P.* (2020) In vivo photopharmacology enabled by multifunctional fibers. ACS Chemical Neuroscience, 11 (22), 3802-3813. DOI: 10.1021/acschemneuro.0c00577

♦ Westphal, M.V.^#; Schafroth, M.A.^#; Sarott, R.C.; Imhof, M.A.; Bold, C.P.; Leippe, P.; Mackie, K.; Trauner, D.*; Carreira, E.M.*; Frank, J.A.* (2017) Synthesis of Photoswitchable D⁹-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling.  Journal of the American Chemical Society, 139, 18206−18212. DOI: 10.1021/jacs.7b06456

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