James Frank, Ph.D.
Assistant Professor, Chemical Physiology & Biochemistry
Joint Appointment, Vollum Institute
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.
# These authors contributed equally to this work
*Corresponding authors
Kosar M, Sarott RC, Sykes DA, Viray AEG, Vitale RM, Tomašević N, Li X, Ganzoni RLZ, Kicin B, Reichert L, Patej KJ, Gómez-Bouzó U, Guba W, McCormick PJ, Hua T, Gruber CW, Veprintsev DB, Frank JA*, Grether U*, Carreira EM*. (2024) Flipping the GPCR Switch: Structure–Based Development of Selective Cannabinoid Receptor 2 Inverse Agonists. ACS Central Sci. In press.
Kosar M, Sykes DA, Viray AEG, Vitale RM, Sarott RC, Ganzoni RL, Onion D, Tobias JA, Leippe P, Ullmer C, Zirwes EA, Guba W, Grether U*, Frank JA*, Veprintsev D*, Carreira EM*. (2023) Platform Reagents Enable Synthesis of Ligand-Directed Covalent Probes: Study of Cannabinoid Receptor 2 in Live Cells. J. Am. Chem. Soc. 145 (28), 15094-15108. DOI: 10.1021/jacs.2c13629.
Hartrampf N, Leitão SM, Winter N, Toombs-Ruane H, Frank JA, Schwille P, Trauner D*, Franquelim HG*. (2023) Structural Diversity of Photoswitchable Sphingolipids for Optodynamic Control of Lipid Raft Microdomains. Biophys. J. 122 (11), 2325-2341. DOI: 10.1016/j.bpj.2023.02.029.
Pritzl SD, Konrad DB, Ober MF, Richter AF, Frank JA, Nickel B, Trauner D, Lohmüller T. (2022) Optical Membrane Control with Red Light Enabled by Red-Shifted Photolipids. Langmuir, 38 (1), 385-393. DOI: 10.1021/acs.langmuir.1c02745.
Tobias JA, Rajic G, Viray AEG, Icka-Araki D, Frank JA*. (2021) Genetically-targeted endocannabinoid uncaging enables optical control of GPR55 in pancreatic β-cells. Chem. Sci. 12, 13506-13512. DOI: 10.1039/D1SC02527A.
Sarott RC, Viray AEG, Pfaff P, Sadybekov A, Rajic G, Katrich V, Carreira EM*, Frank JA*. (2021) Optical Control of Cannabinoid Receptor 2-Mediated Ca2+ Release Enabled By Synthesis of Photoswitchable Probes. J. Am. Chem. Soc. 143 (2), 746-743. DOI: 10.1021/jacs.0c08926.
Frank JA#, 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 Chem. Neurosci. 11 (22), 3802-3813. DOI: 10.1021/acschemneuro.0c00577.
Pritzl SD#, Urban P#, Prasselsberger A, Konrad DB, Frank JA, Trauner D*, Lohmüller T*. (2020) Photolipid Bilayer Permeability is Controlled by Transient Pore Formation. Langmuir. 36 (45), 13509-13515. DOI: 0.1021/acs.langmuir.0c02229.
Scheidt HA#, Kalokaj K#, Konrad DB, Frank JA, Trauner D, Langosch D*, Huster D*. (2020) Irradiation-Induced Lipid Mixing Implies a Causal Role of Lipid Splay in Membrane Fusion. Biochim. Biophys. Acta. Biomembr. 1682, 183438. DOI: 10.1016/j.bbamem.2020.183438.
Morstein J, Dacheux M, Norman D, Shemet A, Donthamsetti P, Citir M, Frank JA, Schultz C, Isacoff E, Parrill A, Tigyi G*, Trauner D*. (2020) Optical Control of Lysophosphatidic Acid Signaling. J. Am. Chem. Soc. 142, 10612-10616. DOI: 10.1021/jacs.0c02154.
# These authors contributed equally to this work
*Corresponding authors
Kosar M, Sarott RC, Sykes DA, Viray AEG, Vitale RM, Tomašević N, Li X, Ganzoni RLZ, Kicin B, Reichert L, Patej KJ, Gómez-Bouzó U, Guba W, McCormick PJ, Hua T, Gruber CW, Veprintsev DB, Frank JA*, Grether U*, Carreira EM*. (2024) Flipping the GPCR Switch: Structure–Based Development of Selective Cannabinoid Receptor 2 Inverse Agonists. ACS Central Sci. In press.
Tobias JA, Rajic G, Viray AEG, Icka-Araki D, Frank JA*. (2021) Genetically-targeted endocannabinoid uncaging enables optical control of GPR55 in pancreatic β-cells. Chem. Sci. 12, 13506-13512. DOI: 10.1039/D1SC02527A.
Sarott RC, Viray AEG, Pfaff P, Sadybekov A, Rajic G, Katrich V, Carreira EM*, Frank JA*. (2021) Optical Control of Cannabinoid Receptor 2-Mediated Ca2+ Release Enabled By Synthesis of Photoswitchable Probes. J. Am. Chem. Soc. 143 (2), 746-743. DOI: 10.1021/jacs.0c08926.
Frank JA#, 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 Chem. Neurosci. 11 (22), 3802-3813. DOI: 10.1021/acschemneuro.0c00577.
Kol M#, Williams B#, Toombs-Ruane H, Franquelim HG, Korneev S, Schwille P, Trauner D*, Holthuis JCM*, Frank JA*. (2019) Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides. eLife. e43230. DOI: 10.7554/eLife.43230.
Westphal MV#, Schafroth MA#, Sarott RC, Imhof MA, Bold CP, Leippe P, Mackie K, Trauner D*, Carreira EM*, Frank JA*. (2017) Synthesis of Photoswitchable D9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling. J. Am. Chem. Soc. 2017, 139, 18206−18212. DOI: 10.1021/jacs.7b06456.
Frank JA, Yushchenko DA, Fine NHF, Duca M, Citir M, Broichhagen J, Hodson DJ*, Schultz C*, Trauner D*. (2017) Optical control of GPR40 signalling in pancreatic b-cells. Chem. Sci. 8, 7604-7610. DOI: 10.1039/c7sc01475a.
Frank JA, Franquelim HG, Schwille P*, Trauner D*. (2016) Optical Control of Lipid Rafts with Photoswitchable Ceramides. J. Am. Chem. Soc. 138 (39), 12981-12986. DOI: 10.1021/jacs.6b07278.
Frank JA, Yushchenko DA, Hodson DJ, Lipstein N, Nagpal J, Rutter GA, Rhee JS, Gottschalk A, Brose N, Schultz C*, Trauner D*. (2016) Photoswitchable Diacylglycerols Enable Optical Control of Protein Kinase C. Nat. Chem. Biol. 12, 755-762. DOI: 10.1038/nchembio.2141.
Frank JA, Moroni M, Moshourab R, Sumser M, Lewin GR, Trauner D*. (2015) Photoswitchable Fatty Acids Enable Optical Control of TRPV1. Nature Commun. 6, 7118. DOI: 10.1038/ncomms8118.
Selected publications
♦ Top three important research papers
# These authors contributed equally to this work
Tobias JM, Rajic G, Viray AEG, Icka-Araki D, Frank JA. (2021) Genetically-targeted photorelease of endocannabinoids enables optical control of GPR55 in pancreatic β-cells. Chem. Sci., 15 Sep 2021. [Advance Article]
♦ Sarott RC, Viray AEG, Pfaff P, Sadybekov A, Rajic G, Katritch V, Carreira E*, Frank JA*. (2021) Optical control of cannabinoid receptor 2–mediated Ca2+ release enabled by synthesis of photoswitchable probes. J. Am. Chem. Soc. 143(2):736-743. *Corresponding authors
Pritzl SD, Urban P, Prasselsperger A, Konrad DB, Frank JA, Trauner D, Lohmüller T. (2020) Photolipid bilayer permeability is controlled by transient pore formation. Langmuir 36(45):13509-13515.
♦ Frank JA#, Antonini MJ#, Chiang PH, Canales A, Konrad DB, Garwood IC, Rajic G, Koehler F, Fink Y, Anikeeva P. (2020) In vivo photopharmacology enabled by multifunctional fibers. ACS Chem. Neurosci. 11(22):3802-3813.
Urban P, Pritzl SD, Ober MF, Dirscherl CF, Pernpeintner C, Konrad DB, Frank JA, Trauner D, Nickel B, Lohmueller T. (2020) A lipid photoswitch controls fluidity in supported bilayer membranes. Langmuir 36(10):2629-2634.
Leippe P, Frank JA. (2019) Designing azobenzene-based tools for controlling neurotransmission. Curr. Opin. Struct. Biol. 57:23-30.
Kol M, Williams B, Toombs-Ruane H, Franquelim HG, Korneev S, Schroeer C, Schwille P, Trauner D, Holthuis JC, Frank JA. (2019) Optical manipulation of sphingolipid biosynthesis using photoswitchable ceramides. Elife Feb 5;8. pii:e43230.
Frank JA#, Broichhagen J#, Yushchenko DA, Trauner D, Schultz C, Hodson DJ. (2018) Optical tools for understanding the complexity of β-cell signaling and insulin release. Nature Rev. Endocrinol. 14(12):721-737.
Urban P, Pritzl SD, Konrad DB, Frank JA, Pernpeintner C, Roeske CR, Trauner D, Lohmüller T. (2018) Light-controlled lipid interaction and membrane organization in photolipid bilayer vesicles. Langmuir 34(44):13368-13374.
Park S, Frank JA, Anikeeva P. (2018) Silicon biointerfaces for all scales. Nature Biomed. Eng. 2(7):471–472.
Fehrentz T, Huber FME, Hartrampf N, Bruegmann T, Frank JA, Fine NHF, Malan D, Danzl JG, Tikhonov DB, Sumser M, Sasse P, Hodson DJ, Zhorov BS, Klöcker N, Trauner D. (2018) Optical control of L-type Ca2+ channels using a diltiazem photoswitch. Nature Chem. Biol. 4(8):764-767.
Leinders-Zufall T, Storch U, Bleymehl K, Mederos Y Schnitzler M, Frank JA, Konrad DB, Trauner D, Gudermann T, Zufall F. (2018) PhoDAGs enables optical control of diacylglycerol-sensitive transient receptor potential channels. Cell Chem. Biol. 25(2):215-223.
♦ 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. J. Am. Chem. Soc. 139(50):18206-18212.
Frank JA, Yushchenko DA, Fine NHF, Duca M, Citir M, Broichhagen J, Hodson DJ, Schultz C, Trauner D. (2017) Optical control of GPR40 signalling in pancreatic β-cells. Chem. Sci. 8(11):7604-7610.
Pernpeintner C#, Frank JA#, Urban P, Roeske CR, Pritzl SD, Trauner D, Lohmüller T. (2017) Light-controlled membrane mechanics and shape transitions of photoswitchable lipid vesicles. Langmuir 33(16):4083-4089.
Frank JA, Franquelim HG, Schwille P, Trauner D. (2016) Optical control of lipid rafts with photoswitchable ceramides. J. Am. Chem. Soc. 138(39):12981-12986.
Frank JA, Yushchenko DA, Hodson DJ, Lipstein N, Nagpal J, Rutter GA, Rhee JS, Gottschalk A, Brose N, Schultz C, Trauner D. (2016) Photoswitchable diacylglycerols enable optical control of protein kinase C. Nature Chem. Biol. 12(9):755-762.
Konrad DB, Frank JA, Trauner D. (2016) Synthesis of redshifted azobenzene photoswitches by late-stage functionalization. Chem. Eur. J. 22(13):4364-4368.
Broichhagen J, Frank JA, Trauner D. (2015) A roadmap to success in photopharmacology. Acc. Chem. Res. 48(7):1947-1960.
Frank JA, Moroni M, Moshourab R, Sumser M, Lewin GR, Trauner D. (2015) Photoswitchable fatty acids enable optical control of TRPV1. Nature Commun. 6:7118.
Broichhagen J, Frank JA, Johnston NR, Mitchell RK, Šmid K, Marchetti P, Bugliani M, Rutter GA, Trauner D, Hodson DJ. (2015) A red-shifted photochromic sulfonylurea for the remote control of pancreatic beta cell function. Chem. Commun. 51(27):6018-6021.
Broichhagen J, Schönberger M, Cork SC, Frank JA, Marchetti P, Bugliani M, Shapiro AM, Trapp S, Rutter GA, Hodson DJ, Trauner D. (2014) Optical control of insulin release using a photoswitchable sulfonylurea. Nature Commun. 5:5116.