Vollum Fellow and Research Assistant Professor, Vollum Institute
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. Frank 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.
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.
♦ Top three important research papers
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. (*contributed equally to this work)
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. (*contributed equally to this work)
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.