Churchill, Grant - University of Oxford - Department of Pharmacology

个人简介

I obtained a bachelor's degree in Agriculture in 1989 and a master's degree in Crop Science in 1992, both from the University of Saskatchewan. My intent was to take over the family farm in the middle of nowhere on the Canadian prairies. I fell in love with research, however, and decided to pursue it as a career (ironically, my sister and I now own and manage said family farm.) Research on structure-activity relationships for the plant hormone abscisic acid generated my interest in how chemistry can be used to probe biological function. I then switched fields and obtained a PhD in Biochemistry, Biophysics and Molecular Biology from the University of Minnesota, studying calcium regulation in the lens of the eye. I came to Oxford in 1998 for what I thought would be 5 years doing a postdoc with Professor Antony Galione, but found Oxford too beguiling to leave. During my time in Oxford I have held the Todd-Bird Junior Research Fellowship at New College, been a Fellow at St Cross College, held a Senior Research Fellowship at New College and am now Medical Tutor at New College and Associate Professor in Chemical Pharmacology in the Department of Pharmacology. When I arrived in Oxford, I thought all teaching did was take away from time for research, but Oxford has taught me that teaching and research can inform one another to great benefit. I've surprised myself and am now passionately committed to teaching with highlights that include developing a satisfyingly popular course called Chemical Pharmacology, as well as a weekly journal club for Final Honour School in Medicine and Biomedical Sciences. I am also very pleased to have received the ‘Most Acclaimed Lecturer Award’ in 2012 within the Medical Sciences Division, as decided by the Oxford University Student Union.

研究领域

I’m interested in small molecules, both endogenous ones that control cellular function and synthetic ones, as either chemical tools to explore basic biology or drugs to treat disease. My lab focuses on two areas: first, basic biology related to calcium signalling with emphasis on the messengers NAADP, cyclic ADP-ribose and inositol phosphates; second, applied research in which we exploit findings from basic biology to identify novel drug targets for which we discover and develop new drugs. In both areas, basic and applied, our approach is pragmatic and tailored to each specific problem. In regard to basic research, we delight in identifying biological questions that we can address with small molecules through techniques such as measurement, labelling, synthesis and computational chemistry. As our main goal is to learn more about basic biology, we put emphasis on tractable solutions applicable for use in intact cells, organs and even whole animals. As an example, we use chemical synthesis as well as physical and computational screening to develop chemical tools such as cell-permeant NAADP and cyclic ADP-ribose, caged NAADP, radioactive NAADP and cADPR and Ned-19. We are gratified that these chemical tools have had widespread adoption by other biologists and can be synthesized in-house or are commercially available, such as Ned-19. In collaboration with colleagues in Pharmacology who are heavy users of these chemical tools, we are attempting to exploit our 'basic' research through a start-up company, IntraBio, for diseases including neurological, inflammatory and infectious. In regard to applied research, we exploit our expertise in basic cellular signalling to identify niche areas of great opportunity, which are grossly undervalued and not being actively pursued by industry. An example of this approach is our project on inhibitors of the enzyme inositol monophosphatase, the possible target of lithium in the treatment of bipolar disorder. Lithium is the current gold standard but is limited by toxicity and side effects. As virtual screening for a 'lithium mimetic' yielded only weak inhibitors, we tried a different approach in which marketed drugs (repurposing) or clinical candidates (rescuing) are physically screened. We found that the shelved drug ebselen inhibited the enzyme and had lithium-like effects in animals. Through a collaboration with Professor Phil Cowen, a clinician in the Department of Psychiatry, we have completed several studies in healthy volunteers. Our results show sufficient promise that ebselen is being taken into a phase 2 clinical trails for efficacy in bipolar disorder through a licensing deal with the biotech Sound Pharmaceuticals.

近期论文

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Masaki, C, Sharpley, AL, Godlewska, BR, Berrington, A, Hashimoto, T, Singh, N, Vasudevan, SR, Emir, UE, Churchill, GC, and Cowen, PJ (2016) Effects of the potential lithium-mimetic, ebselen, on brain neurochemistry: a magnetic resonance spectroscopy study at 7 tesla. Singh, N, Sharpley, AL, Emir, UE, Masaki, C, Herzallah, MM, Gluck, MA, Sharp, T, Harmer, CJ, Vasudevan, SR, Cowen, PJ, and Churchill, GC (2016) Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans. Vasudevan, SR, Singh, N, and Churchill, GC (2014) Scaffold hopping with virtual screening from IP3 to a drug-like partial agonist of the inositol trisphosphate receptor. Singh, N, Halliday, AC, Thomas, JM, Kuznetsova, OV, Baldwin, R, Woon, ECY, Aley, PK, Antoniadou, I, Sharp, T, Vasudevan, SR, and Churchill, GC (2013) A safe lithium mimetic for bipolar disorder. Jagannath, A, Butler, R, Godinho, SIH, Couch, Y, Brown, LA, Vasudevan, SR, Flanagan, KC, Anthony, D, Churchill, GC, Wood, MJA, Steiner, G, Ebeling, M, Hossbach, M, Wettstein, JG, Duffield, GE, Gatti, S, Hankins, MW, Foster, RG, and Peirson, SN (2013) The CRTC1-SIK1 pathway regulates entrainment of the circadian clock. Vasudevan, SR, Moore, JB, Schymura, Y, and Churchill, GC (2012) Shape-based reprofiling of FDA-approved drugs for the H(1) histamine receptor. Aley, PK, Mikolajczyk, AM, Munz, B, Churchill, GC, Galione, A, and Berger, F (2010) Nicotinic acid adenine dinucleotide phosphate regulates skeletal muscle differentiation via action at two-pore channels. Naylor, E, Arredouani, A, Vasudevan, SR, Lewis, AM, Parkesh, R, Mizote, A, Rosen, D, Thomas, JM, Izumi, M, Ganesan, A, Galione, A, and Churchill, GC (2009) Identification of a chemical probe for NAADP by virtual screening. Lloyd-Evans, E, Morgan, AJ, He, X, Smith, DA, Elliot-Smith, E, Sillence, DJ, Churchill, GC, Schuchman, EH, Galione, A, and Platt, FM (2008) Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium.