Research groups
Colleges
Grant C Churchill
Professor of Chemical Pharmacology
- Tutor in Medicine at New College
My work focuses on understanding how small molecules inside cells act as messengers to control physiology and how mimics of these messenger molecules can be used as chemical tools and drugs.
Recently, my group used repurposing to identify ebselen as a lithium mimetic and possible safer treatment for bipolar disorder. We took ebselen from molecule, through mouse to man. We have now licensed ebselen to a biotech who are taking it into phase 2 clinical trials for efficacy in treating bipolar disorder.
In the past, we developed chemical tools and methods related to calcium signalling that provided conclusive evidence that NAADP was a second messenger. Additionally, we used shape-based virtual screening to identify the NAADP antagonist Ned-19, which has greatly facilitated studies of NAADP in intact cells and whole animals.
Currently, we are identifying new chemical tools to help unravel the calcium signalling mechanisms and in so doing identify new drug targets. We are also interested in how NAADP is made and degraded as well as its perplexing desensitization and irreversible binding.
Key publications
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A safe lithium mimetic for bipolar disorder.
Journal article
Singh N. et al, (2013), Nat Commun, 4
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Nicotinic acid adenine dinucleotide phosphate regulates skeletal muscle differentiation via action at two-pore channels.
Journal article
Aley PK. et al, (2010), Proc Natl Acad Sci U S A, 107, 19927 - 19932
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Identification of a chemical probe for NAADP by virtual screening.
Journal article
Naylor E. et al, (2009), Nat Chem Biol, 5, 220 - 226
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Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium.
Journal article
Lloyd-Evans E. et al, (2008), Nat Med, 14, 1247 - 1255
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Shape-based reprofiling of FDA-approved drugs for the H₁ histamine receptor.
Journal article
Vasudevan SR. et al, (2012), J Med Chem, 55, 7054 - 7060
Recent publications
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Increased 5-HT2Areceptor signalling efficacy differentiates serotonergic psychedelics from non-psychedelics
Preprint
Ippolito A. et al, (2024)
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Acetylation turns leucine into a drug by membrane transporter switching.
Journal article
Churchill GC. et al, (2021), Sci Rep, 11
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Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.
Journal article
Jagannath A. et al, (2021), Nat Commun, 12
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A master protocol to investigate a novel therapy acetyl-L-leucine for three ultra-rare neurodegenerative diseases: Niemann-Pick type C, the GM2 Gangliosidoses, and Ataxia Telangiectasia
Preprint
Fields T. et al, (2020)
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Acetylation of L-leucine switches its carrier from the L-amino acid transporter (LAT) to organic anion transporters (OAT)
Preprint
Churchill G. et al, (2020)