Tim Willson, Ph.D.

Research Professor

Tim Willson is chief scientist of the SGC-UNC, an open-discovery network for protein kinases based at the UNC Eshelman School of Pharmacy. He has more than 25 years of experience in pharmaceutical research with a track record in discovery of first-in-class clinical candidates. Throughout his career, Willson has been an advocate for research on pioneer drug targets. He led the Glaxo program on orphan nuclear receptors that uncovered their role in regulation of human metabolism and was co-discoverer of obeticholic acid, a breakthrough medicine for liver diseases targeting FXR. Willson has been a long time supporter of precompetitive chemistry in early drug discovery and was a scientific founder of the SGC Epigenetic Chemical Probes project. He is widely recognized for scientific leadership in chemical biology and was named one of the world’s 400 most influential biomedical researchers. Outside of science, Willson enjoys the challenge of long course triathlons and has completed six Ironman 70.3 distance races.

Description

Willson has been a long-time supporter of precompetitive chemistry as a mechanism to bring innovation to early drug discovery. His team has made potent and selective chemical probes for orphan nuclear receptors widely available in the scientific community. He was a scientific founder of the SGC Epigenetic Chemical Probes project that led to the release into the public domain of more than 30 chemical probes that specifically inhibit enzyme modifiers and protein readers of the histone tails. Willson started a program to develop chemical probes for the understudied protein kinases that has made a set of  more than 800 kinase inhibitors freely available to academic researchers. The open availability of these chemical probes has had widespread scientific impact through their use as tools to study the biology of their cognate proteins.

Citations

  1. Edwards AM, Bountra C, Kerr DJ, Willson TM. Open access chemical and clinical probes to support drug discovery. Nat Chem Biol. 2009 Jul;5(7):436-40. PubMed PMID: 19536100.
  2. Edwards AM, Isserlin R, Bader GD, Frye SV, Willson TM, Yu FH. Too many roads not taken. Nature. 2011 Feb 10;470(7333):163-5. PubMed PMID: 21307913.
  3. Knapp S, Arruda P, Blagg J, Burley S, Drewry DH, Edwards A, Fabbro D, Gillespie P, Gray NS, Kuster B, Lackey KE, Mazzafera P, Tomkinson NC, Willson TM, Workman P, Zuercher WJ. A public-private partnership to unlock the untargeted kinome. Nat Chem Biol. 2013 Jan;9(1):3-6. PubMed PMID: 23238671.
  4. Drewry DH, Willson TM, Zuercher WJ. Seeding collaborations to advance kinase science with the GSK Published Kinase Inhibitor Set (PKIS). Curr Top Med Chem. 2014;14(3):340-2. PubMed PMID: 24283969; PubMed Central PMCID: PMC4435035.

Description

Willson led a team of scientists that uncovered the role of orphan nuclear receptors in human metabolism. Two key discoveries were the role of PPARg as the receptor for the TZD diabetes drugs, and the role of bile acids as the natural hormones for FXR that led to the development of OCA as a breakthrough drug for treatment of liver disorders. The team designed a scientific methodology known as reverse endocrinology in which chemical probes are used to uncover the basic biology of their target receptor in a disease agnostic manner. This strategy has found application in many other protein families, including GPCRs, protein kinases and the epigenetic modifiers of histone tails.

Citations

  1. Kliewer SA, Lehmann JM, Willson TM. Orphan nuclear receptors: shifting endocrinology into reverse. Science. 1999 Apr 30;284(5415):757-60. PubMed PMID: 10221899.
  2. Maloney PR, Parks DJ, Haffner CD, Fivush AM, Chandra G, Plunket KD, Creech KL, Moore LB, Wilson JG, Lewis MC, Jones SA, Willson TM. Identification of a chemical tool for the orphan nuclear receptor FXR. J Med Chem. 2000 Aug 10;43(16):2971-4. PubMed PMID: 10956205.
  3. Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC, Willson TM. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5306-11. PubMed PMID: 11309497; PubMed Central PMCID: PMC33205.
  4. Pellicciari R, Fiorucci S, Camaioni E, Clerici C, Costantino G, Maloney PR, Morelli A, Parks DJ, Willson TM. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem. 2002 Aug 15;45(17):3569-72. PubMed PMID: 12166927.

Positions and Employment

1990-1991: Research Scientist, Merck Sharp $ Dohme, Harlow, UK

1991-2015: Director of Chemical Biology, GlaxoSmithKline, Research Triangle Park, NC, USA

2015: Research Professor, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Chapel Hill, NC, USA

Other Experience and Professional Memberships

1988: Member, American Chemical Society

INSTITUTION AND LOCATION DEGREE  YEAR FIELD OF STUDY
University of Leeds, Leeds, Yorkshire, UK BACHELOR OF SCIENCE      83      Chemistry
University of Southampton, Southampton, Hampshire, UK DOCTOR OF PHILOSOPHY     86     Organic Chemistry
University of Illinois at Urbana-Champaign, Champaign, IL Postdoctoral Fellow      88      Organic Chemistry