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Jian Hui Wu, PhD
 
Senior Investigator, Lady Davis Institute
Associate Professor, Departments of Oncology and Medicine, McGill University

Dr. Wu's Publications Indexed on PubMed
 
Dr. Wu is an Associate Professor (tenured) at McGill University and Senior Investigator at the Lady Davis Institute. His expertise involves structure-based drug design, computational biology and organic chemistry. Dr. Wu’s research focuses on: 1) structure-based identification of novel small molecules that circumvent drug resistance due to mutation in drug targets, and small molecules that modulate protein-protein interactions; and 2) the development of methods in computational biology and chemistry.

Major Research Activities

The development of novel multifunctional antiandrogens as anti-prostate agents. Current treatment for advanced prostate cancer is to suppress androgen receptor (AR) signaling by castration and antiandrogens. However, lethal castration-resistant prostate cancer arises as a result of oncogenic re-activation of the AR. Mutations in AR contribute to aberrant activation of the AR, since a subset of AR mutations have turned the action of clinically used antiandrogen from an AR antagonist into an AR agonist, and the AR mutants themselves can be activated by a series of non-androgen ligands. Dr. Wu and his team have designed and synthesized a novel antiandrogen called SC97, which remains a pure antagonist of the wild type and the clinically relevant T877A, W741C and H874Y mutated androgen receptors. Compound SC97 has two bulky side chains and is a hybrid molecule of two dietary agents. SC97 is currently under preclinical development as a novel antiandrogen for castration-resistant prostate cancer.

Computational studies of the structural and dynamic impact of drug-resistant mutations in drug targets, such as androgen receptor and EGFR, with a view to gaining insights for designing better drug candidates to overcome drug resistance. For example, based on their computational study of the T877A mutated androgen receptor, Dr Wu and his team have designed and synthesized a novel antiandrogen called SC333.

Mining traditional medicinal herbs for novel bioactive compounds as anticancer agents.

Development of the “Binding-Site Match Maker (BSMM)” software for detecting protein pairs that have different three-dimensional folding, but share similar binding sites.

Computational prediction and experimental verification of points of fragility in the signaling networks of hormone-refractory prostate cancer.

Recent Publications

Liu, B.; Geng, G.Y.; Lin, R.T.; Ren, C.Y. and Wu, J.H. Learning from estrogen receptor antagonism: Structure-based identification of novel antiandrogens effective against multiple clinically-relevant androgen receptor mutants. Chem Biol & Drug Des, 2012, 79:300-312.

Weiguo Liu, Jinming Zhou, Guoyan Geng, Qingwen Shi, Francoise Sauriol and Jian Hui Wu. Antiandrogenic, maspin induction and anti-prostate cancer activities of tanshinone IIA and its novel derivatives with modification in ring A. Journal of Medicinal Chemistry, 2012, 55:971-975.

Jeremy Hsieh, Moutih Rafei, Patrick Williams, Elena Birman, Jessica Cuerquis, Jian Hui Wu and Jacques Galipeau. Inducible IL10/IL-4 suppressor B cells inhibit CNS inflammation and T helper 17 Polarization, Molecular Therapy, in press, 2012.
Dr Wu’s research focuses on:

i) Structure-based identification of novel small molecules that circumvent drug resistance due to mutation in drug targets, and small molecules that modulate protein-protein interactions; and

ii) Development of methods in computational biology and chemistry.
 
 

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