譚建業教授

Education
PhD	University of Oxford (1996)
MPhil	Hong Kong Polytechnic University (1992)
BSc	Hong Kong Baptist College (1990)

Positions
2013 – Present	Associate Professor, Faculty of Health Sciences, University of Macau
2011 – 2012	DMPK Design Leader, AstraZeneca
2004 – 2011	Associate Principal Scientist, AstraZeneca
2001 – 2004	Senior Scientist, AstraZenenca
1996 – 2001	Research Chemist, Sirius Analytical Ltd.

Research Interests
Development of small molecule inhibitors targeting cancer metabolism and Alzheimer’s disease Pharmacokinetic and chemical optimizations of drug candidates High throughput compound profiling for supporting drug discovery

Representative Publications
Zhang, Q. Y., Zhou, W., Yu, S., Ju, Y., To, S. K. Y., Wong, A. S. T., Jiao, Y. F., Poon, T., Tam, K. Y., and Lee, L. (2020) Metabolic Reprogramming of Ovarian Cancer Involves ACSL1-mediated Metastasis Stimulation through Upregulated Protein Myristoylation. Oncogene Ju, Y. J., and Tam, K. Y. (2020) 9r, the Cholinesterase and Amyloid Beta Aggregation Dual Inhibitor, as a Multifunctional Agent to Improve Cognitive Deficit and Neuropathology in the Triple-Transgenic Alzheimer’s Disease Mouse Model. Neuropharmacology, 108354 Ju, Y. J., Chakravarty, H., and Tam, K. Y. (2020) An Isoquinolinium Dual Inhibitor of Cholinesterases and Amyloid Beta Aggregation Mitigates Neuropathological Changes in a Triple-Transgenic Mouse Model of Alzheimer’s Disease. Acs Chem Neurosci 11 (20), 3346-3357 Xiang, S. C., Huang, D., He, Q. L., Li, J., Tam, K. Y., Zhang, S. L., and He, Y. (2020) Development of Dual Inhibitors Targeting Pyruvate Dehydrogenase Kinases and Human Lactate Dehydrogenase A: High-Throughput Virtual Screening, Synthesis and Biological Validation. Eur J Med Chem 203, 112579 Chakravarty, H., Ju, Y. J., Chen, W. H., and Tam, K. Y. (2019) Dual Targeting of Cholinesterase and Amyloid Beta with Pyridinium/Isoquinolium Derivatives. Drug Dev Res 81 (2), 1–14 Yang, Z., Chan, K. I., Kwok, H. F., and Tam, K. Y. (2019) Novel Therapeutic Anti-ADAM17 Antibody A9(B8) Enhances EGFR-Tki-Mediated Anticancer Activity in NSCLC. Transl Oncol 12 (11), 1516-1524 Verma, A., Lam, Y. M., Leung, Y. C., Hu, X., Chen, X., Cheung, E., and Tam, K. Y. (2018) Combined Use of Arginase and Dichloroacetate Exhibits Anti-Proliferative Effects in Triple Negative Breast Cancer Cells. J Pharm Pharmacol 71 (3), 306-315 Zhang, W., Hu, X. H., Chakravarty, H., Yang, Z., and Tam, K. Y. (2018) Identification of Novel Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors by Kinase Activity-Based High Throughput Screening for Anticancer Therapeutics. Acs Comb Sci 20 (11), 660-671 Wu, X. L., Kosaraju, J., and Tam, K. Y. (2018) Anti-Neuroinflammatory Effects of SLOH in Abeta-Induced BV-2 Microglial Cells and 3xTg-AD Mice Involve the Inhibition of GSK-3beta. Neurosci Lett 687, 207-215 Zhang, S. L., Yang, Z., Hu, X. H., and Tam, K. Y. (2018) Dichloroacetophenones Targeting at Pyruvate Dehydrogenase Kinase 1 with Improved Selectivity and Antiproliferative Activity: Synthesis and Structure-Activity Relationships. Bioorg Med Chem Lett 28 (21), 3441-3445 Yang, Z., Zhang, S. L., Hu, X. H., and Tam, K. Y. (2018) Inhibition of Pyruvate Dehydrogenase Kinase 1 Enhances the Anti-Cancer Effect of EGFR Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer. Eur J Pharmacol 838, 41-52 Zhang, W., Hu, X., Zhou, W., and Tam, K. Y. (2018) Liquid Chromatography-Tandem Mass Spectrometry Method Revealed That Lung Cancer Cells Exhibited Distinct Metabolite Profiles Upon the Treatment with Different Pyruvate Dehydrogenase Kinase Inhibitors. J Proteome Res 17 (9), 3012-3021 Zhang, S. L., Yang, Z., Hu, X., Chakravarty, H., and Tam, K. Y. (2018) Anticancer Effects of Some Novel Dichloroacetophenones through the Inhibition of Pyruvate Dehydrogenase Kinase 1. Eur J Pharm Sci 123, 43-55 Zhang, S. L., He, Y., and Tam, K. Y. (2018) Targeting Cancer Metabolism to Develop Human Lactate Dehydrogenase (hLDH)5 Inhibitors. Drug Discov Today 23 (7), 1407-1415 Yang, Z., and Tam, K. Y. (2018) Combination Strategies Using EGFR-TKi in NSCLC Therapy: Learning from the Gap between Pre-Clinical Results and Clinical Outcomes. Int J Biol Sci 14 (2), 204-216 Wu, X. L., Kosaraju, J., Zhou, W., and Tam, K. Y. (2018) SLOH, a Carbazole-Based Fluorophore, Mitigates Neuropathology and Behavioral Impairment in the Triple-Transgenic Mouse Model of Alzheimer’s Disease. Neuropharmacology 131, 351-363 Zhou, W., Hu, X. H., and Tam, K. Y. (2017) Systemic Clearance and Brain Distribution of Carbazole-Based Cyanine Compounds as Alzheimer’s Disease Drug Candidates. Sci Rep-Uk 7 (1), 16368 Kosaraju, J., Holsinger, D., Guo, L. X., and Tam, K. Y. (2017) Linagliptin, a Dipeptidyl Peptidase-4 Inhibitor, Mitigates Cognitive Deficits and Pathology in the 3xTg-AD Mouse Model of Alzheimer’s Disease. Mol Neurobiol 54 (8), 6074-6084 Yang, Z., Hu, X. H., Zhang, S. L., Zhang, W., and Tam, K. Y. (2017) Pharmacological Synergism of 2,2-Dichloroacetophenone and EGFR-TKi to Overcome TKi-Induced Resistance in NSCLC Cells. Eur J Pharmacol 815, 80-87 Zhang, W., Zhang, S. L., Hu, X. H., and Tam, K. Y. (2017) Phenyl Butyrate Inhibits Pyruvate Dehydrogenase Kinase 1 and Contributes to Its Anti-Cancer Effect. Eur J Pharm Sci 110, 93-100 Wu, X. L., Kosaraju, J., and Tam, K. Y. (2017) Slm, a Novel Carbazole-Based Fluorophore Attenuates Okadaic Acid-Induced Tau Hyperphosphorylation via Down-Regulating GSK-3beta Activity in Sh-Sy5y Cells. Eur J Pharm Sci 110, 101-108 Zhang, S. L., Zhang, W., Yang, Z., Hu, X. H., and Tam, K. Y. (2017) Synthesis and Biological Evaluation of (R)-3,3,3-Trifluoro-2-Hydroxy-2-Methylpropionamides as Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors to Reduce the Growth of Cancer Cells. Eur J Pharm Sci 110, 87-92 Wu, X. L., Kosaraju, J., Zhou, W., and Tam, K. Y. (2017) Neuroprotective Effect of Slm, a Novel Carbazole-Based Fluorophore, on Sh-Sy5y Cell Model and 3xTg-AD Mouse Model of Alzheimer’s Disease. Acs Chem Neurosci 8 (3), 676-685 Yang, Z., and Tam, K. Y. (2016) Anti-Cancer Synergy of Dichloroacetate and EGFR Tyrosine Kinase Inhibitors in NSCLC Cell Lines. Eur J Pharmacol 789, 458-467 Zhang, S. L., Zhang, W., Xiao, Q. P., Yang, Z., Hu, X. H., Wei, Z. Y., and Tam, K. Y. (2016) Development of Dichloroacetamide Pyrimidines as Pyruvate Dehydrogenase Kinase Inhibitors to Reduce Cancer Cell Growth: Synthesis and Biological Evaluation. Rsc Adv 6 (82), 78762-78767 Zhang, S. L., Hu, X. H., Zhang, W., and Tam, K. Y. (2016) Unexpected Discovery of Dichloroacetate Derived Adenosine Triphosphate Competitors Targeting Pyruvate Dehydrogenase Kinase to Inhibit Cancer Proliferation. J Med Chem 59 (7), 3562-3568 Zhou, W., Wu, X. L., Li, J., Hu, X. H., and Tam, K. Y. (2016) Quantification of Permanent Positively Charged Compounds in Plasma Using One-Step Dilution to Reduce Matrix Effect in Ms. Bioanalysis 8 (6), 497-509 Zhang, W., Zhang, S. L., Hu, X. H., and Tam, K. Y. (2015) Targeting Tumor Metabolism for Cancer Treatment: is Pyruvate Dehydrogenase Kinases (Pdks) a Viable Anticancer Target? Int J Biol Sci 11 (12), 1390 Zhang, S. L., Hu, X. H., Zhang, W., Yao, H. K., and Tam, K. Y. (2015) Development of Pyruvate Dehydrogenase Kinase Inhibitors in Medicinal Chemistry with Particular Emphasis as Anticancer Agents. Drug Discov Today 20 (9), 1112-1119 Zhang, S. L., Yao, H. K., Wang, C. Y., and Tam, K. Y. (2014) Study the Interactions between Human Serum Albumin and Two Antifungal Drugs: Fluconazole and Its Analogue DTP. Bioorg Med Chem Lett 24 (21), 4963-4968
Full Publications List

Research Grants
2020 – 2022	Development of anticancer dichloroacetophenones through the inhibition of pyruvate dehydrogenase kinase 1, MOP 749,500
2018 – 2021	Development of metabolic inhibitor for the treatment of non-small-cell lung carcinoma, MOP 1,460,000
2017 – 2020	Novel Multi-targeting compounds for the treatment of Alzheimer´s disease, MOP 540,000
2015 – 2018	Combination treatment with arginine depleting enzyme and metabolic inhibitor in preclinical cancer models, MOP 1,500,000
2014 – 2017	Preclinical optimization of Aβ peptides aggregation inhibitors as potential drug candidates for the treatment of Alzheimer’s disease, MOP 1,456,000
2013 – 2015	A study of the interactions between vancomycin, nafcillin and biomimetic artificial membranes, MOP 125,000

Patents
S.C. Tsang, K.Y. Tam, X. Gao, “Composite Nanoparticles”, PCT WO2005007284, 27th Jan 2005.

Awards
2009	AstraZeneca Regional Innovation Award
2008	AstraZeneca Publication Award

Professional Recognition
2013	Editor-in-chief, ADMET & DMPK (Scopus and ESCI indexed open access journal)
2009	AstraZeneca Regional Innovation Award (for the contribution to a discovery project using a pro-drug delivery approach)
2008	AstraZeneca Publication Award (Cancer and Infection Chemistry)
2004	Fellow of the Royal Society of Chemistry, UK
1999	Chartered Chemist and member of the Royal Society of Chemistry, UK