S4, Level 3, Faculty of Science (Pharmacy), National University of Singapore
To build a unique, interesting and important research program through a creative combination and transformation of the science that drives cancer biology and toxicology. While so doing, we should always put into perspective, two groups of people: the very needs of the ones whom this work should benefit, and continuously inspire the like-minded ones to carry this dream further and brighter than when it first started.
The overall goal of the lab is to improve the management of liver disorders such as liver cancer and drug-induced liver disease (DILI) through understanding the molecular mechanisms leading to their development and progression. This effort is supported by the use of both in vitro and vivo experimental techniques to characterize molecular signatures unique to the condition and thereby identify new means for disease intervention.
(1) Liver cancer and liver fibrosis
Our group focuses on the characterization of mutations and expression profile of various tyrosine kinases in order to establish their roles in cancer and pre-neoplastic events like fibrosis. Specifically, we are interested in identifying potential tyrosine kinases that might contribute to the pathology of liver diseases. Notable kinases are being evaluated for their suitability as drug targets for chemotherapeutic development. The techniques we employ include but are not limited to high-throughput sequencing, mutation analysis, immunoassays and other biochemical assay development. We perform target characterization on a subset of these targets to better understand the biochemical basis for their effects on host cells. Besides these, we engage in preclinical work through extensive collaborations with clinicians who provide us with clinical samples so that we can correlate our in vitro findings with patient information, in order to determine the clinical relevance of our work. At the same time, we also screen new chemical entities for their anti-tumor potential against liver cancer. Compounds showing relatively good effect in liver cancer cell lines will be chemically optimized through an iterative process to improve on its efficacy.
(2) Drug induced liver injury
A second research emphasis looks at the mechanism and manifestation of drug-induced liver toxicities. Work includes mechanistic studies on drug distribution and metabolism, and the consequential generation and accumulation of toxic metabolites. Collective information of chemically similar compounds are applied for structural toxicity relationship studies. In addition, we explore potential hepatoprotective and cell regenerative approaches as therapeutic options to prevent and to circumvent liver injury.
(3) Toxicological screening platforms
A research cum service arm of my work involves early toxicological screening of drug candidates. I run a testing service as part of the Drug Development Unit in NUS for in-house lead discoveries. As part of this effort, we also emphasize on capability development through optimizing in vitro and in vivo platforms and new biomarkers for toxicity.
Dr. Han Kiat Ho is an associate professor (from July 2015) at the Department of Pharmacy, National University of Singapore (NUS). He received his Bachelor of Science (Pharmacy) with First Class Honors from NUS in 2000, having also won the Lee Kuan Yew Gold Medal and Chalmers Medal in 1999 as one of the top and most proficient graduate of the programme. In 2000, he received the inaugural EDB overseas postgraduate scholarship in life sciences, and was subsequently inducted into A*STAR as the pioneer batch of overseas PhD scholars. With this award, he obtained his PhD in Medicinal Chemistry from the University of Washington in 2005, investigating the molecular mechanisms of specific drug-induced liver toxicity (under the mentorship of Prof Sid Nelson). After which he returned to Singapore for a 3-year post-doctoral fellowship with Prof Axel Ullrich, investigating the roles of tyrosine kinases in various malignancies.
In July 2009, he started his assistant professorship at NUS, and began building his own research program focusing on drug-induced liver toxicity, as well as exploring new drug targets for liver cancer. He also directs a toxicology division within a newly founded Drug Development Unit in NUS and is a young member of the NGS program. He has published more than 55 papers in internationally recognized journals, and has won multiple teaching excellence awards, culminating with the Honour Roll placements at both Faculty and University level in 2013/2014. In 2014, he was appointed a fellow of the prestigious NUS Teaching Academy for a 3-year term.
|Tee Jie Kai
|Tan Yeong Lan
|David Packiaraj Sheela
|Yeo Hui Ling Angie
Final Year Project Students
Ng Wen Wei
Teo Wen Ya
Leong Wei Qi
Ho Lih Maan
Clivia Yap Yao Hua (Co-supervisor)
Chua Pei Siang (Co-supervisor)
PhD Alumni (as supervisor)
|Phua Lee Cheng (2009-2013)|
|Pang Yi Yun (2010-2014)|
|Tan Cheau Yih (2010-2014)|
|Zhao Chun Yan (2011-2015)|
|Mahnaz Darvish Damavandi (2014-2015)|
|Duan Yan (2009-2011)|
|Carrie Soh (2014-2016)|
|Doreen Tan Su Yin (2010-2012)|
|Grace Chang (2012-2014)|
Final Year Project (FYP) Alumni
|Lim Kah Suan (2007/08)||Loh Kep Yong (2012)|
|Poh Weijie (2008/09)||Hazel Chia (2012/13)|
|Oh Jing Wen (2008/09)||Vivien Tham (2012/13)|
|Lee Chern Yih (2009/10)||Wee Hui Ling (2012/13)|
|Vivian Teo (2009/10)||Loh Shi Yeng (2013/14)|
|Joanne Sng (2009/10)||Lim Leng Joon (2013/14)|
|Debra Chan (2010/11)||Jessie Teo (2014/15)|
|Tan An Gie (2010/11)||Tan Yeong Lan (2014/15)|
|Edwin Tan (2010/11)||Tan Yan Zhi (2014/15)|
|Gavin Cheah (2011/12)||Toh Yi Long (2015/16)|
|Jonathan Goh (2011/12)||Eng Mei Chen, Noelle (2015/16)|
|Ng Hui Wen (2011/12)||Natalia Veronica (2015/16)|
UROPS (Undergraduate research project) Alumni
|Ng Kwee Haan (2011/12)|
|Ng Yisi (2012/13)|
|Jenny Levine, Univ of North Carolina (2011)|
|Sonja Chua (2013)|
|Arezou Ghorreshi, Univ Paris Descartes (2014)|
|Xie Jiarong (2015)|
|Alina Yu, Univ of Toronto (2015)|
|Sasanan Trakansuebkul, Kings College London (2016)|
Research Team Member Alumni
|Winnie Wong (2007-2012)|
|Teo Yi Ling (2011)|
|Chew Yun Shan (2011-2012)|
|Angie Yeo (2011-)|
|Ho Jia Pei (2012-13)|
- Wee HL, Ho HK, Li SC. Singapore Med J, 43, 128-34 (2002). Public awareness of diabetes mellitus in Singapore.
- Ho HK, Hu ZH, Tzung SP, Hockenbery DM, Fausto N, Nelson SD, Bruschi, SA. Biochemical Pharmacology, 69, 147-157 (2005). BCL-xL overexpression effectively protects against tetrafluoroethylcysteine-induced intramitochondrial damage and cell death.
- Ho HK, White CC, Fernandez C, Kavanagh TJ, Fausto N, Nelson SD, Bruschi SA. Toxicological Sciences, 86, 354-364 (2005). Nrf2 activation involves an oxidative-stress independent pathway in tetrafluoroethylcysteine-induced cytotoxicity.
- Ho HK, Jia YK, Coe KJ, Gao Q, Doneanu CE, Hu ZH, Bammler TK, Beyer RP, Fausto N, Bruschi SA, Nelson SD. Biochemical Pharmacology, 72, 80-90 (2006). Cytosolic heat shock proteins and heme oxygenase-1 are preferentially induced in response to specific and localized intramitochondrial damage by tetrafluoroethylcysteine.
- Boelsterli UA, Ho HK, Zhou SF, Leow KY. Current Drug Metabolism, 7, 715-727 (2006). Bioactivation and hepatotoxicity of nitroaromatic drugs.
- Coe, KJ, Jia Y, Ho HK, Rademacher P, Bammler TK, Beyer RP, Farin FM, Woodke L, Plymate SR, Fausto N, Nelson SD. Chem Res Tox, 20, 1277-1290 (2007). Comparison of the cytotoxicity of the nitroaromatic drug flutamide to its cyano analog in the hepatocyte cell line TAMH: Evidence for complex I inhibition and mitochondrial dysfunction using toxicogenomic screening.
- Ruhe JE, Streit SS, Hart S, Wong CH, Specht K, Knyazev P, Knyazeva K, Tay LS, Loo HL, Foo P, Wong W, Pok S, Lim SJ, Ong HM, Luo M, Ho HK, Peng K, Lee TC, Bezler M, Mann C, Gaertner S, Hoefler H, Iacobelli S, Peter S, Tay A, Brenner S, Venkatesh B, Ullrich A. Cancer Res, 67, 11368-11376 (2007). Genetic alterations in the tyrosine kinase transcriptome of human cancer cell lines.
- Ho HK , Pok S, Streit SS, Ruhe JE, Hart S, Loo HL, Lim KS, Aung MO, Lim SG, Ullrich A. J Hepatology, 50, 118-127 (2009). FGFR4 Regulates Proliferation, Anti-apoptosis and Alpha-fetoprotein Secretion During Hepatocellular Carcinoma Progression and Represents a Potential Target for Therapeutic Intervention.
- Saha S, New LS, Ho HK, Chui WK, Chan ECY. Tox Letters, 192, 141-149 (2010). Investigation of the role of thiazolidinedinone ring of troglitazone in inducing hepatotoxicity.
- Roidl A, Foo P, Mann C, Bechtold S, Berger HJ, Streit S, Ruhe JE, Hart S, Ullrich A, Ho HK. Oncogene, 29, 1543-1552 (2010). The FGFR4 Y367C Mutant is a Dominant Oncogene in MDA-MD453 Breast Cancer Cells.
- Saha S, New LS, Ho HK, Chui WK, Chan ECY. Tox Letters, 195(2-3), 135-141 (2010). Direct toxicity effects of sulfo-conjugated troglitazone on human hepatocytes.
- Teng WC, Oh JW, New LS, Wahlin MD, Nelson SD, Ho HK and Chan CYE. Mol Pharmacol, 78, 693-703 (2010). Mechanism-based inactivation of Cytochrome P450 3A4 by lapatinib.
- Nayak T, Li J, Phua LC, Ho HK, Ren Y, Pastorin G. ACS Nano, 4(12), 7717-25 (2010). Thin films of functionalized multi-walled carbon nanotubes as suitable scaffold materials for stem cells proliferation and bone formation.
- Chan CY, New LS, Ho HK, Chan EC. Tox Letters, 206(3), 314-24 (2011). Reversible time-dependent inhibition of CYP450 enzymes by duloxetine and the inertness of its thiophen ring towards bioactivation.
- Teo YL, Saetaew M, Chanthawong S, Yap YS, Chan EC, HO HK, Chan A. Breast Cancer Res Treat, 133(2), 703-711 (2012). Effect of CYP3A4 inducer dexamethasone on hepatotoxicity of lapatinib: clinical and in vitro evidence.
- Poh W, Wong W, Ong H, Aung MO, Lim SG, Chua BT, Ho HK. Mol Cancer, 11:14 (2012). Klotho-beta overexpression as a novel target for suppressing proliferation and fibroblast growth factor receptor-4 signaling in hepatocellular carcinoma.
- Chan EC, New LS, Chua TB, Yap CW, Ho HK, Nelson SD. Drug Metab Disp, 40(7), 1414-1422 (2012). Interaction of lapatinib with cytochrome P450 3A5.
- Tian Q, Wong W, Xu Y, Chan Y, Ho HK, Pastorin G, Ang WH. Chem Comm, 48(44), 5467-5469 (2012). Immobilisation of quantum dots by bio-orthogonal PCR amplification and labeling for direct gene detection and quantification.
- Chng HT, Ho HK, Yap CW, Lam SH, Chan EC. J Biomol Screen, 17(7), 974-986 (2012). An investigation of the bioactivation potential and metabolism profile of zebrafish versus human.
- Saha S, Chan DS, Lee CY, Wong W, Yap CW, Chui WK, Chan EC, Ho HK. Eur J Pharmacol 697(1-3), 13-23 (2012). Pyrrolidinediones reduce the toxicity of thiazolidinediones and modify their anti-diabetic and anti-cancer properties.
- Chan A, Ho HK, Cheung YT, Teo YL. Adv Pharmacoepidem Drug Safety, 1:5 (2012). Supportive care in cancer patients: Current challenges and opportunities.
- Zhao C, Tan A, Pastorin G, Ho HK. Biotech Adv, 31(5), 654-68 (2013). Nanomaterial scaffolds for stem cell differentiation and proliferation in tissue engineering.
- Teo YL, Ho HK, Chan A. Cancer Treat Rev 39(2), 199-206 (2013). Risk of tyrosine kinase inhibitors-induced hepatotoxicity in cancer patients: A meta-analysis.
- Phua LC, Mal M, Koh PK, Cheah PY, Chan EC, Ho HK. Cancer Chemother Pharmacol 71(3):817-823 (2013). Investigating the role of nucleoside transporters in the resistance of colorectal cancer to 5-fluorouracil therapy.
- Ho HK, Németh G, Ng YR, Pang E, Szántai-Kis C, Zsákai L, Breza N, Greff Z, Horváth Z; Pató J, Szabadkai I, Szokol B, Baska F, Őrfi L, Ullrich A, Kéri G, and Chua BT. Curr Med Chem, 20:1203-17 (2013). Developing FGFR4 inhibitors as potential anti-cancer agents via in silico design, supported by in vitro and cell-based testing.
- Wong BS, Yoong SL, Jagusiak A, Panczyk T, Ho HK, Ang WH, Pastorin, G. Adv Drug Delivery Rev. 65(15): 1964-2015 (2013). Carbon nanotubes for delivery of small molecule drugs.
- Phua LC, Koh PK, Cheah PY, Ho HK, Chan ECY. J Chromatography B. 15(937):103-113 (2013). Global gas chromatography/time-of-flight mass spectrometry (GC/TOFMS)-based metabonomic profiling of lyophilized human feces.
- Cheung YT, Lim SR, Ho HK, Chan A. Plos One 8(12):e81234 (2013). Cytokines as mediators of chemotherapy-associated cognitive changes: Current evidence, limitations and directions for future research.
- Ho HK, Yeo AHL, Kang TS, Chua BT. Drug Discover Today, 19:51-62 (2014). Current strategies in inhibiting FGFR activities for clinical applications: Opportunities, challenges and toxicological considerations.
- Ng T, Cheung YT, Ng QS, Ho HK, Chan A. Expert Opin Drug Safety, 13:83-92 (2014). Vascular endothelial growth factor inhibitors and cognitive impairment: evidence and controversies.
- Yoong SL, Wong BS, Zhou QL, Chin CF, Li J, Venkatesan T, Ho HK, Yu V, Ang WH, Pastorin, G. Biomaterials 35(2): 748-759 (2014). Enhanced cytotoxicity to cancer cells by mitochondria-targeting MWCNTs containing platinum(IV) prodrug of cisplatin.
- Teo YL Chong XJ, Chue XP, Chau NM, Tan MH, Kanesvaran R, Wee HL, Ho HK, Chan A. Cancer Chemo Pharmacol 73:381-388 (2014). Role of sunitinib and SU12662 on dermatological toxicities in metastatic renal cell carcinoma patients: in vitro, in vivo and outcomes investigation.
- Tan DSY, Yeo AHL, Ho HK, Wee HL, Ong HY. Asian Study of CLOPidogrel (ASCLOP) Responsiveness: Int J Cardiol 171:e21-23 (2014). The contributions of genetic and non-genetic factors.
- Phua LC, Chue XP, Koh PK, Cheah PY, Ho HK, Chan ECY. Cancer Biol Ther 15:1-9 (2014). Non-invasive fecal metabonomic detection of colorectal cancer.
- See M, Shih V, Ho HK, Tang T, Farid M, Quek R, Tao M,Lim ST, Chan A. Proceedings of Singapore Healthcare, 23:13-20 (2014). A Pilot Study to Evaluate the Role of Therapeutic Drug Monitoring of Pegfilgrastim in Lymphoma Patients Receiving Chemotherapy.
- Phua LC, Chue XP, Koh PK, Cheah PY, Chan ECY, Ho HK. Oncology Reports, 32:97-104 (2014). Global fecal microRNA profiling in the identification of biomarkers for colorectal cancer screening among Asians.
- Ho HK, Chua BT, Wong W, Lim KS, Teo V, Ong HT, Chen X, Zhang W, Hui KM, Go ML, Ullrich A. Mol Oncol, 8(7):1266-77 (2014). Benzylidene-indolinones are Effective as Multi-targeted Kinase Inhibitor Therapeutics Against Hepatocellular Carcinoma.
- Tan CY, Lai RC, Wong W, Dan YY, Lim SK, Ho HK. Stem Cell Res Ther, 5(3): 76 (2014). Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models.
- Pang YY, Yeo WK, Loh KY, Go ML, Ho HK. Food Chem Tox, 71:207-216 (2014). Structure-toxicity relationship and structure-activity relationship study of 2-phenylaminophenylacetic acid derived compounds.
- Phua LC, Ng HW, Yeo AHL, Chen E, Lo MSM, Cheah PY, Chan ECY, Koh PK, Ho HK. Oncol Lett 10:2519-2526 (2015) Prevalence of KRAS, BRAF, PI3K, EGFR mutations among Asian metastatic colorectal cancer patients.
- Teo YL, Ho HK, Chan A. Brit J Clin Pharmacol 79:241-253 (2015). Metaboilsm-related pharmacokinetic drug-drug interactions in tyrosine kinase inhibitors: current understanding, challenges and recommendations.
- Teo YL, Ho HK, Chan A. Expert Opin Drug Metab Toxicol 11:231-242 (2015). Formation of reactive metabolites and management of tyrosine kinase inhibitor-induced hepatotoxicity: a literature review.
- Ng T, Chan M, Khor CC, Ho HK, Chan A. Cancer Treat Rev 40(10):1199-1214 (2014). The genetic variants underlying breast cancer treatment-induced chronic and late toxicities: A systematic review.
- Teo YL, Chue XP, Chau NM, Tan MH, Kanesvaran R, Wee HL, Ho HK, Chan A. Target Oncol 10(3):429-437 (2014). Association of drug exposure with toxicity and clinical response in metastatic renal cell carcinoma patients receiving an attenuated dose regimen of sunitinib.
- Tan CY, Saw TY, Fong CW, Ho HK. Redox Biol 4:308-320 (2015). Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury.
- Ho HK, Chan JC, Hardy KD, Chan EC. Drug Metab Rev 47(1):21-8 (2015). Mechanism-based inactivation of CYP450 enzymes: a case study of lapatinib.
- Huleatt PB, Khoo ML, Chua YY, Tan TW, Liew RS, Balogh B, Deme R, Goloncser F, Magyar K, Sheela DP, Ho HK, Sperlagh B, Matyus P, Chai CL. J Med Chem 58:1400-1419 (2015). Novel arylalkenylpropargylamines as neuroprotective, potent, and selective monoamine oxidase B inhibitors for the treatment of Parkinson’s disease.
- Patel DN, Ho HK, Tan LL, Tan MM, Zhang Q, Low MY, Chan CL, Koh HL. Front Pharmacol 6:25 (2015). Hepatotoxic potential of asarones: in vitro evaluation of hepatotoxicity and quantitative determination in herbal products.
- Teo YL, Wee HL, Chue XP, Chau NM, Tan MH, Kanesvaran R, Wee HL, Ho HK, Chan A. Pharmacogenomics J 16:47-53 (2016). Effect of the CYP3A5 and ABCB1 genotype on exposure, clinical response, and manifestation of toxicities from sunitinib in Asian patients.
- Cheung YT, Ng T, Shwe M, Ho HK, Foo KM, Cham MT, Lee JA, Fan G, Tan YP, Yong WS, Madhukumar P, Loo SK, Ang SF, Wong M, Chay WY, Ooi WS, Dent RA, Yap YS, Ng R, Chan A. Ann Oncol. 26:1446-51 (2015). Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.
- Yoong SL, Lau WL, Liu AY, Prendergast D, Ho HK, YU VC, Lee C, Ang WH, Pastorin G. Nanoscale. 7(33):13907-17 (2015). Mitochondria-acting hexokinase II peptides carried by short-length carbon nanotubes with increased cellular uptake, endosomal evasion and enhanced bioactivity against cancer cells.
- Ng T, Teo SM, Yeo HL, Shwe M, Gan YX, Cheung YT, Foo KM, Cham MT, Lee JA, Tan YP, Fan G, Yong WS, Preetha M, Loh WK, Koo SL, Jain A, Lee GE, Wong M, Dent R, Yap YS, Ng R, Khorr CC, Ho HK, Chan A. Neuro Oncol 18:244-251 (2016). BDNF genetic polymorphism (rs6265) is protective against chemotherapy-associated cognitive impairment in patients with early stage breast cancer.
- Tee JK, Ong CN, Bay BH, Ho HK, Leong DT. Wiley Interdiscip Rev Nanomed Nanobiotech 8:414-438 (2016). Oxidative stress by inorganic nanoparticles.
- Bi X, Adriani G, Xu Y, Chakrabotty S., Pastorin G, Ho HK, Ang WH, Chan Y. Anal Chem 87(20):10292-8 (2015). Gene detection in complex biological media using semiconductor nanorods within an integrated microfluidic device.
- Tan SQ, Lee YY, Packiaraj DS, Ho HK, Chai CL. Chem Res Toxicol 28(10):2019-33 (2015). Systematic evaluation of the metabolism and toxicity of thiazolidinone and imidazolidinone heterocycles.
- Zhao C, Andersen H, Ozyilmaz B, Pastorin G, Ho HK. Nanoscale 7(43):18239-49 (2015). Spontaneous and specific myogenic differentiation of human mesenchymal stem cells on polyethylene glycol-linked multi-walled carbon nanotube films for skeletal muscle engineering.
- Ngai MH, So CL, Sullivan M, Ho HK, Chai CL. Chem Med Chem 11:72-80 (2016). Photo-induced isomerisation and hepatoxicities of semaxanib, sunitinib and related 3-substituted indolin-2-ones.
- Duan Y, Wong W, Chua SC, Wee HL, Lim SG, Chua BT, Ho HK. Int J Oncol 48:358-366 (2016). Overexpression of Tyro3 and its implications on hepatocellular carcinoma progression.
- Chia HY, Yau WP, Ho HK. Biopharm Drug Dispos 37:168-181 (2016). Establishing population distribution of drug-metabolizing enzymes activities for the use of salivary caffeine as a dynamic liver function marker in a Singaporean Chinese population.
- Pang YY, Tan YM, Chan, ECY, Ho HK. Chem Res Toxicol 29:1118-31 (2016). Phase I metabolic stability and electrophilic reactivity of 2-phenylaminophenylacetic acid derived compounds.
- Chae JW, Teo YL, Ho HK, Lee JY, Back HM, Yun HY, Karlsson MO, Kwon KL, Chan A. Cancer Chemo Pharmacol. 78(3) 623-632 (2016). BSA and ABCB1 polymorphism affect the pharmacokinetics of sunitinib and its active metabolite in Asian mRCC patients receiving an attenuated sunitinib dosing regimen.
- Darvish M, Ho HK, Kang TS. Mol Genetics Metab Rep. 8:51-60 (2016). Towards the development of an enzyme replacement therapy for the metabolic disorder propionic academia.
- Chan ECY, Ho HK. Technology in Education, online (2011). Investigation of online computer-based formative assessment and traditional closed-book paper-based assessment in pharmacy undergraduate teaching.
- Ho HK. Asian Journal for the Scholarship of Teaching and Learning (2016). Exploring the etiology of for grade moderation: Is there a place for prophylaxis.