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IVY CHUNG Associate Professor Department of Pharmacology, Faculty of Medicine University of Malaya, 50603 Kuala Lumpur Tel: 603-79673199 (office) E-mail: [email protected] EDUCATION 2007 Ph.D. Molecular Pharmacology and Therapeutics State University of New York at Buffalo, Buffalo, NY Thesis advisor: Candace S. Johnson, Ph.D. 2002 B. Eng. Biomolecular Engineering Tokyo Institute of Technology, Tokyo, Japan Thesis advisor: Toshihisa Ishikawa, Ph.D. 2000 Ass. Eng. Materials Chemistry and Bioengineering Oyama National College of Technology, Tochigi, Japan ACADEMIC CAREER 2007- 2011 Postdoctoral research fellow Children’s Hospital Boston/Harvard Medical School, Boston, MA Advisor: Bruce R. Zetter, Ph.D. 2011- current Associate Professor Department of Pharmacology, Faculty of Medicine, University of Malaya, Malaysia AWARDS 2007 Dissertation Award for Excellence in Cancer Research, Roswell Park Cancer Institute 2007 Y2K7 The Young Einstein Decade Lectureship Award, Roswell Park Cancer Institute 2006 Scholar-in-Training Award-AACR Special Conference in Cancer Research Innovation in Prostate Cancer Research 2006 Scholar-in-Training Award-AACR Special Conference in Cancer Research Anti-Angiogenesis and Drug Delivery to Tumors: Bench to Bedside and Back 2002-2007 Ph.D. Graduate Fellowship, Roswell Park Cancer Institute 2000 Excellent Performance in Academy Award, Chemical Society of Japan 2000 Excellent Academic Record Award, Oyama National College of Technology 1995-2002 College Scholarship to Japan, Department of Public Service, Malaysia Ivy Chung, Ph.D. FUNDING INFORMATION Present Funding: 2013-2014 Role: PI UM-Harvard Collaboration Initiatives RM300,000 2013-2015 Role: PI UM Nobel Endeavour Program Towards a Successful Career in Cancer Research (postgraduate student training grant) RM60,000 2013-2015 Role: PI University Malaya Research Grant, Malaysia Role of Cancer-Associated Fibroblasts in the Progression of Endometrial Cancer RM120,000 2012-2013 Role: Co-PI University Malaya Research Grant, Malaysia Stromal Fibroblast as Mediators of Chemoresistance in Oral Carcinoma Cells RM55,000 2011 –2013 Role: PI University Malaya Research Grant, Malaysia RM104,500 Molecular Determinants Underlying the Progression of Normal Endometrium to Endometriosis, Endometrioid Adenocarcinoma of the Ovary and to Endometrial Cancer 2011 –2013 Role: PI UM Cancer Institute High Impact Grant, Malaysia Targeting Tumor-Stellate Cells Interaction for Novel Therapeutics in Pancreatic Cancer RM600,000 Past Funding: 2010 –2011 Role: PI Department of Defense, USA US$100,000 PC094329 Prostate Cancer Post-doctoral Training Grant: Benzimidazole as Novel Therapy for HormoneRefractory Metastatic Prostate Cancer 2005 – 2007 Role: PI Department of Defense, USA US$100,000 PC050202 Prostate Cancer Pre-doctoral Training Grant: Molecular Mechanisms of Differential Effects of Calcitriol on Endothelial Cells Isolated from Prostate Tumor and Normal Microenvironment RESEARCH EXPERIENCE Faculty of Medicine, University of Malaya Associate Professor, Pharmacogenomics Laboratory Kuala Lumpur, Malaysia 2011 – present 1) Targeting stroma-mediated pancreatic adenocarcinoma progression and chemoresistance 2) Molecular determinants underlying progression of endometriosis to endometrial cancer 3) Pharmacogenomic studies on genetic susceptibility in prostate, breast and lympho-hyperproliferative diseases 4) Establishing primary cell cultures from human tumor specimen Harvard Medical School, Children’s Hospital Boston Postdoctoral Fellow; Advisor: Bruce Zetter, PhD. 1) Development of therapeutic agents targeting metastatic prostate cancer - Designed high-throughput screening and discovery of potential lead drugs in vitro Boston, MA, USA 2007 - 2011 Ivy Chung, Ph.D. - Improvised drug formulation for increased drug delivery in vivo Determined drug therapeutic efficacy in preclinical animal models of metastatic cancer Analyzed drug combination in vitro and in vivo for better therapeutic efficacy Elucidated mechanism of actions underlying therapeutic drug-induced apoptosis 2) Role of miRNA in paclitaxel-resistant cancers - Established a new model of secondary paclitaxel-resistance in tumors in vivo - Determined the correlation and functional role of miRNA-135a in paclitaxel resistance 3) Role of tyrosinase in regulating fibromodulin-mediated tumor progression - Established a novel metastatic in vivo model of melanoma tumor - Determined the mechanism underlying fibromodulin-mediated tumor migration and invasion 4) Role of stromal regulation in progression of metastatic pancreatic cancer - Developed tumor-stromal model using transgenic pancreatic adenocarcinoma mouse model - Determined effects of pancreatic stellate cells on tumor progression Roswell Park Cancer Institute, SUNY at Buffalo, USA Buffalo, NY Graduate Student; Advisor: Candace S. Johnson, PhD. 2002 – 2007 Tumor vasculature as a therapeutic target for calcitriol in cancer - Established endothelial cell primary cultures from mouse and human normal and tumor tissues - Utilized molecular approaches to examine vitamin D receptor signaling axis and epigenetic mechanism in tumor and normal endothelium - Examined the role of vitamin D receptor in tumor and non-tumor angiogenesis in vivo Tokyo Institute of Technology, Japan Tokyo, Japan College Student; Advisor: Toshihisa Ishikawa, PhD. 2000 – 2002 Profiling of ATP-binding cassette (ABC) transporters gene expression in human leukemia cells - Designed human specific ABC transporter gene expression assay using quantitative real-time PCR Oyama National College of Technology, Japan Tochigi, Japan Diploma Student; Advisor: Hiroyuki Saito, PhD. 1999 – 2000 Organic synthesis of various thiol compounds - Researched on organic synthesis and analytical chemistry of sulfur-containing compounds for the use of biodegradable polymers Sankyo Co. Ltd Kao Corporation Summer intern Investigated various methodologies in computational chemistry and organic synthesis TEACHING AND TRAINING RESPONSIBILITIES University of Malaya, Kuala Lumpur PhD candidates – Varatha Rajan (2009 – present) Wu Yuan Seng (2011 – present) Kavita S. Subramaniam (2011 – present) Lai Sook Ling (2013 – present) Kwong Soke Chee (2014- present) Tokyo, Japan Tochigi, Japan 1998 Ivy Chung, Ph.D. Undergraduate student – Yap Chee Voon (Bachelor of Biomedical Sciences,UM) (2013-2014) Wee Yong Kiat (Bachelor of Bioinformatics, Multimedia University) (2014) Research assistants – Lai Sook Ling (2012 – 2013) Wong Mei Szin (2013 – 2013) Ala Abu Hammattah (2013) Intan Sofia Omar (2013 - present) Harvard Medical School, Children’s Hospital, Boston, MA Supervision of graduate student – daily mentorship for 12 weeks 2009 Annie Vo Phong Biological and Biomedical Sciences/Harvard Medical School 2009-2010 Arianne Wilson Research Assistant II Roswell Park Cancer Institute, SUNY at Buffalo Supervision of high school students 2005- 2006 Risa Trump Roswell Park Cancer Center Summer Student Program PROFESSIONAL ASSOCIATION AND POSITIONS 2001-2007 200520062006200720112011- Member, ATP-Binding Receptors (ABC) Society Japan Associate member, Association for Cancer Research (AACR) (USA) Member, AACR-Tumor Microenvironment Working Group (USA) Member, AACR-Women in Cancer Research Working Group (USA) Member, Association for Women in Science (AWIS) (USA) Member, Malaysian Association for the Study of Obesity (Malaysia) Member, Malaysian Society of Physiology and Pharmacology (Malaysia) EDITORIAL ACTIVITIES Journal of Health and Translational Medicine (sub-editor, 2012-2013; editor, 2013-present) Oncology (ad hoc reviewer, 2006-present) Cell Adhesion and Migration (ad hoc reviewer, 2010-present) PATENT Compositions for the Treatment of Metastatic Cancer and Methods of Use Thereof. Inventors: Bruce R. Zetter, Ivy Chung and Courtney Barrow. U.S. CMCC 1653 61/180,029; International PCT/US10/35578. Use of MicroRNA to Detect and Reverse Drug Resistance in Tumor Cells. Inventors: Bruce R. Zetter, Amy Holleman and Ivy Chung. US. CMCC 2258 61/471,565 BOOK CHAPTER Chung, I. Tumor fibroblasts: pivotal players in drug resistance. In: Morais, C. ed. Advances in drug resistance research, Nova Science Publishers, N.Y., USA. (In Press) Ivy Chung, Ph.D. PUBLICATIONS 1. Banyard J, Chung I, Wilson A, Vetter G, Le Bechec A, Bielenberg D and Zetter BR. Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model. Scientific Reports 3:3151 (2013). IF: 2.9 (Tier-1) 2. Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR, Stanger BZ, Chung I, Rhim AD and di Magliano MP. Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Research 73(20):6359-74 (2013). IF: 8.65 (Tier-1) 3. Subramaniam KS, Tham ST, Zahurin M, Woo YL, Noor Azmi MA and Chung I. Cancer-associated fibroblasts promote proliferation of endometrial cancer cells. PLoS ONE 8(7): e68923. (2013). IF: 3.9 (Tier-1) 4. Lee ML, Chung I, Fung SY, Kanthimathi MS and Tan NH. Anti-proliferative activity of king cobra (Ophiophagus hannah) venom L-amino acid oxidase. Basic & Clinical Pharmacology & Toxicology doi: 10.1111/bcpt.12155 (2013). IF: 2.12 (Tier-3) 5. Rajavel V, Sattar MZ, Chung I, Abdulla MA, Kassim NM and Abdullah NA. Antioxidant and prooxidant effects of oil palm (Elaeis guineensis) leaves extract in experimental diabetic nephropathy: a duration-dependent outcome. BMC Complementary and Alternative Medicine 13(1):242 (2013). IF: 2.24 (Tier-2) 6. Chung I, Godoy AS*, Montecinos V, Buttyan R, Johnson CS and Smith GA. Role of androgen and vitamin D receptors in endothelial cells from benign and malignant human prostate. American Journal of Physiology – Endocrinology & Metabolism 304(11):E1131-9 (2013). IF: 4.5 (Tier-1) 7. Spivey KA, Chung I, Banyard J, Adini I, Feldman HA and Zetter BR. A role of collagen XXIII in cancer cell adhesion, anchorage-independence and metastasis. Oncogene 31 (18):2362-72 (2012). IF: 6.3 (Tier-1) 8. Olsen RR, Chung I and Zetter BR. Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo. Amino Acids 42 (2-3):549-558 (2012). 9. Chung I, Holleman A*, Olsen RR, Kwak B and Zetter BR. miR-135a as potential biomarker for development of taxane resistance in human cancer. (*, shared first authorship). Oncogene 30 (43):43864398 (2011). IF: 6.3 (Tier-1) 10. Rummel N, Chung I and Shaikh Badar. Determination of albendazole, fenbendazole, and their metabolites in mice plasma by high performance liquid chromatography. J. Pharmaceutical and Biomedical Analysis 34 (18): 2211-2223 (2011). IF:2.94 (Tier-2) 11. Patel N, Chatterjee SK, Vrbanac V, Chung I, Mu CJ, Olsen RR, Waghorne C and Zetter BR. Rescue of paclitaxel sensitivity by repression of prohibitin 1 in drug-resistant cancer cells. Proceedings of the National Academy of Sciences 107(6):2503-2508 (2010). IF:9.6 (Tier-1) 12. Johnson CS, Chung I and Trump DL. Review: The role of vitamin D on normal and tumor endothelium. Journal of Steroid Biochemistry and Molecular Biology 121(1-2):338-42 (2010). IF: 3.9 (Tier-2) Ivy Chung, Ph.D. 13. Chung I, Han GZ, Seshadri M, Gillard BM, Yu WD, Foster BA, Trump DL and Johnson CS. Role of vitamin D receptor in the antiproliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo. Cancer Research 69(3):967-975 (2009). IF: 8.65 (Tier-1) 14. Adachi T, Nakagawa H, Chung I, Hagiya Y, Hoshijima K, Noguchi N, Kuo MT and Ishikawa T. Nrf2dependent and –independent nduction of ABC transporters ABCC1, ABCC2, and ABCG2 in HepG2 cells under oxidative stress. Journal of Experimental Therapeutics and Oncology 6(4):335-348 (2007). 15. Chung I, Karpf AR, Muindi JR, Conroy JM, Nowak NJ, Johnson CS and Trump DL. Epigenetic silencing of CYP24 in tumor-derived endothelial cells contributes to selective growth inhibition by calcitriol. Journal of Biological Chemistry 282(12):8704-14 (2007). IF:5.3 (Tier-1) 16. Chung I, Yu WD, Karpf AR, Flynn G, Bernardi RJ, Modzelewski RA, Johnson CS and Trump DL. Antiproliferative effects of calcitriol on endothelial cells derived from two different microenvironments. J. Steroid Biochemistry and Molecular Biology 103(3-5):768-70 (2007). IF:3.9 (Tier-2) 17. Flynn G, Chung I, Yu WD, Romano M, Modzelewski RA, Johnson CS and Trump DL. Calcitriol (1,25dihydroxycholecalciferol) selectively inhibits proliferation of freshly isolated tumor-derived endothelial cells and induces apoptosis. Oncology 70(6):447-457 (2007). IF:2.2 (Tier-3) 18. Chung I, Wong MK, Flynn G, Yu WD, Johnson CS and Trump DL. Differential antiproliferative effects of calcitriol on tumor-derived and Matrigel-derived endothelial cells. Cancer Research 66: 8565-8573 (2006). IF: 8.65 (Tier-1) ORAL PRESENTATIONS Chung I. Targeting the Fibroblasts in the Microenvironment of Endometrial Cancer. Malaysian Institute of Medical Laboratory Sciences (MIMLS) 24th National Scientific Conference, Kuala Lumpur, Malaysia (2013). Chung I. A novel mechanism of microRNA-induced paclitaxel resistance in tumor cells. Folkman Research Day, Children’s Hospital Boston, Harvard Medical School, Boston, MA (2010). Chung I. Benzimidazoles as novel therapy for castrate-resistant metastatic prostate cancer. Folkman WorkIn-Progress Seminar, Children’s Hospital Boston, Harvard Medical School, Boston, MA (2010). Chung I. Differential anti-proliferative effects of calcitriol on endothelial cells isolated from tumor and nontumor microenvironments. Y2K7 The Young Einstein Decade Lectureship, Roswell Park Cancer Institute, Buffalo, NY (2007). Chung I, Muindi J, Johnson CS and Trump DL. Role of vitamin D and CYP24 in Prostate Vasculature. Innovative Minds in Prostate Research Today (IMPaCT) Meeting (organized by Department of Defense). Atlanta, GA (2007). Chung I, Karpf AR, Muindi JR, Johnson CS and Trump DL. Epigenetic silencing of CYP24 in tumorderived endothelial cells (TDEC) contributes to selective growth inhibition by calcitriol. 13th Workshop on Vitamin D at Victoria, BC, Canada (2006).