TMU Research Center of Cancer Translational Medicine

Hsing-Jien Kung

  • Chair Professor,Taipei Medical University, Taipei, Taiwan
  • Distinguished Chair Professor for Research, National Taiwan University, Taipei
  • Distinguished Professor Emeritus, Department of Biochemistry and Molecular Medicine
  • University of California Davis School of Medicine, Sacramento, CA
  • President Emeritus, NHRI, Taiwan

EDUCATION/TRAINING

INSTITUTION AND LOCATIONDEGREEMM/YYFIELD OF STUDY
National Taiwan UniversityBS06/69Chemistry
California Institute of TechnologyPhD12/75Chemistry
University of California, San FranciscoPostdoc03/78Molecular Virology

RESEARCH INTERESTS

My lab has contributed to our understanding of oncogenes, signal transduction, viral oncogenesis, cancer metabolism and epigenetics. We were credited for the original discovery of dimer structure of retrovirus genome (Cell, 1976), erbB/EGFR as a target gene for retroviral insertion (Cell, 1983, 1986, 1993, Nature, 1981), establishing this locus as a protooncogene, initial cloning of human c-src gene and demonstrating oncogenecity of v-src DNA (PNAS, 1983), and the discoveries of several tyrosine kinase- and viral oncogenes (Nature Cell Biol, 2002, PNAS, 1992, 1998). In the area of prostate cancer, his lab contributed to: the first tyrosine kinase profile (PNAS, 1996), the discovery of truncated AR in CWR22Rv1 (Cancer Res, 2002, 2009), the discovery of IL6 and erbB crosstalk (Nature, 1998), the demonstration of IL6-induced neuroendocrine differentiation (PNAS, 1998), the identification of the first Long-noncoding RNA coactivator of myc (PNAS, 2014) and of HIF-1a (Nat Comm, 2017), the definition of the origin of human retrovirus XMRV (dispelling its involvement in prostate cancer) (Science, 2012), the first demonstration of tumor specific killing of prostate cancer by arginine-deprivation (Cancer Res, 2009), the discovery of chromatin-autophagy (PNAS, 2014), histone demethylase KDM4A as E2F coactivator and tumor metabolism (Cell Reports, 2016), arginine deprivation leads to cGAS-STING activation (Theranostics, 2021) and arginine as an epigenetic regulator of mitochondria (Nature Communication, 2021, Cell Reports, 2023).

My current interests are :1) Metabolic modulation of ferroptosis to overcome prostate cancer drug resistance. 2) Super-enhancers involved in prostate cancer progression. 3) RNA complexes associated with hypoxia and hybrid EMT responses. 4) Exosomal RNAs involved in muscle aging and sarcopenia.

             I was the founding Associate Director of Basic Science of Case Western Reserve University Cancer Center and of UC Davis Cancer Center. I contributed significantly to the development of the basic science programs and the NCI designation for both of these Cancer Centers. I have served in numerous NCI and DOD review panels including OIA, SPORE and PPG study sections. I served as a member of several Cancer Center External Advisory Boards, including those of UC Irvine Chao Family Cancer Center, City of Hope, and Oregon Health and Science Institute Knight Cancer Center. I also served as a member of international advisory boards including UCLA Prostate Cancer SPORE.

           My lab has been extremely blessed with uninterrupted NIH funding for over 35 years including two MERIT awards. I retired from UC Davis in 2013 and returned to Taiwan to be the President of National Health Research Institute with focus on global health. Presently, I am Chair Professor of Taipei Medical University continuing my active research in aging and cancer.

RESEARCH AND PROFESSIONAL EXPERIENCE

  • 1978-1982 Assistant Professor, Department of Biochemistry, Michigan State University
  • 1982-June 1984 Associate Professor, Department of Biochemistry, Michigan State University
  • June 1984-July 1988 Associate Professor, Dept. of Molecular Biology & Microbiology, CWRU School of Medicine
  • July 1988-1998 Professor, Dept. of Molecular Biology & Microbiology, CWRU School of Medicine
  • 1989-1998 Professor, Department of Medicine, Case Western Reserve University School of Medicine
  • 1990-1998 Associate Director of Basic Science, CWRU Cancer Center
  • 1998- 2012 Professor, Dept. Biochemistry and Molecular Medicine, UC Davis, School of Medicine
  • 1998-2018 Deputy Director and Director of Basic Research, UC Davis Cancer Center
  • 2008- 2018 Distinguished Professor, Dept. Biochemistry and Molecular Medicine, UC Davis, School of Medicine2012-2015-2018 President, National Health Research Institutes, Taiwan

Present Appointment

  • Chair Professor, Taipei Medical University
  • Chair Advisor, Taipei Cancer Center
  • Distinguished Chair Professor for Research, National Taiwan University, Institute of Biological Science
  • President Emeritus and Honorary Research Fellow, National Health Research Institute
  • Distinguished Professor Emeritus, University of California, Davis

HONORS

  • Academician of the Academia Sinica, ROC, 1998-present
  • National Taiwan University Outstanding Alumnus, 2024
  • Tang Prize Executive Committee Member 2010-present
  • Rank No. 2 cited scientist in the category of Biochemistry in Taiwan (Research.com, 2022)
  • 0.05% Top Scientists in ScholarGPS world ranking
  • NCI Merit Award (CA39207)
  • NCI Merit Award (CA46613)
  • NIH Norman Salzman Lectureship, 2012
  • Auburn Community Cancer Endowment Chair in Basic Science, UC Davis 2007
  • Joan Oettinger Memorial Award in Lung and Cancer Research, 2006
  • Society of American Asian Scientists in Cancer Research (SAASCR), recipient of annual award-2006
  • UC Davis School of Medicine Faculty Research Award, 2005
  • Goodman-Blum Professor in Cancer Research, CWRU
  • Honorary Distinguished Fellow, NHRI, Taiwan
  • Faculty Research Award, American Cancer Society, 1983-1987
  • Keystone Symposia “Inflammation, microbiota and cancer”, co-organizer (2022-2024)
  • Keystone Symposia “Innate Immune Receptors: Roles in Immunology and Beyond”, co-organizer, (2019)
  • Gordon Conference on Personalized Medicine, Chair and Vice Chair, 2018-2022
  • Honorary Research Fellow, NHRI Life-Time Distinguished Professor, NTHU

Awards and Keynote Speaker

  • Keynote speaker, International Symposium “Precision oncology for personalized cancer therapy” KAIST, Daejeon, Korea 2024
  • Keynote speaker and Chair, international Symposium on Sarcopenia, Taipei Taiwan 2024
  • ICABS speaker , China Medical School, Taiwan, 2024
  • 台大傑出校友2024
  • 中央研究院生化所李卓皓講座,2020
  • 中興大學惠蓀講座,2020
  • 中央研究院吳大猷講座,2017
  • 國立清華大學孫運璿講座,2015
  • 成功大學醫學中心大師系列聯合演講主講者,2020
  • Society of Basic Urology Research, US, 主講者,2019
  • 中國醫藥大學現代生物醫學講座主講者,2019
  • 臺灣生化學會秋令營主講者,2019
  • 生醫年會主講者,2018
  • 凱斯西儲大學癌症中心二十週年慶祝會主講者,2018
  • 中研院基因體中心 Distinguished Seminar 講者,2018
  • UC Davis symposium keynote, 2018

REPRESENTATIVE RECENT PUBLICATIONS (total: 350, h-index 82, D-index 102

  • Yang Y, Zhang X, Cai D, Zheng X, Zhao X, Zou JX, Zhang J, Borowsky AD, Dall’Era MA, Corey E, Mitsiades N, Kung HJ, Chen X, Li JJ, Downes M, Evans RM, Chen HW. Functional inversion of circadian regulator REV-ErbA leads to tumorigenic gene reprogramming Proc Natl Acad Sci U S A. Oct 15;121(42):e2411321121. doi: 10.1073/pnas.2411321121. Epub 2024 Oct 9 (2024).
  • Wang RH, Chen PR, Chen YT, Chen YC, Chu YH, Chien CC, Chien PC, Lo SY, Wang ZL, Tsou MC, Chen SY, Chiu GS, Chen WL, Wu YH, Wang LH, Wang WC, Lin SY, Kung HJ, Wang LH, Cheng HC, Lin KT.Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2. Nat Commun Aug 29;15(1):7463 (2024)
  • Liao TT, Chen YH, Li ZY, Hsiao AC, Huang YL, Hao RX, Tai SK, Chu PY, Shih JW, Kung HJ, Yang MH.Hypoxia-induced long noncoding RNA HIF-1A-AS2 regulates stability of MHC class I protein in head and neck cancer. Cancer Immunol Res. Oct 1;12(10):1468-1484 (2024)
  • Hsieh CL, Do AD, Hsueh CY, Raboshakga MO, Thanh TN, Tai TT, Kung HJ, Sung SY.L1CAM mediates neuroendocrine phenotype acquisition in prostate cancer cells Prostate. Aug 18 (2024)
  • Huo C, Kuo YY, Lin CY, Shiah SG, Li CY, Huang SP, Chen JK, Wang WC, Kung HJ, Chuu CP. The miRNAs 203a/210-3p/5001-5p regulate the androgen/androgen receptor/YAP-induced migration in prostate cancer cells. Cancer Med. Aug;13(16):e70106. doi: 10.1002/cam4.70106 (2024).
  • Wang LY, Hung CL, Wang TC, Hsu HC, Kung HJ, Lin KH. PROTACS as Therapeutic Modalities for drug discovery in castration-resistant prostate cancer. Annu Rev Pharmacol Toxicol. Aug 8. doi: 10.1146/annurev-pharmtox-030624-110238 (2024).
  •  YC, Kelso AA, Karamafrooz A, Chen YH, Chen WK, Cheng CT, Qi Y, Gu L, Malkas L, Taglialatela A, Kung HJ, Moldovan GL, Ciccia A, Stark JM, Ann D. Arginine shortage induces replication stress and confers genotoxic resistance by inhibiting histone H4 translation and promoting PCNA ubiquitination. Cell Rep Mar 23;42(4):112296 (2023).
  • Hung CL, Liu HH, Fu CW, Yeh HH, Hu TL, Kuo ZK, Lin YC, Jhang MR, Hwang CS, Hsu HC, Kung HJ, Wang LY.Targeting androgen receptor and the variants by an orally bioavailable Proteolysis Targeting Chimeras compound in castration resistant prostate cancer. EBioMedicine Apr;90:104500. doi: 10.1016, 2023
  • Jiang N, Xie B, Xiao W, Fan M, Xu S, Duan Y, Hamsafar Y, Evans AC, Huang J, Zhou W, Lin X, Ye N, Wanggou S, Chen W, Jing D, Fragoso RC, Dugger BN, Wilson PF, Coleman MA, Xia S, Li X, Sun LQ, Monjazeb AM, Wang A, Murphy WJ, Kung HJ, Lam KS, Chen HW, Li JJ. Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion Nat Commun. Mar 21;13(1):1511. (2022)
  • Chen CL, Hsu SC, Chung TY, Chu CY, Wang HJ, Hsiao PW, Yeh SD, Ann DK, Yen Y, Kung HJ. Arginine is an epigenetic regulator targeting TEAD4 to modulate OXPHOS in prostate cancer cells. Nat Commun (2021) 12:2398
  • Chu CY, Lee YC, Hsieh CH, Yeh CT, Chao TY, Chen PH, Lin IH, Hsieh TH, Shih JW, Cheng CH, Chang CC, Lin PS, Huang YL, Chen TM, Yen Y, Ann DK, Kung HJ. Genome-wide CRISPR/Cas9 knockout screening uncovers a novel inflammatory pathway critical for resistance to arginine-deprivaiton therapy. (2021) Theranostics 11: 3624
  • Tseng LL, Cheng HH, Yeh TS, Huang SC, Syu YY, Chuu CP, Yuh CH, Kung HJ, Wang WC. Targeting the histone demethylase PHF8-mediated PKCα-Src-PTEN axis in HER2-negative gastric cancer. Proc Natl Acad Sci U S A. (2020) 117:24859
  • Yang CP, Yang WS, Wong YH, Wang KH, Teng YC, Chang MH, Liao KH, Nian FS, Chao CC, Tsai JW, Hwang WL, Lin MW, Tzeng TY, Wang PN, Campbell M, Chen LK, Tsai TF, Chang PC, Kung HJ. Muscle atrophy-related myotube-derived exosomal microRNA in neuronal dysfunction: Targeting both coding and long noncoding RNAs. Aging Cell. 19(5):e13107. (2020)
  • Wu JY, Huang TW, Hsieh YT, Wang YF, Yen CC, Lee GL, Yeh CC, Peng YJ, Kuo YY, Wen HT, Lin HC, Hsiao CW, Wu KK, Kung HJ, Hsu YJ, Kuo CC. Cancer-Derived Succinate Promotes Macrophage Polarization and Cancer Metastasis via Succinate Receptor. Mol Cell. 77(2):213-227.e5. (2020)
  • Cai D, Wang J, Gao B, Li J, Wu F, Zou JX, Xu J, Jiang Y, Zou H, Huang Z, Borowsky AD, Bold RJ, Lara PN, Li JJ, Chen X, Lam KS, To KF, Kung HJ, Fiehn O, Zhao R, Evans RM, Chen HW. RORg is a targetable mastr regulator of cholesterol biosynthesis in a cancer subtype. Nature Commun. (2019) Oct 11;10(1):4621. doi: 10.1038/s41467-019-12529-3.PMID:31604910
  • Cheng CT, Qi Y, Wang YC, Chi KK, Chung Y, Ouyang C, Chen YR, Oh ME, Sheng X, Tang Y, Liu YR, Lin HH, Kuo CY, Schones D, Vidal CM, Chu JC, Wang HJ, Chen YH, Miller KM, Chu P, Yen Y, Jiang L, Kung HJ, Ann DK. Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction.(Nature) Commun Biol. (2018) Oct 26;1:178. PMID:30393775
  • Shih JW*, Chiang WF, Wu ATH, Wu MH, Wang LY, Yu YL, Hung YW, Wang WC, Chu CY, Hung CL, Changou CA, Yen Y, Kung HJ*. Long noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression. Nature Commun. 8:15874. doi: 10.1038/ncomms15874. (2017)
  • Wang LY, Hung CL, Chen YR, Yang JC, Wang J, Campbell M, Izumiya Y, Chen HW, Wang WC, Ann DK, Kung HJ*.  KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis. Cell Rep. 16(11):3016-27. (2016)
  • Wang J, Zou JX, Xue X, Cai D, Zhang Y, Duan Z, Xiang Q, Yang JC, Louie MC, Borowsky AD, Gao AC, Evans CP, Lam KS, Xu J, Kung HJ, Evans RM, Xu Y, Chen HW*.  ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. Nature Medicine. 22(5):488-96. (2016)
  • Changou CA, Chen YR, Xing L, Yen Y, Chuang FY, Cheng RH, Bold RJ, Ann DK, Kung HJ*. Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy. Proc Natl Acad Sci USA.  111(39):14147-52. (2014)
  • Wang HJ, Hsieh YJ, Cheng WC, Lin CP, Lin YS, Yang SF, Chen CC, Izumiya Y, Yu JS, Kung HJ*, Wang WC*. JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism. Proc Natl Acad Sci USA.  111(1):279-84. (2014)