Contact Information
Yun Yen, M.D., Ph.D.
  • Dr. & Mrs. Allen Y. Chao Chair in Developmental Cancer Therapeutics
  • Associate Director for Translational Research
  • Chair and Professor, Molecular Pharmacology
  • Professor, Medical Oncology & Therapeutics Research

Biography

 
Yun Yen, M.D., Ph.D., is the Dr. & Mrs. Allen Y. Chao Chair in Developmental Cancer Therapeutics.

Dr. Yen received his medical degree from Taipei Medical College in Taiwan and his PhD in Pathology and Cell Biology from Thomas Jefferson University, Philadelphia, Pennsylvania. Following residency training at St. Luke's Hospital, Temple University, Dr. Yen completed a fellowship in the Department of Internal Medicine, Hematology and Bone Marrow Transplantation and Oncology Section at Yale University School of Medicine. Subsequently, he joined City of Hope in 1993 as a staff physician. He is currently a professor in Medical Oncology and the Graduate School of Biological Sciences, as well as chief of Biochemical Pharmacology in the Department of Medical Oncology & Therapeutics Research.

Among Dr. Yen’s grant awards are several from the National Institutes of Health, including a prestigious predoctoral fellowship training grant while at Thomas Jefferson University and a K12 training grant while at City of Hope. In addition, he has been awarded U. S. Army Breast Cancer and Prostate Cancer grants, and the National Cancer Institute’s Cancer Therapy Evaluation Program has designated his laboratory the ribonucleotide reductase Real-Time PCR Reference Laboratory.

Dr. Yen holds membership in numerous professional organizations, including the American Association for the Advancement of Science, American Society of Clinical Oncology, Sigma-Xi Scientific Association, and Academy of Science New York. He has published more than 140 abstracts and peer-reviewed journal articles, and he serves as an ad hoc reviewer/referee for several journals and on the editorial board of the Journal of Clinical Colorectal Cancer.

As a highly experienced clinician, clinical investigator and basic scientist, Dr. Yen’s research interests focus on several markers of hepatocellular cancer, as well as investigational therapies for advanced malignancy.

Professional Experience


  • 2008 - present, Dr. & Mrs. Allen Y. Chao Chair in Developmental Cancer Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA
  • 2005 - present, Associate Director for Translational Research, City of Hope Comprehensive Cancer Center, Duarte, CA.
  • 2005 - present, Director, Department of Molecular Pharmacology, City of Hope, Duarte, CA.
  • 2005 - present , Co-leader, Developmental Cancer Therapeutics Program, City of Hope Comprehensive Cancer Center, Duarte, CA.
  • 2003, Section Chief of Hepatobiliary Cancer Division, City of Hope, Duarte, CA.
  • 2003, Professor, City of Hope, and adjunct to University of Southern California School of Pharmacy
  • 1999 - 2004, Chief of Biochemical Pharmacology, Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA
  • 1999 - 2003, Associate Professor, Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA
  • 1993 - present, Staff Physician, Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA
  • 1993 - 1999, Assistant Professor, City of Hope, Duarte, CA
  • 1990 - 1993, Fellow, Department of Internal Medicine, Hematology/Medical Oncology/Bone Marrow Transplantation Yale University School of Medicine, New Haven, CT
  • 1987 - 1990, Residency, Department of Internal Medicine, Temple University, Bethlehem, PA

Education

 
Education/Training
  • 1987, Thomas Jefferson University, Philadelphia, PA, Ph.D., Pathology & Cell Biology
  • 1982, Taipei Medical College, Taipei Taiwan, M.D., Medicine
 

Honors/Awards

 
Awards
  • 2008, Dr. & Mrs. Allen Y. Chao Chair in Developmental Cancer Therapeutics
  • 1999 - present, Advisory Board Member, Cancer Division, National Health Research Institute, Taiwan
  • 1987, NIH predoctoral fellowship training grant, Thomas Jefferson University, Philadelphia, PA.
  • 1984 - 1986, Tuition Scholarship,Thomas Jefferson University, Philadelphia, PA
 

Memberships


  • American Association for Cancer Research
  • American Medical Association
  • American College of Physicians
  • Sigma-Xi Scientific Association
  • American Society of Hematology
  • American Association for the Advancement of Science
  • American Society for Blood and Marrow Transplantation

Publications

Selected Publications
 
Qian S, Somlo G, Zhou BS, Mi S, Mo X, Cheung GM, Lian RJ, Rossi J, Holtz M, Chu P, Yen Y. Ribozyme-mediated down-regulation of fibroblast growth factor receptor 3 inhibits cell growth of human multiple myeloma and is associated with down-regulation of vascular endothelial growth factor. Oligoneucleotide, 15:1-11, 2005.

Chu PG, Schwarz RE, Lau SK, Yen Y, Weiss LM.  Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2.  Am J Surg Pathol, 29(3):359-367, 2005.

Zhu LJ, Somlo G, Zhou BS, Shao J, Bedell V, Slovak ML, Liu XY, Lou JH, Yen Y.  Short-hairpin RNAs inhibit fibroblast growth factor receptor 3 inhibition by short hairpin RNAs leads to apoptosis in multiple  myeloma.  Molecular Cancer Therapeutics, 4:787-798, 2005.

Yen Y.  Growth arrest damage-inducible gene 45β in human liver cancer.  Handbook of Immunohistochemistry and in situ hybridization of Human Carcinomas , second version, 3:207-216, 2005.

Qiu WH, Zhou BS, Chu PG, Chen WG, Chung C, Shih J, Hwu P, Yeh C, Lopez R, Yen Y.  Over-expression of fibroblast growth factor receptor 3 in human hepatocellular carcinoma.  World J Gastroenterol, 11(34);5266-5272, 2005.

Liu X, Zhou B, Xue, L, Shih J, Tye K, Qi Ch, Yen Y.  The ribonucleotide reductase subunit M2B subcellular localization and functional importance for DNA replication in physiological growth of KB cells.  Biochem Pharm, 70: 1288-1297, 2005.

Boo L-M, Lin HH, Chung V, Zhou BS, Louie SG, O’Reilly MA, Yen Y, Ann DK.  HMGA2 potentiates genotoxic stress in part through the modulation of basal and DNA damage-dependent phosphatidylinositol 3-kinase (Pi 3-K)-related protein Kinase activation.  Cancer Research, 65:6622-6630, 2005.

Morgan RJ Jr, Synold TW, Gandara D, Muggia F, Scudder S, Reed E, Margolin K, Raschko J, Leong L, Shibata S, Tetef M, Vasilev S, McGonigle K, Longmate J, Yen Y, Chow W, Somlo, G, Carroll M, Doroshow JH.  Phase I trial of topotecan, carboplatin, and topotecan in the treatment of recurrent or refractory brain or spinal cord tumors.  In press, Neuro-Oncol, 2005.

Cao M-Y, Benatar T, Lee Y, Young AH, Yen Y, Wright JA.  Recent Progress in Cancer Gene Therapy Chapter.  In press, 2005.

Wang T, Tamae D, Lebon T, Shively JE, Yen Y, Li JJ.  The role of peroxiredoxin II in radiation-resistant MCF-7 breast cancer cells.  Cancer Research, 65(22):10338-10346, 2005.

Huang MJ, Lim KH, Tzen CY, Hsu HS, Yen Y, Huang BS.  FGFR mutations in malignant pleural effusion of non-small cell lung cancer: a case report.  Lung Cancer, 49(3): 413-415, 2005.

Qiu W, Zhou B, Darwish D, Shao J, Yen Y.  Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits.  Biochem and Biophys Res Comm, 340(2): 428-434, 2006.

Xue L, Zhou B, Liu X, Wang T, Shih J, Qi C, Heung Y, Yen Y.  Structurally Dependent Redox Property of Ribonucleotide Reductase Subunit p53R2.  Cancer Research, 66: 1900-1905, 2006.

Shao J, Zhou B, Di Bilio A, Zhu L, Wang T, Qi C, Shih J, Yen Y.  A Ferrous-Triapine Complex Mediates Formation of Reactive Oxygen Species That Inactivate Human Ribonucleotide Reductase.  Mol Can Ther, 5(3), 586-592, 2006.

Chung V, Zhou B, Liu X, Zhu L, Boo LM, Nguyen H-V, Ann DK, Song J, Chen Y, Yen Y.  SUMOylation plays a role in gemcitabine- and bortezomib-induced cytotoxicity in human oropharyngeal carcinoma KB gemcitabine-resistant clone.  Mol Can Ther, 5(3), 533-540, 2006.

Zhou B, Shao J, Su L, Yuan Y-C, Qi C, Shih J, Xi B, Chu B, Yen Y.  A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases.  Mol Can Ther, 4(12), 1830-1836, 2005-2006.

Un, F, Qi C, Prosser M, Wang N, Zhou B, Bronner C, Yen Y.  Modulating ICBP90 to Suppress Human Ribonucleotide Reductase M2 Induction Restores Sensitivity to Hydroxyurea Cytotoxicity.  Anticancer Res, 26(4), 2761–2768, 2006.

Shao J, Zhou B, Chu B, Yen Y.  Ribonucleotide Reductase Inhibitors and Future Drug Design.  Current Cancer Drug Targets  6, 409-431, 2006

Zhu L, Yen Y, Shao J, Qi CH, Yen, C Luo J, Zhou B.  Fibroblast growth factor Receptor 3 up-regulates vascular endothelial growth factor expression in L6 cells.  Intl Journal of Pharmacology, 2 (3):  324-330, 2006.
 

Research Focus

 
Cancer Pharmacology and Translational Research
 
Our laboratory focuses on molecular pharmacology and experimental therapeutic research. There are three main projects that are currently being investigated in our lab. Our first project seeks to elucidate the molecular mechanisms of chemotherapeutic drug resistance. We propose to determine the biochemical and molecular mechanisms of cancer drug resistance in human tumor cells.
 
Hydroxyurea has been used in cancer treatment. The targeting enzyme of hydroxyurea is ribonucleotide reductase (RR). RR also is a rate-limiting enzyme for DNA synthesis that is responsible for the conversion of ribonuclotide diphosphate to the deoxyribonucleoside utilized in de novo DNA synthesis or DNA repair. Three subunits of RR have been identified as hRRM1(large subunit) and hRRM2 or p53R2 (small subunit). Our recent experiments have shown that hRRM2 and p53R2 both interact with p53 and play different roles in the cell cycle, DNA repair, and replication. Our current goals are to understand in detail the transcription regulation of RR and its role in cell cycle regulation. Using similar techniques to those necessary for this project, we also are examining the drug resistance mechanisms of purine/pyrimidine analogs on proteosome inhibitions, etc.
 
Our second project focuses on the development of novel chemotherapeutic agents useful for circumventing drug resistance in human cancer. We are currently examining the mechanisms of RR inhibition by a new RR inhibitor, Triapine, in cell-free studies. The in vitro expression and recombination of each subunit of RR has been used to evaluate the pattern of cytotoxicity and resistance of RR inhibitor and in combination with purine and pyrimidine nucleoside analogs. Another major investigation seeking to develop siRNA to inhibit RR is ongoing. Further structure analyses by EPR and crystallization are currently ongoing with colleagues at the University of California at Irvine (UCI).
 
Our third project focuses on preclinical therepeutic research and surrogate markers for enhancing cancer drug therapeutic effect. We are currently evaluating human samples collected from RR inhibitors studies and follow real-time PCR, microarray, and proteomic assay for cross-resistance, collateral sensitivity, and synergistic phenomena in RR inhibitors, and other drug combinations. Our results will aid in the development of drugs that will provide a high assurance of therapeutic benefit. Our laboratory efforts also focus on developing a pilot study in a pre-clinical setting and on conveying clinical samples to labs to answer more scientific questions. Overall, our laboratory focuses on experimental therapy and molecular pharmacology. Our mission is to better understand the molecular mechanisms of drug resistance in human cells. This understanding will help us develop new therapeutic agents and methods to overcome drug resistance.
 
Translational Research Program in Liver Cancers
 
Using microarray technique, we successfully identified that growth arrest DNA damage-inducible gene 45β (GADD45β) genee expression was down-regulated in human hepatocellular cancer. The GADD45β down-regulation strongly correlated with differentiation and a high nuclear grade of human hepatocellular cancer. Our laboratory transfected GADD45β into two human liver cancer cell lines, HepG2 and Hep3B, to restore gene expression. These transfectants presented p53-dependent apoptosis evident by flow cytometry. The p53 regulation and cell cycling involvement is currently under investigation. The preliminary results suggest that GADD45β is a p53 effector gene. The mutation of the p53 alters the GADD45β expression level in the cell and/or hepatocellular cancer tissues. The future planning in clinical applications is to  overexpress GADD45β in human hepatocellular cancer by gene therapy techniques, which is one approach. Moreover, GADD45β apparently also regulated post-transcriptionally may potentially alter mRNA and/or protein stability. A better understanding of the molecular basis of hepatocellular cancer focusing on GADD45β may lead to the design of a new therapeutic target or agent that is currently being discussed.
 

Locations


  • City of Hope - Main Campus (Duarte)
    1500 East Duarte Road
    Duarte, CA 91010