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Ie-Ming Shih, M.D., Ph.D.
Richard W. TeLinde Distinguished Professor, Department of Gynecology and Obstetrics
Professor of Gynecology and Obstetrics
Languages: English, Chinese, Taiwanese
Expertise: Gynecologic/Obstetric Pathology, Pathology
Research Interests: Cancer Pathogenesis; Cancer Diagnostics; Molecular Cancer Therapy
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The Johns Hopkins Hospital
Appointment Phone: 410-502-7774
600 N. Wolfe Street
Sheikh Zayed Tower
Baltimore, MD 21287 map
Dr. Ie-Ming Shih is the Richard TeLinde Distinguished Professor of Gynecologic Pathology at the Johns Hopkins University School of Medicine. Dr. Shih directs the Richard W. TeLinde Gynecologic Pathology Program in the Department of Gynecology and Obstetrics and co-directs the Breast and Ovarian Cancer Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institutions.
Dr. Shih received his M.D. from Taipei Medical University and earned his Ph.D. in pathology from the University of Pennsylvania. Dr. Shih went on to do a clinical fellowship in gynecologic pathology and a research fellowship in cancer genetics at Johns Hopkins before joining the faculty in 2001.
Dr. Shih has published extensively on basic and translational research related to gynecologic pathology and oncology, with nearly 300 original publications and book chapters. His research focuses on molecular and translational studies in various gynecological neoplasms, especially ovarian cancer. His research team helps elucidate the genomic landscape in ovarian clear cell carcinoma, ovarian low-grade serous carcinoma and uterine serous carcinoma. Dr. Shih’s research team has contributed to the discovery and functional characterization of cancer associated genes and the pathway they controlled including ARID1A, Rsf-1, Syk, NAC1 and Notch3 in ovarian cancer. Dr. Shih in collaboration with Dr. Kurman has proposed the dualistic model (Type I and Type II) in ovarian cancer pathogenesis, which has become a well-accepted model in studying ovarian cancer. Based on molecular genetic analysis in ovarian cancer, they are exploring new molecular targets and pathways for experimental therapeutics and are initiating new clinical trials based on their new findings. Currently, Dr. Shih takes one of the leadership roles in the multi-institutional DoD-OCRP Ovarian Cancer Consortium which studies the pathogenesis of the precursor lesions of ovarian high-grade serous carcinoma. He is also a member of the NCI-sponsored CPTAC (Clinical Proteomics Technology Assessment for Cancer) consortium at Johns Hopkins for integrative analysis of proteomics and genomics in ovarian cancer. He sits in several advisory boards such as NCI Ovarian Task Force of Gynecologic Cancer Steering Committee (for clinical trials on gynecologic cancer), Ovarian Cancer Research Foundation, and International Society of Gynecologic Pathology/World Health Organization (WHO) Nomenclature Committee for Gynecologic Neoplasms in addition to SPORE external advisory board and various study sections of NCI, DoD among several others. Besides his clinical, research and teaching obligations, Dr. Shih is a passionate photographer (www.shih-photography.com).
- Richard W. TeLinde Distinguished Professor, Department of Gynecology and Obstetrics
- Director of TeLinde Endowed Gynecologic Pathology Laboratory
- Co-director, Breast and Ovarian Cancer Program, Sidney Kimmel Comprehensive Cancer Center
- Professor of Gynecology and Obstetrics
- Professor of Oncology
- Professor of Pathology
Departments / Divisions
- MD, Taipei Medical University (1988)
- Taipei Medical University / Anatomic Pathology (1989)
- Johns Hopkins University School of Medicine / Pathology (1997)
- The Wistar Institute / Pathology (1994)
- Johns Hopkins University School of Medicine / Pathology (2000)
- American Board of Pathology / Anatomic Pathology (1997)
Research & Publications
Dr. Shih's research team focuses on the molecular pathology of ovarian cancer, the most lethal malignant tumor among gynecological neoplasms. The long-term objectives of his research team are:
A. to understand the molecular etiology in the development of human cancer, and
B. to identify and characterize cancer molecules for cancer detection, diagnosis, and therapy.
Dr. Shih's team uses ovarian carcinoma as a disease model because it is one of the most aggressive neoplastic diseases in women. For the first research direction, they aim to identify and characterize the molecular alterations during initiation and progression of ovarian carcinomas. Previous genome-wide analyses from his team have identified molecular alterations in several new cancer-associated genes including Rsf-1, NAC1, and fatty acid synthase among several others. The investigators have demonstrated the essential roles of these gene products in sustaining tumor growth and survival. Current projects are focusing on elucidating the mechanisms by which these genes function in cancer cells and delineating the cross-talks between those genes and other signaling pathways.
Specifically, they are identifying their downstream targets and pathways, and are determining their roles in maintaining cancer stem cell-like features, invasion and drug resistance. The second research direction is a translation-based study. The team is assessing the clinical significance of an array of new cancer-associated genes in predicting clinical outcome and in the developing potential target-based therapy in mouse preclinical models.
They are also establishing innovative assays for cancer detection and diagnosis by identifying new tumor-associated genetic and protein biomarkers through serial analysis of gene expression, gene expression arrays, proteomics and methylation profiling. The purpose is to develop new tools in detecting human cancer using body fluid samples. In collaboration with several investigators, they are integrating new technologic platforms such as microfluidics, nanotechnology and systems biology in their studies.
Selected PublicationsView all on Pubmed
Bazzaro, M.; Lee, M.K.; Zoso, A.; Stirling, W.L.; Santillan, A.; Shih Ie, M.; Roden, R.B. Ubiquitin-proteasome system stress sensitizes ovarian cancer to proteasome inhibitor-induced apoptosis. Cancer Res. 2006 Apr 1;66(7):3754-3763.
Mao, T.L.; Hsu, C.Y.; Yen, M.J.; Gilks, B.; Sheu, J.J.; Gabrielson, E.; Vang, R.; Cope, L.; Kurman, R.J.; Wang, T.L.; Shih Ie, M. Expression of Rsf-1, a chromatin-remodeling gene, in ovarian and breast carcinoma. Hum Pathol. 2006 Sep;37(9):1169-1175.
Nakayama, K.; Nakayama, N.; Davidson, B.; Katabuchi, H.; Kurman, R.J.; Velculescu, V.E.; Shih Ie, M.; Wang, T.L. Homozygous deletion of MKK4 in ovarian serous carcinoma. Cancer Biol Ther. 2006 Jun;5(6):630-634.
Nakayama, K.; Nakayama, N.; Kurman, R.J.; Cope, L.; Pohl, G.; Samuels, Y.; Velculescu, V.E.; Wang, T.L.; Shih Ie, M. Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms. Cancer Biol Ther. 2006 Jul;5(7):779-785.
Park, J.T.; Li, M.; Nakayama, K.; Mao, T.L.; Davidson, B.; Zhang, Z.; Kurman, R.J.; Eberhart, C.G.; Shih Ie, M.; Wang, T.L. Notch3 gene amplification in ovarian cancer. Cancer Res. 2006 Jun 15;66(12):6312-6318.
Kurman, R.J.; Visvanathan, K.; Roden, R.; Wu, T.C.; Shih Ie, M. Early detection and treatment of ovarian cancer: shifting from early stage to minimal volume of disease based on a new model of carcinogenesis. Am J Obstet Gynecol. 2008 Apr;198(4):351-356.
Sturgeon, C.M.; Duffy, M.J.; Stenman, U.H.; Lilja, H.; Brunner, N.; Chan, D.W.; Babaian, R.; Bast, R.C., Jr.; Dowell, B.; Esteva, F.J.; Haglund, C.; Harbeck, N.; Hayes, D.F.; Holten-Andersen, M.; Klee, G.G.; Lamerz, R.; Looijenga, L.H.; Molina, R.; Nielsen, H.J.; Rittenhouse, H.; Semjonow, A.; Shih Ie, M.; Sibley, P.; Soletormos, G.; Stephan, C.; Sokoll, L.; Hoffman, B.R.; Diamandis, E.P. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008 Dec;54(12):e11-79.
Kuo, K.T.; Mao, T.L.; Jones, S.; Veras, E.; Ayhan, A.; Wang, T.L.; Glas, R.; Slamon, D.; Velculescu, V.E.; Kuman, R.J.; Shih Ie, M. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol. 2009 May;174(5):1597-1601.
Lotan, T.L.; Ye, H.; Melamed, J.; Wu, X.R.; Shih Ie, M.; Epstein, J.I. Immunohistochemical panel to identify the primary site of invasive micropapillary carcinoma. Am J Surg Pathol. 2009 Jul;33(7):1037-1041.
Tsai-Turton, M.; Santillan, A.; Lu, D.; Bristow, R.E.; Chan, K.C.; Shih Ie, M.; Roden, R.B. p53 autoantibodies, cytokine levels and ovarian carcinogenesis. Gynecol Oncol. 2009 Jul;114(1):12-17.
Chen, X.; Stoeck, A.; Lee, S.J.; Shih, I.M.; Wang, M.M.; Wang, T.L. Jagged1 expression regulated by Notch3 and Wnt/beta-catenin signaling pathways in ovarian cancer. Oncotarget. 2010 Jul;1(3):210-218.
Elliott, K.S.; Zeggini, E.; McCarthy, M.I.; Gudmundsson, J.; Sulem, P.; Stacey, S.N.; Thorlacius, S.; Amundadottir, L.; Gronberg, H.; Xu, J.; Gaborieau, V.; Eeles, R.A.; Neal, D.E.; Donovan, J.L.; Hamdy, F.C.; Muir, K.; Hwang, S.J.; Spitz, M.R.; Zanke, B.; Carvajal-Carmona, L.; Brown, K.M.; Hayward, N.K.; Macgregor, S.; Tomlinson, I.P.; Lemire, M.; Amos, C.I.; Murabito, J.M.; Isaacs, W.B.; Easton, D.F.; Brennan, P.; Barkardottir, R.B.; Gudbjartsson, D.F.; Rafnar, T.; Hunter, D.J.; Chanock, S.J.; Stefansson, K.; Ioannidis, J.P. Evaluation of association of HNF1B variants with diverse cancers: collaborative analysis of data from 19 genome-wide association studies. PLoS One. 2010;5(5):e10858.
Gross, A.L.; Kurman, R.J.; Vang, R.; Shih Ie, M.; Visvanathan, K. Precursor lesions of high-grade serous ovarian carcinoma: morphological and molecular characteristics. J Oncol. 2010;2010:126295.
Hong, S.K.; Chaturvedi, R.; Piazuelo, M.B.; Coburn, L.A.; Williams, C.S.; Delgado, A.G.; Casero, R.A., Jr.; Schwartz, D.A.; Wilson, K.T. Increased expression and cellular localization of spermine oxidase in ulcerative colitis and relationship to disease activity. Inflamm Bowel Dis. 2010 Sep;16(9):1557-1566.
Jinawath, N.; Vasoontara, C.; Jinawath, A.; Fang, X.; Zhao, K.; Yap, K.L.; Guo, T.; Lee, C.S.; Wang, W.; Balgley, B.M.; Davidson, B.; Wang, T.L.; Shih Ie, M. Oncoproteomic analysis reveals co-upregulation of RELA and STAT5 in carboplatin resistant ovarian carcinoma. PLoS One. 2010;5(6):e11198.
Jones, S.; Wang, T.L.; Shih Ie, M.; Mao, T.L.; Nakayama, K.; Roden, R.; Glas, R.; Slamon, D.; Diaz, L.A., Jr.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E.; Papadopoulos, N. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 2010 Oct 8;330(6001):228-231
Kuo, K.T.; Mao, T.L.; Chen, X.; Feng, Y.; Nakayama, K.; Wang, Y.; Glas, R.; Ma, M.J.; Kurman, R.J.; Shih Ie, M.; Wang, T.L. DNA copy numbers profiles in affinity-purified ovarian clear cell carcinoma. Clin Cancer Res. 2010 Apr 1;16(7):1997-2008.
Liu, K.J.; Brock, M.V.; Shih Ie, M.; Wang, T.H. Decoding circulating nucleic acids in human serum using microfluidic single molecule spectroscopy. J Am Chem Soc. 2010 Apr 28;132(16):5793-5798
Park, J.T.; Chen, X.; Trope, C.G.; Davidson, B.; Shih Ie, M.; Wang, T.L. Notch3 overexpression is related to the recurrence of ovarian cancer and confers resistance to carboplatin. Am J Pathol. 2010 Sep;177(3):1087-1094.
Satoh, H.; Moriguchi, T.; Taguchi, K.; Takai, J.; Maher, J.M.; Suzuki, T.; Winnard, P.T., Jr.; Raman, V.; Ebina, M.; Nukiwa, T.; Yamamoto, M. Nrf2-deficiency creates a responsive microenvironment for metastasis to the lung. Carcinogenesis. 2010 Oct;31(10):1833-1843.
Sheu, J.J.; Guan, B.; Choi, J.H.; Lin, A.; Lee, C.H.; Hsiao, Y.T.; Wang, T.L.; Tsai, F.J.; Shih Ie, M. Rsf-1, a chromatin remodeling protein, induces DNA damage and promotes genomic instability. J Biol Chem. 2010 Dec 3;285(49):38260-38269.
Shih Ie, M.; Chen, L.; Wang, C.C.; Gu, J.; Davidson, B.; Cope, L.; Kurman, R.J.; Xuan, J.; Wang, T.L. Distinct DNA methylation profiles in ovarian serous neoplasms and their implications in ovarian carcinogenesis. Am J Obstet Gynecol. 2010 Dec;203(6):584 e581-522.
Ueda, S.M.; Yap, K.L.; Davidson, B.; Tian, Y.; Murthy, V.; Wang, T.L.; Visvanathan, K.; Kuhajda, F.P.; Bristow, R.E.; Zhang, H.; Shih Ie, M. Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas. J Oncol. 2010;2010:285191.
Davidson, B.; Stavnes, H.T.; Holth, A.; Chen, X.; Yang, Y.; Shih, I.M.; Wang, T.L. Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from breast carcinoma in effusions. J Cell Mol Med. 2010 Jan 30.
Shih, I.M.; Nakayama, K.; Wu, G.; Nakayama, N.; Zhang, J.; Wang, T.L. Amplification of the ch19p13.2 NACC1 locus in ovarian high-grade serous carcinoma. Mod Pathol. 2011 Jan 14;Epub 1/14/11.
Activities & Honors
- Molecular diagnostics for malignant effusion, NCI/NIH , 2004 - 2012
- The Roles of HBXAP Gene in Ovarian Cancer, NCI/NIH , 2008 - 2013
- Pathogenesis of ovarian serous borderline tumors, NCI/NIH , 2007 - 2011
- Consortium Planning Award , Department of Defense, Ovarian Cancer Research Program , 2009 - 2010
- Nanobiosensing Method for Point Mutation Detection of Cancer, NCI/NIH , 2008 - 2010
- Notch3 Signaling Pathway in the Ovarian Carcinoma, American Cancer Society , 2008 - 2012
- American Association for Cancer Research
- United States and Canadian Association of Pathologists
- NCI/NIH, Member of Cancer Molecular Pathobiology Study Section (CAMP), 2006 - 2011
- NCI/NIH, L (12)B Cancer Diagnostic & Treatment Study Section, 2005 - 2007
Member of Onc
- NCI/NIH, IMAT (R21/R33) New innovative technology in cancer, 2002
Ad Hoc member
- NCI/NIH, Cancer Biomarkers Research Group, 2008
Early Detection Network (EDRN)
- Ovarian cancer research program, US DoD, 2005 - 2009