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Antonia Sepulveda Chair, Department of Pathology Ralph E. Loewy Professor of Oncology Professor of Pathology Office Phone: 202-677-6607 Email: Email Department: Pathology |
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Education
- MD, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal, 1984
- PhD in Biology, Baylor College of Medicine, Houston, Texas, 1996
Biography
Antonia R. Sepulveda MD, PhD is a professor in and chairwoman of the Department of Pathology at George Washington University (GW). She is an expert in gastrointestinal pathology and genomic and molecular diagnostic pathology. Before joining GW, Dr. Sepulveda was the director of the Division of Gastrointestinal Pathology at Columbia University in New York, where she was also director of the gastrointestinal pathology fellowship program and vice-chair for translational research.
Her clinical practice provides specialized gastrointestinal, biliary and pancreas pathology diagnostic services with integration of molecular testing utilizing genomics and specific tumor biomarkers for personalized cancer management and precision medicine of digestive organ cancers and pre-cancer conditions (esophageal cancer and Barrett's esophagus, gastric, colorectal, pancreas, and biliary pre-cancer lesions and cancers).
Dr. Sepulveda is the medical director of the Genomic and Molecular Pathology division at GW University Department of Pathology, which provides testing for cancer and pre-cancer to meet the needs of precision cancer therapies and molecular virology testing, including COVID-19 SARS-CoV-2 testing.
Dr. Sepulveda's leadership is nationally and internationally recognized. She has been the lead co-chair for the “Molecular testing guidelines for colorectal cancer”, a combined initiative of the American Society for Clinical Pathology, College of American Pathologists Pathology and Laboratory Quality Center, Association for Molecular Pathology and the American Society of Clinical Oncology. Dr. Sepulveda has held many leadership positions and is currently President-elect and member of the Board of Directors of the Association for Molecular Pathology (AMP).
Dr. Sepulveda’s research laboratory receives funding from the NCI and is focused on innovative cancer and pre-cancer biomarkers to improve cancer prevention and treatment. The Sepulveda laboratory integrates cutting edge experimental approaches to define the molecular mechanisms and to discover biomarkers of gastric, esophageal, colorectal and pancreatic cancers and pre-cancer lesions. Dr. Sepulveda has over 170 publications (original research, reviews, chapters and books).
Clinical Expertise
Dr. Sepulveda’s clinical practice focus is to provide pathology diagnosis of digestive, pancreatic and biliary tract diseases with integration of molecular testing for personalized cancer therapies.
Dr. Sepulveda and her team provide diagnostic services for molecular pathology: mutation reports from Next Generation Sequencing gene panels, microsatellite instability, DNA mismatch repair IHC, PDL1 scores, HER2 amplification by CISH and other tests (link to genomic and molecular pathology diagnostic services at GW Department of Pathology).
Research
The Sepulveda's Research Laboratory is located in the George Washington University Cancer Center. Studies are centered primarily in digestive organ cancers (esophagus, stomach, colorectum, biliary tract and pancreas), toward discoveries of underlying molecular mechanisms, biomarkers for cancer risk, prediction of response to therapies and of inherited cancers.
Specific areas of ongoing research in the Sepulveda laboratory include:
Genomics and mechanisms of esophageal and gastric adenocarcinoma, pre-cancer lesions and Barrett’s esophagus:
-Genome wide and transcriptomic analyses of pre-cancer and cancer lesions using next generation sequencing (NGS), gene expression microarrays, and single cell RNAseq techniques.
Immune microenvironment of esophageal and gastrointestinal tract (esophageal, gastric and colorectal) pre-cancer and cancer lesions and immunotherapy biomarkers
-Characterization of immune microenvironment with multiplex quantitative immunofluorescence (qMIF) and digital pathology applications.
-Transcriptomic analysis and biomarker validations in tissue microarrays.
Genomic and transcriptomic biomarkers of pre-cancer and cancers
-Novel biomarker characterization for actionable mutations, transcript fusions, and genomic alterations for precision therapies
Publications
1. Kunze B, Wein F, Fang HY, Anand A, Baumeister T, Strangmann J, Gerland S, Ingermann J, Münch NS, Wiethaler M, Sahm V, Sastre AH, Lange S, Lightdale CJ, Bokhari A, Falk GW, Friedman RA, Ginsberg GG, Iyer PG, Jin Z, Nakagawa H, Shawber CJ, Nguyen T, Raab WJ, Dalerba P, Rustgi AK, Sepulveda AR, Wang KK, Schmid RM, Wang TC, Abrams JA, Quante M. Notch Signaling Mediates Differentiation in Barrett's Esophagus and Promotes Progression to Adenocarcinoma. Gastroenterology. 2020 Apr 20:S0016-5085(20)30516-3. doi: 10.1053/j.gastro.2020.04.033. Online ahead of print. PMID: 32325086
Chang W, Wang H, Kim W, Liu Y, Deng H, Liu H, Jiang Z, Niu Z, Sheng W, Nápoles OC, Sun Y, Xu J, Sepulveda A, Hayakawa Y, Bass AJ, Wang TC. Hormonal Suppression of Stem Cells Inhibits Symmetric Cell Division and Gastric Tumorigenesis. Cell Stem Cell. 2020 May 7;26(5):739-754.e8. doi: 10.1016/j.stem.2020.01.020. Epub 2020 Mar 5. PMID: 32142681
Jorge L Sepulveda, Elena V Komissarova, Sarawut Kongkarnka, Richard Friedman, Jon M Davison, Brynn Levy, Diana Bryk, Vaidehi Jobanputra, Armando Del Portillo, Gary W Falk, Charles J Lightdale, Julian A Abrams, Timothy C Wang, Antonia R SepulvedaHigh-Resolution Genomic Alterations in Barrett’s Metaplasia of Patients Who Progress to Esophageal Dysplasia and Adenocarcinoma. Int J Cancer, 2019 Nov 15;145(10):2754-2766. PMID: 31001805
Del Portillo A, Komissarova EV, Bokhari A, Hills, C, de Gonzalez AK, Kongkarnaka, S, Remotti HE, Sepulveda JL, and Sepulveda AR. Downregulation of Friend Leukemia Integration 1 (FLI1) Follows the Stepwise Progression to Gastric Adenocarcinoma. 2019, Oncotarget. 10(39):3852-3864. PMID: 31231464.
Maurer HC, Holmstrom SR, He J, Su T, Ahmed A, Hibshoosh H, Chabot JA, Oberstein PE, Sepulveda AR, Genkinger JM, Zhang J, Iuga AC, Bansal M, Califano A, and Olive KP. “Experimental microdissection enables functional harmonization of pancreatic cancer subtypes”. Gut. 2019 Jan 18. PMID: 30658994
Fazlollahi L, Remotti HE, Iuga A, Yang HM, Lagana SM, Sepulveda AR. HER2 Heterogeneity in Gastroesophageal Cancer Detected by Testing Biopsy and Resection Specimens. Arch Pathol Lab Med. 2018 Apr;142(4):516-522. PMID: 28782986
Mariano J. Alvarez, Prem S. Subramaniam, Adina Grunn, Gabrielle Rieckhof,,Elena V Komissarova, Elizabeth A Hagan, Lisa Bodei, Paul A. Clemons, Filemon S. Dela Cruz, Deepti Dhall, Daniel Diolaiti, Douglas A. Fraker, Afshin Ghavami, Daniel Kaemmerer, Mark Kidd, Kyoung M. Kim, Hee C. Kim, Lakshmi P. Kunju, Ülo Lange, Zhong Li, Jeeyun Lee, Virginia LiVolsi, Allison R. Rainey, Helen Ramotti, Jakob Regberg, Robert Roses, Anil Rustgi, Antonia R. Sepulveda, Stefano Serra, Chanjuan Shi, Xiaopu Yuan, Massimo Barberis, Roberto Bergamaschi, Arul M. Chinnaiyan, Tony Detre2, Shereen Ezzat, Andrea Frilling, Merten Hommann, Dirk Jaeger, Michelle K. Kim, Beatrice S. Knudsen, Andrew L. Kung, Emer Leahy, David C. Metz, Jeffrey W. Milsom, Young S. Park, Diane Reidy-Lagunes, Stuart Schreiber, Laura H. Tang, Kay Washington, Bertram Wiedenmann, Roswitha Pfragner, Irvin Modlin, Andrea Califano. A Precision Oncology Approach to the Pharmacological Targeting of Mechanistic Dependencies in Neuroendocrine Tumors. Nat Genet. 2018 Jul;50(7):979-989. PMID: 29915428
Jung Hoon Son, Benjamin Lebwohl, Antonia R Sepulveda, Stephen M Lagana. Utilization Rate of Helicobacter pylori Immunohistochemistry Is Not Associated with the Diagnostic Rate of Helicobacter pylori Infection. Appl Immunohistochem Mol Morphol. 2018 Nov 28. PMID: 30499817
9. Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, Kopetz SE, Lieu C, Lindor NM, Minsky BD, Monzon FA, Sargent DJ, Singh VM, Willis J, Clark J, Colasacco C, Rumble RB, Temple-Smolkin R, Ventura CB, Nowak JA. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017 May 1;35(13):1453-1486. PMID: 28165299
10. Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, Kopetz SE, Lieu C, Lindor NM, Minsky BD, Monzon FA, Sargent DJ, Singh VM, Willis J, Clark J, Colasacco C, Rumble RB, Temple-Smolkin R, Ventura CB, Nowak JA. . Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. The Journal of Molecular Diagnostics, 2017 Mar;19(2):187-225. PMID: 28185757.
Cancer Genome Atlas Research Network. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell. 2017 Aug 14;32(2):185-203.e13. PMID: 28810144
Hayakawa Y, Sethi N, Sepulveda AR, Bass AJ, Wang TC. Oesophageal adenocarcinoma and gastric cancer: should we mind the gap? Nat Rev Cancer. 2016 Apr 26;16(5):305-18. PMID: 27112208
Del Portillo A, Lagana SM, Yao Y, Uehara T, Jhala N, Ganguly T, Nagy P, Gutierrez J, Luna A, Abrams J, Liu Y, Brand R, Sepulveda JL, Falk GW, Sepulveda AR. Evaluation of Mutational Testing of Preneoplastic Barrett's Mucosa by Next-Generation Sequencing of Formalin-Fixed, Paraffin-Embedded Endoscopic Samples for Detection of Concurrent Dysplasia and Adenocarcinoma in Barrett's Esophagus. J Mol Diagn. 2015. pii: S1525-1578(15)00081-1. PMID: 26068095.
Salomao M, Luna A, Sepulveda JL, Sepulveda AR. Mutational analysis by next generation sequencing of gastric type dysplasia occurring in hyperplastic polyps of the stomach: Mutations in gastric hyperplastic polyps. Exp Mol Pathol. 2015. 99(3):468-73. PMID: 26325218
Amaravadi RK, Hamilton K, Ma X, Piao S, Chapman P, Del Portillo A, Nathanson KL, Carlino MS, Long GV, Puzanov I, Xu X, Morrissette JD, Flaherty KT, Sosman JA, Goodman G, McArthur G, Rustgi A, Metz D, Schuchter LM, Sepulveda AR. Prolonged BRAF inhibitor treatment can lead to the development of multiple gastrointestinal polyps. Clin Cancer Res. 2015. 21(23):5215-21. PMID: 26202952
Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.
- Bayer
- Bristol-Myers Squibb
- Merck
- Roche