Researcher’s Profile

Antonia R. Sepulveda, MD, PhD

Vice Chair for Translational Research
Director, Division of Gastrointestinal Pathology

Antonia R. Sepulveda MD, PhD is Professor and Vice Chair for Translational Research and Director of the Division of Gastrointestinal Pathology at Columbia University Medical Center. She is an expert in gastrointestinal pathology and molecular diagnostic pathology of cancer. Her clinical practice provides specialized gastrointestinal, biliary and pancreas pathology diagnostic services with integration of molecular testing utilizing genomics, epigenomics 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 cancers and pre-cancer risk lesions). Dr. Sepulveda leadership is nationally 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 research is focused on an innovative integromics cancer research program exploring computationally generated networks integrating the molecular mechanisms and biomarkers of gastric and esophageal and pancreatic cancers and pre-cancer lesions. Through these cutting edge approaches Dr. Sepulveda hopes to define novel tumor types and regulatory pathways of cancer development and progression, and biomarkers for their diagnosis and therapy. Dr. Sepulveda has over 120 publications (original research, reviews, chapters and books).



Sepulveda JL, Gutierrez-Pajares JL, Luna A, Yao Y, Tobias JW, Thomas S, Woo Y, Georgio F, Komissarova E, Califano A, Wang TC, Sepulveda AR*. High Definition CpG Methylation of Novel Genes in Gastric Carcinogenesis Identified by Next Generation Sequencing. Modern Pathology. 2016 Feb;29(2):182-93.  PMID: 26769141

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

Margolskee, E, Koehne de Gonzalez, A, Moreira RK, Lagana, SL, Sepulveda, AR, Remotti, H, Lefkowitch, JH, Bao, F, Salomao, M. Immunohistochemical and targeted mutational analysis of hepatocellular adenomas. Diagn Pathol. 2016 Mar 9;11(1):27.  PMID:26961851

Lee Y, Urbanska A, Hayakawa Y, Wang H, Andrew Au, Luna A, Chang W, Jin G, Bhagat G, Abrams J, Friedman R, Varro A, Wang K, Boyce M, Rustgi A, Sepulveda A, Quante M, Wang TW. Gastrin stimulates a Cholecystokinin-2-Receptor-expressing cardia progenitor cell and promotes progression of Barrett's-like esophagus. Oncotarget, 2017 Jan 3;8(1):203-214. PMID: 27448962

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. Press release June 8 2015.

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

Hayakawa Y, Ariyama H, Stancikova J, Asfaha S, Muley A, Shibata W, Wang H, Dubeykovskaya ZA, Westphalen CB, Renz BW, Tailor Y, Nagar K, Tomita H, Hara A, Sepulveda AR, Setlik W, Gershon MD, Ding L, Subhrajit S, Konieczny SF, Worthley DL, Korinek V, Wang TC. CXCL12/CXCR4-dependent perivascular niche regulates quiescent Mist1+ gastric stem cells and contributes to cancer development. Cancer Cell. 14;28(6):800-14. 2015. PMID:26585400

Molecular and histologic considerations in the assessment of serrated polyps. Yang HM, Mitchell JM, Sepulveda JL, Sepulveda AR*. Arch Pathol Lab Med. 2015 Jun;139(6):730-41. PMID: 26030242

New Insights into the Genetics of Fetal Megacystis: ACTG2 Mutations, Encoding γ-2 Smooth Muscle Actin in Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (Berdon Syndrome). Tuzovic L, Tang S, Miller RS, Rohena L, Shahmirzadi L, Gonzalez K, Li X, LeDuc CA, Guo J, Wilson A, Mills A, Glassberg K, Rotterdam H, Sepulveda AR, Zeng W, Chung WK, Anyane-Yeboa K. Fetal Diagn Ther. 2015. PMID: 25998219

Lagana S, Hsiao S, Bao F, Sepulveda A, Moreira R, Lefkowitch J, Remotti H. HepPar-1 and Arginase-1 in small intestinal and ampullary adenocarcinoma. Arch Pathol Lab Med. 2015 Jun;139(6):791-5. doi: 10.5858/arpa.2013-0249-OA. PMID: 26030248

Zutter MM, Bloom KJ, Cheng L, Hagemann IS, Kaufman JH, Krasinskas AM, Lazar AJ, Leonard DG, Lindeman NI, Moyer AM, Nikiforova MN, Nowak JA, Pfeifer JD, Sepulveda AR, Willis JE, Yohe SL. The Cancer Genomics Resource List 2014. Arch Pathol Lab Med. PMID: 25436904.

Frank R, Li S, Ahmad NA, Sepulveda AR, Jhala NC. Mesothelin expression in pancreatic mucinous cysts. Am J Clin Pathol. 142(3):313-9, 2014. PMID: 25125620.

Fasanella KE, Bista RK, Staton K, Rizvi S, Uttam S, Zhao C, Sepulveda A, Brand RE, McGrath K, Liu Y. Nuclear Nano-architecture Markers of Gastric Cardia and Upper Squamous Esophagus Detect Esophageal Cancer "Field Effect". J Cancer. 4(8):626-634, 2013. PMID: 24155774.

Sohal DP, Mykulowycz K, Uehara T, Teitelbaum UR, Damjanov N, Giantonio BJ, Carberry M, Wissel P, Jacobs-Small M, O'Dwyer PJ, Sepulveda A, Sun W. A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. Ann Oncol. (12):3061-5, 2013. PMID: 24146220.

Kim J, Hoffman JP, Alpaugh RK, Rhim AD, Reichert M, Stanger BZ, Furth EE, Sepulveda AR, Yuan CX, Won KJ, Donahue G, Sands J, Gumbs AA, Zaret KS. An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression. Cell Rep. 3 (6):2088-2099, 2013. PMID: 23791528.

Uehara T, Ma D, Yao Y, Lynch JP, Morales N, Ziober A, Feldman M, Ota H, Sepulveda AR*. H. pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer. Dig Dis Sci. 58(1):140-149, 2013. PMID: 22945475. * (Highlighted in Editorial)

Aisner DL, Deshpande C, Baloch Z, Watt CD, Litzky LA, Malhotra B, Sepulveda A, Langer C, Evans T, Van Deerlin VM. Evaluation of EGFR mutation status in cytology specimens: An institutional experience. Diagn Cytopathol.  41(4):316-23, 2013. PMID: 22102479.

McAfee Q, Zhang Z, Samanta A, Levi SM, Ma XH, Piao S, Lynch JP, Uehara T, Sepulveda AR, Davis LE, Winkler JD, Amaravadi RK. A novel autophagy inhibitor with single agent antitumor activity reproduces the intestinal phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A. 109(21):8253-8258, 2012. PMID: 22566612.

Kong J, Crissey MA, Sepulveda AR, Lynch JP. Math1/Atoh1 Contributes to Intestinalization of Esophageal Keratinocytes by Inducing the Expression of Muc2 and Keratin-20. Dig Dis Sci. 57(4):845-857, 2011. PMID: 22147253.

Kong J, Crissey MAS, Stairs DB, Sepulveda AR, Lynch JL. Cox2 and beta-catenin/TCF signaling intestinalize human esophageal keratinocytes when cultured under organotypic conditions. Neoplasia. 13 (9):792-805, 2011. PMID: 21969813.

Yang Y, Nakagawa H, Tetreault MP, Billig J, Victor N, Goyal A, Sepulveda AR, Katz J.  Krüppel-like factor 5 loss in the context of p53 mutation or loss drives invasive human squamous cell cancer. Cancer Res. 71(20):6475-6484, 2011. PMID: 21868761.

Ma H, Lu C, Ziegler J, Liu A, Sepulveda A, Okada H, Lentzsch S, Mapara MY. Absence of Stat1 in donor CD4+ T cells promotes the expansion of Tregs and reduces graft-versus-host disease in mice. J Clin Invest. 121(7):2554-2569, 2011. PMID: 21670504.

King CE, Cuatrecasas M, Castells A, Sepulveda AR, Lee JS, Rustgi AK. LIN28B Promotes Colon Cancer Progression and Metastasis. Cancer Res. 71(12): 4260-4268, 2011. PMID: 21512136.

Sheikh SZ, Hegazi RA, Kobayashi T, Onyiah JC, Russo SM, Matsuoka K, Sepulveda AR, Li F, Otterbein LE, Plevy SE. An Anti-Inflammatory Role for Carbon Monoxide and Heme Oxygenase-1 in Chronic Th2-Mediated Murine Colitis. J Immunol. 186(9): 5506-5513, 2011. PMID: 21444764.

Ma HH, Ziegler J, Li C, Sepulveda A, Bedeir A, Grandis J, Lentzsch S, Mapara MY. Sequential activation of inflammatory signaling pathways during graft-versus-host disease (GVHD): Early role for STAT1 and STAT3. Cell Immunol. 268(1): 37-46, 2011. PMID: 21376308.

Uno JK, Rao KN, Matsuoka K, Sheikh SZ, Kobayashi T, Li F, Steinbach EC, Sepulveda AR, Vanhaesebroeck B, Sartor RB, Plevy SE. Altered Macrophage Function Contributes to Colitis in Mice Defective in the Phosphoinositide-3 Kinase Subunit p110δ. Gastroenterology. 139(5):1642-1653, 2010. PMID: 20637203.

Sepulveda AR*, Yao Y, Yan W, Park DI, Kim JJ, Gooding W, Abudayyeh S, Graham DY. CpG Methylation and Reduced Expression of O6-Methylguanine DNA Methyltransferase is Associated with H. pylori Infection. Gastroenterology. 138(5): 1836-44, 2010. PMID: 20044995.

Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pesci M, Harrison J, Plevy SE. Infliximab Prevents Crohn's Disease Recurrence after Ileal Resection. Gastroenterology. 136(2): 441-450, 2009. PMID: 19109962.

Yoshizawa K, Jelezcova E, Brown AR, Foley JF, Nyska A, Cui X, Hofseth LJ, Maronpot RM, Wilson SH, Sepulveda AR, Sobol RW. Gastrointestinal hyperplasia with altered expression of DNA polymerase beta. PLoS One 4(8): e6493, 2009. PMID: 19654874.

Davé SH, Tilstra JS, Matsuoka K, Li F, Demarco RA, Beer-Stolz D, Sepulveda AR, Fink MP, Lotze MT, Plevy SE. Ethyl pyruvate decreases HMGB1 release and ameliorates murine colitis. J Leukoc Biol.  86(3): 633-6443, 2009. PMID: 19454652.

Liu A, Tetzlaff MT, Vanbelle P, Elder D, Feldman M, Tobias JW, Sepulveda AR, Xu X. MicroRNA Expression Profiling Outperforms mRNA Expression Profiling in Formalin-fixed Paraffin-embedded Tissues. Int J Clin Exp Pathol. 2(6), 519-527, 2009. PMID: 19636399.

Gologan A, Acquafondata M, Dhir R., Sepulveda AR*. PIgR-Negative Tumors Represent a More Aggressive Type of Adenocarcinomas of Distal Esophagus and Gastroesophageal Junction. Arch Pathol Lab Med. 132(8): 1295-1301, 2008. PMID: 18684029.

Dore MP, Sepulveda AR, Pedroni A, Realdi G, Delitala G. Reversal of elevated pancreatic enzymes after Helicobacter pylori eradication.  Intern Emerg Med.  3(3): 269-70, 2008. PMID: 18264669.

Bo J, Kimbrell HZ, Sepulveda A, Yu G. Lymphoepithelial Cysts of the Pancreas:  Endosonography guided fine needle aspiration. Diagn Cytopathol. 36(9): 662-665, 2008. PMID: 18677749.

O'Keefe SJ, Chung D, Mahmoud N, Sepulveda AR, Manafe M, Arch J, Adada H, van der Merwe T. Why do African Americans get more colon cancer than Native Africans? J Nutr. Jan;137(1 Suppl): 175S-182S, 2007. PMID: 17182822.

Davé SH, Tilstra JS, Matsuoka K, Li F, Karrasch T, Uno JK, Sepulveda AR, Jobin C, Baldwin AS, Robbins PD, Plevy SE. Amelioration of chronic murine colitis by peptide-mediated transduction of the IkappaB kinase inhibitor NEMO binding domain peptide. J Immunol. 179(11): 7852-7859, 2007. PMID: 18025231.

Krasinskas AM, Yao Y, Randhawa P, Dore MP, Sepulveda AR. Helicobacter pylori may play a contributory role in the pathogenesis of primary sclerosing cholangitis. Dig Dis Sci. 52(9): 2265-2270, 2007. PMID: 17393314.

Beatty PL, Plevy SE, Sepulveda AR, Finn OJ. Cutting edge: transgenic expression of human MUC1 in IL-10-/- mice accelerates inflammatory bowel disease and progression to colon cancer. J Immunol. 179(2): 735-739, 2007. PMID: 17617560.

Park DI, Kang MS, Oh SJ, Kim HJ, Cho YK, Sohn CI, Jeon WK, Kim BI, Han WK, Kim H, Ryu SH, Sepulveda AR. HER-2/neu overexpression is an independe