Research Summary

Clinically, I am a Molecular Pathologist focused on using advanced, cutting edge tests to drive personalized medicine in cancer diagnostics and treatment.

My lab works to understand the process of premalignant progression to invasive cancer, specifically focusing on cancers (esophageal and gastric adenocarcinoma) and pre-malignant conditions (columnar and intestinal metaplasia or Barrett’s esophagus) of the upper gastrointestinal tract as a model system.

As a disease that is often closely monitored and sampled, Barrett’s esophagus and esophageal adenocarcinoma provides an idea system to study the changes leading up to and driving invasive disease. Additionally, Barrett’s esophagus and esophageal adenocarcinoma are extremely important diseases to understand in their own as esophageal adenocarcinoma has one of the fastest rising incidences of any solid tumor and despite our understanding that it arises from a metaplastic field, we still do an extremely poor job of identifying patients early before advanced disease develops.

We have taken the approach to first understand the factors important in human tissues through advanced ‘omics’ and digital imaging approaches and then use this understanding to build model systems and functional studies. It is our goal to use the knowledge and understanding gained in these studies to develop novel biomarkers, screening strategies, and treatments to identify and treat people early before advanced disease develops.

Research Funding

  • April 15, 2016 - March 31, 2022 - Early TP53 Mutations and Genomic Doubling as a Novel Path for Barrett's Esophagus Progression , Principal Investigator . Sponsor: NIH, Sponsor Award ID: K08DK109209

Education

The Ohio State University, B.S,  06/2001, Chemical Engineering
The Ohio State University, Ph.D., 06/2009, Molecular Biology
The Ohio State University, M.D., 06/2009. Medicine
Brigham and Women's Hospital, 06/2011, Resident, Pathology
Harvard Medical School, 06/2012, Fellow, Molecular Genetic Pathology
Brigham and Women's Hospital, 06/2013, Resident/Gastrointestinal Pathology Fellow

Selected Publications

Kumar A, Rara M, Yu M, Wen KW, Grady WM, Chak A, Iyer PG, Rustgi AK, Wang TC, Rubenstein JH, Liu Y, Kresty L, Westerhoff M, Kwon RS, Wamsteker E, Wang T, Berry L, Canto MI, Shaheen NJ, Wang KK, Abrams JA, Stachler MD. Molecular Analysis of Persistent and Recurrent Barrett's Esophagus in the Setting of Endoscopic Therapy. Clin Transl Gastroenterol. 2024 Aug 1;15(8):e00751. doi: 10.14309/ctg.0000000000000751. PubMed PMID: 39007490; PubMed Central PMCID: PMC11346883.

Stachler MD, Jin RU. Molecular Pathology of Gastroesophageal Cancer. Clin Lab Med. 2024 Jun;44(2):239-254. doi: 10.1016/j.cll.2023.08.005. Review. PubMed PMID: 38821643.

Stachler MD, Ain QU. Refining definitions of Barrett's oesophagus to improve clinical resource utilisation. Gut. 2024 Apr 5;73(5):715-716. doi: 10.1136/gutjnl-2023-331458. PubMed PMID: 38216329.

Qurat-Ul-Ain, Frei NF, Khoshiwal AM, Stougie P, Odze R, Camilleri-Broet S, Ferri L, Duits LC, Bergman J, Stachler MD. Feasibility Study Utilizing NanoString's Digital Spatial Profiling (DSP) Technology for Characterizing the Immune Microenvironment in Barrett's Esophagus Formalin-Fixed Paraffin-Embedded Tissues. Cancers (Basel). 2023 Dec 18;15(24). doi: 10.3390/cancers15245895. PubMed PMID: 38136440; PubMed Central PMCID: PMC10742302.

Rubenstein JH, Stachler MD. TSP-9: A Barrett's Esophagus Biomarker Better Than Pathologists?. Gastroenterology. 2023 Nov;165(5):1106-1107. doi: 10.1053/j.gastro.2023.08.041. Epub 2023 Sep 1. PubMed PMID: 37659675.

Bao C, Tourdot RW, Brunette GJ, Stewart C, Sun L, Baba H, Watanabe M, Agoston AT, Jajoo K, Davison JM, Nason KS, Getz G, Wang KK, Imamura Y, Odze R, Bass AJ, Stachler MD, Zhang CZ. Genomic signatures of past and present chromosomal instability in Barrett's esophagus and early esophageal adenocarcinoma. Nat Commun. 2023 Oct 4;14(1):6203. doi: 10.1038/s41467-023-41805-6. PubMed PMID: 37794034; PubMed Central PMCID: PMC10550953.

Odze R, Frei N, Khoshiwal AM, Duits LC, Bergman J, Stachler MD. Degree of crypt atypia correlates with progression to high-grade dysplasia/adenocarcinoma in non-dysplastic Barrett's oesophagus. Histopathology. 2023 Sep;83(3):406-413. doi: 10.1111/his.14959. Epub 2023 May 18. PubMed PMID: 37199687; PubMed Central PMCID: PMC10562012.

Chatterjee A, Azevedo-Martins JM, Stachler MD. Interleukin-33 as a Potential Therapeutic Target in Gastric Cancer Patients: Current Insights. Onco Targets Ther. 2023;16:675-687. doi: 10.2147/OTT.S389120. eCollection 2023. Review. PubMed PMID: 37583706; PubMed Central PMCID: PMC10424681.

Strasser MK, Gibbs DL, Gascard P, Bons J, Hickey JW, Schürch CM, Tan Y, Black S, Chu P, Ozkan A, Basisty N, Sangwan V, Rose J, Shah S, Camilleri-Broet S, Fiset PO, Bertos N, Berube J, Djambazian H, Li R, Oikonomopoulos S, Fels-Elliott DR, Vernovsky S, Shimshoni E, Collyar D, Russell A, Ragoussis I, Stachler M, Goldenring JR, McDonald S, Ingber DE, Schilling B, Nolan GP, Tlsty TD, Huang S, Ferri LE. Concerted epithelial and stromal changes during progression of Barrett's Esophagus to invasive adenocarcinoma exposed by multi-scale, multi-omics analysis. bioRxiv. 2023 Jun 11;. doi: 10.1101/2023.06.08.544265. PubMed PMID: 37333362; PubMed Central PMCID: PMC10274886.

Stachler MD. Bridging the Gap between Diseases of the Stomach and Lower Esophagus. Cancer Discov. 2023 Jun 2;13(6):1291-1293. doi: 10.1158/2159-8290.CD-23-0348. PubMed PMID: 37264822.

Moore J, Hekman R, Blum BC, Lawton M, Lehoux S, Stachler M, Pleskow D, Sawhney MS, Cummings RD, Emili A, Qureshi A. Pilot Study Showing Feasibility of Phosphoproteomic Profiling of Pathway-Level Molecular Alterations in Barrett's Esophagus. Genes (Basel). 2022 Jul 7;13(7). doi: 10.3390/genes13071215. PubMed PMID: 35885999; PubMed Central PMCID: PMC9325186.

Frei NF, Stachler MD. Today's Mistakes and Tomorrow's Wisdom in Development and Use of Biomarkers for Barrett's Esophagus. Visc Med. 2022 Jun;38(3):173-181. doi: 10.1159/000521706. Epub 2022 Feb 2. Review. PubMed PMID: 35814971; PubMed Central PMCID: PMC9210037.

Redston M, Noffsinger A, Kim A, Akarca FG, Rara M, Stapleton D, Nowden L, Lash R, Bass AJ, Stachler MD. Abnormal TP53 Predicts Risk of Progression in Patients With Barrett's Esophagus Regardless of a Diagnosis of Dysplasia. Gastroenterology. 2022 Feb;162(2):468-481. doi: 10.1053/j.gastro.2021.10.038. Epub 2021 Oct 29. PubMed PMID: 34757142; PubMed Central PMCID: PMC9341495.

Stachler MD, Jin RU. Molecular Pathology of Gastroesophageal Cancer. Surg Pathol Clin. 2021 Sep;14(3):443-453. doi: 10.1016/j.path.2021.05.008. Epub 2021 Jul 8. Review. PubMed PMID: 34373095.

Wu Z, Zhou J, Zhang X, Zhang Z, Xie Y, Liu JB, Ho ZV, Panda A, Qiu X, Cejas P, Cañadas I, Akarca FG, McFarland JM, Nagaraja AK, Goss LB, Kesten N, Si L, Lim K, Liu Y, Zhang Y, Baek JY, Liu Y, Patil DT, Katz JP, Hai J, Bao C, Stachler M, Qi J, Ishizuka JJ, Nakagawa H, Rustgi AK, Wong KK, Meyerson M, Barbie DA, Brown M, Long H, Bass AJ. Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence. Nat Genet. 2021 Jun;53(6):881-894. doi: 10.1038/s41588-021-00859-2. Epub 2021 May 10. PubMed PMID: 33972779; PubMed Central PMCID: PMC9124436.

Uppaluri R, Campbell KM, Egloff AM, Zolkind P, Skidmore ZL, Nussenbaum B, Paniello RC, Rich JT, Jackson R, Pipkorn P, Michel LS, Ley J, Oppelt P, Dunn GP, Barnell EK, Spies NC, Lin T, Li T, Mulder DT, Hanna Y, Cirlan I, Pugh TJ, Mudianto T, Riley R, Zhou L, Jo VY, Stachler MD, Hanna GJ, Kass J, Haddad R, Schoenfeld JD, Gjini E, Lako A, Thorstad W, Gay HA, Daly M, Rodig SJ, Hagemann IS, Kallogjeri D, Piccirillo JF, Chernock RD, Griffith M, Griffith OL, Adkins DR. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Clin Cancer Res. 2020 Oct 1;26(19):5140-5152. doi: 10.1158/1078-0432.CCR-20-1695. Epub 2020 Jul 14. PubMed PMID: 32665297; PubMed Central PMCID: PMC7547532.

van der Wel MJ, Coleman HG, Bergman JJGHM, Jansen M, Meijer SL. Histopathologist features predictive of diagnostic concordance at expert level among a large international sample of pathologists diagnosing Barrett's dysplasia using digital pathology. Gut. 2020 May;69(5):811-822. doi: 10.1136/gutjnl-2019-318985. Epub 2019 Dec 18. PubMed PMID: 31852770.

Sethi NS, Kikuchi O, Duronio GN, Stachler MD, McFarland JM, Ferrer-Luna R, Zhang Y, Bao C, Bronson R, Patil D, Sanchez-Vega F, Liu JB, Sicinska E, Lazaro JB, Ligon KL, Beroukhim R, Bass AJ. Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model. Nat Genet. 2020 Feb;52(2):219-230. doi: 10.1038/s41588-019-0574-9. Epub 2020 Feb 5. PubMed PMID: 32025000; PubMed Central PMCID: PMC7031028.

Zhang H, Schaefer A, Wang Y, Hodge RG, Blake DR, Diehl JN, Papageorge AG, Stachler MD, Liao J, Zhou J, Wu Z, Akarca FG, de Klerk LK, Derks S, Pierobon M, Hoadley KA, Wang TC, Church G, Wong KK, Petricoin EF, Cox AD, Lowy DR, Der CJ, Bass AJ. Gain-of-Function RHOA Mutations Promote Focal Adhesion Kinase Activation and Dependency in Diffuse Gastric Cancer. Cancer Discov. 2020 Feb;10(2):288-305. doi: 10.1158/2159-8290.CD-19-0811. Epub 2019 Nov 26. PubMed PMID: 31771969; PubMed Central PMCID: PMC7007383.

Frei NF, Stachler MD, Bergman JJGHM. Risk stratification in Barrett's esophagus patients with diagnoses of indefinite for dysplasia: the definite silver bullet has not (yet) been found. Gastrointest Endosc. 2020 Jan;91(1):11-13. doi: 10.1016/j.gie.2019.09.020. PubMed PMID: 31865984.

Stachler MD. Colorectal Adenocarcinoma, Not Just One Disease. Cell Mol Gastroenterol Hepatol. 2019;8(2):293-294. doi: 10.1016/j.jcmgh.2019.04.012. Epub 2019 May 23. PubMed PMID: 31129094; PubMed Central PMCID: PMC6717931.

Soong TR, Nayor J, Stachler MD, Perencevich M, Jajoo K, Saltzman JR, Lindeman NI, Srivastava A. Clinicopathologic and genetic characteristics of interval colorectal carcinomas favor origin from missed or incompletely excised precursors. Mod Pathol. 2019 May;32(5):666-674. doi: 10.1038/s41379-018-0176-6. Epub 2018 Nov 19. PubMed PMID: 30455417.

Yu M, Maden SK, Stachler M, Kaz AM, Ayers J, Guo Y, Carter KT, Willbanks A, Heinzerling TJ, O'Leary RM, Xu X, Bass A, Chandar AK, Chak A, Elliott R, Willis JE, Markowitz SD, Grady WM. Subtypes of Barrett's oesophagus and oesophageal adenocarcinoma based on genome-wide methylation analysis. Gut. 2019 Mar;68(3):389-399. doi: 10.1136/gutjnl-2017-314544. Epub 2018 Jun 8. PubMed PMID: 29884612; PubMed Central PMCID: PMC6565505.

Qureshi AP, Stachler MD, Haque O, Odze RD. Biomarkers for Barrett's esophagus - a contemporary review. Expert Rev Mol Diagn. 2018 Nov;18(11):939-946. doi: 10.1080/14737159.2018.1538793. Epub 2018 Nov 1. Review. PubMed PMID: 30345836.

Stachler MD, Camarda ND, Deitrick C, Kim A, Agoston AT, Odze RD, Hornick JL, Nag A, Thorner AR, Ducar M, Noffsinger A, Lash RH, Redston M, Carter SL, Davison JM, Bass AJ. Detection of Mutations in Barrett's Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma. Gastroenterology. 2018 Jul;155(1):156-167. doi: 10.1053/j.gastro.2018.03.047. Epub 2018 Mar 31. PubMed PMID: 29608884; PubMed Central PMCID: PMC6035092.

Johncilla M, Stachler M, Misdraji J, Lisovsky M, Yozu M, Lindeman N, Lauwers GY, Odze RD, Srivastava A. Mutational landscape of goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix is distinct from typical carcinoids and colorectal adenocarcinomas. Mod Pathol. 2018 Jun;31(6):989-996. doi: 10.1038/s41379-018-0003-0. Epub 2018 Feb 8. PubMed PMID: 29422640.

Pectasides E, Stachler MD, Derks S, Liu Y, Maron S, Islam M, Alpert L, Kwak H, Kindler H, Polite B, Sharma MR, Allen K, O'Day E, Lomnicki S, Maranto M, Kanteti R, Fitzpatrick C, Weber C, Setia N, Xiao SY, Hart J, Nagy RJ, Kim KM, Choi MG, Min BH, Nason KS, O'Keefe L, Watanabe M, Baba H, Lanman R, Agoston AT, Oh DJ, Dunford A, Thorner AR, Ducar MD, Wollison BM, Coleman HA, Ji Y, Posner MC, Roggin K, Turaga K, Chang P, Hogarth K, Siddiqui U, Gelrud A, Ha G, Freeman SS, Rhoades J, Reed S, Gydush G, Rotem D, Davison J, Imamura Y, Adalsteinsson V, Lee J, Bass AJ, Catenacci DV. Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma. Cancer Discov. 2018 Jan;8(1):37-48. doi: 10.1158/2159-8290.CD-17-0395. Epub 2017 Oct 4. PubMed PMID: 28978556; PubMed Central PMCID: PMC5894850.

Zhou J, Wu Z, Wong G, Pectasides E, Nagaraja A, Stachler M, Zhang H, Chen T, Zhang H, Liu JB, Xu X, Sicinska E, Sanchez-Vega F, Rustgi AK, Diehl JA, Wong KK, Bass AJ. CDK4/6 or MAPK blockade enhances efficacy of EGFR inhibition in oesophageal squamous cell carcinoma. Nat Commun. 2017 Jan 6;8:13897. doi: 10.1038/ncomms13897. PubMed PMID: 28059068; PubMed Central PMCID: PMC5227099.

Stachler MD, Rinehart EM, Garcia E, Lindeman NI. PIK3CA Mutations are Common in Many Tumor Types and are Often Associated With Other Driver Mutations. Appl Immunohistochem Mol Morphol. 2016 May-Jun;24(5):313-9. doi: 10.1097/PAI.0000000000000195. PubMed PMID: 26067136.

Derks S, Nason KS, Liao X, Stachler MD, Liu KX, Liu JB, Sicinska E, Goldberg MS, Freeman GJ, Rodig SJ, Davison JM, Bass AJ. Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma. Cancer Immunol Res. 2015 Oct;3(10):1123-1129. doi: 10.1158/2326-6066.CIR-15-0046. Epub 2015 Jun 16. PubMed PMID: 26081225; PubMed Central PMCID: PMC4596773.

Stachler MD, Taylor-Weiner A, Peng S, McKenna A, Agoston AT, Odze RD, Davison JM, Nason KS, Loda M, Leshchiner I, Stewart C, Stojanov P, Seepo S, Lawrence MS, Ferrer-Torres D, Lin J, Chang AC, Gabriel SB, Lander ES, Beer DG, Getz G, Carter SL, Bass AJ. Paired exome analysis of Barrett's esophagus and adenocarcinoma. Nat Genet. 2015 Sep;47(9):1047-55. doi: 10.1038/ng.3343. Epub 2015 Jul 20. PubMed PMID: 26192918; PubMed Central PMCID: PMC4552571.

Kaz AM, Grady WM, Stachler MD, Bass AJ. Genetic and Epigenetic Alterations in Barrett's Esophagus and Esophageal Adenocarcinoma. Gastroenterol Clin North Am. 2015 Jun;44(2):473-89. doi: 10.1016/j.gtc.2015.02.015. Epub 2015 Apr 1. Review. PubMed PMID: 26021206; PubMed Central PMCID: PMC4449457.

Stachler M, Jia Y, Sharaf N, Wade J, Longtine J, Garcia E, Sholl LM. Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping. Appl Immunohistochem Mol Morphol. 2015 May-Jun;23(5):389-96. doi: 10.1097/PAI.0000000000000086. PubMed PMID: 25221956.

Stachler MD, Rinehart E, Lindeman N, Odze R, Srivastava A. Novel molecular insights from routine genotyping of colorectal carcinomas. Hum Pathol. 2015 Apr;46(4):507-13. doi: 10.1016/j.humpath.2015.01.005. Epub 2015 Jan 14. PubMed PMID: 25683705.

Baden LR, Liu J, Li H, Johnson JA, Walsh SR, Kleinjan JA, Engelson BA, Peter L, Abbink P, Milner DA Jr, Golden KL, Viani KL, Stachler MD, Chen BJ, Pau MG, Weijtens M, Carey BR, Miller CA, Swann EM, Wolff M, Loblein H, Seaman MS, Dolin R, Barouch DH. Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans. J Infect Dis. 2015 Feb 15;211(4):518-28. doi: 10.1093/infdis/jiu485. Epub 2014 Aug 26. PubMed PMID: 25165165; PubMed Central PMCID: PMC4318919.

Hong YS, Kim J, Pectasides E, Fox C, Hong SW, Ma Q, Wong GS, Peng S, Stachler MD, Thorner AR, Van Hummelen P, Bass AJ. Src mutation induces acquired lapatinib resistance in ERBB2-amplified human gastroesophageal adenocarcinoma models. PLoS One. 2014;9(10):e109440. doi: 10.1371/journal.pone.0109440. eCollection 2014. PubMed PMID: 25350844; PubMed Central PMCID: PMC4211679.

Kanarek N, Grivennikov SI, Leshets M, Lasry A, Alkalay I, Horwitz E, Shaul YD, Stachler M, Voronov E, Apte RN, Pagano M, Pikarsky E, Karin M, Ghosh S, Ben-Neriah Y. Critical role for IL-1β in DNA damage-induced mucositis. Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):E702-11. doi: 10.1073/pnas.1322691111. Epub 2014 Jan 27. PubMed PMID: 24469832; PubMed Central PMCID: PMC3926043.

Baker K, Rath T, Flak MB, Arthur JC, Chen Z, Glickman JN, Zlobec I, Karamitopoulou E, Stachler MD, Odze RD, Lencer WI, Jobin C, Blumberg RS. Neonatal Fc receptor expression in dendritic cells mediates protective immunity against colorectal cancer. Immunity. 2013 Dec 12;39(6):1095-107. doi: 10.1016/j.immuni.2013.11.003. Epub 2013 Nov 27. PubMed PMID: 24290911; PubMed Central PMCID: PMC3902970.

Cheney PP, Stachler MD, Knowles MK. Single molecule tracking of P-glycoprotein in live cells reveals dynamic heterogeneity. Annu Int Conf IEEE Eng Med Biol Soc. 2012;2012:3159-62. doi: 10.1109/EMBC.2012.6346635. PubMed PMID: 23366596.

Giardino AA, Ramaiya NH, Shinagare AB, Jagannathan JP, Stachler MD, Raut CP. Case report: Calcifying fibrous tumor presenting as an asymptomatic pelvic mass. Indian J Radiol Imaging. 2011 Oct;21(4):306-8. doi: 10.4103/0971-3026.90700. PubMed PMID: 22223947; PubMed Central PMCID: PMC3249950.

 

Stachler MD, Chen I, Ting AY, Bartlett JS. Site-specific modification of AAV vector particles with biophysical probes and targeting ligands using biotin ligase. Mol Ther. 2008 Aug;16(8):1467-73. doi: 10.1038/mt.2008.129. Epub 2008 Jun 17. PubMed PMID: 18560418.

Arnold GS, Sasser AK, Stachler MD, Bartlett JS. Metabolic biotinylation provides a unique platform for the purification and targeting of multiple AAV vector serotypes. Mol Ther. 2006 Jul;14(1):97-106. doi: 10.1016/j.ymthe.2006.02.014. Epub 2006 Apr 19. PubMed PMID: 16624620.

Stachler MD, Bartlett JS. Mosaic vectors comprised of modified AAV1 capsid proteins for efficient vector purification and targeting to vascular endothelial cells. Gene Ther. 2006 Jun;13(11):926-31. doi: 10.1038/sj.gt.3302738. PubMed PMID: 16482202.

 

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