• Welcome to the O'Hagan Laboratory

  • Research

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    The overall focus of the O’Hagan lab is to determine how epigenetic factors contribute to cancer initiation, progression, and therapy response. Previously, we focused on how the acute chromatin response to inflammation and/or DNA damage causes heritable epigenetic changes during carcinogenesis. Currently, we are interested in how standard of care therapies and activated signaling pathways lead to altered epigenetic states that promote cancer progression and therapy resistance. We approach our overall research theme from several different directions:

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    1) Elucidating the role of epigenetic factors in secretory cell specification in colorectal cancer.

    BRAF activating mutations occur in approximately 10% of metastatic colorectal cancer and are associated with worse prognosis due to an inferior response to standard chemotherapy. We have demonstrated that BRAF mutant colorectal cancer uniquely contains enteroendocrine cell progenitors that promote cancer cell survival via secreted factors and that the differentiation state of these tumors is regulated by the lysine demethylase LSD1. We are currently exploring the role of enteroendocrine cells in promoting therapy resistance in BRAF mutant colorectal cancer and the mechanisms by which epigenetic factors regulate secretory cell differentiation in these cancers. We are also studying how secretory cells present in colorectal cancer interact with and alter the tumor immune microenvironment.

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    2) The role of altered DNA methylation in establishing and maintaining platinum resistance in ovarian cancer.

    Development of chemoresistance is one of the primary causes for high mortality rates in ovarian cancer. Several groups have established that epigenetic mechanisms like aberrant promoter DNA hypermethylation are linked to the development of platinum resistance. We are investigating how aberrant DNA methylation and subsequent transcriptional repression is initiated during acquisition of platinum resistance. Ovarian cancer stem cells are also enriched in recurrent platinum resistant tumors. Additional work in our group examines how the DNA damage response is altered in ovarian cancer stem cells to allow them to survive platinum treatment.

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    3) The mechanism by which signaling pathway activation alters the function of chromatin remodelers.

    Oncogenic mutations often result in aberrant activation of signaling pathways in cancer cells. Signaling pathways can alter the function of chromatin remodelers, which can in turn modify expression of genes that affect signaling pathways. We are exploring the connections between signaling pathway activation, function of chromatin remodelers, transcriptional responses, and cancer cell plasticity.

  • Join our group

    Graduate Students

    We accept graduate students through the following programs:

    Postdoctoral Fellows

    Please contact Dr. Heather O’Hagan

  • Lab Members

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    Heather M. O’Hagan, Ph.D.

    Associate Professor of Medical & Molecular Genetics,

    Medical Sciences Program

    B.S. Biology, College of William & Mary

    Ph.D. Cellular and Molecular Biology, University of Michigan Medical School

     

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    Ahmed Ghobashi

    Genome, Cell and Developmental Biology Graduate Student

    B.S. School of Pharmacy, Alexandria University, Egypt

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    Chris Ladaika

    Genome, Cell and Developmental Biology Graduate Student

    B.S. Molecular Genetics, The Ohio State University

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    Rosie Lanzloth

    Genome, Cell and Developmental Biology Graduate Student

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    Truc Vuong

    Cell, Molecular and Cancer Biology Graduate Student

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  • Will Boulton

    Undergraduate Researcher

    Jane Kimani

    Undergraduate Researcher

  • Former lab members

    Shruthi Sriramkumar, Ph.D. (former graduate students) - Postdoctoral researcher, Dr. Rugang Zhang's lab at The Wistar Institute

    Riddhi Sood, Ph.D. (former graduate student) - Field Application Scientist, Thermo Fisher Scientific

    Samuel Miller, Ph.D. (former graduate student) - Computational Biologist, Cellarity

    Sudha S. Savant, Ph.D. (former postdoc) - Senior Application Scientist, Beckman Coulter Life Sciences

    Ning Ding, Ph.D. (former graduate student) - Scientist, Biogen

    Ashley R. Maiuri, Ph.D. (former postdoc) – Toxicology Consultant, Integrated Nonclinical Development Solutions

    Emily Bonham (former undergraduate researcher)

    Timothy Matthews (former undergraduate researcher)

    Abriana Warren (former undergraduate researcher)

    Lauren Lad (former undergraduate researcher)

    Mariel Carozza (former undergraduate researcher)

    Michael Peng (former undergraduate researcher)

    Sikai Xiao (former laboratory technician) - Graduate Student Dartmouth College

    Victoria Duffin (former laboratory technician) – Laboratory technician at IUPUI

  • Publications

    Select O'Hagan Lab Publications

     

    For full list see: https://www.ncbi.nlm.nih.gov/myncbi/heather.o'hagan.1/bibliography/public/

    or https://scholar.google.com/citations?user=EK8xP0YAAAAJ&hl=en

     

    GhobashiAH, VuongTT, Kimani JW, Ladaika CA, Hollenhorst PC, O’Hagan HM. (2023). Activation of AKT induces EZH2-mediated β-catenintrimethylation in colorectal cancer. iScience. 26(9):107630. 

     

    Sriramkumar S, Sood R, HuntingtonTD, Ghobashi AH, Vuong TT, Metcalfe TX, Wang W, Nephew KP, O'Hagan HM. (2022) Platinum-inducedmitochondrial OXPHOS contributes to cancer stem cell enrichment in ovarian cancer. J Transl Med. 20(1):246.

     

    Miller SA, Policastro RA, Sriramkumar S, Lai T, Huntington TD, Ladaika CA, Kim D, Hao C, Zentner GE, O’Hagan HM. (2021) LSD1 and aberrant DNA methylation mediate persistence of enteroendocrine progenitors that support BRAF mutant colorectal cancer. Cancer Research. 81(14):3791-3805.

     

    DeStefano Shields CE, White JR, Chung L, Wenzel A, Hicks JL, Tam AJ, Chan JL, Dejea CM, Fan H, Maiuri AR, Sriramkumar S, Podicheti R, Rusch DB, Wang H, De Marzo AM, Huso DL, Besharati S, Anders RA, Baylin SB, O'Hagan HM#, Housseau F#, Sears CL#. (2021) Bacterial-driven inflammation and mutant BRAF expression combine to promote murine colon tumorigenesis that is sensitive to immune checkpoint therapy. Cancer Discovery. 11(7):1792-1807. #Co-corresponding authors

     

    Miller SA, Ghobashi AH, O’Hagan HM. (2021) Consensus molecular subtyping of colorectal cancers is influenced by goblet cell content. Cancer Genetics. 254-255:34-39.

     

    Sriramkumar S, Matthews TD, Ghobashi AH, Miller SA, VanderVere-Carozza PS, Pawelczak KS, Nephew KP, Turchi JJ, O’Hagan HM. (2020) Platinum-Induced Ubiquitination of Phosphorylated H2AX by RING1A is Mediated by Replication Protein A in Ovarian Cancer. Molecular Cancer Research. 18(11):1699-1710.

     

    Miller SA, Policastro RA, Savant SS, Sriramkumar S, Ding N, Lu X, Mohammad HP, Cao S, Kalin JH, Cole PA, Zentner GE, O’Hagan HM. (2019) LSD1 mediates AKT activity in PIK3CA mutant colorectal cancer. Molecular Cancer Research. 18(2):264-277. Featured as the February 2020 “Editor’s Pick”.

     

    Maiuri AR, Savant SS, Podicheti R, Rusch DB, O'Hagan HM. (2019) DNA methyltransferase inhibition reduces inflammation-induced colon tumorigenesis. Epigenetics. 14(12):1209-1223.

     

    Ding N, Miller S, Savant SS, O’Hagan HM. (2019) JAK2 regulates mismatch repair protein-mediated epigenetic alterations in response to oxidative damage. Environmental & Molecular Mutagenesis. 60(4):308-319.

     

    Savant SS, Sriramkumar S, O’Hagan HM. (2018) The Role of Inflammation and Inflammatory Mediators in the Development, Progression, Metastasis, and Chemoresistance of Epithelial Ovarian Cancer. Cancers. 10(8). pii: E251. Selected as "Editor's Choice Article".

     

    Maiuri, AR, Li, H, Stein, BD, Tennessen, JM, and O'Hagan, HM. (2018) Inflammation-induced DNA methylation of DNA polymerase gamma alters the metabolic profile of colon tumors. Cancer & Metabolism. 6, 9. eCollection 2018.

     

    Tang J, Pulliam N, Özeş A, Buechlein A, Ding N, Keer H, Rusch D, O'Hagan HM, Stack MS, and Nephew KP. (2018) Epigenetic Targeting of Adipocytes Inhibits High-Grade Serous Ovarian Cancer Cell Migration and Invasion. Mol Cancer Res. 16(8):1226-1240.

     

    Maiuri AR, Peng M, Sriramkumar S, Kamplain CM, DeStefano Shields CE, Sears CL, and O'Hagan HM. (2017) Mismatch Repair Proteins Initiate Epigenetic Alterations during Inflammation-Driven Tumorigenesis. Cancer Res. 77(13):3467-3478. Epub 2017 May 18.

     

    Ding N, Bonham EM, Hannon BE, Amick TR, Baylin SB and O'Hagan HM. (2016). Mismatch repair proteins recruit DNA methyltransferase 1 to sites of oxidative DNA damage. J Mol Cell Bio. 8(3): 244-54. Epub July 17, 2015.

     

    O'Hagan HM, Wang W, Sen S, Destefano Shields C, Lee SS, Zhang YW, Clements EG, Cai Y, Van Neste L, Easwaran H, Casero RA, Sears CL and Baylin SB. (2011). Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG islands. Cancer Cell. 20(5): 606-19. PMCID: PMC3220885.

     

    O'Hagan HM, Mohammad HP and Baylin SB. (2008). Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island. PLoS Genet. 4(8): e1000155. PMCID: PMC2491723.

  • News

    Fall 2023

    Rosie and Truc passed their preliminary exams!

    Jane recieved travel awards to attend the Annual Biomedical Research Conference for Minoritized Scientists (ABRCMS).

    Spring 2023

    Chris received the Doane and Eunice Dahl Wright Fellowship to support his graduate research and an IUSCCC Trainee Pilot Award.

    Fall 2021

    Shruthi successfully defended her PhD thesis!

    Ahmed and Chris presented their work at the IUSCCC Cancer Research Day where Ahmed received a 2nd place poster presentation award.

    Spring 2021

    Heather's promotion to Associate Professor was approved by the IU Board of Trustees.

    Sam and Riddhi successfully defended their PhD theses!

    Ahmed received the Doane and Eunice Dahl Wright Fellowship to support his graduate research.

    Fall 2020

    Shruthi Sriramkumar presented her work at the 2020 Annual EMGS meeting.

    Spring 2019

    Shruthi received the Doane and Eunice Dahl Wright Fellowship to support her graduate research.

    Sam, Shruthi and Riddhi presented their work at the IUSCC Cancer Research Day where Sam and Shruthi received 1st and 2nd place poster presentation awards in the basic sciences.

    Shruthi and Riddhi presented their work at the 21st Annual Midwest DNA Repair Symposium at Washington University in St. Louis where Shruthi won a poster presentation award.

    Sam presented his work at the Cancer Genetics and Epigenetics Gordon Research Conference. Sam received travel awards from the IU Graduate and Professional Government and the IU College of Arts and Sciences to attend this conference.

    Shruthi presented her work at the AACR Annual Meeting.

    Fall 2018

    Sam received the 2018 CTSI Kroenke Poster Award for his poster presentation at the 2018 Indiana CTSI Annual Meeting.

    Shruthi received a IUB Graduate & Professional Student Government Fall Travel Award.

    Sudha received an IUSM Postdoctoral Travel Award to attend the AACR Intestinal Stem Cells and Colon Cancer: Biology to Therapy meeting.

    August 2018

    Dr. Ning Ding successfully defended his thesis and obtained his PhD.

    May 2018

    Ning, Riddhi, Sam, Shruthi, and Sudha presented their work at IU Simon Cancer Center’s Cancer Research Day.

    Ning received a 2nd place poster presentation award in Translational / Clinical Research at Cancer Research Day.

    Shruthi received a 3rd place poster presentation award in Basic Science at Cancer Research Day.

    August 2017

    Ning Ding received the Doane and Eunice Dahl Wright Fellowship to support his graduate research.

    June 2017

    Samuel Miller received an Indiana CTSI Translational Sciences Predoctoral Training Award to support his graduate research.

    May 2017

    Shruthi Sriramkumar and Ning Ding presented their work at the 19th Annual Midwest DNA Repair Symposium at Wright State University.

    Ning Ding won a second place award for his platform presentation at the 19th Annual Midwest DNA Repair Symposium.

  • Connect With Us

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    Heather’s email is hmohagan@indiana.edu

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    Heather’s office phone: 812-855-3035

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    We are located in Biology Building, Indiana University, Bloomington, Indiana University

  • Funding

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    National Institute of Environmental Health Sciences R01

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    Research Enhancement Grant and Pilot Funding for Research Use of Core Facilities

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    Pilot Award

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    Doane and Eunice Dahl Wright Fellowships (to Ning Ding, Shruthi Sriramkumar, Ahmed Ghobashi, Chris Ladaika)

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    Department of Defense Ovarian Cancer Research Program