Research
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:
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 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.
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.
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.
Lab Members
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
Chris Ladaika
Genome, Cell and Developmental Biology Graduate Student
B.S. Molecular Genetics, The Ohio State University
Rosie Lanzloth
Genome, Cell and Developmental Biology Graduate Student
B.S. Biology for Health, Reims Champagne Ardenne University
M.Sc. Biology Forensic Science, Strathclyde University
Truc Vuong
Cell, Molecular and Cancer Biology Graduate Student
B.S. Biology, University of Utah
M.S. Biomedical Informatics, University of Utah
Averi Chakraborty
Cell, Molecular and Cancer Biology Graduate Student
B.Tech M.Tech. Biotechnology, Kalinga Institute of Industrial Technology
Daisy Robles-Magallanes
Biotechnology Masters Student
B.S. Neuroscience, Indiana University
Joo Mi Yi, Ph.D.
Visiting Associate Research Professor
Associate Professor, Department of Microbiology and Immunology, Inje University
Ph.D. Biology, Pusan National University, Korea
Ph.D. Kyoto University, Japan
M.S., B.S. Biology, Pusan National University
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Will Boulton
Undergraduate Researcher
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Rena Han
Undergraduate Researcher
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Lab photos
Connect With Us
Heather’s email is hmohagan@
iu.edu 
Heather’s office phone: 812-855-3035
We are located in Biology Building, Indiana University, Bloomington, Indiana University
Funding
National Institute of Environmental Health Sciences R01
Research Enhancement Grant and Pilot Funding for Research Use of Core Facilities
Pilot Award
Doane and Eunice Dahl Wright Fellowships (to Ning Ding, Shruthi Sriramkumar, Ahmed Ghobashi, Chris Ladaika)
Department of Defense Ovarian Cancer Research Program
National Cancer Institute R01
