The latest issue of the journal Cancer Genomics and Proteomics features new research published by Elliott Associate Professor of Biology Dr. Kristian M. Hargadon ’01. Dr. Hargadon’s latest work describes a novel role for the FOXC2 transcription factor as a driver of melanoma progression, and his study represents the first to investigate FOXC2 function in the context of this particular type of cancer. Dr. Hargadon began investigating FOXC2’s role in melanoma progression in 2015, after previous work in his laboratory demonstrated elevated FOXC2 gene expression in a highly aggressive mouse melanoma model. Over the last 4 years, Dr. Hargadon has involved several Hampden-Sydney College students in projects designed to understand FOXC2 function in melanoma cells. This work included the use of CRISPR-Cas9 gene-editing technology to engineer a novel FOXC2-deficient melanoma cell line that exhibited delayed outgrowth in experimental animals. Subsequent gene expression analyses using this novel cell line demonstrated that FOXC2 regulates several oncogenic pathways in melanoma cells, including drug resistance and responsiveness to important components of the immune system. The significance of this work in the mouse model is highlighted by similar findings in tumor biopsies of melanoma patients. Dr. Hargadon and his students analyzed patient data from The Cancer Genome Atlas and found that high FOXC2 gene expression correlates with poor patient survival following treatment with either chemotherapy or immunotherapy. These findings suggest that FOXC2 might serve as a useful biomarker in predicting melanoma patient response to these therapeutic modalities, and they also highlight the utility of Dr. Hargadon’s mouse model for investigating how FOXC2 promotes drug and immune resistance in melanoma cells in future studies.

This multi-year project included contributions from 6 H-SC students, all of whom worked with Dr. Hargadon through either Hampden-Sydney College’s Summer Research Program or its Honors Capstone Program. These students are included as co-authors on the research paper in Cancer Genomics and Proteomics and are listed below:

Jefferson Thompson ’16 – attending Arkansas College of Osteopathic Medicine
Coleman Johnson ’19 – attending Virginia Commonwealth University School of Medicine
Corey Williams ’19 – attending Virginia Commonwealth University School of Medicine
David Bushhouse ’19 – attending Northwestern University Interdisciplinary Biological Sciences Ph.D. Program
Eli Strong ’20 – will attend George Washington University School of Medicine in 2020
Brian Tarnai ’20 – will attend George Washington University School of Medicine in 2020

Dr. Hargadon’s research article is available at: http://cgp.iiarjournals.org/content/16/6/491.full.pdf+html