MGH Research Scholar Jonathan Whetstine, PhD, is investigating ways to prevent or overcome treatment-resistance in cancer.

Uncovering Epigenetic factors Regulating Copy Number and Drug Resistance

Jonathan Whetstine, PhD
Jonathan Whetstine, PhD
Tepper Family MGH Research Scholar 2014-2019
Associate Investigator, Mass General Cancer Center
Associate Professor of Medicine, Harvard Medical School

My laboratory is interested in understanding how the chromatin microenvironment regulates gene expression while maintaining a stable genome.

We interrogate this relationship by studying the role of histone modifying enzymes in both human culture and C. elegans models.

We have initiated these types of studies by focusing on a specific class of chromatin regulators, Jmjc-containing histone demethylases, that I discovered as a postdoctoral fellow.

Since this discovery, my laboratory has started screening both solid and hematopoietic cancer for genomic anomalies in this class of enzymes.

Additionally, we have begun examining their molecular roles at a biochemical, molecular and in vivo level.

We have uncovered roles for histone demethylases in modulating copy number and are expanding these analyses to additional chromatin modulators. We are also assessing the impact that these copy gain events have on cancer cell drug response.

In addition to the basic science, we are collaborating with oncologists to determine whether genomic alterations in chromatin regulators or their associated copy gains will allow us to modify conventional chemotherapy to treat these cancer subtypes and whether these changes will serve as novel molecular diagnostic.