Major Research Interests

Overview
Tumor cells utilize a very diverse array of mechanisms to proliferate uncontrolled and metastasize. Irrespective of the underlying cause of a tumor, essentially all tumor-specific changes ultimately converge in the altered “expression” of genes in the cell. The goal of our work is to understand the molecular processes by which tumor-specific changes in gene activity lead to tumorigenesis and tumor progression. More importantly, we aim to utilize this information to identify better and more efficient therapies for various gastrointestinal tumors.

Targeting epigenetics for anti-cancer therapy
Since essentially all tumor-specific changes that occur during the formation and metastasis of cancer ultimately converge on the genetic material, it makes the processes which control gene activity ideal anti-cancer targets. In fact, researchers worldwide, as well as numerous pharmaceutical companies, have made significant progress in identifying new approaches to target “epigenetic” processes in cancer. Numerous clinical studies are ongoing which will help to determine which types of cancer may respond best to these therapies.

“Bromodomain” proteins in gastrointestinal cancers
The Johnsen group has been studying a specific group of “epigenetic” regulators called “bromodomain” proteins. These proteins essentially function as the “middle man” which convert different signaling processes into changes in the ability of a gene to be in an “on” or “off” state. Importantly, these proteins can be specifically targeted by small molecule drugs, many of which are in early clinical trials for different types of cancer. We are currently examining the molecular mechanisms by which bromodomain proteins work in cancer as well as deciphering the characteristics of individual tumors, which determine whether they will respond to these treatments. In this way, we hope to uncover new approaches to be able to identify specific therapeutic approaches for treating individual patients based on the molecular makeup of their tumors, an approach frequently referred to as “precision oncology”.