Damon Runyon News

Dr. Stinson studies the mechanism of non-homologous end joining (NHEJ), the primary method used by our cells to repair DNA double strand breaks (DSBs), a particularly toxic form of DNA damage in which a single piece of DNA is completely broken into two pieces. He is examining how the NHEJ machinery modifies DNA at DSBs to allow re-joining of the DNA molecule. This work will contribute to our knowledge of cancer development and treatment, as defects in NHEJ result in predisposition to cancer, and a number of common cancer treatments introduce DSBs that are primarily repaired by NHEJ.

Cancer cell metabolism differs from that of healthy cells because cancer cells have extreme requirements for energy. An organelle inside the cell called the lysosome has recently been defined as a “metabolic signaling center,” which senses cellular nutrient levels and communicates them to a growth regulator protein called mTORC1. Dr. Zoncu proposes to synthesize novel molecules that can specifically disable the lysosomal-mTORC1 signaling pathway as a new means of starving cancer cells and thus blocking tumor growth.

Variations in drug efficacy and toxicity between patients are a major limitation to the long-term treatment of cancer. Even if the initial treatment is successful, cancers can return due to the emergence of cancer drug resistance. Dr. Turnbaugh seeks to determine how the gut microbiome (bacteria residing in the human body) contributes to drug efficacy and resistance. He will combine microbiology and pharmacology approaches to identify new microbiome-based biomarkers for monitoring and predicting acquired drug resistance.

Dr. Romero is a biomedical engineer whose expertise is in the area of microfluidics. He proposes to develop new technology that can be used to detect circulating tumor cells (CTCs) in the bloodstream. CTCs are cells that have detached from a solid primary tumor and entered into the bloodstream; they can go on to colonize distant sites and form metastases. Detecting CTCs is an enormous challenge, as the cells are present at an ultra-low abundance (1 out of billions of blood cells).

Dr. Dixon aims to determine whether the altered metabolism of cancer cells creates new vulnerabilities that can exploited therapeutically. “Reductive stress” is a cellular concept in which too much glutathione could lead to cell growth arrest and death. He is investigating how a gene called NRF2 balances the demand for new glutathione synthesis with the need to avoid glutathione-mediated reductive stress.

[Island Outreach Foundation Innovator of the Damon Runyon-Rachleff Innovation Award]

Humans and the microbes in and on our bodies (“microbiota”) continuously interact in ways that influence health and disease—ways that we do not yet fully understand. Dr. Crawford, a chemical biologist, focuses on defining the bacterial contributions to colorectal cancer. DNA-damaging toxins (genotoxins) produced by bacteria in the human gut serve as cancer risk factors. He has developed an innovative genomics platform called M-PAIR, which he will use to identify novel cancer risk factors produced by the bacteria in the human gut.

The RAS oncogene is mutated in 20% of all human cancers. Different types of mutations occur that promote cancer initiation and progression, yet we do not yet understand the specificity of how each mutation affects RAS’ ability to promote cancer. Unfortunately, despite decades of scientific effort, there are no effective therapies to directly target RAS mutant cancers. Dr. Burd proposes novel, mutation-specific studies of RAS in a variety of tumor types, starting with melanoma, thyroid cancer, and acute myeloid leukemia (AML).