Damon Runyon News

High levels of oxidative stress are a hallmark of many cancers; while it has long been appreciated to be a major impediment to cancer proliferation, the molecular mechanisms underlying its role in this process remain poorly understood. Using cutting-edge proteomic techniques, Dr. Bar-Peled is investigating how cancer cells respond to oxidative stress and exploring the different signaling pathways required by cancer cells to reduce the oxidative stress burden. His research may provide therapeutic avenues for targeting certain lung cancers.

Dr. Touhara [Robert A. Swanson Family Fellow] is focusing on enteroendocrine cells which are found in the wall of the gut and secrete hormones that regulate glucose levels, food intake and stomach emptying. Abnormal activity of these cells often causes common gastrointestinal disorders such as irritable bowel syndrome and carcinoid tumors. Dr. Touhara aims to elucidate interactions of the enteroendocrine cells with the enteric nervous system which controls gut motility and communicates with the brain. This research may lead to new drug targets and treatments for disorders of the gut.

Dr. Shoba aims to develop a new class of small molecules that will target transcription factors, which regulate gene expression. These proteins are mutated in many cancers but are considered undruggable because current compounds fail to block the interaction between transcription factors and their binding partners. Dr. Shoba aims to disrupt these functional interactions by recruiting enzymes called kinases found in the human body to chemically modify the transcription factors and thus inhibit oncogenic activity.

Dr. Patel is focusing on neural tube development. The neural tube serves as the embryonic precursor to the central nervous system. Opposing signaling gradients help pattern the tube into distinct progenitor domains that eventually give rise to a variety of sensory and motor neurons in the body. Dr. Patel aims to understand the underlying transcriptional logic governing neural tube development by combining high-throughput CRISPR-based screens and single-cell sequencing. By doing so, he hopes to generate comprehensive gene expression phenotypes across a range of genetic perturbations.

Dr. Ong [The Mark Foundation for Cancer Research Fellow] is investigating the molecular basis of paraneoplastic syndromes, which occur when a cancer causes unusual symptoms due to hormones produced by the tumor or antibodies produced by the immune system. They can affect the function of various distant tissues and organs in cancer patients, with deadly consequences. Dr. Ong is utilizing a new genetic tumor model in Drosophila that simulates many human paraneoplastic disorders: cachexia, immune dysfunction and early lethality.

Dr. Nusse [Robert Black Fellow] studies how immune cells contribute to liver regeneration after injury. Injuries to mammalian tissues are typically repaired through a stepwise process of inflammation and debris clearance, followed by proliferation of progenitor cells and tissue reorganization. During chronic injury, this process can malfunction leading to excessive inflammation, uncontrolled tissue growth and cancer initiation. Dr.

Dr. Moy is focusing on key genes and pathways that control metastasis of colorectal cancer to the liver. Dr. Moy’s research could potentially lead to new treatment strategies that can block or delay metastatic progression of colorectal cancer and other gastrointestinal malignancies. Understanding this process at the molecular level has the potential to impact patient survival.

Dr. McLaughlin [HHMI Fellow] is using the developing nervous system to study metastasis, the primary cause of cancer-related fatalities. In metastasis, cell surface and secreted molecules enable cells to travel through diverse environments and invade distant tissues. Likewise, growing axons in the developing nervous system use similar sets of cell surface proteins to traverse long distances to form precise connections with their synaptic partner cells. Dr.

Dr. McGinn studies how bacterial pathogens sense and manipulate their human hosts. Dr. McGinn is focusing on the tick-borne bacterial pathogen Rickettsia parkeri, which can only survive within eukaryotic host cells. By uncovering novel interactions between host and pathogen, his work may reveal new insights into how human cells work and what goes awry in disease states.

Dr. Liu is combining single-molecule fluorescence and force spectroscopy to study dynamic interactions between meiotic double-strand break (DSB) proteins and DNA. Meiotic recombination initiates with DSBs that are generated by the protein Spo11. Spo11 and its partner proteins ensure that DSBs occur at the right chromosome sites and at the right time. Dysregulated DSBs lead to chromosome instability, a hallmark of cancer cells. Dr.