Damon Runyon News

Dr. Nguyen is analyzing the bacterial enzyme Cas9, which has emerged to be a versatile tool to manipulate the genome. He aims to develop an efficient method for selective delivery to and activation of Cas9 in cancer cells. The developed methodology will hopefully set the foundation for rapidly creating genetic models to interrogate signaling pathways implicated in cancer and to investigate novel drug screening approaches that identify new drug targets for cancer treatment.

Dr. Woo [HHMI Fellow] is using protein structures to illustrate the mechanisms of cancer-related processes. His research aims to overcome limitations of current techniques by using recent breakthroughs in “programmable DNA self-assembly” to develop protein framework structures that contain “pockets” with tunable size and shape for structural studies. If successful, his efforts will provide a general tool for structural biology and in turn benefit the mechanistic studies and therapeutic development for cancer.

Dr. Tsai [Kenneth G. and Elaine A. Langone Fellow] seeks to understand how the signaling pathway directed by the protein Sonic Hedgehog (Shh) regulates cell-cell adhesion molecules required for correct spatial organization of the neuro-epithelium. Abnormal Shh signaling is associated with several types of cancer, and aberrant regulation of cell-cell adhesion could lead to tumor metastasis. His findings may ultimately lead to understanding and prevention of metastasis in Shh-associated cancers.

Dr. Jiang [Merck Fellow] is studying the CRISPR-Cas system, which has been adopted as a robust and versatile platform for genome engineering in human cells as well as other experimental systems. He aims to use a combination of biochemical experiments, mutagenesis, and biophysical approaches to investigate the detailed molecular mechanism of RNA-guided DNA targeting and recognition by CRISPR-Cas9.

Dr. Liu [Layton Family Fellow] studies lung biology. The lung is innervated by diverse types of sensory neurons, collectively called pulmonary sensory neurons. These neurons detect a variety of physiological stimuli from the lung and inform the central nervous system about the state of the lung. Lung cancer, one of the most common cancers with a high rate of lethality, is associated with symptoms such as chronic cough, shortness of breath, and referred cranial facial pain.

Dr. Martin [Marion Abbe Fellow] focuses on genomic instability, a hallmark of virtually all cancers that underlies the mutations and aneuploidy (incorrect chromosome number) changes that perturb oncogenes and tumor suppressor genes (TSGs). Patient tumor sequencing has unveiled common genomic alterations across different cancers. Recent work described how the cancer genome is shaped by the loss of many genes and gene clusters.

Dr. Norman is investigating the role that “epigenetic” differences play in cancer cells’ ability to develop drug resistance. These epigenetic changes result in altered gene expression. He will use a new technique called CRISPRi to systematically tune the expression of different parts of the genome and measure their effect on drug resistance. He hopes that these studies will identify new avenues for reducing resistance and expand our knowledge of the role epigenetic factors play in leukemia and other cancers.

Dr. Whicher focuses on a cellular structure called the voltage-gated potassium channel Eag1, which can promote tumor growth and is aberrantly expressed in many types of cancer including breast, colon, prostate, lung, and liver. He is determining the structure and mechanism of Eag1 in order to elucidate how Eag1 promotes cancer growth, with the eventual goal of developing Eag1 modulators as potential anti-cancer therapies.

Dr. Mao is studying the cell’s cytoskeleton, which provides the physical structure and shape of a cell. The cytoskeleton is an attractive target for cancer chemotherapy because of its central function in mitosis or cell division, but these chemotherapeutic agents have very high toxicity. He hypothesizes that the next generation of chemotherapy will benefit from the inhibition of these toxin response pathways. He will examine how cells respond to such drugs, with the goal of applying these findings to attenuate the drugs’ side effects.

Dr. Wolfe studies KRAS, a cancer-promoting protein that is activated by mutations in most forms of cancer. Tumor cells can become “addicted” to the presence of overactive KRAS protein, such that they die when KRAS is suddenly removed. He will focus his research on an exciting new class of inhibitors that cause active KRAS to be rapidly degraded. He aims to explore the effects of depleting KRAS on cancer cells, understand the mechanism by which these novel KRAS inhibitor drugs cause the protein to be degraded, and optimize the efficacy of these drugs.