Damon Runyon News

Dr. Zinshteyn [HHMI Fellow] is using a combination of high-throughput genetic and biochemical techniques to identify the fundamental mechanisms underlying a process called nonsense-mediated decay (NMD). NMD enables cells to detect and destroy messages that are the result of potentially damaging genetic mutations. This process augments many genetic diseases and is important for cancer cells to adapt to the hostile tumor environment.

Dr. Yin is using newly developed state-of-the-art single cell sequencing technology to examine how DNA repair mechanisms go awry and contribute to cancer initiation and progression, as well as response to chemotherapy. Cancer cells usually have characteristic loss-of-heterozygosity, copy number variation and other types of genome rearrangements.

Dr. Wu is investigating the mechanism of dendritic cell (DC) missing-self recognition and migration. DCs recognize and present antigens to lymphocytes, a process that is essential for shaping host immune responses against infection and cancer. How DCs recognize altered self cells (such as cancer cells and pathogen-infected cells) remains poorly understood. These studies should significantly enhance our understanding of DC biology and eventually contribute to the development of new strategies to harness DC function for immunotherapy against cancer.

Dr. Westcott is developing improved in vivo models for studying the complex interactions between colorectal cancer and the immune system. The powerful genome editing technology CRISPR-Cas9 will be leveraged to rapidly generate a suite of novel mouse models of colorectal cancer harboring distinct mutational signatures seen in human cancer. He will use genome-wide sequencing and preclinical studies to dissect the role of these mutational signatures in promoting cancer cell detection by the immune system, and in modulating response to immunotherapies.

Dr. Tsai is developing next-generation diagnostics for low abundance cellular cancer samples. By measuring 40 or more markers simultaneously on individual tumor cells deposited on glass slides, he hopes to enable definitive diagnoses of blood and lymph node cancers without the need for invasive surgery or a histopathology laboratory. These methods will also provide a unique way to study these cancers, by merging traditional light microscopy with automated antibody-based multi-marker analysis.

Dr. Torabi is studying a highly abundant cellular long noncoding RNA (lncRNA) called MALAT1 (metastasis associated lung adenocarcinoma transcript 1), which serves as a prognostic factor in several human cancers.  MALAT1 is stabilized via formation of a complex triplex structure called expression and nuclear retention element (ENE). He aims to identify additional MALAT1-like ENEs in the genome through an in vitro evolutionary process in combination with bioinformatics studies.

Dr. Srinivas is combining new live imaging technologies, synthetic biology, and mathematical modeling to quantitatively analyze gene expression patterns in space and time during development. Predictive understanding of such patterns and how they go awry during mutations could help us uncover the molecular mechanisms underlying diseases such as cancer. Combining such knowledge with the ability to synthetically alter gene expression patterns could also lead to novel therapeutic approaches.

Dr. McKeown [HHMI Fellow] studies the innate immune system and its key role in suppressing many types of cancers. It is unclear why some cancers respond well to immunity-based therapies while others escape treatment and continue to spread. Her research is aimed at characterizing a new layer of host immunity composed of retrogenes of essential host proteins. She believes that these retrogenes act to inhibit viral infection by acting as nonfunctional “decoys” of host proteins required for the viral life cycle.

Dr. Liang [William Raveis Charitable Fund Fellow] is investigating the novel involvement of the Fanconi anemia DNA repair pathway in coordinating DNA replication and RNA transcription to maintain genome stability. Fanconi anemia (FA) is a multigenic disorder marked by progressive bone marrow failure and a strong cancer predisposition. He is employing a combination of biochemical and in vivo approaches to study the mechanism by which FA proteins attenuate aberrant DNA and RNA lesions to prevent cancers.

Dr. Leonard focuses on regulatory T cells-immune cells that normally prevent autoimmunity, but are co-opted by cancers in order to evade anti-tumor immune attack. He will use a combination of biochemistry, structural biology, and mouse models in order to understand how regulatory T cells recognize “self,” and how this process is exploited in prostate cancer.