Damon Runyon News

Dr. Didychuk is investigating the mechanism by which the Kaposi’s sarcoma herpesvirus (KSHV) co-opts the cellular host machinery to produce its own gene products in a manner distinct from other viruses and host cells. This research should reveal insights into this unique mode of transcriptional control. KHSV is an oncogenic virus that causes various cancers including, Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease, in immunocompromised individuals.

In response to nutrient changes in the environment, pancreatic cancer cells can adjust the rate of mRNA translation to selectively regulate the rate of protein production. However, the specific codons—the trinucleotide sequences that correspond to specific amino acids—and regulatory mechanisms used are not known. Dr. Banh’s research aims to decipher the laws governing how codons regulate mRNA translation in response to the nutrient environment in pancreatic cancers.

Dr. Johnson studies how cancer cells trigger innate immune signaling pathways, facilitating their recognition and destruction by the host immune system. One way cancer cells differ from normal cells is their abnormal nuclei, which are often prone to spontaneously rupture. Although nuclear envelope rupture has been implicated in innate immune activation, the mechanism by which this occurs remains unclear. Dr.

Dr. Lin [HHMI Fellow] is studying how small RNAs called miRNAs are specifically targeted for destruction in cells. Because miRNAs are key regulators of gene expression, both miRNA production and destruction must be controlled in an accurate and timely manner. Dysregulation of these processes contributes to cancer progression. Dr. Lin is developing biochemical and high-throughput sequencing approaches to uncover the rules governing miRNA destruction and how they change in cancer.

Dr. Gardner [Kenneth G. and Elaine A. Langone Fellow] is studying acquired resistance to targeted therapies in lung cancer. Many targeted therapies used in cancer treatment are capable of controlling disease for a period of time, but in most cases, the disease finds a way to resist or adapt. For instance, some patients treated with epidermal growth factor receptor (EGFR) inhibitors for adenocarcinoma develop resistance to this class of drugs when their cancer transforms to small cell lung cancer (SCLC). Dr.

Dr. Wilson is developing molecular tools to specifically modify RNA as a potential pathway to novel cancer therapeutics. RNA modification affects RNA fate and influences the way genes are expressed, including cell cycle control, cell differentiation, and transcript stability, which have been linked to a variety of diseases, including cancer. Dr. Wilson aims to use the CRISPR/Cas9 homologs to alter RNA translation, ultimately leading to an increased understanding of the role of the transcriptome— all of the messenger RNA molecules expressed from the genes of an organism.

Dr. Gates [HHMI Fellow] is focusing on the 26S proteasome, part of the Ubiquitin Proteasome System (UPS), which is important for protein quality control and cellular regulation. The proteasome degrades aggregated and misfolded proteins, which are tagged with a ubiquitin molecule for disposal in normal cells. Proteasomes are also critical in helping cancer cells survive by disposing of malfunctioning proteins, so inhibiting the proteasomal degradation mechanism is an effective cancer drug target. Dr.

Dr. Zhang is developing small molecules that promote targeted protein degradation in human cancers. Conventional small molecule anticancer drugs act by directly inhibiting the functions of proteins. Although targeted cancer therapies have been successful in recent years, many oncogenic proteins are still considered “undruggable” because the conventional drug design strategy fails to interfere with these proteins.

Dr. Nandagopal [Philip O’Bryan Montgomery Jr. MD Fellow] is focusing on genes in the bHLH family and their role in signal integration to help decide whether cells grow and divide, differentiate, migrate, or even die. bHLH genes are involved in fate choices in stem cells of the brain, intestines, skin, and other tissues. They are also commonly misregulated in cancers, such as neuroblastomas and glioblastomas. By comparing signal integration by bHLH circuits in normal and cancer cells, Dr. Nandagopal aims to discover how errors in fate decisions occur, and how they can be corrected. 

Dr. Yang is examining tumor heterogeneity in search of new diagnostic markers and potential therapeutic targets. A tumor consists of not only cancer cells, but also immune cells, fibroblasts and other stromal components. The diverse cell types and cell states may promote disease progression and lead to therapeutic resistance, which is one of the greatest challenges in precision medicine. Dr. Yang aims to understand how heterogeneity is generated and regulated by using single cell functional genomic tools.