Damon Runyon News

Emerging evidence implicates the pathogenic bacterium C. difficile as an initiator of colorectal cancer. C. difficile exposure can lead to chronic recurrent disease that is difficult to clear with antibiotics. The generation of spores is a well-studied mechanism used by C. difficile to persist; however, other mechanisms of recurrent infection remain poorly understood. Dr. Price [Merck Fellow] hypothesizes that biofilms may function as reservoirs of C. difficile and aims to elucidate their role in disease relapse.

One way cancer cells evade immune attack is by constructing a thin material barrier called the glycocalyx on their surface to evade detection and destruction by surveilling immune cells. Tiny changes in the glycocalyx thickness, as small as 10 nanometers, can affect the anti-tumor activity of immune cells, including CAR T cells. Dr. Park’s [Merck Fellow] goal is to develop strategies to endow CAR T cells with the ability to penetrate the glycocalyx barrier in solid tumors such as breast cancer and glioblastoma.

Dr. Omollo [Robert A. Swanson Family Fellow] studies how bacteria have evolved to achieve precise gene expression using strategically placed transcription terminators. In cancer cells, specific mutations lead to uncontrolled transcription of certain genes, resulting in elevated gene expression that fuels cancer progression. Using bacteria as a model, Dr. Omollo aims to uncover how RNA polymerases in cancer cells evade termination signals to maintain high levels of gene expression, encouraging cancer spread. Dr.

The immune system has the capability to destroy cancer cells harboring mutated genes. Cells display peptides derived from these mutated genes (i.e., portions of the mutant protein) on a molecule called the major histocompatibility complex I (MHC I), triggering cytotoxic T cells to eliminate the cancer cells. Unfortunately, this surveillance system is weak and often subverted by cancer cells. Dr.

Adoptive cell therapy (ACT) is poised to expand the curative potential of immunotherapy. ACT works by administering T cells that have been genetically engineered to express tumor-specific T cell receptors (TCRs) so that they recognize a particular cancer antigen. Dr. Gormally’s [Dennis and Marsha Dammerman Fellow] work addresses two major challenges that currently limit the effectiveness of ACTs against solid tumors: identifying antigen targets that can be recognized by the immune system, and designing TCRs that target those antigens with exquisite specificity. Dr.

B cells, especially those that target cancer antigens, are crucial for fighting tumors; however, not everyone develops them. Our gut bacteria play a vital role in training B cells to recognize a wider range of threats. Dr. Brewer’s [HHMI Fellow] research explores how these gut bacteria influence the specificity of B cells, and thus our body’s ability to combat tumors. Dr. Brewer’s research aims to determine if the “training” of B cells by gut bacteria early in life influences their later responses to vaccines and cancer.

The bacterium Staphylococcus epidermidis (S. epi) is nearly universally present on human skin, and certain strains are capable of eliciting immune responses that can be redirected against tumor antigens. Dr. Barkal is investigating how to harness the immunomodulatory properties of S. epi to develop a new class of T cell immunotherapy that is potent and tumor antigen-specific, avoiding the systemic side effects associated with current immunotherapies. Specifically, she is using a melanoma model to explore how to modulate T cell production with S.

Only up to 20% of patients with advanced ovarian cancer will survive five years after diagnosis. This is largely due to the cancer’s resistance to traditional chemotherapy and the current lack of targeted therapies that work with chemotherapy to improve response. Dr. Mullen’s lab has identified a new target, COP9 Signalosome Subunit 5 (COPS5), to treat ovarian cancer. Her team has found that inhibiting COPS5 with a drug called CSN5i-3 drastically improves ovarian cancer response to chemotherapy.

Dr. Weeks [Damon Runyon-Timmerman Traverse Clinical Investigator] plans to develop computerized models that can review images of blood cells and predict a patient’s risk of developing acute myeloid leukemia. Because computers can capture small changes in images better than humans looking at cells under a microscope, such a model could connect data about the shapes and appearance of blood cells to the presence of pre-leukemia genetic changes known as clonal hematopoiesis.

Gene expression is a complex process, and sometimes mistakes are made, resulting in the generation of aberrant or “junk” RNAs. Dr. Insco previously discovered that cellular failure to “clean up” this junk RNA can contribute to the development and progression of melanoma. Her work is now focused on targeting aberrant RNA to treat cancer. First, she will identify compounds that specifically target melanomas that are unable to clean up their junk RNAs. Second, she will investigate how immune cells can be activated to attack melanoma cells that have high levels of aberrant RNAs.