Damon Runyon News

Dr. Bartman [The Mark Foundation for Cancer Research Fellow] studies the unique nutritional requirements of cancer cells compared to healthy tissues. Dr. Bartman will use mass spectrometry measurements of labeled nutrients and computational modeling to quantify metabolic fluctuations in both pancreatic cancer cells and healthy organs in mice.

Dr. Andreeva investigates the role of a molecule called NLRP3 in the assembly of inflammasommes, multiprotein complexes that form in response to cellular infection or stress. NLRP3 acts as a sensor inside the cell that detects danger signals and activates the inflammasome complex to trigger inflammation and cell death. Dr. Andreeva aims to uncover the step-by-step mechanism of NLRP3 activation and regulation to understand how to prevent "false alarms" that cause disease.

Immunotherapy drugs, which spur the body's own immune system to attack tumors, hold great promise but still fail in many patients. Dr. Griffin aims to identify therapeutic targets that can enhance the efficacy and scope of immunotherapy in melanoma and other cancer types. His unique approach focuses on retrotransposons, repetitive sequences of DNA that are evolutionary remnants of viruses and comprise upwards of 50% of the human genome. These genetic elements are usually silenced via DNA methylation but can activate an immune response at certain times. Dr.

Immunotherapies using checkpoint inhibitors have shown amazing results in certain solid cancers. However, there are vast differences in treatment outcomes for patients who have remarkably similar cancers (based on histology and genetics) and many patients develop resistance. In addition, predicting who will benefit from the treatment has been unreliable. Recent research found that the diversity and specific quality of microbes that colonize the intestines (the gut microbiome) can impact the success of cancer immunotherapy, but there is no consensus about the underlying mechanisms. Dr.

Mutations in the cancer-causing oncogene JAK2 are a hallmark of myeloproliferative neoplasms (MPNs), a blood disorder characterized by over-production of mature blood cells. While currently available JAK2 inhibitors improve symptoms, they are unsuccessful at completely eradicating diseased cells, so remissions are rare. Using genetically engineered mice, Dr. Dunbar will investigate how MPN cells remain dependent on JAK2 signaling for cell growth, and how additional mutations in the epigenome (the proteins involved in regulating gene expression) might contribute to drug resistance.

Prostate cancer is the second leading cause of cancer death in men in the United States. Remarkably, work over the past decade has demonstrated that even the worst prostate cancers are dependent on the same signaling pathways that govern normal prostate behavior. Dr. Shoag’s objective is to identify drugs that have activity against the normal prostate and can be used to understand and treat prostate cancer. Dr. Shoag will apply novel statistical and machine learning approaches on large scale clinical data to discover new therapies and pathways important in prostate cancer.

Acute myeloid leukemia (AML), the most common type of blood cancer, is curable in less than 30% of all patients. Recently, chimeric antigen receptor (CAR) T cell therapy has successfully cured patients with certain types of leukemia. This approach has not yet been effective for treatment of AML, in part because these cells look very similar to certain types of healthy blood cells that are critical for life. Dr.

Defects in the cellular DNA repair machinery can promote cancer formation and cause cancer cells to rely on back-up DNA repair processes. These cancer cells are particularly vulnerable to drugs called PARP inhibitors, which target a DNA repair process known as homologous recombination. Dr. Chan hypothesizes that a similar treatment strategy can be used for cancers with deficiencies in DNA mismatch repair, which causes microsatellite—short, repeated sequences of DNA—instability (MSI). Microsatellite instability is found most often in certain colon, stomach, uterine and ovarian cancers.

Dr. Nachtergaele is investigating the roles of RNA methylation, a process that chemically tags mRNA to alter gene expression and protein production. She has discovered a novel enzyme (m1A) that modifies RNA in this way and aims to uncover how malfunctions in this process can lead to cancer. Her investigations will expand the understanding of how mRNA modifications are regulated and result in altered cell signaling and growth in normal and cancer cells.  Building on this knowledge, her goal is to identify novel therapeutic targets for cancer.

Dr. Norman aims to build a computational model of cancer genetics and understand the roles played by the complex interaction of genes. Though some cancers are characterized by very specific mutations, other cancers display a host of relatively common mutations, along with a string of infrequent mutations. He has developed technology to collect and integrate large data sets of experimental results with patient data to create a predictive model. This can be used to understand how a patient’s unique spectrum of mutations combine to give rise to cancer.