Damon Runyon News

Mitochondria harbor independent genetic material known as mitochondrial DNA (mtDNA). This compact, circular molecule encodes proteins essential for the assembly of the mitochondrial electron transport chain to generate energy in form of ATP. Like nuclear DNA, mtDNA is susceptible to damage and mutations. One of the most common disease-causing aberrations of mtDNA is termed “common deletion.” This aberration disrupts mitochondrial function, resulting in neuromuscular diseases and potentially certain cancers, including colorectal cancer.

Normal tissues naturally weed out harmful cells to prevent cancer. But when cancer develops, this defense system breaks down, allowing the cancer to attack healthy cells for its own growth. The Shaffer lab is set to explore this process, called cell competition, in esophageal cancer. By employing precise tracking and advanced spatial analysis, Dr. Shaffer [Bakewell Foundation Innovator] aims to reveal how cell competition contributes to cancer development and how it might be harnessed to prevent it.

To power directional movement, cells build dynamic sheet-like protrusions at their leading edge. How individual molecules are coordinated to produce these changes in cell morphology is poorly appreciated. Dr. Sim [Connie and Bob Lurie Fellow] uses immune cell migration as a model system to investigate the self-organization of a protein assembly known as the WAVE complex, which facilitates the formation of these protrusions in migratory cells. Her work will harness recent advances in electron microscopy and protein prediction and design to study the mechanism of the WAVE complex.

Studies have shown that lung tumors are sustained through the formation of new blood vessels from pre-existing ones in a process called angiogenesis. Moreover, tumor cells secrete signaling proteins that help them communicate with each other and evade immune detection. However, most of these studies have been on late-stage lung tumors; our understanding of cell-cell interactions in the tumor environment during lung cancer initiation and early stages remains poor. Dr. Sengupta [Deborah J.

The cellular response to DNA damage is coordinated by an enzyme known as ATM kinase. Mutations in ATM are found in approximately 1% of the population and contribute to an increased risk of both hereditary and sporadic cancers, including breast cancer. Dr. Kim’s research investigates how ATM suppresses the production of double-stranded RNAs (dsRNAs) in response to DNA damage. These dsRNAs play a critical role in tumor progression. Dr.

Most cancers develop in the epithelial tissue, which includes the skin and internal organ linings.  Hemidesmosomes (HDs) are adhesive structures that anchor epithelial cells to the underlying base layer and maintain tissue integrity. While HD disassembly occurs normally during wound healing, tumor cells can exploit this process to detach and spread to other parts of the body. Dr. Bagde is studying how HD components interlock like Lego blocks to form stable HDs in healthy tissues and how they disassemble in cancerous tissues. To investigate this phenomenon, Dr.

Drug therapies that selectively target proteins that drive the growth of tumor cells are rapidly becoming the standard of care for many cancers. However, tumors are often able to evade inhibition by targeted anti-cancer drugs by activating other proteins, leading to drug resistance. Dr. Gier [HHMI Fellow] is developing a new therapeutic approach that repurposes existing drugs to release highly toxic cargoes, known as payloads, that aggregate in drug-resistant cancer cells and kill them. As a general platform, it is applicable to a wide range of solid and liquid cancers. Dr.

Dr. Zhang is studying a unique three-stranded nucleic acid structure, called an R-loop, to understand its role in cancer development and find ways to target and control its formation. R-loops consist of a DNA-RNA hybrid and a displaced strand of DNA. R-loops occur frequently in human genomes, and while they play an important role in blood cell differentiation and immune cell function, they can also interfere with DNA repair and promote genome instability, giving rise to leukemia. However, the dynamic nature of R-loop formation hampers the detection of this structure in a small cell sample.

Dr. Miltiadous is investigating how the gut microbiome affects the immune system in children undergoing a cancer treatment called allogeneic hematopoietic cell transplantation (allo-HCT), which is often used for aggressive pediatric cancers like leukemia and lymphoma. While it can be life-saving, allo-HCT can also induce complications caused by immune overactivation, including graft-versus-host disease. Molecules called bile acids, produced with the help of gut microbes, help balance the immune response, reducing harmful inflammation and improving recovery.

One of the persistent challenges in treating high-risk pediatric leukemia, particularly in cases of acute megakaryoblastic leukemia (AMKL), is the high incidence of relapse due to resistance to standard treatments such as chemotherapy and bone marrow transplantation. T cell therapy has shown potential in treating various types of leukemia, offering the prospect of overcoming mechanisms that tumor cells employ to evade traditional therapies.