Damon Runyon News

Certain immunotherapies work by instructing macrophages, a type of innate immune cell, to attack the tumor by phagocytosing, or eating cancer cells. However, macrophages rarely eat an entire cancer cell within a solid tumor. Instead, they nibble pieces off the cancer cell, a process called trogocytosis. While phagocytosis kills the cancer cell, trogocytosis usually doesn’t – and worse, nibbling removes the markers on the cancer cell that allow the immune system to recognize it as a threat. Dr.

Acute myeloid leukemia (AML) is hard to cure compared to other childhood leukemias and lymphomas. Current standard-of-care AML treatment is very toxic; childhood AML survivors often have side effects later in life from their treatment, including heart disease, infertility, and additional cancers. There is a pressing need for new AML treatments that are less toxic and more effective. Dr. Decker’s research is focused on developing novel inhibitors of a protein called N-Ras, one of the most common mutations in pediatric AML. Dr.

CAR T cells, or genetically engineered immune cells, have transformed the treatment of cancer in recent years, achieving cures for many patients who previously faced terminal diagnoses. Despite the remarkable impact that CARs have had on patients and families, however, fewer than 5% of cancer patients currently benefit from these therapies. A major barrier to broader CAR applications lies in the identification of tumor-specific targets: only ~0.00000001% of the cell surface distinguishes tumor cells from healthy cells.

Hepatocellular carcinoma (HCC) is the most common liver cancer and has one of the highest cancer-related mortality rates. Conventional cancer immunotherapies, which largely focus on enhancing T cell activity, are unfortunately effective in only a small minority of HCC patients. Though dendritic cells (DCs) are essential for T cell activation, their potential as an immunotherapeutic target remains poorly understood. Dr. Cao is investigating how a unique, hyperactivated state of DCs can be harnessed to enhance anti-tumor immunity in a genetically engineered mouse model of HCC.

Fibroblasts are one of the earliest known cell types and they contribute to many of the most burdensome lung diseases, including cancers, fibrosis, and emphysema; however, they are surprisingly poorly understood. Dr. Crowley [HHMI Fellow] will examine the different types of fibroblasts in the mouse lung to determine where they come from and how they function normally, as well as how they change with injury and disease.

Dr. Wahlster is studying the developmental origins of acute lymphoblastic leukemia (ALL), the most common childhood cancer and leading cause of death in children. The goal of Dr. Wahlster’s research is to understand the biological processes that drive blood cancer development. Applying innovative genomic tools, her work seeks to decipher how cancer-predisposing genetic variants impact early blood cell development and facilitate the acquisition of secondary genetic changes found in ALL. She aims to leverage these insights to guide the development of novel, mechanism-based treatments. Dr.

Attaching a small molecule known as ubiquitin to a protein, in a process called ubiquitylation, targets that protein for degradation. By utilizing the ubiquitylation machinery, scientists are now able to target cancer-causing proteins for degradation, a strategy that has proven effective with drugs such as Lenalidomide/Revlimid to treat multiple myeloma.

A majority of pancreatic cancer cases harbor a mutation in the KRAS gene, which is involved in cancer initiation, progression, and chemotherapy resistance. Drugs targeting KRAS mutations are often met with resistance due to limited drug penetration into the tumor. Since pancreatic cancer progression involves increased tissue stiffening, KRAS signaling might be controlled by tissue stiffness. Dr. Jain is studying the mechanisms that underlie tissue stiffness-dependent KRAS signaling at the molecular level.

Dr. Perry is investigating how a key immune cell in the tumor microenvironment, the macrophage, contributes to cancer’s development and progression. His work focuses on triple-negative breast cancer, as it remains one of the deadliest cancers, especially to young women and Black women, with decades of treatment efforts failing to improve patient outcomes. Specifically, Dr. Perry aims to combine novel methods of manipulating and imaging the cellular metabolism to better understand how macrophages contribute nutrients to help cancer cells meet their nutrient demand and escape treatment.

Immune cells called macrophages can swallow bacteria and contain them in membrane-bound compartments called phagosomes. From inside the phagosome, some bacteria stimulate immune pathways in the cytosol, but it is unclear how immune signals are transmitted across the membrane from the phagosome into the cytosol. To investigate, Dr. Jastrab [Robert Black Fellow] has developed a macrophage infection model using mutants of the bacterium Staphylococcus aureus that stimulate an immune complex in the cytosol called the inflammasome.