Damon Runyon News

T cell therapies have led to promising results in treating blood cancers, but new approaches are required to translate these results to solid tumors. In solid tumors, T cells face unique challenges in the tumor microenvironment (TME), which limits the persistence and efficacy of adoptive T cell therapies. In T cell lymphomas (TCLs), tumor cells overcome many of the same challenges through acquired mutations. Fueled by natural selection, tumor mutations produce novel and elegant solutions to address T cell deficits in the TME.

Osteosarcoma is the most common bone tumor and primarily affects children and adolescents. Unfortunately, treatment approaches and outcomes for osteosarcoma patients have not significantly improved for 40 years. Dr. Morrow’s work is focused on understanding normal bone development and how this development goes awry, giving rise to osteosarcoma. He hopes this improved understanding will lead to new treatment approaches for pediatric osteosarcoma patients. Dr.

Antimicrobial resistance is a growing crisis that imperils our ability to protect patients immunocompromised by cancer treatment. Despite this, the few new antibiotics currently in clinical trials primarily use established mechanisms of action. Identification of new targets for antimicrobial drugs is thus an urgent clinical need. Recent work has shown that bacteria can tolerate substantial inhibition of many proteins thought to be essential for growth, rendering them poor drug targets. The mechanisms that cause this robustness are poorly understood.

Pancreatic cancer remains unresponsive to current chemotherapy and immunotherapy treatments. However, with the recent development of mRNA vaccines and drugs that target cancer cell mutations, there is hope for a new generation of immune-based therapies. The ability of adaptive immune cells, called cytotoxic T cells, to kill cancer cells is central to anti-tumor immunity. Using mouse models of human pancreatic cancer, Dr. Evavold [Merck Fellow] plans to identify the flags presented by cancer cells that enable T cells to recognize them as foreign and kill them.

Diffuse midline gliomas (DMG) are uniformly fatal pediatric brain cancers in desperate need of novel treatments. Immunotherapies have offered some hope to patients, but durable clinical success remains elusive, highlighting the enormous challenge of selectively targeting these recalcitrant tumors while preserving healthy tissue. Dr.

Brain cancers are one of the most common causes of cancer-related death and represent 120 molecularly distinct diseases. Despite advances in clarifying the genetic landscape of these cancers, they remain clinically intractable, underscoring the need to elucidate the complex factors contributing to their heterogeneity. As neuronal activity is known to govern the development of neural circuits and neuroplasticity, it is critical to consider these neural networks in the context of disease. Dr.

Dr. Gill [HHMI Fellow] is studying cell-cell communication via quorum sensing in developing biofilms. Biofilms are communities of bacteria that take on a three-dimensional structure and often develop striking visual features like wrinkles. Resident bacteria exploit this complexity to resist antimicrobial treatments and cause disease, particularly in healthcare settings, where biofilms pose serious threats to immunocompromised chemotherapy patients.

In the past decade, new therapies that train the immune system to recognize and kill tumor cells have revolutionized cancer care. Unfortunately, immunotherapies have been largely ineffective in pediatric solid tumors, including osteosarcoma, the most common bone cancer. Dr. Smith aims to understand why immunotherapies have failed by studying a mouse model closely resembling human osteosarcoma. Importantly, these mice have an intact immune system, unlike models that transplant human tumors into mice. By combining complex modeling with single cell and spatial techniques, Dr.

Successful immune responses against cancer require immune cells of various types to control each other’s proliferation, differentiation, and death. These interactions collectively constitute a set of intercellular signaling circuits. A fundamental challenge in cancer research is to understand the relationship between the architecture and functions of these circuits. Dr.

Pediatric diffuse midline gliomas (DMG) are incurable brain cancers with no long-term survivors. To date, radiation therapy remains the standard of care but improves survival by only a few months. Despite intense research efforts over the past four decades, there is still a lack of mechanistic understanding of the biology underlying DMG radioresistance. Dr. Lo Cascio is studying how DMG tumors exploit interactions with surrounding normal neurons to survive radiation-induced cell death.