Damon Runyon News

Proteins found on the surface of cells are key agents in cancer progression, as they play a role in cell signaling and metastasis. Targeted protein degradation has emerged as a therapeutic strategy to modulate what are considered “undruggable” proteins. Specifically, lysosomal-targeting protein degradation (LTPD), which uses the cancer cell’s own degradation machinery to break down proteins, has demonstrated therapeutic potential.

T lymphocytes, an important component of the immune system, recognize infected or cancerous cells with great specificity, ensuring targeted elimination. These potent cells are kept in check by regulatory T cells, the guardians of the immune system. While essential for curtailing excessive inflammation and preventing autoimmunity, their immunosuppressive properties can promote the development and progression of cancer. Regulatory T cells are distinguished by the presence of a protein called Foxp3, which plays a critical role in their differentiation, function and fitness.

Brain cancers are the leading cause of cancer-related deaths in children. A significant percentage of these tumors are classified as gliomas—diseases for which new therapies are desperately needed. A protein called tyrosine kinase FGFR1 is altered in 10% of pediatric gliomas. Dr. Apfelbaum aims to investigate critical genes in FGFR1-altered pediatric gliomas to understand the biological mechanisms driving these cancers.

Sugar molecules on the surface of cells can be arranged in many different patterns, and it is the exact structure of a sugar that gives it its unique function. In sugars on the surface of cancer cells, the location of sulfate (SO4-) groups changes as the tumor grows and spreads. The study of sulfated sugars has been stymied, however, by the difficulty of synthesizing them in the laboratory. Dr. LaPorte’s research aims to remove this roadblock by developing a chemical reaction that easily constructs biologically important sugars with a sulfate group bound to them.

Dr. Cuevas-Navarro’s [Berger Foundation Fellow] research project focuses on targeting mutations in the RAS genes (HRAS, NRAS, and KRAS), present in about 30% of cancer patients and notorious for driving aggressive tumor growth. Dr. Cuevas-Navarro aims to mitigate these mutations’ effects by using pharmacological agents to enhance a biochemical process that regulates RAS proteins. His project will investigate the mechanism of action of these compounds and assess their effectiveness in patient-derived cancer models.

The Western diet, characterized by low dietary fiber and high saturated fat content, is strongly correlated with incidence of CRC. This diet rapidly alters the composition and function of the gut microbiome, inducing microbial imbalance and inflammation, two major hallmarks of CRC. These changes are thought to be caused by diet-induced oxygenation of the gut environment. Most beneficial gut bacteria cannot survive this oxygenated environment, but harmful microbes can thrive in this setting and further exacerbate inflammatory responses.

Leukemia is a cancer of the immune system and is a major cause of death from cancer in children and young adults. Chimeric antigen receptor (CAR) T cell therapy, which involves genetic engineering of a cancer patient’s own immune system cells to fight cancer, has demonstrated curative potential. Despite excellent initial responses to treatment, however, leukemia recurs in up to half of pediatric leukemia patients after CAR T treatment.

Peptide drugs, which mimic the function of natural peptides such as hormones or growth factors, have emerged as a promising strategy for the treatment of cancer. Despite their potential, however, very few have reached the clinic in the past decade, primarily due to their off-target toxicity. The design of a suitable system to deliver peptides in a site-specific manner would address a major challenge in the development of anticancer peptide drugs.

Dr. Zhang [Timmerman Traverse Fellow] aims to engineer T cells with synthetic cell adhesion molecules (synCAMs) to augment current approaches for immunotherapy. This project represents a fundamentally new strategy for CAR T cell engineering that could overcome tumor escape from immunotherapy across multiple forms of cancer.

Epithelial to Mesenchymal Transition (EMT) is a crucial biological process that occurs during early development. It allows epithelial cells, which line the inner and outer surfaces of the body, to undergo a profound transformation in cellular identity and migrate and populate the embryo. Unfortunately, numerous cancer types exploit this mechanism, allowing cancer cells to detach from the tissue of origin and disseminate throughout the body, significantly worsening patients’ prognoses. Dr.