Damon Runyon News

Over 90% of cancer deaths are caused by metastasis, the spread of cancer cells to distant organs, where uncontrolled cancer cell growth lethally compromises organ function. Despite recent advances, current treatments fail to effectively control metastasis. Dr. Ganesh is growing colorectal cancer cells, removed from patients during surgery, as three-dimensional “organoids.” This cutting-edge technology models the complexity of human organs more accurately than cells growing in a dish.

Mitochondria, the “power plants” of the cell, carry their own DNA that encodes proteins important to producing the energy necessary to run a normal cell. Most cancers also depend on mitochondria to promote the growth and division of tumor cells. Dr. McFadden has shown that a form of thyroid cancer called Hürthle cell carcinoma carries mutations in the mitochondrial DNA, which are maintained in primary tumors and metastases resected from the same patients.

Although small cell lung cancer (SCLC) is initially highly responsive to chemotherapy, the disease recurs in nearly all patients in less than a year. There are currently no approved targeted therapies for when the cancer returns. Previous studies have demonstrated that SCLCs require sustained neuroendocrine differentiation for survival, suggesting that targeting this process could be a good therapeutic strategy. Dr.

Dr. Wu focuses on hepatoblastoma, the most common childhood liver malignancy and the cancer with the fastest growing incidence rate in children under the age of five years. Hepatoblastoma is characterized by a low overall mutational burden, but carries activating mutations in the Wnt signaling pathway. Using new techniques to culture cancer cells derived from patients, Dr.

Dr. Qadeer investigates the mechanisms underlying medulloblastoma (MB), the most common form of malignant brain tumors in children. Group 3 MB is a particularly aggressive subgroup, for which there are few actionable targets for therapies. Dr. Qadeer aims to understand how the genes and pathways regulated by the proteins MYC and TGFb mediate the transformation of neural precursor cells to malignant group 3 MB tumors. This work may also help elucidate tumor heterogeneity and resistance to current alkylating chemotherapies.

Dr. Gadek focuses on the Sonic Hedgehog (Shh) signaling pathway, which can be altered in rhabdomyosarcoma (RMS) patients. RMS is the most common soft-tissue sarcoma in children, but survival rates and treatments for high-risk patients have not improved in three decades. Dr. Gadek will examine the timing of tumor development and the role of Shh signaling in tumor location and formation. This may lead to diagnostic markers and tools for identifying high-risk patients with altered Sonic Hedgehog signaling, which could improve treatment options and outcomes.

Dr. Brown studies acute lymphoblastic leukemia (ALL), an aggressive leukemia and one of the most common malignancies in children and adolescents. Despite significant progress, relapse is associated with high rates of drug resistance and poor prognosis. As a result, relapsed ALL is the leading cause of cancer-related death in children. Dr. Brown will use large-scale genetic (DNA) and transcriptomic (RNA) data and leukemia animal models to dissect how a small number of ALL cells are able to escape the cytotoxic effects of chemotherapy.

Dr. Zinder [Lorraine W. Egan Fellow] studies telomeres that cap the ends of chromosomes and the role they play in cancer development. Telomeres normally shorten every time a cell divides until they become so short that cell division stops. Dr. Zinder is focusing on shelterin, a multiprotein complex that binds to telomeres to protect them from being mistaken as damaged DNA. Mutations in the shelterin components are found in both cancer and premature aging diseases.

Dr. von Diezmann is a biophysicist who studies how cells regulate the pathway used to repair broken DNA. Errors in specific DNA repair pathways are an early step in the development of many cancers, such as with defects in homologous recombination for breast, ovarian, and pancreatic cancers. The Diezmann lab uses high-resolution microscopy techniques to visualize the process by which DNA breaks are designated for specific repair fates, working primarily in live meiotic nuclei of the model organism C. elegans.

Dr. Tintori is studying nematode worms from Chernobyl, Ukraine, to investigate the biological effects of continuous radiation exposure. While ionizing radiation is known to cause cancer, little is known about the levels that increase health risks or how animals adapt to high radiation environments. Dr. Tintori is comparing worms from Chernobyl, the area with the highest known levels of background radiation on the planet, to similar animals that have not been exposed.