Damon Runyon News

Dr. Eichel is studying how proteins travel across cellular membranes and are sorted to different areas of the cell. This highly regulated mechanism generates distinct membrane domains of the cell with unique protein compositions, which are essential for cellular functions. Dr. Eichel hopes to understand how membrane trafficking plays a role in cancer biology, including loss of cellular polarization, uncontrolled cell growth, invasion, and metastasis.

Dr. Zhang [HHMI Fellow] is studying the mechanisms that promote recurrent DNA double strand break clusters (RDCs) in the brain and liver, and how these breaks in the DNA are repaired to maintain genomic stability and suppress tumors. Recently, RDCs were found in neural stem and progenitor cells. This work may reveal if DNA breaks in RDC genes predispose individuals to genomic variations that could contribute to cancers and other diseases.

Dr. Dann is studying how the addition of the amino acid arginine to proteins regulates their biological activity. When this process malfunctions, cancerous genes are transcribed into proteins. Dr. Dann will use high-resolution mass spectrometry to identify arginine-modified proteins in cells, chemical biological tools to decipher the role of such modification in determining protein function, and functional genomics to understand how this process regulates the genome.

Dr. Hirschi is creating a tool to investigate specific glutamate receptor subpopulations and elucidate their role in cancer mechanisms. Glutamate receptors on neurons are involved with learning and memory in a time- and tissue-specific manner and abnormal function can lead to cancer. Detailed understanding of how glutamate receptors work may provide insight into new therapies for cancers ranging from gliomas to peripheral malignancies, such as pancreatic cancer.

Ewing sarcoma is an aggressive bone tumor that occurs in children and young adults. Cure rates, particularly when disease has spread, are low with currently available treatments. Dr. Guenther aims to identify critical genes on which Ewing sarcoma cells are dependent for survival, with the goal of discovering weaknesses in these cancer cells that may be exploited to stop cancer growth. CITED2 is of particular interest as a Ewing sarcoma-specific dependency gene based on a genome-wide screen in hundreds of cancer cell lines.

Immunotherapy has resulted in positive outcomes for patients with melanoma, lung cancer, and other malignancies; however, most patients do not have meaningful responses to this treatment strategy. Tumors that fail to respond to immunotherapy have effectively hidden themselves from detection by the host immune system. Understanding how cancers create an immune-excluded environment promises to lead to the development of more highly effective immunotherapies.

Adenocarcinoma is the most common type of lung cancer. Approximately 10% of patients with lung adenocarcinoma will have a tumor that simultaneously carries mutations in genes called KRAS and LKB1. Patients that have a lung cancer harboring both these mutations develop resistance to chemotherapy more rapidly, are more likely to develop brain metastases, and have a worse overall prognosis. Currently, there are no targeted therapies available for patients with this type of lung cancer.

The treatment of metastatic melanoma has been transformed over the past decade with the development of (1) targeted therapies that target a very common gene mutation (BRAF mutations in 50-60% of tumors) in melanoma and (2) two different types of immune therapies that induce the immune system to attack the cancer (CTLA-4 and PD-1 inhibition). However, not all patients respond to either targeted or immune therapy, and there is evidence suggesting that patients who quickly develop resistance on the initial therapy (whether targeted or immune) have worse outcomes (e.g.

Pancreatic cancer is the third most common cause of cancer-related deaths in the United States. This cancer is normally treated with a combination of different chemotherapies. While treatment is initially effective, the cancer quickly learns how to evade therapy and regrow. Using novel assays to analyze individual pancreatic cancer cells obtained from patients, Dr. Singh will investigate how these cells change their identity to grow and resist chemotherapy.

Tyrosine kinases are enzymes that act as “on” and “off” switches for signals in cells and are important in regulating cellular activity, such as cell division. They can become mutated, stuck in the "on" position, and cause unregulated growth of the cell, which is a necessary step for the development of cancer. Kinase inhibitors have been developed as cancer treatments, but they have not been sufficiently effective and are susceptible to drug resistance.  Dr.