Damon Runyon News

Dr. Adams [Marion Abbe Fellow] studies a specialized subset of immune cells that secrete potent antitumor cytokines called type I interferons (IFN-I). Within a tumor, these cells, called plasmacytoid dendritic cells (pDCs), are impaired, which contributes to an immunosuppressive state and cancer progression. Dr. Adams aims to uncover the molecular mechanisms that govern IFN-I production and pDC dysfunction in cancer.

Head and neck cancers usually begin in the squamous cells that line the mucosal surfaces inside the mouth, nose and throat. Even with aggressive treatment including surgery, radiation therapy and chemotherapy, these tumors often recur with poor prognosis. Dr. Mowery will use patient samples and mouse models to investigate why these cancers are resistant to radiation treatment and to test new therapeutic approaches to improve outcomes for patients.

Cancer cells harboring many genetic changes in their DNA often express novel proteins called neoantigens that activate the immune system to recognize and attack the tumor. Based on this mechanism, researchers are developing novel treatments to stimulate the immune system's response against a tumor, but this approach may not work for pediatric cancers that carry few genetic mutations. Dr. Knoechel's research is investigating alternative ways neoantigens can be generated, such as splicing or epigenetic changes, which occur frequently in leukemia and pediatric cancers.

Immune checkpoint inhibitors, a standard of care for metastatic melanoma, release the brakes on a patient's T cells, so they can attack a tumor. Some patients, however, relapse when resistance to treatment occurs. Dr. Kalbasi will lead a clinical trial to test a new immunotherapy treatment approach for patients with this deadly skin cancer, who did not respond to standard therapies. He will identify patients whose melanoma tumor cells express a protein called IL13Ra2.

There is a critical need for new therapeutic approaches to treat advanced stage rectal cancer, which has increased incidence in younger people and poor prognosis. Working with a multidisciplinary team, Dr. Aguilera is leading a randomized clinical trial that combines an anti-CD40 agonist immunotherapy with radiation and chemotherapy for locally advanced rectal cancer. The drug aims to activate the protein CD40 on dendritic cells which plays a critical role in generating T-cell immunity. As part of the study, Dr.

Dr. Patel studies rhabdomyosarcoma (RMS), a fast-growing childhood cancer that can spread from muscles to other parts of the body. Dr. Patel has discovered that each RMS tumor consists of different subpopulations of cells that mimic different stages of early muscle development. He will characterize how chemotherapy or radiation therapy selects for specific subpopulations of resistant cancer cells that survive treatment within both patient tissue and in patient-derived models of cancer. Using this information, Dr.

Dr. Eldred is focusing on retinoblastoma, a tumor of the eye that primarily occurs in children. She is developing three-dimensional tissue cultures that replicate the complexity of the human retina. Using these retinal “organoid” models, Dr. Eldred will generate mutations of the retinoblastoma (RB1) gene in previously healthy tissue to observe the effects of different mutations on the formation and growth of retinoblastoma. She hopes this will also shed light on the roles of tumor-causing oncogenes and tumor suppressors involved in retinoblastoma progression.

DNA stores the information for making all the proteins in an organism. Transfer RNA (tRNA) plays a key role in building the proteins from this blueprint. tRNA molecules recognize specific sequences (three-letter codons) and deliver the corresponding amino acids needed to make a protein. Dr. Hsu recently found that certain starvation conditions can cause some tRNAs to be modulated in colorectal cancer cells. He will study the changes in tRNA levels that occur in response to cellular starvation states.

The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the development of immune-activating checkpoint inhibitors, given alone or with chemotherapy. However, most patients' tumors eventually develop resistance to these drugs. Dr. Vokes [The Mark Foundation for Cancer Research Physician-Scientist] is investigating this process by collecting data on the genetic and immune features of pre- and post-treatment tumors.

Squamous cell skin cancer or cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the United States. In cases when the tumor cannot be surgically removed, treatment options are limited. Dr. Ji is focusing on intratumoral heterogeneity, the diversity of cell types and tumor cell subpopulations that characterize these tumors. Current cSCC treatments do not effectively target all subpopulations within a tumor, which leads to survival of some cancer cells and therapeutic resistance.