Genome instability is a hallmark of cancer. Yet genome maintenance and mechanisms of genome instability are not clearly understood. This proposal continues the collaboration between Dr. Paul Hasty at the Health Science Center at San Antonio and Dr. Cristina Montagna at Albert Einstein College of Medicine in New York. They will explore the involvement of TREX2 in both the suppression and development of genomic instability. TREX2 is a 3'?5' exonuclease that removes 3' mismatches in DNA. However, its biological function is not known.

Hispanic women along the Texas-Mexico border experience more cases of and deaths from cervical cancer compared to the nation. Cervical cancer is preventable using the HPV vaccine, which is recommended for girls/boys and women/men aged 11-26. Compared to U.S. Hispanic girls, a smaller proportion of Texas Hispanic girls (ages 13-17) (65% vs. 58%) receive ?1 dose HPV vaccine and fewer complete the vaccine series (?3 doses; 42% vs. 35%).

Glioblastoma (GBM) are the most malignant primary brain tumor and patients with GBM (grade IV glioma) have a survival time of approximately 14 months. Estrogen plays a crucial role during brain development and differentiation. Epidemiological and experimental evidence suggests tumor suppressive role of estrogen on brain tumors. However, the molecular mechanisms by which estrogen mediate protection against GBM remains unknown. Estrogen functions are mediated by two ER-subtypes: ER? that functions as tumor promoter and ER? that functions as a tumor suppressor.

The purpose of this study is to (1) produce and test a vaccine that is made from a patient’s tumor cells and white blood cells to determine if it can prevent melanoma recurrence; (2) to look at the safety of the vaccine (what side effects it has); and (3) to look at the immune system’s response to this vaccine.

Glioblastoma is the most common and most aggressive of the primary malignant brain tumors in adults. Annually there are approximately 13,000 cases of GBM diagnosed, with historical 1 year and 5 year survival rates of 34.6% and 4.75% respectively. While concomitant chemoradiotherapy with temozolomide remains the standard of care for initial treatment, all patients eventually require salvage therapy and angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) pathway are standard in this setting.

Applied Research

The South Texas Pediatric NCI Community Oncology Research Program (STP NCORP) for Minority and Underserved is composed of five independent Children's Oncology Group (COG) institutions. The catchment area (South Texas and most of Central Texas) serves a large population of patients spread over 90,000 square miles. The population is young and in majority Hispanic (> 50%) with a significant portion of patients under the age of 18 living in poverty, particularly in the Texas-Mexico border region.

The candidate's long-term career goal is to become an independently funded physician- scientist who is actively engaged in translating basic research findings into clinical therapeutics. The proposed career development plan integrates didactic coursework with mentored research experience in the design and conduct of cancer immunology research to provide the candidate with the necessary components for a successful career in patient-oriented research.

Basic Research

Basic Research