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%).

Basic Research

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 (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.

It is now generally accepted that G protein coupled receptors (GPCRs) can form multimeric complexes with the same (homomers) or different (heteromers) GPCR partners. We have learned a vast amount about these GPCR oligomers from studies conducted with heterologous expression systems where individual receptor protomers can be labeled and high-resolution microscopy techniques can be applied along with rigorous biochemical and cell signaling methods.

Basic Research

Triple negative breast cancers (TNBCs) are those devoid of estrogen and progesterone receptors and HER2 overexpression. They are heterogeneous cancers that disproportionately affect young women, African Americans and Hispanics. The prognosis for patients with metastatic TNBC is poor with only 30% surviving 5 years. There is an unmet need for more effective therapies for these breast cancers. Recent molecular profiling of TNBC tumors revealed 6 distinct subtypes with different molecular defects and identified cell lines representative of each of these subtypes.

DNA hypermethylation of promoter CpG islands is known to be associated with transcriptional silencing in endometrial cancer. We recently identified a unique set of CpG island loci that are hypermethylated in non- recurrent tumors but coordinately hypomethylated (or less methylated) in primary tumors that subsequently recurred. The loci can be highly susceptible to de novo DNA methylation (i.e., a default state) partly attributed to the high expression of DNA methyltransferase 1 (DNMT1) and Polycomb Repressor Complex 2 (PRC2).

The objective of this study is to better understand the underlying mechanism of Continuous Diffusion of Oxygen (CDO) and to demonstrate its clinical effectiveness by initially identifying biomarkers in patients with chronic lower extremity ulcers, and then observing the effect of CDO on the wound biomarkers as wound healing progresses. Due to our current understanding of the hypoxic conditions in chronic wound healing, we hypothesize that the effects of CDO involve both the reduction of proteases from inflammatory cells and the facilitation of angiogenesis to prevent hypoxia.