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.

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.

The overall goal of the proposed training program is to train physician scientists for careers in translational biomedical imaging research. This goal will be met through a unique 6-year, residency/PhD training program, which combines a radiology residency with a doctoral degree in imaging science (Rahal et al., 2007). This training program is hosted by the University of Texas Health Science Center at San Antonio (UTHSCSA), a large, research-oriented institution with outstanding imaging-research resources and a long history of federally funded, imaging research.

Applied Research

The applicant's career goal is to become an independent scientist in the field of aging. A comprehensive mentoring plan has been developed to ensure her career development. This research project will address a potential mechanism underlying the paradoxical relationship discovered in C. elegans whereby some mitochondrial electron transport chain (ETC) mutations are associated with increased longevity.

Little is known about the etiology or risk factors for autism, a disease affecting 1 in 50 children in the U.S. While genetic and environmental factors are thought to act together, the specific mechanisms are not known and the measurement of environmental risk factors during critical periods of neurodevelopment has been lacking. This case-control study seeks to apply a novel dental biomarker of early life metal exposure, including in utero, to identify risk factors for ASD.

Cancer is the leading cause of death worldwide. In the US, it claims more lives in Americans younger than 85 years of age compared to any other cause. As a nation, hundreds of billions of dollars are spent annually on cancer research and care, but cancer death rates have not changed significantly for most advanced-stage cancers. These grim statistics point to a need for novel and effective cancer prevention strategies, as prevention can be more clinically effective and is clearly more cost effective than most cancer treatment strategies.

The long-term goal of this proposal is to understand the mechanism of action of calcium signaling pathways in airway smooth muscle in order to identify novel bronchodilators for the clinic. The immediate goals for this proposal are twofold. The research will provide an understanding (at the cellular level) of how a novel bronchodilator, UCL 1684, modulates SK channels and causes airway smooth muscle relaxation.

The long-term goal of this study is to improve the health and well-being of older Americans. Our immediate goal is to examine how disruption of mitochondrial function is linked with the aging process. In recent years, it has become clear that defects in the electron transport chain of mitochondria, the key site of energy production in cells are linked with many age-related diseases - including heart disease, Type II diabetes, Parkinson Disease, Alzheimer's dementia, and cancer. 15% of the US population suffers from these chronic degenerative disorders.

Demyelination in the central nervous system, resulting from genetic mutations or autoimmune disease (e.g. multiple sclerosis, MS), causes hearing impairments such as sudden hearing loss, inability to localize sound and/or tinnitus. Such deficits are generally attributed to the decrements in conduction velocity and temporal fidelity that accompany axon demyelination. However, the direct impact of demyelination on synapse functional parameters, including presynaptic excitability, neurotransmitter release and synaptic plasticity, is largely unknown in the auditory nervous system.