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.

Given the continuing rise of the U.S. Hispanic population, reversing the Hispanic childhood obesity epidemic is critical to the nation's future health. Mexican American children and those from socioeconomically disadvantaged families often are far more overweight and obese than their peers, heightening their risk for obesity-related health complications.

RESEARCH

Increased serum uric acid or hyperuricemia is a risk factor for kidney and heart disease and gout. The uric acid transporter SLC2A9 regulates uric acid concentrations in blood by regulating uric acid reabsorption and secretion in kidneys. Alteration in the transporter activity can result in hyperuricemia thus increasing the risk for kidney disease gout and heart disease. Thus evaluating the complete variation in the SLC2A9 gene will help us gain better understanding of the mechanism in Mexican Americans as well as American Indians.

TxBiomed will communicate with the Strong Heart Study Steering Committee regarding CALiCo/PAGE administrative issues, actively participate in project and working group conference calls, data analysis and manuscript preparation and attend PAGE Steering Committee calls and in-person meetings.

The prevalence of diabetes and its complications has increased among older adults, and new models of care are needed to combat this trend among vulnerable populations. According to the Chronic Care Model (CCM), optimal chronic illness care requires linkages with community-based resources. Research based upon the CCM suggests that self-management support for older adults with diabetes may be bolstered by linkages between primary care providers and senior centers, but studies of such linkages are rare.

Steadily decreasing rates of cardiovascular disease (CVD) in the US threaten to be reversed because of rapid increases in obesity and diabetes. The proposed study will take advantage of the Strong Heart Study data in American Indians to further our understanding of CVD and its risk factors, especially diabetes and obesity, which will lead to more effective prevention and therapy and reduce the burden of CVD morbidity and mortality.

Metabolic disorders including obesity, dyslipidemia and diabetes appear to be associated with monocyte dysfunction, yet the molecular mechanisms underlying monocyte dysfunction in vivo are only poorly understood. Our recent studies showed that metabolic stress promotes the dysregulation and hyper-activation of monocyte responses to chemokines and that monocyte dysfunction is a critical and rate-limiting step in the development and progression of atherosclerosis.

Chemokine-driven transmigration of monocytes into the subendothelial space is a fundamental and rate- limiting process in atherogenesis. Our preliminary data show that this process is dysregulated by metabolic stress and that increased monocyte responsiveness to chemokines appears to accelerate atherosclerotic plaque development. We have now uncovered a novel thiol redox-sensitive mechanism in monocytes that upon dysregulation by metabolic disorders, 'primes' and transforms monocytes into a hyper-chemotactic pro- atherogenic phenotype.