Current projects and Area of interest:
1. Zuni Health Initiative – Educational intervention of patient activation in Diabetes, NIH (2009 – 2019);
2. PCORI-Reducing Health Disparity in Chronic Kidney Disease in Zuni Indians –PCORI (2013 – 2016);
3. UNMHSC –CTSC Community Engagement Core -NIH
4. CYP19A1 Gene and Pharmacogenetics of Response –Veterans Administration
5. Epigenomic Changes in Progression of Pre-Diabetes to Diabetes -CTSC
6. Fatalism and Knowledge of Diabetes in Urban and Reservation American Indians -CTSC
7. Exercise Intervention for Zuni Children –CTSC
1. Family Investigation of Nephropathy and Diabetes: The project is a joint consortium of more than eight university and NIDDK to identify genome segments that modulate the risk for the onset and/or progression of diabetic nephropathy and intermediate phenotypes in EA, AI, AA and MA populations.
2. Genetics of kidney disease in Zuni Indians: The present project is designed to identify genome segments and environmental-genetic interactions that modulate the risk for the onset and/or progression of all cause nephropathy and intermediate phenotypes in Zuni Indians.
3. Heavy Metals Exposure among Zuni Jewelers and Proteomics: Our hypothesis is that exposure to heavy metals lead to activation of oxidative and inflammatory stress pathways which alter important proteomic and metabolomic profiles. The resulting changes have the potential to alter endothelial function and accelerate atherosclerosis thereby increasing the risk for renal and cardiovascular disease (CVD). In the present pilot study we will utilize proteomic and metabolomic approaches to identify protein markers of metabolic pathways of oxidative and inflammatory stress that occurs in response to environmental exposures.
4. Cytokine Gene Polymorphism in CRIC Cohort: The principal aims of this proposal are: (1) Determine the prevalence of cytokine gene polymorphisms and haplotypes of interleukin-1 (IL-1), IL-1 receptor antagonist, IL-6, IL-10, tumor necrosis factor-α, and transforming growth factor-β among chronic renal insufficiency cohort (CRIC) participants; and (2) Evaluate the association between specific gene polymorphisms/ haplotypes and (a) plasma cytokines, (b) the rate of decline of renal function, and (c) incidence of, severity of and mortality from CVD in the CRIC cohort.
5. Inhibition of Hemodialysis-associated Inflammation: Inflammation and oxidative stress play a major role in the CVD mortality that is associated with ESRD. The transcription factor nuclear factor kB (NFkB) is well known as a regulator of genes controlling the inflammatory and oxidative responses. We propose that attenuating the over-activation of NFkB may be a new approach to the development of therapies for prevention of inflammatory and oxidative stress-associated complications of CVD in ESRD. Our approach of limiting the activity of NFkB with curcumin and resveratrol analog supplement might be of clinical importance for reduction in oxidized macromolecules and pro-inflammatory stress markers in HD. This natural analog treatment and other measures that can reduce the NFkB activity thus reducing the ROS and cytokines should be beneficial for minimizing oxidative / inflammatory damage to leukocytes and endothelial cells.
6. Metabolomic pathway in different stages of chronic kidney disease (CKD): The broad goal of this study is to develop enhanced understanding of how cellular and oxidative / inflammatory stresses leading to mitochondrial dysfunction and thus progressive loss of kidney function and accelerated development of cardiovascular disease (CVD) in CKD. Our clinical translational objective is to gather data critical for a subsequent large scale interventional study designed to decrease cellular stress, alleviate oxidative stress, reduce inflammation and thus lower the CVD mortality in patient with CKD. Coordination between the clinical data and the ex-vivo study as proposed here will be emphasized to achieve maximal understanding of the pathophysiology of CKD progression, uremia and CVD.
7. ER/Mitochondrial Axis, ROS, and DNA Methylation in Diabetics: The broad goal of this study is to develop enhanced understanding of how cellular and oxidative / inflammatory stresses leading to mitochondrial dysfunction and changes in DNA methylation leading to the progressive loss of kidney function in diabetic CKD. Our clinical translational objective is to gather data critical for a subsequent large scale interventional study designed to decrease cellular stress, alleviate oxidative stress, reduce inflammation and thus lower the mortality in patient with diabetic CKD. Coordination between the clinical data and the ex-vivo study as proposed here will be emphasized to achieve maximal understanding of the pathophysiology of diabetes, CKD progression and uremia.