Our work is presently focused on the altered energetics relevant to kidney disease. Using the tools of mass spectrometry for measuring small molecules in biosamples and imaging the localization of the metabolites in kidney compartments provides a powerful approach to understand the biochemical underpinnings of kidney diseases. Samples from large well defined cohorts of diabetic and non-diabetic chronic kidney disease informs us on the relevant pathways and interrogation in cell and animal models will give insights into the mechanisms involved. A major area of interest is the role of different sources of oxygen radicals and links with mitochondrial function and metabolism. We are a key component of the newly established NIH-funded Kidney Precision Medicine Project and provides tissue imaging mass spectrometry for human kidney biopsies. Developing multi-omic capacity and analysis to feed into a Precision Medicine approach for nephrology is our overall goal.
- How does mitochondrial function change in response to glucose and other nutrient stresses?
- How does small molecules inform us about biochemical changes and mitochondrial function in humans and experimental models of disease?
- Characterization of insightful biomarkers in human kidney tissues and biosamples to support Precision Medicine for kidney disease.
- Pena, M.J., de Zeeuw D., Andress, D., Brennan, J.J., Correa-Rotter, R., Coll, B., Kohan, D.E., Makino, H., Perkovic, V., Remuzzi, G., Tobe, S.W., Toto, R., Parving, H.H., Sharma, S., Corringham, T., Sharma, K., Heerspink, H.J. The effects of atrasentan on urinary metabolites in patients with type 2 diabetes and nephropathy. Diabetes Obesity Metabolism, 2017 in press. PMID: 28019071
- E Börgeson, V Wallenius, G. H. Syed, M Darshi, J. Lantero Rodriguez, C. Biörserud, M Ragnmark Ek, P Björklund, M Quiding-Järbrink, L Fändriks, C Godson, K Sharma. High-fat diet-induced pathophysiology is reduced by AICAR in an adiponectin-independent manner, Diabetologia, 2017 Apr;60(4):729-739. PMID: 28188334
- Miyamoto, S., C-C, Hsu, Hamm, G., Darshi, M., Diamond-Stanic, M., Decleves, A-E., Slater, L., Pannathur, S., Stauber, J., Dorrestein, P., Sharma, K. Mass spectrometry imaging reveals elevated glomerular ATP/AMP in diabetes/obesity and identifies sphingomyelin as a possible mediator. EBioMedicine. 2016; 7:121-34. PMCID: PMC4909366.
- You YH, Quach T, Saito R, Pham J, Sharma K. Metabolomics reveals a key role for fumarate.