Research
The primary interest of our research group is to delineate the molecular mechanisms through which diabetic nephropathy progresses. We are also studying the molecular mechanisms by which cisplatin induces nephrotoxicity.
Mitochondrial dysfunction: Mitochondria are highly organelles undergoing coordinated cycles of fission and fusion, referred as ‘mitochondrial dynamics’, to maintain their shape, distribution and size. Cells maintain a characteristic mitochondrial morphology ranging from fragmented to fused elongated networks maintaining their fitness and optimal ATP production under different metabolic conditions. Mitochondrial fission divides this double-membrane organelle into daughter mitochondria, while mitochondrial fusion joins independent and separate mitochondria into one mitochondrion. A major focus of our lab is to understand the biological functions of mitochondrial dynamics and how changes in mitochondrial morphology contribute to the pathogenesis of diabetic kidney disease (Wang W et al. Cell Met. 2012 15:186-200, and Galvan DL,et al: J. Clin. Invest. 2019 129:2807-2823).
Non-coding RNAs: We are witnessing a paradigmatic shift in the practice of medicine whereby the concept of targeting RNAs as diagnostic and therapeutic strategies are rapidly evolving. Lon noncoding RNAs (lncRNAs) are a highly heterogeneous group of non-coding transcripts that participate in the regulation of almost every stage of gene expression, as well as being involved in a variety of disease states. Dysregulation of several lncRNAs have also been implicated in progression of diabetic nephropathy and because of the tissue-specific characteristics of lncRNAs, they are considered as the next generation of biomarkers and promising therapeutic targets for diabetic nephropathy progression. Our laboratory has been on the forefront of identifying multiple miRNAs and their downstream effectors in the kidney. We have recently published novel observations on the potential effects of miRNAs in diabetic nephropathy (Long J. et al: J. Biol. Chem. 2010, 285:23457–23465; and Long J. et al: J. Biol. Chem. 2011, 286: 11837-11848). These collective efforts have significantly accelerated the process of assessing the role of miRNAs in the pathobiology of diabetic nephropathy.
Onco-nephrology: The question has been asked of many of us interested in the kidney–cancer connection: Why onco-nephrology? And why is there a great need for more research and expertise in onco-nephrology? Rapid advances in cancer therapy have changed the landscape of oncology with new chemotherapy agents, targeted therapies, immune-targeted therapies, and many other innovative approaches that have resulted in improved survival and decreased tumor progression. As result, an increasing number of cancer patients are referred to nephrologists because of a myriad of kidney disorders. Recognizing this changing landscape, we have begun to address this rapidly growing area of nephrology focusing primarily on renal cell carcinoma (RCC). We study the critical effect of mitochondrial one-carbon metabolism activity on alteration of the epitranscriptomic landscape. Our recently published work in the journal of Oncogene uncovers how MTHFD2, a mitochondrial one-carbon metabolism enzyme, modulates the methyl-donor pool, leading to epitranscriptomic landscape remodeling and progression of RCC (Green NH, et al: Oncogene. 2019 38:6211-6225).