Kidney disease kills about 90,000 Americans per year, which is more than both breast and prostate cancers combined. The methods for diagnosing kidney damage are insensitive, nonspecific and have not changed for over 100 years. Moreover, the approaches to treat kidney disease are limited to supportive care, dialysis and transplantation, which really does not cure the disease. Advancing our mechanistic understanding of cellular and molecular pathways regulating kidney disease is of great interest because such findings are likely to provide more effective ways for early diagnosis, prevention, and therapeutic interventions. We use cellular systems, mouse models as well as human biospecimens and apply methodologies at the interface of bioinformatics, cell & molecular biology, systems toxicology and translational science in understanding kidney disease. The research areas being pursued in our lab are:
Problem: Traditional markers of kidney injury, serum creatinine, blood urea nitrogen, etc, lack the sensitivity and/or specificity to adequately detect injury before considerable loss of kidney function.
Solution: Our previous work in collaboration with Predictive Safety Testing Consortium led to first kidney toxicity biomarker (Kidney Injury Molecule-1) qualified by the US-FDA and EMA in 2008. Advancing the biomarker work forward, we have recently used cutting edge next generation sequencing technology to identify a panel of biomarkers (microRNAs as well as proteins) for early detection of kidney disease.
Impact: It is our hope that extensively validated, sensitive, and specific translational biomarkers coupled with rapid and economic technologies for non-invasive detection of the onset and severity of kidney injury will be beneficial in drug development, environmental health screening, and kidney medicine.
Problem: Fibrosis is the underlying cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD).
Solution: To fully characterize the molecular perturbations in a fibrotic kidney, we have conducted several discovery profiling experiments using small RNA sequencing, mRNA sequencing and targeted proteomics.A significant effort in the lab is currently dedicated towards deciphering functional roles of the top candidates in fibrosis pathogenesis.
Impact: We hope that this will not only reveal novel mechanisms underlying fibrosis but also identify precision medicines for a disease that remains to be an unmet medical need with no effective therapies.
Problem: Drugs and environmental chemicals play an important role in the high incidence and prevalence of kidney toxicity, which in many circumstances can be prevented or at least minimized by predictive toxicity screening.
Solution: We propose to transform the traditional in vivo, dose-response based toxicity assessment by developing in vitro, high throughput, multi-dimensional signature that represents a biography of the damaged kidney cell.
Impact: The overall goal is to advance regulatory science by transforming kidney safety assessment using tools and technologies at the interface of quantitative systems pharmacology.
Problem: Although it has been known that kidney (just like liver) can regenerate following injury at the pathological level, very little is known about the molecular factors that regulate the tissue repair process.
Solution: We are not only characterizing the critical role of epigenetic modifications as well as key transcription factors in kidney tissue repair but are also testing the efficacy of endogenously synthesized soluble peptides in their ability to modulate/enhance epithelial and endothelial repair in the kidney following injury.
Impact: Given that kidney regeneration is a major determinant of outcome for patients with kidney damage, these studies aim at providing opportunities for the use of novel molecules as therapeutic agents in kidney disease.