SUMMARY
The research of Navin R. Gupta, M.D., uses human stem cell-derived kidney tissue to model relevant kidney diseases, identify disease-specific pathways and conduct clinical trials in a dish. These clinical trials in a dish are aimed at identifying lead therapeutic candidates for drug development. Dr. Gupta has particular interest in modeling genetic kidney diseases, such as variations of polycystic kidney disease (PKD), using samples from participating individuals to create his stem cell-based kidney organoid models.
Organoid technology helps personalize approaches to medicine, going beyond the traditional treatment approach of inhibiting signals activated in disease to include methods of gene therapy in patient-specific kidney models. Such personalized approaches try to correct naturally occurring mutations. Dr. Gupta develops models of kidney injury and repair toward understanding pathways involved in the progression from acute to chronic kidney disease. He combines kidney organoid and kidney-on-chip technologies to stimulate flow-induced blood vessel formation and maturation in these lab-grown mini kidneys.
Outside of his research using kidney organoids for disease modeling, Dr. Gupta maintains an inpatient and outpatient nephrology practice. He is a general nephrologist and internist and is affiliated with the Mayo Clinic Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center. Dr. Gupta specializes in the diagnosis, monitoring and treatment of PKD.
Focus areas
- Preclinical models of gene therapy in PKD. Dr. Gupta is an active recipient of a Polycystic Kidney Disease Research Resource Consortium Award funded via the National Institutes of Health. With this award, he evaluates the feasibility of gene therapy in the treatment of autosomal recessive PKD.
- Kidney organoids on chip. With support from a Harvard Stem Cell Institute inter-lab fellowship award, Dr. Gupta participated in research that found that fluidic shear stress stimulates vascularization and maturation of kidney organoids. This fluid shear stress provides a critical step toward translational utility for regenerative medicine. Next the kidney organoid-on-chip model was used to find that mechanical stimulation is a pathological feature of autosomal recessive kidney disease and to identify potential disease-modifying therapeutic targets.
- Tubular DNA damage and repair mechanisms. This research was enabled by National Institutes of Health funding. The study involved modeling human kidney injury and repair mechanisms in a tubular DNA damage model in kidney organoids. Specifically, an MDM2-RAD51-FANCD2 axis of homologous recombination was found to govern intrinsic repair, with tissue loss stimulating the progression from acute kidney injury to chronic kidney disease phenotypes.
Significance to patient care
The overall goal of Dr. Gupta's research is to improve drug discovery for kidney diseases using human kidney organoid models. These models allow high-throughput screening of therapeutic compounds, enable patient-specific personalized medicine approaches, supply the only model for human disease in the absence of a faithful animal model and overcome interspecies differences that lead to failures in clinical trials when lab animals are used to study human diseases.