Research Description
Kidney disease caused by diabetes, or diabetic kidney disease (DKD), is the leading cause of end-stage kidney disease requiring dialysis. Current therapeutic options are limited and are only able to slow disease progression. A complete understanding of how DKD develops and progresses has been slowed by the widespread nature of its effects through numerous tissue compartments and cell types. Each kidney is comprised of nearly one million individual functional units called nephrons, made up of a filter component (glomerulus) and downstream tubular component, with an interstitial space between nephrons. Much is known about the role of glomerulus injury in worsening DKD, and this injury results in protein leakage through the filter, which must be handled by the proximal tubule (first tubule segment). While less studied, tubular and interstitial disease is also prominent in DKD, and this study proposes a series of experiments to more precisely define cellular changes in the tubules and interstitium with glomerular protein leakage to identify new targets for drug development. Imaging mass cytometry (IMC), a powerful tool that precisely defines more than 40 proteins at a time, will be used to reconstruct 2-dimensional models of the human kidney with DKD with and without protein leakage, and determine the precise cell types present, their location, abundance, activation states, and signs of cell injury and stress. With the improved understanding of DKD gained from this study, this work will help to identify therapeutic targets for the treatment of DKD.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?My project focuses on investigating the progression of diabetic kidney disease, aiming to unravel the mechanisms leading to kidney failure. Using advanced tissue imaging modalities, we aim to characterize cellular injury within the kidney and understand the interplay between immune cells and kidney cells, crucial factors influencing kidney tissue vulnerability to disease. By elucidating the pathways associated with kidney failure in various forms of diabetic kidney disease, our research aims to pave the way for targeted therapeutic interventions. The goal is to develop treatments that specifically target these identified pathways, thereby altering the natural course of the disease. Ultimately, this project holds the potential to contribute significantly towards the prevention and treatment of diabetic kidney disease by offering insights into novel therapeutic targets.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Diabetic kidney disease affects approximately one half of all patients with type 2 diabetes and one third of patients with type 1 diabetes and is the leading cause of kidney failure requiring dialysis in Western countries. Research on the mechanisms of disease in diabetic kidney disease is almost exclusively based on studies in animals, and the translation of results to human disease is challenging due to inherent differences between humans and animals. My research aims to clarify the key players, interactions, and environmental factors within human kidney tissues driving these poor clinical outcomes for so many patients with diabetic kidney disease. By better understanding the cellular processes that are closely tied to tissue dysfunction, we can design more specific drug therapies to prevent kidney failure in patients with diabetic kidney disease.
Why important for you, personally, to become involved in diabetes research? What role will this award play?As a physician-scientist who has personally cared for many patients affected by diabetic kidney disease, my motivation to engage in diabetes research stems from witnessing firsthand the devastating impact it has on patients and their families. Having treated numerous patients navigating the progression of diabetic kidney disease leading to kidney failure, I've recognized the urgent need to explore ways to prevent and manage this condition more effectively. Being involved in diabetic kidney disease research holds great personal significance given the opportunity to contribute meaningful advancements that can alleviate the suffering and improve the quality of life for individuals like the patients I have cared for. Receiving this award marks an essential milestone in my career, providing crucial support at the beginning stages of my journey in studying diabetic kidney disease. This support will enable me to make impactful strides towards understanding, managing, and ultimately mitigating the progression of diabetic kidney disease.
In what direction do you see the future of diabetes research going?The future of diabetes research appears to be heading towards more personalized and precise treatments. With advancements in technology and our understanding of genetics, there's a growing focus on tailoring therapies to individual characteristics, such as genetic predispositions and lifestyle factors. I anticipate a continued emphasis on innovative approaches, including the development of targeted therapies, precision medicine, and advanced monitoring systems, all aimed at not only managing but potentially preventing diabetes and its complications more effectively.