Our laboratory has a strong interest in the biology of ion channels and calcium signaling, with the goal to harness our foundational work in this space for the development of novel precision medicine therapeutics.
We are currently focused on rare, genetically defined kidney diseases, for which there is tremendous unmet need. We ultimately hope to use the transformative potential of this work to also address areas of unmet need in highly prevalent, hard-to-treat diseases affecting millions of people worldwide, including the modern epidemic of diabetic kidney disease.
Recent efforts in our lab were focused on Transient Receptor Potential channels (TRP) as regulators of actin dynamics and cell motility. Our work uncovered TRPC5 and TRPC6 as calcium influx pathways regulating the activity of the RhoGTPases Rac1 and RhoA.
We were also recently successful in translating our insights from TRPC5 biology into a targeted approach for kidney disease therapeutics. Our work revealed the calcium-permeable TRPC5 channel as a key mediator of proteinuric kidney disease. We also showed that genetic deletion or inhibition of TRPC5 protects the kidney filter.
Significant effort in the laboratory is also directed toward understanding the mechanisms linking calcium signaling to disrupted cellular metabolism, with important connections to the modern epidemic of obesity and diabetes.
Harnessing the highly interdisciplinary nature of our team at Harvard Institutes of Medicine and the Broad Institute, students, postdoctoral fellows and staff scientists on our team bring their unique expertise in ion channel biophysics, pharmacology, cell biology, biochemistry, imaging, in vivo studies and computational biology to solve complex scientific problems.