Mohona Gupta, PhD

2026 Jared J. Grantham Research Fellowship

Institution: University of California San Francisco

Project Title: Mechanism-Guided Restoration of Polycystin Function in ADPKD

Provide a brief overview of the research you will conduct with help from the grant.

ADPKD is one of the most common inherited causes of kidney failure, yet there are currently no therapies that directly repair the disease-causing proteins themselves. My research focuses on a major unanswered challenge in the field: many ADPKD mutations appear to produce partially functional polycystin proteins that fail to properly traffic to the primary cilium, the kidney cell's signaling hub. Using engineered kidney cell models, advanced cilia imaging, and small-molecule screening, I aim to identify "corrector" compounds that restore these mutant proteins to the cilium and recover the critical signaling pathways lost during disease progression. By bridging this missing signaling link, this work could help establish a precision-medicine framework in which specific patient mutations are matched to targeted therapies rather than treated with a one-size-fits-all approach.

What inspired you to focus your research in this area?

What drew me to this field was the striking contrast between scale and consequence: a microscopic cellular structure, once considered biologically insignificant, can ultimately determine whether an entire organ remains functional or progresses toward failure. ADPKD affects millions worldwide and carries an enormous lifelong burden for patients and families, often leading to progressive kidney enlargement, chronic pain, dialysis, or transplantation after decades of relentless cyst growth. I was especially inspired by the possibility that understanding how primary cilia regulate kidney signaling and architecture at the most fundamental level could help uncover transformative therapeutic strategies for a disease where treatment options remain limited.

What impact do you hope your research will have on patients?

I hope my research helps move ADPKD treatment beyond slowing disease progression toward directly correcting the underlying molecular defects that drive cyst formation and kidney failure. By understanding how specific PKD1 mutations disrupt polycystin trafficking and ciliary signaling, this work aims to lay the foundation for precision medicine strategies in which therapies are tailored to the functional consequences of individual patient variants. Ultimately, I hope these advances contribute to delaying or preventing dialysis and transplantation while improving long-term quality of life for patients and families affected by inherited kidney disease.

What are your career goals at the end of the grant period? Five years out? Ten years out?

By the end of the grant period, I hope to establish a rigorous mechanistic framework linking specific PKD1 variant classes to defects in polycystin trafficking, ciliary calcium signaling, and downstream cyst-promoting transcriptional programs in ADPKD. Over the next five years, my goal is to build an independent translational research program that integrates molecular physiology, human genetics, and functional genomics to systematically define how distinct disease-causing variants alter ciliary signaling networks and therapeutic responsiveness. Ten years from now, I hope to lead a laboratory that advances precision medicine approaches for renal ciliopathies by moving from gene discovery alone toward mechanism-based therapeutic stratification—where the molecular and functional consequences of individual patient mutations directly inform targeted intervention strategies.

What are the major challenges to beginning a career in nephrology research today?

Modern nephrology research is increasingly interdisciplinary, requiring young investigators to navigate genetics, physiology, imaging, computational biology, and translational science simultaneously. At the same time, kidney diseases often develop slowly over many years, meaning impactful discoveries require long-term investment and sustained funding support. Despite these challenges, this is also an exciting period for the field because emerging technologies are finally allowing us to study kidney disease mechanisms with a level of precision that was previously impossible.

What advice would you give to others to encourage them to apply for this grant funding?

Do not wait until your science feels "perfect" before applying. Some of the most important scientific advances begin as bold, evolving ideas, and programs like KidneyCure provide young investigators not only with funding, but also with confidence and validation at a pivotal stage in their careers.

Something you may not know about me is…

that I am deeply passionate about science communication and making complex biology accessible to broader audiences beyond academia. I strongly believe that scientific discovery becomes even more meaningful when it can inspire curiosity and understanding outside the laboratory.

In my free time I like to…

enjoy music, dance, photography, traveling, mentoring students, and exploring creative ways to communicate science through storytelling and visual media.