# The interaction between mechanical forces and cytoskeletal impairments in podocyte mediated kidney disease

> **NIH NIH K01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $150,736

## Abstract

Project Summary/Abstract
This K01 grant proposal describes a five-year mentored training program designed to transition Dr. Di Feng to
become an independent academic investigator. Dr. Feng obtained her Ph.D. at the Medical College of
Wisconsin under the mentorship of Dr. Allen Cowley. She is now completing her postdoctoral fellowship in the
lab of Dr. Martin Pollak, an international leader in studying the genetics of glomerular kidney disease. Dr. Feng
has focused her research on elucidating the mechanism by which mutations in ACTN4 – an important
cytoskeleton protein – lead to a form of glomerular kidney disease called focal segmental glomerulosclerosis
(FSGS). The inability to better characterize the podocyte dysfunction that underlies FSGS has hindered the
field in establishing more specific, personalized treatments beyond broad immunosuppression and anti-
hypertensive therapy. Dr. Feng has focused her research on the mutant podocyte’s response to the
mechanical stresses it experiences while filtering blood flow in the glomerulus. She has so far shown that the
biophysical changes conferred by disease-causing mutant ACTN4 render the podocyte brittle, exhibiting failure
of contractile forces and actin cytoskeleton disruption in response to periodic stretch. In the current proposal,
Aim 1 seeks to further define the impaired response of human podocytes caused by mutant ACTN4, not only to
stretch but also to shear stress. She will employ organ-on-a-chip methods to better simulate these stresses
while quantifying the associated biomechanical and molecular responses of podocytes. Aim 2 will determine
whether post-translational phosphorylation of ACTN4 also impairs the response of podocytes to mechanical
stress, using mouse models and biomechanical studies of podocytes isolated from these mice. Aim 3 plans to
use CRISPR/Cas technology to generate a mutant ACTN4 rat model and use intravital microscopy to measure
the in vivo mechanical stresses within mutant and WT glomeruli. Through the proposed research, she will learn
organ-on-a-chip methods, mass spectrometry, super-resolution imaging, and intravital microscopy. She has
assembled a team of mentors and advisors under Dr. Pollak entailing leaders in these respective disciplines,
including Dr. Donald Ingber, Dr. Bruce Molitoris, Dr. Hanno Steen, Dr. Douglas Richardson, as well as Dr.
Roger Tung, who will provide advice related to the translational value of her work. Dr. Feng will spend 95% of
her time under this award toward the proposed research, and her training plan includes didactic courses,
seminars, and career development workshops at Harvard. The proposed project will make Dr. Feng
competitive for independent research awards, for which she plans to apply her findings from ACTN4 and the
above multidisciplinary methods to further study how defects in the actin-based cytoskeleton impair the
podocyte’s response to the mechanical stresses experienced in vivo. The advancement of her goals will take
p...

## Key facts

- **NIH application ID:** 10225541
- **Project number:** 5K01DK114329-04
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Di Feng
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $150,736
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225541

## Citation

> US National Institutes of Health, RePORTER application 10225541, The interaction between mechanical forces and cytoskeletal impairments in podocyte mediated kidney disease (5K01DK114329-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10225541. Licensed CC0.

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