# Kidney Protection by AMPK

> **NIH VA IK2** · MICHAEL E DEBAKEY VA MEDICAL CENTER · 2021 · —

## Abstract

This proposal describes a 5-year research training and career development plan designed to facilitate Dr.
Pan’s transition from junior to independent investigator. She completed Internal Medicine residency and a T32
Nephrology Research Fellowship at Baylor. She joined BCM as an Assistant Professor in Nephrology in July
2013. The application is devised to make use of research resources and expertise of successful investigators
at BCM. Dr. Pan has created a Career Advisory Committee consisting of senior investigators dedicated to
mentoring young scientists to provide guidance with her research and career development. Dr. David Sheikh-
Hamad, Professor of Medicine (Nephrology) at BCM, will serve as her primary mentor. He is funded by a VA
Merit award and NIH R01 and is an expert in renal inflammation, ischemia/reperfusion (I/R) kidney injury, and
the anti-oxidant actions of stanniocalcins. Her co-advisors are: 1) William E. Mitch, MD, an expert in muscle
metabolism; 2) Qiang Tong, PhD, an innovator in sirtuin research; 3) Lee-Jun Wong, PhD, an expert in
mitochondrial genetics and function; and 4) Vijay Yechoor, MD, a successful investigator in insulin resistance
and diabetes. Dr. Pan’s career development plan includes frequent meetings with her mentors, didactics to
increase scientific knowledge, and attending conferences to present her research.
 Acute kidney injury (AKI) is common and associated with increased morbidity/mortality, and progression to
chronic kidney disease. However, the therapeutic options for AKI remain limited. ATP/nutrient depletion and
oxidative stress play important roles in the pathogenesis. Our data suggest that stanniocalcin-1 (STC1)
suppresses ROS and confers resistance to I/R kidney injury (a model for ischemic AKI) through AMPK
activation, preferentially the AMPK2 isoform. Moreover, STC1 induces the mitochondrial longevity gene
SIRT3 via AMPK activation. SIRT3 has been shown to suppress ROS, and this grant will test the Central
Hypothesis that: STC1/AMPKα2/SIRT3 is an inducible and adaptive energy sensing pathway that suppresses
mitochondrial superoxide production and protects from I/R kidney injury. Using in vitro hypoxia/reoxygenation
injury model, Aim I will examine whether selective siRNA knockdown of AMPK2 diminishes STC1-induced
cytoprotection and SIRT3 expression. Using double mutant STC1 Tg/AMPKα1 KO or STC1 Tg/AMPKα2 KO
mice, Aim II will examine in vivo whether STC1-induced renoprotection is mediated through preferential
activation of AMPKα2. Using SIRT3 Tg and SIRT3 KO mice, as well as in vitro overexpression or siRNA-
mediated knockdown of SIRT3, Aim III will determine whether SIRT3 overexpression is protective from
ischemic kidney injury. Aim IV will examine the role of SIRT3 in the observed sexual dimorphism in ischemic
AKI, and the effect of sex hormone modulation on SIRT3/AMPK expression. Our studies identify
STC1/AMPKα2/SIRT3 as novel therapeutic targets for the treatment of ischemic AKI, and the propos...

## Key facts

- **NIH application ID:** 10265338
- **Project number:** 5IK2BX002912-05
- **Recipient organization:** MICHAEL E DEBAKEY VA MEDICAL CENTER
- **Principal Investigator:** Jenny Szu-Chin Pan
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-01-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10265338

## Citation

> US National Institutes of Health, RePORTER application 10265338, Kidney Protection by AMPK (5IK2BX002912-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10265338. Licensed CC0.

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