# Regulation of SGK1-mediated Pathological Cardiac Hypertrophy by Non-Canonical ERAD

> **NIH HL F31** · UNIVERSITY OF ARIZONA · 2026 · $41,731

## Abstract

Project Summary: Heart disease is the leading cause of mortality and is often preceded by pathological cardiac
hypertrophy due to chronic hypertension and sustained increases in cardiac afterload. While initially an adaptive
response to maintain cardiac output and systemic blood supply, pathological cardiac hypertrophy eventually
leads to a decompensated state of heart failure (HF). The initial adaptive aspect of hypertrophic growth requires
increases in protein synthesis, which must be balanced by adequate protein folding, and degradation of
misfolded, potentially toxic proteins. Without this balance, cardiac myocytes cannot maintain protein
homeostasis, or proteostasis, which threatens functional cellular integrity and viability. The endoplasmic
reticulum (ER) is a central node in proteostasis, with ~40% of proteins trafficked through this organelle,
underscoring the importance of ER proteostasis in the heart. An important feature of ER proteostasis is
recognition and degradation of terminally misfolded proteins through ER associated degradation (ERAD). While
ERAD canonically recognizes misfolded ER proteins, we have recently identified the first and only described
non-ER substrate for ERAD, serum/glucocorticoid regulated kinase 1 (SGK1), a pro-growth, cytosolic (non-ER)
kinase. Intriguingly, SGK1 is not misfolded, yet is targeted to the cytosolic face of the ER for proteasome-
mediated degradation via ERAD and requires the ER E3 ubiquitin ligase, HRD1. Further, we have found that
SGK1 degradation by ERAD is impaired in human hypertrophic heart failure and in a mouse model of pressure
overload-induced heart failure. SGK1 promotes growth in cancer cells, and our work and others’ have
demonstrated relevance for SGK1 in cardiac pathology, but none have investigated whether SGK1 is required
for the development of pathological cardiac hypertrophy and if this is mediated by impairing its degradation at
the ER via ERAD. Our hypothesis is that the cytosolic kinase, SGK1, 

## Key facts

- **NIH application ID:** 11260216
- **Project number:** 5F31HL172675-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Sukriti  Bagchi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $41,731
- **Award type:** 5
- **Project period:** 2024-12-01T00:00:00 → 2029-06-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11260216

## Citation

> US National Institutes of Health, RePORTER application 11260216, Regulation of SGK1-mediated Pathological Cardiac Hypertrophy by Non-Canonical ERAD (5F31HL172675-02). Retrieved via AI Analytics 2026-07-09 from https://api.ai-analytics.org/grant/nih/11260216. Licensed CC0.

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