# BLRD Research Career Scientist Award Application

> **NIH VA IK6** · VA NORTHERN CALIFORNIA HEALTH CARE SYS · 2024 · —

## Abstract

The overall goal of my research is to understand mechanisms underlying pathophysiology in chronic
diseases, in particular heart failure (HF) and Alzheimer’s disease (AD). I aim to discover unknowns, establish
new paradigms, and identify novel targets for drug screening and clinical therapy. We apply integrative
approaches that include single molecule analysis, live-cell imaging, genomic and proteomic analysis, and
transgenic model animals to understand the fundamentals of intracellular signaling networks and their functional
roles in development of diseases. Over the past 16 years, I have received continuous funding from NIH, VA, and
private agencies. I am currently supported by two NIH R01 grants, a VA merit award, and a joint California
TRDRP grant. The results from my laboratory have significantly deepened our understanding of signaling
regulation and offered novel therapeutic targets for HF and AD. Through these endeavors, I have received an
AHA established investigator award in 2010 and established myself as a global leader in cardiac signaling
transduction.
 In the early years, my research focuses on novel features of cardiac beta-adrenergic receptor (bAR)
signaling such as spatiotemporal regulation of cAMP-PKA cascades in cardiac contractile function. Over the past
10 years, I have expanded my research program to understand regulatory signaling networks in disease
development under chronic conditions such as inflammation and metabolic disorders. One of the highlights is
that we have described a membrane protein complex of insulin receptor (InsR) and b2AR broadly expressed in
different tissues. Activation of b2AR and InsR are critical regulatory mechanisms of both cardiovascular function
and metabolism. These receptors also modulate cognitive function including memory and learning, pain, emotion
and stress in the central nerve system. Dysregulation of these receptor signaling pathways has been linked to
development of HF and AD. Our recent studies have opened an exciting avenue in understanding cardiovascular
complications and neurodegenerative diseases associated with diabetes and metabolic syndromes. Several
active projects below are supported by ongoing funding from NIH and VA. The current VA merit grant aims to
characterize the essential roles of two proteins GRK5 and SAP97 in reduction (desensitization) of adrenaline
stimulation of a signaling molecule nitric oxide to enhance cardiac output. We will find how this regulation goes
wrong in heart diseases and thus offers novel strategies to treat heart diseases.

## Key facts

- **NIH application ID:** 10726581
- **Project number:** 5IK6BX005753-03
- **Recipient organization:** VA NORTHERN CALIFORNIA HEALTH CARE SYS
- **Principal Investigator:** YANG Kevin XIANG
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-10-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10726581

## Citation

> US National Institutes of Health, RePORTER application 10726581, BLRD Research Career Scientist Award Application (5IK6BX005753-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10726581. Licensed CC0.

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