# BLR&D Research Career Scientist Award Application

> **NIH VA IK6** · VA SALT LAKE CITY HEALTHCARE SYSTEM · 2022 · —

## Abstract

I have been studying prostaglandins and other lipid-derived mediators that regulate
renal function for a long time. Over the years, we have defined the role of COX-
2/mPGES-1/PGE2-mediated prostaglandin pathway, nuclear receptors PPARgamma
and liver X receptor, and nitro-oleic acid in renal health and disease. Our recent work
has demonstrated an important interplay between the lipid mediators and (pro)renin
receptor-mediated intrarenal renin-angiotensin system after the demonstration that renal
PRR and intrarenal renin are under the control of COX-2/EP4 pathway. Our results
suggest that (pro)renin receptor serves as a common downstream pathway leading to
fine-tuning urinary Na+ and water excretion and long-term control of blood pressure. The
seminal discoveries include the following: 1) activation of PRR with prorenin but not
renin stimulates epithelial Na+ channel, 2) PRR controls the in vivo renin activity, ENaC
and aquaporin- 2 expression in the collecting duct, 3) deletion of collecting duct PRR
results in diabetes insipidus and downregulation of aqoporine-2, 4) soluble PRR (sPRR)
stimulates renal aquoporine-2 and urine concentrating capability, and 5) site-1 protease
(S1P) but not furin or ADAM19 contributes to the generation of sPRR. During the past 5
years, we have published 22 papers on this topic in highly prestigious journals such as
PNAS, JASN, Hypertension, etc. In 2016, I was selected to deliver Lewis K. Dahl
Memorial Lecture at the Council on Hypertension in Orlando. My research program has
been well funded by extramural grants. During this reporting period, I have received
multiple NIH RO-1 grants and a Merit Review Award with total costs exceeding $10M.
The recent submission of the renewal application of the Merit Award has been selected
for funding. I have published a total of 161 peer-reviewed articles and delivered more
than 100 lectures all over the world. Our work is highly relevant to the VA mission since
a significant number of veterans are affected by hypertension and renal disease for
which PRR is believed to play a major role and may serve as a novel target for new
drug development. Importantly, my research has high translational potential in the areas
of chronic kidney disease (CKD) and metabolic disease. I have developed multiple
technologies at various stages from preclinical evaluation to Phase II clinical trial for
treatment of these diseases. So far, I holds 5 patents with 3 on the use of nitro-oleic
acid for the treatment of CKD and metabolic disease and 1 on the similar therapeutic
use of sPRR. The nitro-oleic acid technology was licensed to Complexa, Inc, a biotech
company that has successfully completed multiple Phase I clinical trials on nitro-oleic
acid (commercialized as CXA-10), raised $100 million, and launched a Phase II clinical
trial with CXA-10 in 2018. A second technology related to the development of a
recombinant soluble PRR as an insulin-sensitizing agent is currently under preclinical
evaluation. ...

## Key facts

- **NIH application ID:** 10454237
- **Project number:** 5IK6BX005223-03
- **Recipient organization:** VA SALT LAKE CITY HEALTHCARE SYSTEM
- **Principal Investigator:** Tianxin Yang
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454237

## Citation

> US National Institutes of Health, RePORTER application 10454237, BLR&D Research Career Scientist Award Application (5IK6BX005223-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10454237. Licensed CC0.

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