# Role of the ubiquitin Ligase adaptor FBXL13 on Salt-sensitive hypertension

> **NIH NIH K01** · WAYNE STATE UNIVERSITY · 2020 · $54,633

## Abstract

Candidate: Gustavo Ares, Ph.D., is a Research-Scientist Instructor training in the integrative renal physiology
related to hypertension at Henry Ford Health system. In this revised application, Dr. Ares aims to determine
whether a high salt diet stimulates the E3 ubiquitin-ligase FBXL13-NKCC2 interaction, enhancing NKCC2
degradation, favoring NaCl excretion thereby preventing an increase in blood pressure. Dr. Ares' immediate goal
is to acquire the research training and professional skills necessary to transition to an independent extramurally
funded investigator. His long-term goal is to establish his own research program with a focus on identifying novel
targets of loops diuretics and pharmacological interventions to treat hypertension. Dr. Ares' Career
Development Plan consists of improving his: 1) research skills; 2) Networking and collaborations; 3)
professional development through attendance of presentations at weekly journal clubs, seminars, course and
national scientific meetings; 4) mentoring skills; 5) writing manuscripts and grants. Dr. Ares' progress will be
assessed thru bi-weekly to monthly meetings with each member of the mentoring team. Environment: Dr. Ares
and his mentor, have assembled a strong team of co-mentors and advisors to guide him through the research
project. Primary mentor: Dr. Pablo Ortiz a NIH-funded scientist with strong records of successful in renal
physiology and hypertension. Secondary mentor: Dr. Jeffery L. Garvin is a professor of physiology at CWRU
Cleveland, with extensive experience in regulation of salt and water transport along the renal nephron.
Secondary mentor: Dr. Peter Kaiser, professor and Chair of Biological Chemistry at UC Irvine, has extensive
experience in the ubiquitin-proteasome system, and the E3-ubiquitin ligases with special interest in the Skp1-
Cullin-FBox family complex. The supportive research team includes T. Pavlov, Ph.D. and Mariela Mendez, Ph.D.
working in renal physiology; Pamela Harding Ph.D., N-E. Rhaleb, Ph.D., Suresh Palaniyandi, Ph.D. working in
cardiovascular physiology/pathophysiology. Research: Hypertension is a highly prevalent condition involving
the kidney's inability to excrete excess salt. Abnormally enhanced NaCl reabsorption thru the apical Na+/K+/2Cl-
cotransporter (NKCC2) by the thick ascending limb of the loop of Henle (TAL) is associated with salt-sensitive
hypertension in humans. NKCC2 inhibitors has many side effects, therefore they are not used. This project study
the role of a novel E3 ubiquitin ligase FBXL13 on NaCl reabsorption and blood pressure regulation under normal
or high salt diet. In Aim I, we study the effect of high salt on NKCC2 ubiquitination, surface phosphor (Thr96-101
and Ser126) and total NKCC2 expression and activity. In Aim II, we will study the FBXL13-NKCC2 interaction. In
Aim III We study the role of FBXL13 on NaCl reabsorption and blood pressure regulation. This application will
advance our knowledge which may lead to new strategies fo...

## Key facts

- **NIH application ID:** 10336608
- **Project number:** 7K01DK123192-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Gustavo R Ares-Sarmiento
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $54,633
- **Award type:** 7
- **Project period:** 2020-07-08 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10336608

## Citation

> US National Institutes of Health, RePORTER application 10336608, Role of the ubiquitin Ligase adaptor FBXL13 on Salt-sensitive hypertension (7K01DK123192-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10336608. Licensed CC0.

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