# Characterizing the role of MINK1 in Congenital Heart Disease and mucociliary clearance

> **NIH NIH F31** · YALE UNIVERSITY · 2021 · $8,559

## Abstract

Project Summary/ Abstract
Congenital Heart Disease (CHD) is the most common birth defect affecting approximately 1% of all live births
in the US and is one of the leading causes of infant mortality. A severe form of CHD can result from Heterotaxy
(Htx), a disorder of the left-right (LR) patterning during embryonic development. A recent genetic analysis of
heterotaxy patients identified a novel CHD candidate gene, mink1. Mink1 encodes a serine-threonine
germinal-center kinase with known functions in the JNK and PCP/Wnt signaling pathways. However, it has no
known role in LR patterning or cardiac development. Using CRISPR knockout strategies in the high-throughput
human disease model, Xenopus, loss of mink1 leads to cardiac and LR patterning defects, and defects in
motile cilia formation and resulting fluid flow. The overall goal of this proposal is to investigate the
molecular mechanism by which mink1 affects LR patterning, heart development, and cilia formation in
the Xenopus (frog) model system. The first aim will use loss of function experiments to determine the
required role for mink1 during the LR patterning cascade b testing molecular markers. Mechanistic hypotheses
will be guided by an analysis of temporal and spatial expression of mink1 in the whole embryo and the left-right
organizer. The second aim will use loss of function experiments to determine the requirement for mink1 during
formation of motile cilia on the multi-ciliated cells of the Xenopus epidermis, which recapitulates a common
mucociliary defect found in CHD patients. Hypotheses will be directed by a review of relevant literature
including a role in regulation of multi-ciliated cell fate specification through Notch signaling or a requirement for
Mink1 during basal body docking and/or establishment of polarity. The third aim will determine the role of each
mink1 domain in the context of cilia formation on multi-ciliated cells and LR patterning/cardiac development.
Then it will be determined if the patient mutation in the kinase-encoding domain is determination to function
using multiple functional assays in Xenopus. Altogether, these experiments will improve our understanding of
cardiac development and the role of mink1 in the pathogenesis of CHD. In the future, this will benefit genetic
testing and counseling, as well as improve outcomes in CHD because treatments can be tailored to genotype
rather than solely on CHD phenotype. In addition, this application details the applicant's training plan including
research mentorship, advanced coursework, training in new techniques, and the development of skills in
scientific professionalism, writing, and presentation of data. The research and training outlined in this
application will prepare the applicant to pursue a career performing patient-driven research as an independent
research scientist.

## Key facts

- **NIH application ID:** 10375331
- **Project number:** 5F31HL140791-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Vaughn Colleluori
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $8,559
- **Award type:** 5
- **Project period:** 2018-05-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375331

## Citation

> US National Institutes of Health, RePORTER application 10375331, Characterizing the role of MINK1 in Congenital Heart Disease and mucociliary clearance (5F31HL140791-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10375331. Licensed CC0.

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