# Identification of Molecular Mechanisms Underlying Early Atherosclerosis

> **NIH NIH K01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $110,403

## Abstract

Abstract
This K01 proposal describes a research and career development plan for Genesio Karere, Ph.D., the goal of
which is to prepare Dr. Karere for an independent career focused on identification of molecular and epigenetic
mechanisms underlying initiation and progression of atherosclerosis using a baboon model of human
atherosclerosis. Dr. Karere has experience in genetics, genomics and molecular biology, which will enable
completion of Aim 1 of the study. However, to complete all Aims and be competitive as an independent
research investigator, Dr. Karere will require additional research skills, including immunohistochemistry (IHC),
in vitro reporter assays, CRISPR-Cas9 genome-editing, laser capture microdissection, proteomics and
metabolomics techniques. In addition, Dr, Karere will receive didactic training through formal coursework in
Cell Biology and Research Ethics at the University of Texas Health Science Center, San Antonio (UTHSCSA).
Informal training will be provided in the areas of grant writing and preparation of effective presentations. The
applicant will receive guidance from primary mentor, Dr. Laura Cox (Texas Biomedical Research Institute,
TBRI), and co-mentors, Drs. Henry McGill (TBRI), Marcel Daadi (TBRI), Cun Li (University of Wyoming) and
Michael Mahaney (University of Texas Rio Grande Valley). Drs. Edward Dick (TBRI), Michael Olivier (TBRI),
Mark Labordoni (Southwest Research Institute, SWRI), Xiangle Sun (UNTHSC) and Alexander Pertsemlidis
(UTHSCSA) will serve consultants to enable Dr. Karere to establish an independent research career and
successful program. Over the past three decades, TRBI has developed a unique baboon resource for research
on atherosclerosis. This baboon colony includes seven generations of pedigreed, genotyped baboons that
have been phenotyped for more than 200 quantitative traits related to dyslipidemia, and genetically
characterized in relation to a baboon linkage map.
It is well known that cardiovascular disease (CVD), the leading cause of death in the United States, is caused
by atherosclerosis, which begins in childhood as arterial intimal lipid deposits and progresses to plaques in
adulthood. However, the genetic, epigenetics and molecular mechanisms that underlie initiation and
progression of atherosclerotic lesions are not known. The research plan described in this application will begin
to fill that gap. Since it is not tenable to obtain tissue samples from healthy individuals, the baboon model of
atherosclerosis described here provides a suitable alternative.
Recent advancements in science have identified regimes for lowering serum cholesterol and retarding clinical
end-points. However, these therapies are limited due to side effects, intolerance and ineffectiveness for some
individuals. The limitations underscore the need for novel therapies for these individuals. We predict that
miRNA-mediated molecular mechanisms are involved in the initiation and progression of atherosclerotic
lesions i...

## Key facts

- **NIH application ID:** 9984852
- **Project number:** 5K01HL130697-06
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Genesio Karere
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $110,403
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984852

## Citation

> US National Institutes of Health, RePORTER application 9984852, Identification of Molecular Mechanisms Underlying Early Atherosclerosis (5K01HL130697-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984852. Licensed CC0.

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