Karere, Genesio Mugambi 0918 print.jpg

Assistant Professor,
Department of Internal Medicine,
Section Molecular Medicine
Center for Precision Medicine
Wake Forest School of Medicine

Genesio Mugambi Karere, Ph.D.

Center Affiliations       


Address

Email

Education and


University of Nairobi, Kenya
University of Nairobi, Kenya
University of California at Davis, Davis, CA
University of California at Davis, Davis, CA

 

Center for Precision Medicine


Nutrition Research Center (NRC) Building, Medical Center Blvd, Winston-Salem, NC 27157
gkarere@wakehealth.edu

Training


B.S. Biology (12/1990)
M.S. Biology of Conservation (12/2000)
M.S. Genetics (8/2005)
Ph.D. Genetics (3/2009)

Prior Positions

1994-95               Director, De Brazza’s Monkey Monitory Project, Kenya
1996                    Consultant, Kimana Game Reserve, Kenya
1999-2001           Research Scientist, Institute of Primate Research, Nairobi, Kenya
2001-2002           Research Scientist, Tana River Primate Research Project, Kenya
2002-2003           Post Graduate Researcher, California National Primate Research Center
2003-2009           Graduate Research Assistant, University of California at Davis, Davis, California
2009-2015           Post Doctoral Scientist, Texas Biomedical Research Institute, San Antonio, TX
2015-2018           Staff Scientist, Texas Biomedical Research Institute, San Antonio, TX
2018-present      Assistant Professor, Department of Internal Medicine, Section of Molecular Medicine,
                            Wake Forest Baptist Health Sciences

Complete List of Published Work

Research Focus

Main Technologies and Methods

RNA-Sequencing/Quantitative PCR
RT-PCR
Ingenuity Pathway Analysis (IPA)
Immunohistochemistry
In-situ hybridization
Reporter Assay

Dr. Karere has a broad training in genetics, genomics and molecular biology. At Wake Health, he is interested in deciphering microRNA (miRNA) biomarkers and molecular mechanisms that trigger development of atherosclerosis disorder. Atherosclerosis is a thickening of the walls of arteries caused by high levels of “bad” cholesterol in the blood, which leads to cardiovascular disease and stroke. According to Science Daily, by 2030, approximately 116 million people in the U.S. will have some form of cardiovascular disease, the leading cause of death in developed countries. Dr. Karere’s research premise is that “early detection and treatment of atherosclerosis prior to progression to life-threatening plaques can save money and millions of lives”.
Currently, Dr. Karere’s lab is focused on identifying circulating blood elements, miRNA biomarkers, indicative of extent of early atherosclerosis in obese children and adolescents. He is collaborating with clinicians and biomedical researchers at the Children’s Hospital in San Antonio, Texas, and the Brenner Children’s Hospital at Wake Forest Baptist Medical Center, NC. In addition, Dr. Karere is investigating the molecular mechanisms that underlie early atherosclerosis in a baboon model. The ultimate questions that Dr. Karere wants to answer include: Is there a panel of circulating miRNAs that predicts the extent of atherosclerosis, and what role does these miRNAs play in molecular mechanisms that trigger the initiation and progression of the disorder. Dr. Karere hopes to reveal sensitive and accurate biomarkers and novel therapeutic targets to detect and nub atherosclerosis prior to progression to heart disease and/or stroke.


Inside the Lab

Childhood obesity, which is strongly linked to heart disease, is increasing in the US. Currently, much attention is given to the management and treatment of heart disease in its later stages with little effort given to managing the disease early on due to the lack of accurate clinical biomarkers for early detection. Before heart disease is evident, individuals often develop lesions that may progress to plaques in the arteries. This arterial plaque blocks or reduces proper blood flow to the brain and heart, leading to strokes or heart attacks. Identifying children and young adults at high risk by early detection and intervention could help prevent progression of lesions to plaques and stem the development of later-stage heart disease. The goal of Dr. Karere’s current study is to discover markers that can be easily measured in the blood samples of adolescents in order to develop inexpensive and accurate diagnostic tests. He is analyzing blood samples from high-risk Hispanic adolescents along with data from a small ultrasound machine that measures the size of lesions in carotid arteries to determine whether adolescents with lesions in their arteries express unique miRNAs in their blood and whether these miRNAs correspond to lesion size. By discovering miRNAs that tell us the size of lesions; accurate and noninvasive diagnostic tests could be developed to catch and treat early onset heart disease.

To identify miRNA-related molecular mechanisms that underlie early atherosclerosis, Dr. Karere’s lab is leveraging on baboon arteries, including coronary, aortic arch, descending aorta, carotid and common iliac arteries collected from baboons fed high cholesterol, high fat diet (similar to western style diet) for 2 years (n=110), and a control group (n=20). The tissues were fixed in formalin to preserve the integrity of the tissues. Baboons are genetically similar to humans and exhibit many of the same chronic disease responses. Currently, Dr. Karere is focusing on coronary early atherosclerosis to identify miRNA biomarkers and miRNA-related molecular mechanisms underlying development of the disorder. His lab is using RNA sequencing, immunohistochemistry, in situ hybridization, and reporter assays to dissect the vascular cellular transcriptomics and to validate results. In addition, we are using CRISPR-Cas9 technology to edit genes that are identified as candidate genes to find miRNA interactions involved in the development of atherosclerosis that could serve as targets for drug therapies.

The baboon findings could be translated to humans. Most human studies have focused on semi-clinical late stage atherosclerosis, because of difficulties collecting samples and conducting studies at the early stages of atherosclerosis in a healthy human. Most humans with early onset atherosclerosis are considered to be relatively healthy and unaware of the issue until it has reached the late stages and has developed into cardiovascular disease. Additionally, it is difficult to control a person’s diet in the strict manner necessary to capture valid scientific data.

We are further interested in assessing the effect of a western style diet on leukocyte telomere attrition and the link to atherosclerosis. For that, we are working with samples collected from a two-year dietary challenged baboon cohort (n=110); we also measured telomere length in an age-sex matched control group of baboons fed a baseline diet for two years to assess the effect of aging.  Results suggest that a western diet may accelerate telomere shortening.

Understanding early atherosclerosis is significant in providing insights toward potential interventions prior to progression of lesions to life threatening plaques. In this regard, Dr. Karere is also interested in other scientific aspects related to early atherosclerosis, including proteomics, methylation and histone acetylation, and microbiome metabolomics and genomics.