2005 — 2007 |
Keene, Keith L |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Chromosome 6q and Diabetes in African Americans @ Wake Forest University Health Sciences
DESCRIPTION (provided by applicant): This application proposes to identify the gene(s) contributing to the 6q linkage peak that has been identified in African American families that have type 2 diabetes mellitus (T2DM). The positional cloning method will be used to evaluate and determine potential candidate genes in this region. We believe we have identified a novel diabetes gene in this region, Estrogen Receptor alpha (ESR1), which would represent the first diabetes gene positionally identified using data from an African American population. We aim to further explore single nucleotide polymorphisms and haplotypes that show association with T2DM in ESR1, as well as analyze SNPs in additional candidate genes, in order to determine if there is any association in those genes as well. Association findings will then be analyzed through functional assays to determine if there is the associated SNPs/haplotypes serve a biological function. Understanding how polymorphisms in ESR1, or any other candidate genes located under the 6q linkage peak, will provide critical information that will aid in understanding the pathophysiology of T2DM and how these variations contribute to the disease across different populations.
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1 |
2016 — 2018 |
Brewer, Michael Scott (co-PI) [⬀] Keene, Keith L |
R15Activity Code Description: Supports small-scale research projects at educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists but that have not been major recipients of NIH support. The goals of the program are to (1) support meritorious research, (2) expose students to research, and (3) strengthen the research environment of the institution. Awards provide limited Direct Costs, plus applicable F&A costs, for periods not to exceed 36 months. This activity code uses multi-year funding authority; however, OER approval is NOT needed prior to an IC using this activity code. |
Genetic Evaluation of Two Novel Loci Associated With Recurrent Stroke @ East Carolina University
Abstract Stroke is the fourth leading cause of death in the United States and the number one cause of serious, long term disability. Of the nearly 800,000 annual strokes, approximately 25% will be recurrent events. Unfortunately, recurrent strokes are more deadly and most likely to cause disability when compared to a first stroke. Genetic studies focusing on recurrent stroke have been extremely limited. We have identified two novel gene regions associated with recurrent stroke and aim to use next generation DNA sequencing (NGS) to fine-map these regions to hone in on the likely causal variants. For 182 recurrent stroke patients from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, we will utilize NGS platforms to identify all genetic variants across 1.5 Mb spanning the two novel gene regions associated with recurrent stroke. High priority variants will be genotyped in all 2,100 VISP participants and analyzed for association with recurrent stroke. NGS is a cutting edge technology that provides a powerful approach to identify novel and important genetic contributors to recurrent stroke, a phenotype that has been poorly studied. This approach may allow improved personalization of risk assessment and targeted prevention. Moreover, VISP participants include both African Americans (AA) and European Americans, therefore this proposal may identify genetic risk variants specific to populations of African descent that might not otherwise be identified in other studies focused primarily on populations of European ancestry. These variants may help address why African Americans have nearly 2x greater risk of suffering a stroke, and are more likely to die following a stroke, as compared to European Americans. Furthermore, these findings may have broader implications by providing insight on other issues influencing recurrent stroke such as the ability to control manageable risk factors (e.g. hypertension and atrial fibrillation) and likewise one?s response to treatment for anticoagulation, antiplatelet, and antihypertensive medications. Moreover, these finding may reflect post stroke treatment response to tissue plasminogen activator (tPA), the only FDA approved treatment for ischemic stroke. Aligned with the goals of the NIH Academic Research Enhancement Award (AREA) Program (R15), we aim to explore a significant research question while exposing students to research, in particular learning cutting edge skills in Genomics, Population Genetics, Biotechnology techniques involving NGS library preparations, and Bioinformatics skills focused on analyzing NGS data and performing statistical analyses for genetic studies.
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0.948 |
2020 — 2021 |
Hauck, Fern R Keene, Keith L Mychaleckyj, Josyf |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Using Integrative Omics as Biomarkers and Diagnostic Tools For Sids
Project Summary Sudden Infant Death Syndrome (SIDS) is the second leading cause of death (closely behind congenital and genetic abnormalities), in the postneonatal period (infants 1 month to 1 year of age), despite declines in incidence of over 50% following the Back to Sleep (now called the Safe to Sleep) risk reduction campaign. In 2017, 1400 infants in the US died of SIDS. Extensive research has identified a number of epidemiological risk factors for SIDS, and more recent research has begun to provide evidence of a potential role for genetic susceptibility in the pathophysiology of the disorder. In the United States, African American and American Indian/Alaska Native babies, in particular are at higher risk for SIDS. Advances in technology now allow for more exhaustive interrogations of genomic contributors to disease. The goal of this proposal is to comprehensively evaluate genetic and epigenetic determinates of SIDS and identify gene expression, DNA methylation and metabolomics profiles that might serve as novel biomarkers in infants at greater risk of death from SIDS. We will utilize liver, heart and blood specimens from the Chicago Infant Mortality Study (CIMS), the largest known collection of cardiac tissue from SUID deaths in the US and heart and blood specimens from the NIH NeuroBioBank (NBB) to investigate genetic, epigenetic, and transcriptomic influences of SIDS. We will employ an omics approach encompassing next generation sequencing (exome plus RNA), genome wide epigenetics, and metabolomics profiling to identify novel biomarkers that are predictive of SIDS. These findings could lead to diagnostic tests and early detection of high risk infants, resulting in preventative measures to eliminate SIDS. This study will also be the first to successfully use an integrative ?Omics approach to address genetic, epigenetic, and metabolomics contributors for SIDS.
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0.946 |