Research Appreciation Day
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RAD is an institutional tradition encompassing medicine, public health and basic science. The program provides an opportunity for students, faculty and staff to share their research efforts with the campus community and the public. The program encourages the development of joint research projects and increases the community's awareness of the outstanding quality and range of research conducted at UNT Health Science Center.
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Browsing Research Appreciation Day by Author "Abraham Daniel, Ann"
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Item Epigenetic Risk Factors for Mild Cognitive Impairment, Alzheimer’s Disease and Metabolic Dysfunction in Mexican Americans(2018-03-14) Silzer, Talisa; Sun, Jie; Phillips, Nicole; Johnson, Leigh; O'Bryant, Sid; Barber, Robert C.; Abraham Daniel, AnnPurpose: Alzheimer’s is the most common form of dementia and the 5th leading cause of death for those over 651. The population of Mexican American elders will grow seven-fold by 20502 with rates of mild cognitive decline (MCI) and Alzheimer’s disease (AD) increasing exponentially1. Mexican Americans are diagnosed with MCI and AD at younger ages than non-Hispanic whites3; 4. In addition, Mexican Americans who are diagnosed with AD are 1) less likely to carry the ApoEε4 genotype3-5., 2) suffer a greater burden of type 2 diabetes3; 6, 3) experience greater metabolic-related cognitive decline7; 8 and 4) display a proteomic signature of AD that is heavily metabolic in nature4; 9, compared to non-Hispanic whites, whose proteomic signature for AD is dominated by inflammatory proteins. We hypothesized that differentially methylated regions of DNA (DMRs) are associated with age at onset of cognitive decline (MCI/AD) and metabolic dysfunction (metabolic syndrome/type 2 diabetes) in Mexican Americans. Methods: To test this hypothesis, we assayed genomic DNA methylation in samples from 14 female Mexican American participants enrolled in the Health and Aging Brain study in Latino Elders (HABLE). Participants were diagnosed with cognitive decline (n=4), metabolic dysfunction (n=3), both (n=4), or as a control (n=3). We isolated DNA from leukocytes and bisulfite treated the samples before running them on an Illumina MethylationEPIC chip in accordance with manufacturer’s recommendations to assay genomic DNA methylation. Results: Several interesting biological pathways showed significantly different methylation status between groups. When the participants were split on cognitive decline, DNA in the amyloid secretase, EGF receptor signaling, PDGF signaling, gonadotropin-releasing hormone receptor and Wnt signaling pathways were significantly hypermethylated in cases. In comparison, analyses based on metabolic dysfunction showed significant DNA hypomethylation in the beta1 and beta2 adrenergic receptor signaling pathways and hypomethylation of the gonadotropin releasing hormone receptor pathway in cases. Conclusions: The etiology of cognitive decline appears to differ between Mexican Americans and non-Hispanic whites. Future work will resolve how dementia risk differs between these and other ethnic groups. The knowledge gained from these studies will be critical to a better understanding of AD pathophysiology and the development of ethnicity-focused AD treatment options. Acknowledgements: Research reported here was supported by the National Institute On Aging of the National Institutes of Health under Award Number R01AG054073. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research team also thanks the local Fort Worth community and participants of the Health & Aging Brain Study.Item Role of DNA Methylation in Risk for Alzheimer's Disease and Type 2 Diabetes in a Mexican American Cohort(2021) Barber, Robert C.; Abraham Daniel, Ann; Hall, Courtney; Sun, Jie; Phillips, Nicole; Silzer, TalisaPURPOSE: Age related diseases such as Alzheimer's disease (AD) and type 2 diabetes (T2D) are respectively the 6th and 7th leading cause of mortality in the US. Mexican Americans, the largest ethnic minority group in the US, have an increased likelihood of developing T2D compared to their Caucasian counterparts. With the elderly Mexican American population (≥65 years old) likely to multiply 7-fold by 2050, prevalence of AD alongside T2D is predicted to increase too. Mexican Americans have an earlier onset of AD and a metabolic heavy predisposition for AD compared to Caucasians who develop inflammation-based AD. The risk for T2D and AD is multifactorial involving epigenetic factors such as methylation, which is the addition of a methyl group to the cytosine base of DNA. We aim to establish an epigenetic association between AD and T2D unique to the Mexican American population. METHODS: Participants from the Texas Alzheimer's Research and Care Consortium (TARCC), which consists of Mexican American individuals diagnosed with either AD only, T2D only or AD and T2D matched with a Caucasian counterpart were selected. Peripheral blood was drawn from participants and individual methylation profiles collected using the Illumina Infinium MethylationEPIC chip array. Differential methylation will be assessed using the Chip Analysis Methylation Pipeline (ChAMP) package in R. RESULTS: Results obtained will be analyzed using pathway and gene set enrichment analysis tools. CONCLUSIONS: Identifying possible methylation sites associated with T2D and AD unique to the Mexican American population could contribute towards developing ethnicity-specific biomarkers and treatments.Item Role of methylation in risk for cognitive impairment in Mexican Americans(2023) Abraham Daniel, Ann; Silzer, Talisa; Sun, Jie; Zhou, Zhengyang; Hall, Courtney; Phillips, Nicole R.; Barber, Robert C.Purpose: Mexican Americans (MAs) are the largest aging (›65 years old) and growing US ethnic minority group, with a unique risk for cognitive impairment (CI) in comparison to non-Hispanic whites (NHWs). MAs have an earlier age of onset and a risk for CI that is largely metabolism related in contrast to NHWs who have a more inflammation-based risk for CI. CI is defined in this study as individuals diagnosed with either Alzheimer’s disease (AD), or mild cognitive impairment (MCI) (a likely precursor to AD). Risk for CI is multifactorial and involves an epigenetic form of gene regulation called DNA methylation, which involves the addition of a methyl group to the cytosine base of DNA. DNA methylation patterns can be altered or possibly reversed through changes in environmental factors such as diet and lifestyle. Our aim was to identify differentially methylated sites of the genome associated with CI and determine DNA methylation profiles that are specific to MAs and NHWs. Methods: Peripheral blood was drawn from 551 Texas Alzheimer's Research and Care Consortium participants (299 MAs and 252 NHWs) and DNA was typed on the Illumina Infinium MethylationEPIC chip array, assessing >850,000 CpG genomic sites. Participants were compared according to cognitive status (control versus CI(AD/MCI)) among each ethnic group. Beta values that represent relative degree of methylation were normalized using the Beta MIxture Quantile dilation (BMIQ) method. Differential methylation between control and CI was assessed using the Chip Analysis Methylation Pipeline (ChAMP), limma and cate packages within R studio. Results: Two significant differentially methylated sites were associated with CI at an FDR-adjusted p-value threshold <0.05: cg13135255 in MAs and cg27002303 in NHWs. Three differentially methylated sites were suggestively associated with CI at an FDR-adjusted p-value threshold <0.1: cg01887506 and cg10607142 in MAs, and cg13529380 in NHWs. Four of the five significant and suggestively differentially methylated sites were hypermethylated in CI compared to normal controls, except for hypomethylated site cg13529380. The site most significantly associated with CI was cg13135255 within the CREBBP gene in MAs (FDR-adjusted p-value = 0.029). The CREBBP protein is a histone acetyltransferase, involved in epigenetic regulation, and plays a role in memory formation. Conclusion: This is the first study to report these specific CpG sites as either significantly or suggestively associated with CI among MAs and NHWs. These sites may be used in addition to other methylated sites to develop risk assessments that are ethnicity specific for CI. Following further validation and replication in other cohorts these sites may aid development of ethnic specific therapeutics that could deter or delay CI in the future.