NHGRI DIR Seminar Series - K. Sean Kimbro
Channel: National Human Genome Research Institute
Date: 2022-10-20

Seminar Title: The Biology of Health Disparities: Ancestry-Driven Drug Discovery

October 6, 2022 - K. Sean Kimbro, Ph.D., is a professor of Biological and Biomedical Sciences at the North Carolina Central University. His current research — funded by a transformative R01 grant — focuses on the molecular characterization of hormonal cancers (including prostate and breast cancer), which disproportionately affect individuals of African ancestry and other various ethnic groups. In this seminar, Dr. Kimbro shows how his research can have the potential to strengthen our understanding of ancestry-related host immunity as a contributor to the biology of health disparities. A question-and-answer session follows the presentation.

About the National Human Genome Research Institute (NHGRI) Division of Intramural Research (DIR) Seminar Series: The NHGRI DIR Seminar Series sponsors a monthly series of talks by intramural and special guest speakers celebrating genetics and genomics research. Speakers are selected by NHGRI intramural faculty and trainees and cover research topics of interest to a wide audience.

Relevant Links:
NHGRI DIR Seminar Series: https://www.genome.gov/event-calendar/NHGRI-Division-of-Intramural-Research-Seminar-Series 
 
About K. Sean Kimbro: https://www.nccu.edu/employee/kkimbro 
 
NIH Grant: Addressing the Biology of Health Disparities by Targeting Geographical Ancestry-Driven Variants of Immunity: https://reporter.nih.gov/project-details/10273703

Chapters: 
0:00 - Introduction (Julie Segre)
3:14 - Start of Presentation (K. Sean Kimbro)
4:41 - About North Carolina Central University
6:25 - Kimbro Lab
7:04 - Migration and Forced Migration
8:43 - Unnatural Selection
10:14 - American Descendants of Enslaved Africans (ADEA)
14:04 - Protective Innate Immune Variants in Racial/Ethnic Disparities of Breast and Prostate Cancer
15:22 - Signatures of Environmental Genetic Adaptation Pinpoint Pathogens as the Main Selective Through Human Evolution
16:17 - IRA and TLR3 Sequence Variants May Alter Breast Cancer Risk Among African American Women
17:35 - Research Papers
18:39 - What would it look like to design drugs from a different perspective?
19:25 - 2020 Drug Trials Snapshot Summary Report
20:46 - Share of world population by major regions
21:28 - Race-based Drugs (BIDIL)
22:27 - Ancestral-Driven Drug Discovery
23:06 - Ancestral characterization of 1018 cell lines highlights disparities and reveals gene expression and mutual differences
24:08 - Genetic Ancestry Analysis Reveals Misclassification of Commonly Used Cancer Cell Lines
26:20 - New Approach: Addressing the Biology of Health Disparities by Targeting Geographical 
Ancestry-driven Variants of Immunity
29:38 - Molecular Profiling and Ancestral Proportions Triple Negative Breast Cancer (TNBC) Cell Lines
30:23 - The neuroendocrine mechanisms of chronic stress
31:40 - IC50s with Norepinephrine
33:20 - Increased circulating cytokine levels in African American women with obesity and elevated HbA1c
34:50 - Importance of Targeting IL-4 and IL-13 receptors for cancer therapy
35:24 - IL4/IL4R-activated signaling pathways that promote growth phenotypes
35:59 - Linear Map of IL4R
36:25 - IL4R Variants of Interest
43:05 - Acknowledgements
44:03 - Q&A Session
37:07 - Prevalence of selected innate immunity sequence variants in TNBC cell lines
38:21 - AlphaFold outputs for IL4R wt and variants
39:40 - Goal
41:48 - Things to think about