The COBRE Program in the """"""""Molecular Mechanisms and Genetics of Autoimmunity"""""""" at the Oklahoma Medical Research Foundation (OMRF) has sponsored 14 studies, generated >240,000,000 genotypes, published 130 important manuscripts, made possible the funding of multiple NIH grants, and has resulted in recruiting of 8 new faculty members (Susan Kovats, PhD, Amr Sawaiha, MD, Mary Beth Humphrey, MD, PhD, Kathy Moser, PhD, Pat Gaffney, MD, Jonathan Wren, PhD, Courtney Gray-McGuire, PhD, and Marta Alarcon-Riquelme, MD, PhD). All in all, we have met the standard for success. Our mantra is professional growth through mentoring and through building relevant infrastructure. Several of our junior scientists have done well. For example, Swapan K. Nath, PhD, identified ITGAM (aka CD11b, MAC-1, CR3) as a gene for systemic lupus erythematosus and R77H as its probable causative polymorphism. His essential findings ^ have been confirmed in multiple other studies. Swapan Nath, Mary Beth Humphrey, MD, PhD, Amr Sawaiha, MD, Susan Kovats, PhD, and Ken Kaufman, PhD have been funded respectively, by an R01. another R01 an R03, an R21, and a VA Merit Award. With its emphasis on mentoring our COBRE Program has changed our scientific culture toward open, mutual encouragement of faculty, whether senior or junior. This has also served to develop careers in science and to produce oustanding scientific results. To begin the coming five years we present 4 research projects, a recruiting study and one pilot study. Each COBRE scientist funded holds the potential promise for an independent career, producing critical insights and experiments. Scientifically, they will be supported by Nucleic Acid and Data Analysis Cores with mentoring and other functions under an Administrative Core. In addition, the recruiting successes will be continued with a Recruiting Core designed to provide adjunct support to the expansion underway at the OMRF. With the competitive renewal, our plan is to build as many productive scientific careers as possible, to populate our institutions with as many exceptional faculty members as possible, to enhance our international reputation for scientific excellence in autoimmunity, and to produce critically important new discoveries in the process.

Public Health Relevance

Autoimmune diseases are estimated to afflict as many as 50,000,000 of our fellow citizens. This COBRE Program will study process, identify genes, and develop knowledge basic to understanding these disorders, concentrating on systemic lupus erythematosus, a potentially deadly autoimmune disease, found mainly in young women, so that the new knowledge will lead to new diagnostics, prognostics and therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103456-10
Application #
8464172
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Program Officer
Caldwell, Sheila
Project Start
2004-07-01
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
10
Fiscal Year
2013
Total Cost
$2,412,482
Indirect Cost
$973,351
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
077333797
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Patel, Zubin; Lu, Xiaoming; Miller, Daniel et al. (2018) A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus. Hum Mol Genet :
Arabnejad, M; Dawkins, B A; Bush, W S et al. (2018) Transition-transversion encoding and genetic relationship metric in ReliefF feature selection improves pathway enrichment in GWAS. BioData Min 11:23
Lareau, C A; DeWeese, C F; Adrianto, I et al. (2017) Polygenic risk assessment reveals pleiotropy between sarcoidosis and inflammatory disorders in the context of genetic ancestry. Genes Immun 18:88-94
Ching, Travers; Peplowska, Karolina; Huang, Sijia et al. (2016) Pan-Cancer Analyses Reveal Long Intergenic Non-Coding RNAs Relevant to Tumor Diagnosis, Subtyping and Prognosis. EBioMedicine 7:62-72
Wu, Ying-Yu; Kumar, Ramesh; Iida, Ryuji et al. (2016) BANK1 Regulates IgG Production in a Lupus Model by Controlling TLR7-Dependent STAT1 Activation. PLoS One 11:e0156302
Seixas, Cecília; Choi, Soo Young; Polgar, Noemi et al. (2016) Arl13b and the exocyst interact synergistically in ciliogenesis. Mol Biol Cell 27:308-20
Díaz-Barreiro, A; Bernal-Quirós, M; Georg, I et al. (2016) The SLE variant Ala71Thr of BLK severely decreases protein abundance and binding to BANK1 through impairment of the SH3 domain function. Genes Immun 17:128-38
Polgar, Noemi; Lee, Amanda J; Lui, Vanessa H et al. (2015) The exocyst gene Sec10 regulates renal epithelial monolayer homeostasis and apoptotic sensitivity. Am J Physiol Cell Physiol 309:C190-201
Wu, Ying-Yu; Georg, Ina; Díaz-Barreiro, Alejandro et al. (2015) Concordance of increased B1 cell subset and lupus phenotypes in mice and humans is dependent on BLK expression levels. J Immunol 194:5692-702
Lu, Xiaoming; Zoller, Erin E; Weirauch, Matthew T et al. (2015) Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression. Am J Hum Genet 96:731-9

Showing the most recent 10 out of 42 publications