When the Human Genome Project successfully sequenced the last of the more than 3 billion nucleotides that make up the human genome in 2003, it was hailed as the operating manual for the approximately 20,000 genes that determine all of the shared and unique characteristics that determine a human being. Little did we know that it was just the beginning.
Today, we know that roughly 90% of the genetic variations within the human genome that are responsible for unique traits and, possibly, enhanced disease risk are not found in those ~ 20,000 genes, but are instead in regions of non-coding DNA; regions once coined “junk DNA”. We also know that many of these non-coding genetic variations are located in regulatory regions that control gene expression. The unique characteristics of an individual, as well as the risk for developing complex heritable diseases, are the result of thousands of inherited non-coding genetic variations that collectively modify gene expression.
I have dedicated my research career to identifying which non-coding genetic variations are associated with the debilitating autoimmune disease, systemic lupus erythematosus (lupus), and how those genetic variations function to disrupt the immune system, leading to inflammation, organ failure, and, in some cases, premature death. By improving our understanding of the complex regulatory mechanisms embedded within the human genome, we hope to advance early detection strategies and the development of more effective treatments for lupus.
My primary research focus is to decipher the complex genetic landscape of lupus and other autoimmune diseases. Like other autoimmune diseases, lupus is characterized by a production of autoantibodies that attack a wide variety of tissues and organs resulting in systemic inflammation and organ failure.
Our work has contributed significantly over the last decade to establish a strong genetic basis for lupus, and to provide important information about how genetic variations influence immune cell function to drive lupus development and progression. We use state-of-the-art high throughput sequencing technologies coupled with bioinformatics and functional analyses to systematically evaluate how genetic variations associated with lupus alter the genetic landscape and subsequent gene expression. Our overall objective is to develop a comprehensive view of the genetic landscape of lupus that can then be used to develop new or improved predictive and monitoring tools for patients with lupus.
B.S., Saint John’s University, Collegeville, MN, 1983
M.D., University of Minnesota, Minneapolis, MN, 1991
Honors and Awards
1996 Midwest Trainee Investigator Award, American Federation for Clinical Research
1997 Molecular Genetics Fellowship, University of Minnesota
1998 Participant, Genetic-Epidemiological Studies of Complex Diseases, Cold Spring Harbor Laboratory
1999 NIH NIAMS Clinical Investigator Award
2000 Young Investigator Award, Department of Medicine, University of Minnesota
2005 Cancer and Leukemia Group B Junior Faculty Research Award
2006 Faculty Career Development Award, Department of Medicine, University of Minnesota
2008, 2011 The Merrick Award for Outstanding Research, Merrick Foundation, Oklahoma City, OK
2013 Edward L. and Thelma Gaylord Prize for Scientific Achievement, Oklahoma City, OK
2013 J.G. Puterbaugh Chair in Medical Research, Oklahoma Medical Research Foundation, Oklahoma City, OK
OMRF Scientific Promotions Committee (2017-present)
OUHSC MD/PhD Program Steering Committee (2010-present)
OMRF Post-Doctoral Training Committee (2017-present)
Member, Scientific Advisory Committee, SLE Biomarkers Working Group (2004 to present)
Member, Scientific Advisory Committee, DeCide Clinical Trial, University of Chicago Medical School (2005 to present)
Member, SLEGEN Consortium Data Analysis Committee (2006 to present)
Adjunct Associate Professor, University of Oklahoma Health Sciences Center (2008 to present)
JoVE Editorial Board Member, Clinical and Translational Medicine (2014-present)
Member, Scientific Advisory Panel, The International Foundation for Autoimmune Arthritis (IFAA) (2014 to present)
Co-Chair, American College of Rheumatology Abstract Selection Committee, Genetics, Genomics and Proteomics category (2014 to present)
Standing Member, NIH Hypersensitivity, Autoimmune and Immune-mediated (HAI) Disease NIH Study Section (2015 to 2019)
Member, External Advisory Committee, The Medical University of South Caroline Clinical Resource Center (MUSC CRC) (2016 to present)
American Society of Hematology
American Society of Clinical Oncology
American Society of Human Genetics
American Association for Cancer Research
American College of Rheumatology
Henry Kunkel Society
Joined OMRF Scientific Staff in 2007
Raj P, Song R, Zhu H, Riediger L, Jun DJ, Liang C, Arana C, Zhang B, Gao Y, Wakeland BE, Dozmorov I, Zhou J, Kelly JA, Lauwerys BR, Guthridge JM, Olsen NJ, Nath SK, Pasare C, van Oers N, Gilkeson G, Tsao BP, Gaffney PM, Gregersen PK, James JA, Zuo X, Karp DR, Li QZ, Wakeland EK. Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus. Genome Biol 21:281, 2020 November, PMID: 33213505, PMCID: PMC7677828
Chai G, Webb A, Li C, Antaki D, Lee S, Breuss MW, Lang N, Stanley V, Anzenberg P, Yang X, Marshall T, Gaffney P, Wierenga KJ, Chung BH, Tsang MH, Pais LS, Lovgren AK, VanNoy GE, Rehm HL, Mirzaa G, Leon E, Diaz J, Neumann A, Kalverda AP, Manfield IW, Parry DA, Logan CV, Johnson CA, Bonthron DT, Valleley EMA, Issa MY, Abdel-Ghafar SF, Abdel-Hamid MS, Jennings P, Zaki MS, Sheridan E, Gleeson JG. Mutations in Spliceosomal Genes PPIL1 and PRP17 Cause Neurodegenerative Pontocerebellar Hypoplasia with Microcephaly. Neuron, 2020 November, PMID: 33220177
Arabnejad M, Montgomery CG, Gaffney PM, McKinney BA. Nearest-Neighbor Projected Distance Regression for Epistasis Detection in GWAS With Population Structure Correction. Front Genet 11:784, 2020 July, PMID: 32774345, PMCID: PMC7387719
Kondo Y, Fu J, Wang H, Hoover C, McDaniel JM, Street R, Patra D, Song J, Pollard L, Cathey S, Yago T, Wiley G, Macwana S, Guthridge J, McGee S, Li S, Griffin C, Furukawa K, James JA, Ruan C, McEver R, Wierenga KJ, Gaffney PM*, Xia L (*Co-senior author). Site-1 protease deficiency causes human skeletal dysplasia due to defective inter-organelle protein trafficking. JCI Insight. 2018 Jul 26;3(14):121596. PMID: 30046013 PMCID: PMC6124414
Pelikan RC, Kelly JA, Fu Y, Lareau CA, Tessneer KL, Wiley GB, Wiley MB, Glenn SB, Harley JB, Guthridge JM, James JA, Aryee MJ, Montgomery C, Gaffney PM. Enhancer histone-QTLs are enriched on autoimmune risk haplotypes and influence gene expression within chromatin networks. Nat Commun. 2018 Jul 25;9(1):2905. PMID: 30046115 PMCID: PMC30046115
Langefeld CD, et al. (Gaffney PM – author #107 of 108; corresponding author). Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun. 2017 Jul 17;8:16021. PMID: 28714469 PMCID: PMC5520018
Graham RR, Cotsapas C, Davies L, Hackett R, Lessard CJ, Leon JM, Burtt NP, Guiducci C, Parkin M, Gates C, Plenge RM, Behrens TW, Wither JE, Rioux JD, Fortin PR, Graham DC, Wong AK, Vyse TJ, Daly MJ, Altshuler D, Moser KL, Gaffney PM. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet. 2008 Sep;40(9):1059-61. PMID: 19165918 PMCID: PMC2772171
International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), et al. (Gaffney PM – author #28 of 42). Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008 Feb;40(2):204-10. PMID: 18204446 PMCID: PMC3712260
Gaffney PM, Kearns GM, Shark KB, Ortmann WA, Selby SA, Malmgren ML, Rohlf KE, Ockenden TC, Messner RP, King RA, Rich SS, Behrens TW. A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families. Proc Natl Acad Sci USA. 1998 Dec 8;95(25):14875-9. PMID: 9843983 PMCID: PMC24543
Genes & Human Disease Research Program, MS 57
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-2572
Fax: (405) 271-3045
Satish Pasula, Ph.D.
Associate Staff Scientist
Yao Fu, Ph.D.
Assistant Staff Scientist
Richard Pelikan, Ph.D.
Senior Bioinformatics Scientist
David Murphy, Ph.D.
Research Project Director
Assistant Director of Infrastructure & Research Computing
Kandice Tessneer, Ph.D.
Science Writer Specialist
Senior Laboratory Manager
Project Coordinator II
Administrative Assistant II
News from the Gaffney lab
The National Institutes of Health awarded grants worth more than $4 million to two OMRF scientists. Patrick Gaffney, M.D., and Courtney Griffin, Ph.D., were each awarded five-year R01 grants to research genes related to lupus and vascular development, respectively. After identifying two genes associated with lupus—a chronic autoimmune disease that affects an estimated 2 million […]
The National Institutes of Health has awarded 17 grants worth a total of $14.7 million to OMRF. The grants are part of the $10 billion in economic stimulus funds that will be provided for medical research through the American Recovery and Reinvestment Act of 2009. The grants will fund OMRF research on a wide array […]
OMRF has received a $10 million grant from the National Institutes of Health to study the autoimmune disease lupus. The five-year award comes from the National Institute of Allergy and Infectious Diseases at the NIH. The grant will support research on the genetic origins of lupus, which affects up to an estimated 2 million Americans […]
Four Oklahomans joined the Oklahoma Medical Research Foundation’s Board of Directors at OMRF’s semiannual board meeting Wednesday. Also at the meeting, three OMRF scientists were honored. Joining the board are Dave Bialis, Ramsey Drake and Cliff Hudson of Oklahoma City and Harold Hamm of Enid. Bialis is president of Cox Oklahoma. His civic involvement includes […]
An international consortium of scientists led by OMRF investigator John B. Harley, M.D., Ph.D., has identified multiple genes linked to lupus, a devastating autoimmune disease that affects as many as 2 million Americans and 15 million people worldwide. The group’s findings appear online in two related articles in the Feb. edition of the journal Nature […]
The Oklahoma Medical Research Foundation today announced the addition of four scientists to the faculty of its Arthritis & Immunology Research Program. The four new faculty members are Patrick Gaffney, M.D., Kathy Moser, Ph.D., Jonathan Wren, Ph.D., and Igor Dozmorov, Ph.D. “Their recruitment gives us a depth of scientific commitment and expertise that is unparalleled […]