Genes determine your height, hair color and even, in some cases, whether or not you will get certain diseases. Much of what scientists know about human disease today has been learned from the study of genetics, and in my lab, we focus on how genes can trigger the onset of disease. In particular, we study the role that genes play in cancer and autoimmune disease.
Today, approximately 5 percent of colon cancers are known to have genetic causes. Our lab is now looking for other genetic factors that could trigger the disease. By pinpointing a genetic basis for certain colon cancers, it may be possible to determine those at high risk of developing them. Such insight could be crucial into extending the lives of patients, as colon cancer is often curable when treated early.
We also study the genetic factors that lead to the development of autoimmune diseases. We focus our work on two such conditions—lupus and sarcoidosis.
In lupus, the body’s immune system attacks its own cells and tissues. Our lab is working to identify the genes responsible for the initial launching of these attacks. By discovering the point where the immune system turns on itself, scientists can develop ways to stop the disease’s progression before damage occurs. Finding new treatments for lupus represents a major unmet medical need, as it has been 50 years since the FDA approved a new treatment for this debilitating, sometimes fatal disease that affects up to 10 million people worldwide.
Sarcoidosis occurs when small nodules form in and around organs, leading to arthritis-like swelling and inflammation. This poorly understood condition is more common and severe in African Americans than in Caucasians. By studying family members with the disease, we hope to find the genes that cause this condition, information that ultimately could lead to more effective methods of treatment.
My laboratory is focused on the identification of genes predisposing to complex diseases, particularly colon cancer and inflammatory disorders like systemic lupus erythematosus (SLE) and sarcoidosis. We are also involved in the development of new statistical and computational tools to aid in the discovery of these genes.
Colorectal cancer is the second leading cause of cancer mortality in adult Americans with each American carrying a 6% lifetime risk of developing the disease. While early stage cancers can be highly curable, late stage colon cancers remain incurable. Both somatic and germline mutations have been associated with the development of colon cancer and its precursor adenomatous colon polyps (ACPs). However, familial colon cancers with known cause: Familial Adenomatous Polyposis (FAP) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC) account for <1% and ~5% of all colon cancer cases annually, respectively. Our studies, in collaboration with our colleagues at Case Western Reserve University, are aimed at identifying additional alleles predisposing to colon neoplasia vital to describing individuals at high risk for developing colon cancer, and for whom colon cancer screening and early detection can have potentially life-saving benefits.
SLE is a systemic autoimmune disease most frequently and severely affecting women and has diverse clinical manifestations involving the joints, kidneys, brain, and several other organ systems. OMRF and our studies have played a major role in a longstanding effort devoted to identifying genes involved in SLE. The focus of my most recent work in this area is the identification of genes involved in the targets of the earliest autoimmune response. Identification of these genes would give us insight into the biological mechanisms underlying SLE and, potentially, other autoimmune disorders and therefore the ability to intervene in disease progression before or at the earliest stages of clinical presentation.
Sarcoidosis, a systemic granulomatous disease, has been associated with various environmental exposures and infectious agents, as well as family history. It is characterized by the presence of granulomas in the liver, lymph glands, bone marrow, brain, and most frequently, the lungs. Sarcoidosis is more prevalent in women and, in the United States, African Americans are both more commonly and more severely affected than Caucasians. Our studies, together with our collaborators at Henry Ford Health Systems, have identified a major genetic component on chromosome 5 unique to African Americans. Current studies focus on using ancestry-specific information to help elucidate the exact location of these genes.
B.A. (honors), Oklahoma City University, 1995
M.S., University of Oklahoma Health Sciences Center, 2000
Ph.D., Case Western Reserve University, Cleveland, OH, 2004
Honors and Awards
1995 Outstanding Science Student Award, Oklahoma City University
1995 Rhodes Scholar Semifinalist, Oxford University
1999 2nd Place, College of Public Health Graduate Student Research Competition, University of Oklahoma Health Sciences Center
2000 Graduate Student Association Award, University of Oklahoma Health Sciences Center
2000-2002 NHLBI trainee fellow, Case Western Reserve University Division of Genetic and Molecular Epidemiology
2001 Nominee for C.W. Cotterman Award, American Society of Human Genetics
2002-2003 Student of the Year Award, Case Western Reserve University Division of Genetic and Molecular Epidemiology
2012 J. Donald and Patricia Capra Award for Scientific Achievement
Editor, BMC Genetics, Genetic Analysis Workshop (2004-2005)
Reviewer, Human Heredity (2005-present)
Reviewer, Genes and Immunity (2005-present)
Reviewer, BioTechniques (2005-present)
Reviewer, The Journal of Clinical Endocrinology & Metabolism (2006-present)
Editorial Board Member, Open Genetics Journal (2007)
Reviewer, BMC Genetics, Genetic Analysis Workshop (2007)
Reviewer, Annals of Human Genetics (2007-present)
Reviewer, Biometrical Journal (2007-present)
American Association for Cancer Research
American Association for the Advancement of Science
American Statistical Association
American Society of Human Genetics
International Genetic Epidemiology Society
Joined OMRF Scientific Staff in 2008.
Leehan KM, Pezant NP, Rasmussen A, Grundahl K, Moore JS, Radfar L, Lewis DM, Stone DU, Lessard CJ, Rhodus NL, Segal BM, Scofield RH, Sivils KL, Montgomery C, Farris AD. Minor salivary gland fibrosis in Sjögren's syndrome is elevated, associated with focus score and not solely a consequence of aging. Clin Exp Rheumatol. 2017 Oct 23. PMID:29148407
Leehan KM, Pezant NP, Rasmussen A, Grundahl K, Moore JS, Radfar L, Lewis DM, Stone DU, Lessard CJ, Rhodus NL, Segal BM, Kaufman CE, Scofield RH, Sivils KL, Montgomery C, Farris AD. Fatty infiltration of the minor salivary glands is a selective feature of aging but not Sjögren's syndrome. Autoimmunity. 2017 Oct 8:1-7. PMID:28988489
Li H, Reksten TR, Ice JA, ..., Farris AD, ..., Gaffney PM, James JA, T..., Montgomery CG, Scofield RH, Kovats S,..., Lessard CJ, Sivils KL. Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons. PLoS Genet. 2017 Jun 22;13(6):e1006820. PMID: 28640813
Adrianto I, Montgomery C. Estimating Allele Frequencies. Methods Mol Biol. 2017;850:59-76. PMID:22307694
Joachims ML, Leehan KM, Lawrence C, Pelikan RC, Moore JS, Pan Z, Rasmussen A, Radfar L, Lewis DM, Grundahl KM, Kelly JA, Wiley GB, Shugay M, Chudakov DM, Lessard CJ, Stone DU, Scofield RH, Montgomery CG, Sivils KL, Thompson LF, Farris AD. Single-cell analysis of glandular T cell receptors in Sjögren's syndrome. JCI Insight. 2016 Jun 2;1(8). pii: e85609. [Abstract] PMCID: PMC4922426
Bello GA, Brown MA, Kelly JA, Thanou A, James JA, Montgomery CG. Development and validation of a simple lupus severity index using ACR criteria for classification of SLE. Lupus Sci Med. 2016 Mar 10;3(1):e000136. eCollection 2016. [Abstract] PMID: 27026812
Fischer A, Ellinghaus D, Nutsua M, Hofmann S, Montgomery CG, Iannuzzi MC, Rybicki BA, Petrek M, Mrazek F, Pabst S, Grohe C, Grunewald J, Ronninger M, Eklund A, Padyukov L, Mihailovic-Vucinic V, Jovanovic D, Sterclova M, Homolka J, Nothen MM, Herms S, Gieger C, Strauch K, Winkelmann J, Boehm BO, Brand S, Buning C, Schurmann M, Ellinghaus E, Baurecht H, Lieb W, Nebel A, Muller-Quernheim J, Franke A, Schreiber S, GenPhenReSa Consortium. Identification of immune-relevant factors conferring sarcoidosis genetic risk. Am J Respir Crit Care Med 2015. [Abstract] EPub
Levin AM, Adrianto I, Datta I, Iannuzzi MC, Trudeau S, Drake WP, Li J, Montgomery CG, Rybicki BA. Association of HLA-DRB1 with Sarcoidosis susceptibility and progression in
African Americans. Am J Respir Cell Mol Biol 2015. [Abstract] EPub
* Kottyan LC, Zoller EE, Bene J, ..., Lessard CJ, ...., Montgomery CG, ..., Nath SK, , ..., Merrill JT, James JA, Guthridge JM, Scofield RH, Alarcon-Riquelme M, ..., Moser Sivils KL, Gaffney PM, et al. The IRF5-TNPO3 association with systemic lupus erythematosus (SLE) has two components that other autoimmune disorders variably share. Hum Mol Genet 24:582-596, 2014. [Abstract]
Arthritis & Clinical Immunology Research Program, MS 58
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-2584
Fax: (405) 271-2578
Indra Adrianto, Ph.D.
Research Assistant Member
Lori Garman, Ph.D.
Assistant Staff Scientist
Assistant Director of Infrastructure & Research Computing
Richard Pelikan, Ph.D.
Dustin Fife, Ph.D.
Senior Data Analyst