Our group has been working on the genetics of lupus for over 15 years. We have identified several genes for lupus, such as PDCD1 and BANK1, and we have also contributed to the better understanding of the mechanisms in which the gene variants affect gene function, a field in which we have gained experience.
The last few years have witnessed an explosion of data where genes for several common diseases have been identified. This data can now be exploited fully to understand the mechanisms in which the genes function or interact to lead to a disease.
The aim of our research is precisely to understand those interactions and translate them into biologically relevant information that we can test experimentally.
We are also focusing on less-studied populations, in particular Hispanics. Hispanics with lupus have a very severe disease and usually develop kidney inflammation, one of the major complications of lupus. We aim to understand if the mixture of European and Native American and/or Amerindian genetic variation may predispose these individuals to a higher risk of developing a more severe clinical picture.
M.D., Escuela Mexicana de Medicina, Universidad LaSalle and Universidad Nacional Autónoma de México,
Mexico City, Mexico, 1985
Ph.D., Stockholm University, Sweden, 1994
Honors and Awards
1980 Scholarship for medical studies, UNAM, Mexico
1985-1987 Research fellow, Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición, Mexico
1984 Consejo Nacional de Ciencia y Tecnología, México, award for doctoral studies abroad
1992 Namowitsky fellowship
1994-1996 Postdoctoral fellow, Department of Medical Genetics, BMC, Uppsala University, Sweden
1999, 2001-2002 Graduate school student director, Genome Program, Swedish Foundation for Strategic Research
2004-2009 Researcher, Royal Academy of Sciences (KVA), Sweden (in competition)
2006-2008 Honorary Principal Investigator, Pasteur Institute of Montevideo, Uruguay
2008-2009 Esther Z. Greenberg Scholar, Oklahoma Medical Research Foundation
2009-2011 Professor in Genetic Epidemiology of Inflammatory Diseases
Member, editorial boards for Genes and Immunity, Journal of Autoimmunity, Autoimmunity and Arthritis & Rheumatism
Ad-hoc referee for Rheumatology, Genes & Immunity, American Journal of Human Genetics, Human Genetics,
Arthritis & Rheumatism, Nature Genetics and Cell
Grant evaluator for several European Funding agencies
Member, SLEGEN Consortium and the Nordic Center of Excellence in Genetics, awarded by the Nordic Council of Ministers and the Wallenberg Foundation
Joined OMRF Scientific Staff in 2009.
The identification of genes for lupus will lead to a better understanding of disease pathogenesis. My group has been working for several years in the identification of new genes for lupus. Within the various genes for lupus known to date, we identified PDCD1 and BANK1. These studies include the understanding of the functional basis of the variants or mutations underlying lupus susceptibility. Thus, we study in detail the new susceptibility genes to determine if functional variation in each gene affects gene expression or splicing or might have other consequences on gene function.
However most genetic risks identified to date have very small individual effects on the lupus phenotype. Whether gene-gene interactions might underlie major effects on the risk to develop lupus is one of the goals of our research. Further, we take a step forward and ask ourselves if the genetic interactions reflect true biological processes, and we investigate if the interacting genes code for proteins that may bind to each other or interact functionally in the same biological process.
A second goal in our studies is to identify susceptibility genes of Amerindian origin (Native American or Native Latin American) in individuals of Hispanic ancestry. Hispanics develop at times a severe lupus with many clinical complications and understanding how ancestry and admixture contributes to development of the disease is part of our studies.
For our studies, we count with numerous national and international collaborations that have provided us with an extensive resource of samples.
Morris DL, Fernando MM, Taylor KE, Chung SA, Nititham J, Alarcon-Riquelme ME, Barcellos LF, Behrens TW, Cotsapas C, Gaffney PM, Graham RR, Pons-Estel BA, Gregersen PK, Harley JB, Hauser SL, Hom G, Langefeld CD, Noble JA, Rioux JD, Seldin MF, Systemic Lupus Erythematosus Genetics Consortium, Vyse TJ, Criswell LA. MHC associations with clinical and autoantibody manifestations in European SLE. Genes Immun 2014. [Abstract] EPub
Mayes MD, Bossini-Castillo L, Gorlova O, Martin JE, Zhou X, Chen WV, Assassi S, Ying J, Tan FK, Arnett FC, Reveille JD, Guerra S, Teruel M, Carmona FD, Gregersen PK, Lee AT, López-Isac E, Ochoa E, Carreira P, Simeón CP, Castellvi I, González-Gay MA, Spanish Scleroderma Group, Zhernakova A, Padyukov L, Alarcón-Riquelme M, Wijmenga C, Brown M, Beretta L, Riemekasten G, Witte T, Hunzelmann N, Kreuter A, Distler JH, Voskuyl AE, Schuerwegh AJ, Hesselstrand R, Nordin A, Airo P, Lunardi C, Shiels P, van Laar JM, Herrick A, Worthington J, Denton C, Wigley FM, Hummers LK, Varga J, Hinchcliff ME, Baron M, Hudson M, Pope JE, Furst DE, Khanna D, Phillips K, Schiopu E, Segal BM, Molitor JA, Silver RM, Steen VD, Simms RW, Lafyatis RA, Fessler BJ, Frech TM, Alkassab F, Docherty P, Kaminska E, Khalidi N, Jones HN, Markland J, Robinson D, Broen J, Radstake TR, Fonseca C, Koeleman BP, Martin J. Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis. Am J Hum Genet 94:47-61, 2014. [Abstract]
Oparina NY, Delgado-Vega AM, Martinez-Bueno M, Magro-Checa C, Fernandez C, Castro RO, Pons-Estel BA, D'Alfonso S, Sebastiani GD, Witte T, Lauwerys BR, Endreffy E, Kovacs L, Escudero A, Lopez-Pedrera C, Vasconcelos C, da Silva BM, Frostegard J, Truedsson L, Martin J, Raya E, Ortego-Centeno N, de Los Angeles AM, de Ramon GE, Palma MJ, Alarcon-Riquelme ME, Kozyrev SV. PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6. Ann Rheum Dis 2014. [Abstract] EPub
Sanchez E, Rasmussen A, Riba L, Acevedo-Vasquez E, Kelly JA, Langefeld CD, Williams AH, Ziegler JT, Comeau ME, Marion MC, Garcia-De La Torre I, Maradiaga-Cecena MA, Cardiel MH, Esquivel-Valerio JA, Rodriguez-Amado J, Moctezuma JF, Miranda P, Perandones CE, Castel C, Laborde HA, Alba P, Musuruana JL, Goecke IA, Anaya JM, Kaufman KM, Adler A, Glenn SB, Brown EE, Alarcon GS, Kimberly RP, Edberg JC, Vila LM, Criswell LA, Gilkeson GS, Niewold TB, Martin J, Vyse TJ, Boackle SA, Ramsey-Goldman R, Scofield RH, Petri M, Merrill JT, Reveille JD, Tsao BP, Orozco L, Baca V, Moser KL, Gaffney PM, James JA, Harley JB, Tusie-Luna T, Pons-Estel BA, Jacob CO, Alarcón-Riquelme ME. Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations. Arthritis Rheum 64:3687-3694, 2012. [Abstract]
Sanchez E, Webb RD, Rasmussen A, Kelly JA, Riba L, Kaufman KM, Garcia de la Torre I, Moctezuma JF, Maradiaga-Ceceña MA, Cardiel-Rios MH, Acevedo E, Cucho-Venegas M, Garcia MA, Gamron S, Pons-Estel BA, Vasconcelos C, Martin J, Tusié-Luna T, Harley JB, Richardson B, Sawalha AH, Alarcón-Riquelme ME. Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus. Arthritis Rheum 62:3722-3729, 2010. [Abstract]
Castillejo-Lopez C, Delgado-Vega AM, Wojcik J, Kozyrev SV, Thavathiru E, Wu YY, Sanchez E, Pollmann D, Lopez-Egido JR, Fineschi S, Dominguez N, Lu R, James JA, Merrill JT, Kelly JA, Kaufman KM, Moser KL, Gilkeson G, Frostegard J, Pons-Estel BA, D'Alfonso S, Witte T, Callejas JL, Harley JB, Gaffney PM, Martin J, Guthridge JM, Alarcón-Riquelme ME. Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK. Ann Rheum Dis 71:136-142, 2012. [Abstract]
Kozyrev SV, Abelson AK, Wojcik J, Zaghlool A, Linga Reddy MV, Sanchez E, Gunnarsson I, Svenungsson E, Sturfelt G, Jönsen A, Truedsson L, Pons-Estel BA, Witte T, D’Alfonso S, Barizzone N, Danieli MG, Gutierrez C, Suarez A, Junker P, Laustrup H, González-Escribano MF, Martin J, Abderrahim H, Alarcón-Riquelme ME. Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nat Genet 40:211-216, 2008. [Abstract]
Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, Ortmann WA, Koeuth T, González Escribano MF; Argentine and Spanish Collaborative Groups, Pons-Estel B, Petri M, Daly M, Gregersen PK, Martín J, Altshuler D, Behrens TW, Alarcón-Riquelme ME. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 38:550-555, 2006. [Abstract]
Arthritis & Clinical Immunology Research Program, MS 24
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-4031
Fax: (405) 271-4110