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Scofield, Robert H. “Hal”

Robert H. “Hal” Scofield, M.D.

Robert H. “Hal” Scofield, M.D.

Member

Adjunct Associate Professor, Department of Pathology and Department of Medicine, University of Oklahoma Health Sciences Center

Autoimmune diseases are especially frustrating, because they involve the immune system.  Normally, the immune system protects the body from harmful bacteria and infections.  But in autoimmune diseases, the immune system turns against the body, causing weakness and pain and sometimes leads to premature death.

In my laboratory, we’re working on three major projects.  The biggest is trying to develop a new animal model of Sjögren’s syndrome.  Why create an animal model of a disease?  So we can learn more about the disease and find new and better treatments for patients.  Sjögren’s syndrome is an autoimmune disease that targets glands that produce saliva and tears.  Patients with the disease can live very painful lives, because saliva and tears play important roles in keeping our eyes and mouths clean and disease-free.

We’re also looking at the genetics of systemic lupus erythematosus, more often called just lupus, and how it affects black families.  African Americans are more likely to have lupus and to have more severe cases of the disease.  We’re hoping to figure out which genes play a role in the disease and how to predict and prevent the disease from occurring.

Our last focus is the correlation between lupus in men and the rare disease Klinefelter’s syndrome.  Men are 10 times less likely to have lupus than women and Klinefelter’s (in which the man has an extra X chromosome) happens to only one in 17,000 men – but male lupus patients are much more likely to also have Klinefelter’s syndrome.  We think this could play a role in why lupus affects women so much more frequently than men.

Education
B.A., Texas A&M University, 1980
M.D., University of Texas Southwestern Medical School, Dallas, 1984

Honors and Awards
Distinguished Student, Texas A&M University
1987 Stewart Wolf Award
Outstanding Medicine Resident
1988-1989 W.W. Rucks Fellowship
1989-1991 Presbyterian Health Foundation Fellowship
1989 Visiting Professor’s Award
1989 Outstanding Paper, OUHSC Housestaff Scientific Session
1990 Best Paper in Internal Medicine, OUHSC Housestaff, Scientific Session
1990 Lloyd Rader Scholarship, Outstanding Postgraduate Trainee, OUHSC
1992-1997 Physician Scientist Award, NIH, Institute of Musculoskeletal and Skin Diseases
1992 The Merrick Award for Outstanding Research, OMRF
1995 Internal Medicine Faculty Teaching Award, Department of Medicine, OUHSC
1996 OUHSC Provost Award for research by an Assistant Professor
1994 Henry Christian Award, American Federation of Medical Research (national meeting)
1998 Fellow, American College of Physicians
2001 James A. Shannon Director’s Award (NIAMS and the Office for Research on Women’s Diseases)
2002 OUHSC Provost Award for research by a senior faculty member
2003-present Oklahoma Health Research Committee (appointed by Governor Brad Henry)
2004 Ethel Baxter Award for Outstanding Sjogren’s Syndrome Abstract, American College of Rheumatology National Meeting

Other Activities
Serves on the Medical Records Committee for University Hospital; representative to the American Federation of Clinical Research; Vice-Chairman, Research and Development Committee, Department of Veteran’s Affairs Medical Center; member of the Medical Residency Education Review Committee, Department of Medicine, OUHSC; Chairman, Institutional Review Board, OMRF; member, Research Committee, Department of Medicine, OUHSC; volunteer physician, Little Flower Clinic.

Memberships
American College of Physicians
American College of Rheumatology
American Federation of Clinical Research
The Endocrine Society
American Association for the Advancement of Science
American Diabetes Association
Oklahoma Rheumatism Association
The Society of General Internal Medicine
The New York Academy of Sciences
American Association of Immunologists

Joined OMRF Scientific Staff in 1991.

My laboratory concentrates on three major projects. First, we have developed a new animal model of Sjögren’s syndrome. This is a common autoimmune rheumatic illness in which there is autoimmune targeting of the salivary and lacrimal glands. Most people with the illness have antibodies in their sera binding the Ro and La proteins. When BALB/c mice are immunized with short peptides (15-18 amino acids in length) from the 60 kD Ro sequence, the mice first develop antibodies and T cell responses recognizing the peptide of immunization. Shortly thereafter there is intra- and intermolecular spreading such that these animals develop autoantibodies binding other epitopes of 60 kD Ro as well as anti-La and and anti-Ro52. We find lymphocytic infiltrates in the salivary glands of immunized animals whose structure and composition are similar to those found in the salivary glands of humans with Sjögren’s syndrome. Also, mice have a decrease in stimulated salivary flow. Thus, these mice recapitulate human Sjögren’s syndrome. Disease can be adoptively transferred by either cells or sera. Experiments are ongoing to determine the specificities of the cell type required for adoptive transfer as well as the specificity of immunoglobulin required for transfer of disease.

In regard to the genetics of SLE, my lab is pursuing the established and confirmed genetic linkage at 11q13 found in Black American SLE families. Black Americans have SLE more frequently and more severely than do White Americans. The strongest linkage is among families with severe disease. The linkage interval has been narrowed by typing of microsatellites within the region. In addition, typing of a large number of single nucleotide polymorphisms has been carried out. Several possible genetic associations are being pursued, including the catalase gene promoter region. We are also interested in the role of prolidase deficiency in autoimmunity.

Finally, we are investigating the association of SLE in men with the presence of Klinefelter’s syndrome (47,XXY). Klinefelter’s syndrome is present in 1 in 17,000 live male births, but our data indicate that 5 of 207 men with SLE have 47,XXY. Meanwhile, Turner’s syndrome (45,XO females) is not commonly found among women with SLE. Thus, we hypothesize that the female-to-male predilection of SLE is due to a gene dose effect on the X chromosome.

Recent Publications

Ritterhouse LL, Lu R, Shah HB, Robertson JM, Fife DA, Maecker HT, Du H, Fathman CG, Chakravarty EF, Scofield RH, Kamen DL, Guthridge JM, James JA. Vitamin D Deficiency in a Multiethnic Healthy Control Cohort and Altered Immune Response in Vitamin D Deficient European-American Healthy Controls. PLoS One 9:e94500, 2014. [Abstract]

* Guthridge JM, Lu R, Sun H, Sun C, Wiley GB, Dominguez N, Macwana SR, Lessard CJ, Kim-Howard X, Cobb BL, Kaufman KM, Kelly JA, Langefeld CD, Adler AJ, Harley IT, Merrill JT, Gilkeson GS, Kamen DL, Niewold TB, Brown EE, Edberg JC, Petri MA, Ramsey-Goldman R, Reveille JD, Vila LM, Kimberly RP, Freedman BI, Stevens AM, Boackle SA, Criswell LA, Vyse TJ, Behrens TW, Jacob CO, Alarcon-Riquelme ME, Sivils KL, Choi J, Joo YB, Bang SY, Lee HS, Bae SC, Shen N, Qian X, Tsao BP, Scofield RH, Harley JB, Webb CF, Wakeland EK, James JA, Nath SK, Graham RR, Gaffney PM. Two Functional Lupus-Associated BLK Promoter Variants Control Cell-Type- and Developmental-Stage-Specific Transcription. Am J Hum Genet 94:586-598, 2014. [Abstract]

Kurien BT, D'Sousa A, Bruner BF, Gross T, James JA, Targoff IN, Maier-Moore JS, Harley IT, Wang H, Scofield RH. Prolidase deficiency breaks tolerance to lupus-associated antigens. Int J Rheum Dis 2013. [Abstract] EPub

Selected Publications

Aggarwal R, Sestak AL, Chakravarty EF, Harley JB, Scofield RH. Excess Female Siblings and Male Fetal Loss in Families with Systemic Lupus Erythematosus. J Rheumatol 40:430-434, 2013. [Abstract]

Kurien BT, Dsouza A, Igoe A, Lee YJ, Maier-Moore JS, Gordon T, Jackson M, Scofield RH. Immunization with 60 kD Ro peptide produces different stages of pre-clinical autoimmunity in a Sjogren's syndrome-model among multiple strains of inbred mice. Clin Exp Immunol  173:67-75, 2013.[Abstract]

Lessard CJ, Li H, Adrianto I, Ice JA, Rasmussen A, Grundahl KM, Kelly JA, Dozmorov MG, Miceli-Richard C, Bowman S, Lester S, Eriksson P, Eloranta ML, Brun JG, Goransson LG, Harboe E, Guthridge JM, Kaufman KM, Kvarnstrom M, Jazebi H, Graham DS, Grandits ME, Nazmul-Hossain AN, Patel K, Adler AJ, Maier-Moore JS, Farris AD, Brennan MT, Lessard JA, Chodosh J, Gopalakrishnan R, Hefner KS, Houston GD, Huang AJ, Hughes PJ, Lewis DM, Radfar L, Rohrer MD, Stone DU, Wren JD, Vyse TJ, Gaffney PM, James JA, Omdal R, Wahren-Herlenius M, Illei GG, Witte T, Jonsson R, Rischmueller M, Ronnblom L, Nordmark G, Ng WF, for UK Primary Sjogren's Syndrome Registry, Mariette X, Anaya JM, Rhodus NL, Segal BM, Scofield RH, Montgomery CG, Harley JB, Sivils KL. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome. Nat Genet 45:1284-1292, 2013. [Abstract]

Dillon SP, Kurien BT, Li S, Bruner GR, Kaufman KM, Harley JB, Gaffney PM, Wallace DJ, Weisman MH, Scofield RH. Sex chromosome aneuploidies among men with systemic lupus erythematosus. J Autoimmun 38:J129-J134,2012. [Abstract]

Kurien BT, Porter A, Dorri Y, Iqbal S, D'Sousa A, Singh A, Asfa S, Cartellieri M, Mathias K, Matsumoto H, Bachmann M, Hensley K, Scofield RH. Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal may differentially induce Sjögren's syndrome or systemic lupus erythematosus in BALB/c mice. Free Radic Biol Med 50:1222-1233, 2011. [Abstract]

Scofield RH, Bruner GR, Namjou B, Kimberly RP, Ramsey-Goldman R, Petri M, Reveille JD, Alarcón GS, Vila LM, Reid J, Harris B, Li S, Kelly JA, Harley JB. Klinefelter's syndrome (47,XXY) in male systemic lupus erythematosus patients: Support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum 58:2511-2517, 2008. [Abstract]

View all publications in PubMed

Arthritis & Clinical Immunology Research Program, MS 38
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104

Phone: (405) 271-7061
Fax: (405) 271-7063
E-mail: Hal-Scofield@omrf.org

Mollie Rangnow
Administrative Assistant

Skyler Dillon
Affiliate

Biji Kurien, Ph.D.
Affiliate