Back to Main

Faculty Detail    
Campus Address CHIL PARK Zip 1711
Phone 205-939-9438
Other websites

Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pediatrics   Ped - Rheumatology Professor
Secondary  Medicine  Med - Immunology/Rheumatology Associate Professor
Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor
Center  Center for AIDS Research  Center for AIDS Research Professor

Graduate Biomedical Sciences Affiliations
Pathobiology and Molecular Medicine 

Biographical Sketch 
B.S. (Biomedical Sciences), University of California, Riverside, CA
Pre-doctoral fellow (Howard Hughes Medical Institute), National Institutes of Health, Bethesda, MD
Ph.D. (Immunology), University of Chicago, Chicago, IL
M.D. UCLA, Los Angeles, CA
Residency (Pediatrics), Stanford Children’s Hospital, Palo Alto, CA
Fellowship (Pediatric Rheumatology), University of Washington, Seattle, WA
Post-doctoral Fellow (Howard Hughes Medical Institute scholar), Stanford University, Palo Alto, CA

1985 Watkins Award (outstanding male graduate), University of California at Riverside
1985 Summer Externship/Scholarship, Riverside Medical Clinic/University of California at Riverside, Biomedical Sciences Department
1986 Graduate Scholarship, The International Fraternity of Phi Gamma Delta
1986 Research Scholar, Howard Hughes Medical Institute/National Institutes of Health
1988 Lucille P. Markey Charitable Trust recipient, University of Chicago
1988 Dean's Fund recipient, University of Chicago
1991 Outstanding Performance in the Field of Immunology, University of Chicago
1996 Postdoctoral Research Fellowship, Howard Hughes Medical Institute
1997 Travel Award, American College of Rheumatology Research & Education Foundation
1997 Senior Scholar Award, American College of Rheumatology/Merck
1998 Child Health Research Center Scholar, Stanford University Medical Center
1999 Arthritis Foundation Investigator Award
1999 Elizabeth Glaser Pediatric AIDS Foundation Scholar
2000 Child Health Research Center Scholar, Children's Hospital of Philadelphia (CHOP)
2000 Junior Clinical Investigator Award, General Clinical Research Center, CHOP
2000 Doris Duke Charitable Foundation, Clinical Research Scientist, alternate recipient
2000 Searle Scholar, representative of the University of Pennsylvania Medical School
2000 MAPS-CHRC National Meeting, invited presenter
2001 Mary L. Smith Charitable Trust grant recipient
2001 Junior Faculty Exchange Program with EULAR, American College of Rheumatology/Merck
2002 Society for Pediatric Research Young Investigator Travel Award
2002 American Association of Immunologists Junior Faculty Travel Award
2002 Arthritis National Research Foundation grant recipient
2002 Dorough Lupus Foundation grant recipient
2002 Society for Pediatric Research, elected member
2003 Arthritis Foundation, Travel Award, Arthritis Research Conference
2004 Nickolett Family Awards Program for JRA Research grant recipient
2004 The Ethel Brown Foerderer Fund for Excellence fellow/grant recipient
2005 Nickolett Family Awards Program for JRA Research grant recipient
2006 American Association of Immunologists Junior Faculty Travel Award
2006 Keynote Speaker, UMDNJ Department of Medicine Residents Research Day
2006 Kassie McMullen Biglaw Memorial Research Award, Lupus Foundation of America
2007 First Holder of Arthritis Foundation, Alabama Chapter Endowed Chair in Pediatric Rheumatology, University of Alabama at Birmingham School of Medicine
2011 American College of Rheumatology REF/AMGEN Pediatric Rheumatology Visiting Professor
2011 Nominee, Council member of Society for Pediatric Research (SPR)
2011 UAB Health Care Leadership Academy, selected member
2012 UAB Health Care Leadership Academy, elected to advisory board
2012 Alabama Society for Rheumatic Diseases, elected as President
2012 Senior Host, ACR/EULAR Exchange Program

Society Memberships
Organization Name Position Held Org Link
Alabama Society for the Rheumatic Diseases   President 2012-2013   
American Association of Immunologists  Clinical Immunology Committee (2007-2010) 
American College of Rheumatology  Juvenile Idiopathic Arthritis Treatment Guidelines, Core Expert Panel member 
Arthritis Foundation  Board of Directors, Southeast Region 
Arthritis Foundation  Southeast Region Board of Directors (2010-2015) 
Childhood Arthritis & Rheumatology Research Alliance (CARRA) 
Pediatric Rheumatology Collaborative Study Group 
Society for Pediatric Research 

Research/Clinical Interest
CD4 T Lymphocyte Transcriptional Regulation
CD154 (CD40 ligand) dysregulation in lupus. Systemic lupus erythematosus, the prototypic autoimmune disorder, affects 1 in 2,000 women in the United States. CD154Although the etiology and pathogenesis are unclear, the over-expression of the TNF family member, CD154, on CD4 T lymphocytes clearly contributes to disease pathology, both in mouse models and in humans with disease. Our ultimate goal is to identify cis- and trans-acting elements that contribute to the dysregulated expression of CD154 in SLE and other autoimmune disorders. We initially characterized the human CD154 transcriptional promoter and demonstrated its cyclosporin A (CsA) sensitivity. We TF Regulate CD154are currently probing the hCD154 gene locus by DNase I hypersensitive site mapping to identify novel regulatory elements. We have identified and partially characterized a 5' transcriptional enhancer, a 3' transcriptional enhancer, and a 3' untranslated mRNA stability element. In addition, we have identified an uncharacterized 5' hypersensitive site farther upstream of the transcription start site. We are currently exploring the activities of these various CD154 regulatory elements as transgenes in a mouse model of SLE. In conjunction, we have identified various transcription factors and RNA binding proteins, which had not been previously described to regulate CD154 expression. We are currently exploring these factors for their contributions to CD154 dysregulation in SLE. Host transcription factors exploited by HIV-1. HIV-1, the cause of AIDS, has infected over 40 million individuals world-wide. Although vast improvements in therapy have been developed over the last decade, HIV-1 cannot be totally NFAT Binding HIVeliminated from the host due to its ability to enter a resting or latent state in CD4 T cells. Because HIV-1 relies on host transcription factors to replicate, we are exploring the role of the calcium activated nuclear factor of activated T cells (NFAT) transcription factors in regulating HIV-1 transcription. We and others have shown that the CsA-sensitive NFAT proteins bind to the proximal HIV-1 promoter/long terminal repeat (LTR) in vitro and up-regulate HIV-1 transcription. We have further demonstrated that NFAT proteins bind to the integrated HIV-1 LTR in primary human CD4 T cells in vivo by chromatin immunoprecipitation, and this binding is disrupted by the regulatory T cell transcription factor, FOXP3. In addition, we are attempting to exploit NFAT activation as a means of activating HIV-1 LTR activity in latently infected cells. Recently, we identified a novel binding site for the c-maf transcription factor located adjacent to the proximal NFAT sites in the HIV-1 LTR. Our studies reveal synergistic transcriptional activation and increased infection of HIV-1 by c-maf, NFAT2, and NFkB in primary human IL-4-producing CD4 T cells. Thus, c-maf will likely be a novel therapeutic target in the treatment of HIV-1.

Selected Publications 
Publication PUBMEDID
Host Factor Transcriptional Regulation Contributes to Preferential Expression of HIV Type 1 in IL-4-Producing CD4 T Cells.

Zhang M, Clausell A, Robinson T, Yin J, Chen E, Johnson L, Weiss G, Sabbaj S, Lowe RM, Wagner FH, Goepfert PA, Kutsch O, Cron RQ.

J Immunol. 2012 Sep 15;189(6):2746-57. 
Risk factors for temporomandibular joint arthritis in children with juvenile idiopathic arthritis.

Stoll ML, Sharpe T, Beukelman T, Good J, Young D, Cron RQ.

J Rheumatol. 2012 Sep;39(9):1880-7. 
Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment.

Ravelli A, Grom AA, Behrens EM, Cron RQ.

Genes Immun. 2012 Jun;13(4):289-98. 
Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis.

Mehta J, Genin A, Brunner M, Scalzi LV, Mishra N, Beukelman T, Cron RQ.

Arthritis Rheum. 2010 Aug;62(8):2499-509. 
FOXP3 inhibits activation-induced NFAT2 expression in T cells thereby limiting effector cytokine expression.

Torgerson TR, Genin A, Chen C, Zhang M, Zhou B, Añover-Sombke S, Frank MB, Dozmorov I, Ocheltree E, Kulmala P, Centola M, Ochs HD, Wells AD, Cron RQ.

J Immunol. 2009 Jul 15;183(2):907-15. 
High prevalence of temporomandibular joint arthritis at disease onset in children with juvenile idiopathic arthritis, as detected by magnetic resonance imaging but not by ultrasound.

Weiss PF, Arabshahi B, Johnson A, Bilaniuk LT, Zarnow D, Cahill AM, Feudtner C, Cron RQ.

Arthritis Rheum. 2008 Apr;58(4):1189-96. 
Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis.

Behrens EM, Beukelman T, Paessler M, Cron RQ.

J Rheumatol. 2007 May;34(5):1133-8.  
2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features.

Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM, Ilowite NT, Kimura Y, Laxer RM, Lovell DJ, Martini A, Rabinovich CE, Ruperto N.

Arthritis Care Res (Hoboken). 2011 Apr;63(4):465-82.  
Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series.

Nigrovic PA, Mannion M, Prince FH, Zeft A, Rabinovich CE, van Rossum MA, Cortis E, Pardeo M, Miettunen PM, Janow G, Birmingham J, Eggebeen A, Janssen E, Shulman AI, Son MB, Hong S, Jones K, Ilowite NT, Cron RQ, Higgins GC.

Arthritis Rheum. 2011 Feb;63(2):545-55. 
Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients.

Miettunen PM, Narendran A, Jayanthan A, Behrens EM, Cron RQ.

Rheumatology (Oxford). 2011 Feb;50(2):417-9. 
Determinants of the establishment of human immunodeficiency virus type 1 latency.

Duverger A, Jones J, May J, Bibollet-Ruche F, Wagner FA, Cron RQ, Kutsch O.

J Virol. 2009 Apr;83(7):3078-93. 
FOXP3 inhibits HIV-1 infection of CD4 T-cells via inhibition of LTR transcriptional activity.

Selliah N, Zhang M, White S, Zoltick P, Sawaya BE, Finkel TH, Cron RQ.

Virology. 2008 Nov 25;381(2):161-7. 
A T-cell-specific CD154 transcriptional enhancer located just upstream of the promoter.

Brunner M, Zhang M, Genin A, Ho IC, Cron RQ.

Genes Immun. 2008 Oct;9(7):640-9. 

Lupus, HIV-1, CD4 T Cell, Transcription, Nuclear Factor of Activated T Cells, Macrophage Activation Syndrome