Arthritis Foundation, Alabama Chapter
Professor of Pediatrics & Medicine
Director, Division of Pediatric Rheumatology
Director, Pediatric Rheumatology Fellowship Program

Address:

Children's Park Place, Suite 210
1601 4^th Avenue South
Birmingham, AL 35233-1711

Telephone: (205) 996-9191
FAX: (205) 996-9545
Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Administrative Assistant: Jamie Burchfield
Telephone: (205) 996-9191 

For a detailed CV, please click here 

Education
 

B.S. (Biomedical Sciences), University of California, Riverside, CA, 1985
Pre-doctoral fellow (Howard Hughes Medical Institute), National Institutes of Health, Bethesda, MD, 1986-1987
Ph.D. (Immunology), University of Chicago, Chicago, IL, 1990
M.D., UCLA, Los Angeles, CA, 1991
Residency (Pediatrics), Stanford Children's Hospital, Palo Alto, CA, 1991-1994
Fellowship (Pediatric Rheumatology), University of Washington, Seattle, WA, 1994-1997
Post-doctoral Fellow (Howard Hughes Medical Institute), Stanford University, Palo Alto, CA, 1997-1999

Research Description

CD154 (CD40 ligand) dysregulation in lupus.  Systemic lupus erythematosus, the prototypic autoimmune disorder, affects 1 in 2,000 women in the United States. . Although 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 are 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 eliminated 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. In addition, we are exploring the inhibition of HIV-1 transcription in FoxP3-expressing regulatory T cells (Tregs), as well as the ability of these cells to inhibit HIV-1 expression in neighboring non-Treg CD4 T cells.
 

Potential projects for trainees

• Data collection on the effect of intra-articular steroid and infliximab treatment of TMJ arthritis
• Exploration of the functional impact of HLH mutations (from children with MAS) on the cytolytic pathway
• Optimization of lentiviral vectors for gene transfer of CD154 into hematopoetic stem cells and CD4 T cells
• Determining the domains of NFAT1 and NFAT2 which differentially allow for transactivation of the HIV-1 LTR
• The role of NFAT2 in driving CD4 T cell effector cell development

Selected Publications

Cron, R.Q., Bandyopadhyay, R., Genin, A., Brunner, M., Kersh, G.J., Yin, J., Finkel, T.H., and Crow, M.K. 2006. Egr-1 is required for CD154 transcription. J. Immunol. 176:811-818. PMID: 16393964

Selliah, N., Zhang, M., Desimone, D., Kim, H., Brunner, M., Ittenbach, R.F., Rui, H., Cron, R.Q.*, and Finkel, T.H. 2006. The gc-cytokine regulated transcription factor, STAT5, activates HIV-1 replication in resting CD4 T-cells. Virology 344:283-291. (* - co-senior author) PMID: 16289657

Yin, J., Ma, Z., Shivers, D.K., Cron, R.Q., and Finkel, T.H. 2006. Effective gene suppression using small interfering RNA in hard-to-transfect human T cells. J. Immunol. Methods 312:1-11. PMID: 16603179

Von Feldt, J.M., Scalzi, L.V., Cucchiara, A.J., Morhtala, S., Kealey, C., Flagg, S.D., Genin, A., Van Dyke, A.L., Nackos, E., Chander, A., Gehrie, E., Cron, R.Q., and Whitehead, A.S. 2006. Homocysteine levels and disease duration independently correlate with coronary artery calcification in patients with systemic lupus erythematosus. Arthritis Rheum. 54:2220-2227. PMID: 16802358

Von Feldt, J.M, Latif, S., Genin, A., and Cron, R.Q. 2008. Neither cell-surface nor soluble CD154 levels are associated with coronary artery disease in systemic lupus erythematosus.  J. Rheumatol. 35:359-360. PMID: 18260168 

Brunner, M., Zhang, M., Genin, A., Ho, I.-C., and Cron, R.Q. 2008. A T-cell-specific CD154 transcriptional enhancer located just upstream of the promoter. Genes Immun. 9:640-649. PMID: 18719603  

Selliah, N., Zhang, M., White, S., Zoltick, P., Sawaya, B., Finkel, T.H., and Cron, R.Q. 2008. FOXP3 inhibits HIV-1 infection of CD4 T-cells via inhibition of LTR transcriptional activity. Virology 381:161-167. PMID: 18829063

Duverger, A., Jones, J., May, J., Bibollet-Rusch, F., Wagner, F.A., Cron, R.Q., and Kutsch, O. 2009. Determinants of HIV-1 latency establishment. J. Virol. 83:3078-3093. PMID: 19144703  

Torgerson, T.R., Genin, A., Chen, C., Zhang, M., Zhou, B., Anover, S., Frank, M.B., Dozmorov, I., Ocheltree, E., Kulmala, E., Centola, M., Ochs, H.D., Wells, A.D., and Cron, R.Q. 2009. FOXP3 inhibits activation-induced NFAT2 expression in T cells thereby limiting effector cytokine expression. J. Immunol. 183:907-915. PMID: 19564342

Mehta, J., Genin, A., Brunner, M., Scalzi, L.V., Mishra, N., Beukelman, T., and Cron, R.Q. 2010. 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. Arthritis Rheum. 62: 2499-2509. PMID: 20506525

Miettunen PM, Narendran A, Jayanthan A, Behrens EM, Cron RQ. 2010. Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients. Rheumatology (Oxford). 50(2):417-9. PMID: 20693540 

Cron RQ, Beukelman T. 2010. Guilt by association - what is the true risk of malignancy in children treated with etanercept for JIA? Pediatr Rheumatol Online J. 8:23. PMID: 20712883 

Rider LG, Wu L, Mamyrova G, Targoff IN, Miller FW; Childhood Myositis Heterogeneity Collaborative Study Group. 2010. Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies. Rheumatology (Oxford). 49(12):2381-90. PMID: 20802007

Record JL, Beukelman T, Cron RQ. 2011. Combination therapy of abatacept and anakinra in children with refractory systemic juvenile idiopathic arthritis: a retrospective case series. J Rheumatol. 38(1):180-1. PMID: 21196588

Mannion M, Cron RQ. 2011. Successful treatment of pediatric IgG4 related systemic disease with mycophenolate mofetil: case report and a review of the pediatric autoimmune pancreatitis literature. Pediatr Rheumatol Online J. 9(1):1. PMID: 21205323 

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. 2011. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis Rheum. 63(2):545-55. PMID: 21280009

Möller JC, Cron RQ, Young DW, Girschick HJ, Levy DM, Sherry DD, Kukita A, Saijo K, Pessler F. 2011. Corticosteroid-induced spinal epidural lipomatosis in the pediatric age group: report of a new case and updated analysis of the literature. Pediatr Rheumatol Online J. 9(1):5. PMID: 21284882 

Davì S, Consolaro A, Guseinova D, Pistorio A, Ruperto N, Martini A, Cron RQ, Ravelli A; MAS Study Group. 2011. An international consensus survey of diagnostic criteria for macrophage activation syndrome in systemic juvenile idiopathic arthritis. J Rheumatol. 38(4):764-8. PMID: 21285158

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. 2011. 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. Arthritis Care Res (Hoboken). 63(4):465-82. PMID: 21452260

Stoll ML, Sharpe T, Beukelman T, Good J, Young D, Cron RQ. 2012. Risk factors for temporomandibular joint arthritis in children with juvenile idiopathic arthritis. J Rheumatol. 39(9):1880-7. PMID: 22589268

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. 2012. Host Factor Transcriptional Regulation Contributes to Preferential Expression of HIV Type 1 in IL-4-Producing CD4 T Cells.  J Immunol. 189(6): 2746-2757.  PMID:  22875803  (This article was featured in the "In This Issue" section of the Journal of Immunology, which highlights articles that are among the top 10% of articles published in the journal.)