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Faculty Detail    
Name RANDALL QUENTIN CRON
Arthritis Foundation, Alabama Chapter, Endowed Chair
Professor of Pediatrics and Medicine
Pediatric Rheumatology Fellowship Director		  
Campus Address CHIL PARK Zip 1711
Phone  (205) 939-9438
E-mail  rcron@uab.edu
Other websites Cron lab
Adult Rheum
Peds Rheum
SOM profile
     

Education
Undergraduate  University of California at Riverside    1985  BS Biomedical Sciences (Honors) 
Fellowship  National Insitutes of Health    1987  Howard Hughes Medical Institute Research Scholar 
Graduate  University of Chicago    1990  PhD in Immunology 
Graduate  UCLA    1991  MD 
Residency  Stanford University    1994  Pediatrics 
Fellowship  University of Washington    1997  Pediatric Rheumatology 
Fellowship  Stanford University    1999  Howard Hughes Medical Institute Postdoctoral Fellow 

Certifications
American Board of Pediatrics (ABP)  2001 
Pediatric Advanced Life Support  2004 
Antonio J. Reginato Musculoskeletal Ultrasonography Course, Cooper (UMDNJ)  2005 
Pediatric Rheumatology Board, ABP  2005 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Ped - Rheumatology  Ped - Rheumatology Professor
Secondary  Med - Immunology/Rheumatology  Med - Immunology/Rheumatology Associate Professor
Center  Center for AIDS Research  Center for AIDS Research Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  UAB Immunology Institute  UAB Immunology Institute Professor

Graduate Biomedical Sciences Affiliations
Immunology 
Pathobiology and Molecular Medicine 

Biographical Sketch 
"Dr. Cron is Professor of Pediatrics & Medicine and Director of the Division of Pediatric Rheumatology at the University of Alabama at Birmingham (UAB). He developed and is the Director of the Pediatric Rheumatology Fellowship program at Children’s of Alabama. He is also Director of the Alabama Center for Childhood Arthritis and Rheumatic Disorders and is the inaugural holder of the Arthritis Foundation, Alabama Chapter Endowed Chair in Pediatric Rheumatology at UAB. Dr. Cron attended the University of California at Riverside for undergraduate studies (B.S. in Biomedical Sciences) and then the National Institutes of Health as a Howard Hughes Medical Institute pre-doctoral fellow prior to receiving a PhD in Immunology from the University of Chicago. He attended UCLA for medical school and completed Pediatric residency training at Stanford Children’s Hospital. He completed his fellowship training in Pediatric Rheumatology at the University of Washington in Seattle and subsequently worked as a Howard Hughes Medical Institute postdoctoral fellow at Sanford University Medical Center. His first faculty appointment was at the University of Pennsylvania/Children’s Hospital of Philadelphia in 1999 prior to recruitment to UAB in 2007 to create a new Division of Pediatric Rheumatology, now 6 faculty members strong. Dr. Cron’s lab studies CD4 T cell transcription as it relates to HIV-1 infection and systemic lupus erythematosus. His lab also studies the impact on natural killer cell lysis by mutations in genes present in patients with macrophage activation syndrome He clinical research interests include the diagnosis and treatment of temporomandibular joint arthritis in juvenile arthritis and the diagnosis and treatment of macrophage activation syndrome." AWARDS/HONORS: 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 2012 selected by peers as “Super Doctor” (~top 5% of physicians in region) [superdoctors.com] 2012 Department of Pediatrics Excellence in Teaching Award 2013 Rud Polhill/KPRI grant recipient 2013 Invited Lecturer, EuroTMjoint Meeting, Aarhus, Denmark 2013 Alabama Society for Rheumatic Diseases, re-elected as President 2013 selected as a Top Rheumatologist in Birmingham, AL by Internat. Assoc. of Health Care Profess. 2013 Department of Pediatrics Excellence in Teaching Award 2013 Invited Lecturer, AAOMS (American Association of Oral and Maxillofacial Surgeons) Annual Meeting, Orlando, FL 2013 Invited Lecturer, 10th Annual Lectureship in Oral & Maxillofacial Surgery, UAB 2014 American College of Rheumatology RRF/AMGEN Pediatric Rheumatology Visiting Professor 2014 Invited Lecturer, EuroTMjoint Meeting, Tampere, Finland

Society Memberships
Organization Name Position Held Org Link
Alabama Society for the Rheumatic Diseases   President 2012-2014   
American Association of Immunologists  Clinical Immunology Committee (2007-2010)  http://www.aai.org/ 
American College of Rheumatology  Juvenile Idiopathic Arthritis Treatment Guidelines, Core Expert Panel member   http://www.rheumatology.org/ 
Arthritis Foundation  Board of Directors, Southeast Region   http://www.arthritis.org/ 
Arthritis Foundation  Southeast Region Board of Directors (2010-2015)  http://www.arthritis.org/alabama/ 
Childhood Arthritis & Rheumatology Research Alliance (CARRA)   Regional Liason to Arthritis Foundation  http://www.carragroup.info/ 
EURO TMJoint  Medical Treatment Subcommittee  http://eurojoint.eu/ 
OMERACT  TMJ Arthritis MRI Reader  http://www.omeract.org/ 
Pediatric Rheumatology Collaborative Study Group     http://www.prcsg.org/ 
Society for Pediatric Research   Abstract Selection Committee  http://www.aps-spr.org/spr/default.htm 
 



Research/Clinical Interest
Title
CD4 T Lymphocyte Transcriptional Regulation
Description
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. Macrophage activation syndrome (MAS) is an often lethal complication of many rheumatic diseases. Recent advances suggest that cytotoxic defects in CD8 T cells and NK cells exist in MAS, similar to familial hemophagocytic lymphohistiocytosis (fHLH). fHLH is caused by homozygous defects in genes involved in the lymphocyte cytolytic pathway (e.g. perforin, syntaxin 11, STXBP2, MUNC13-4, RAB27A). We have identified several MAS patients with single copy mutations in these same fHLH genes and demonstrate that they alter NK cell lysis in a partially dominant negative fashion by delaying cytotoxic granule release. Some of these mutations are common in up to 3-4% of the North American population. Screening for these mutations may be valuable in the near future to identify individuals at risk for developing MAS. In addition, immunosuppressive therapy with the IL-1 blockade could be administered to help combat the lethal nature of MAS.

Selected Publications 
Publication PUBMEDID
IL-15 prolongs CD154 expression on human CD4 T cells via STAT5 binding to the CD154 transcriptional promoter.

Lowe RM, Genin A, Orgun N, Cron RQ.

Genes Immun. 2014 Apr-May;15(3):137-44. 		 24500400 
Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation.

Duverger A, Wolschendorf F, Anderson JC, Wagner F, Bosque A, Shishido T, Jones J, Planelles V, Willey C, Cron RQ, Kutsch O.

J Virol. 2014 Jan;88(1):364-76. 		 24155393 
MHCII is required for alpha-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration.

Harms AS, Cao S, Rowse AL, Thome AD, Li X, Mangieri LR, Cron RQ, Shacka JJ, Raman C, Standaert DG.

J Neurosci. 2013 Jun 5;33(23):9592-600 		 23739956 
An AP-1 binding site in the enhancer/core element of the HIV-1 promoter controls the ability of HIV-1 to establish latent infection.

Duverger A, Wolschendorf F, Zhang M, Wagner F, Hatcher B, Jones J, Cron RQ, van der Sluis RM, Jeeninga RE, Berkhout B, Kutsch O.

J Virol. 2013 Feb;87(4):2264-77. 		 22955471 
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. 		 22875803 
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. 		 22589268 
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. 		 22418018 
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.  		 21452260 
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. 		 21280009 
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. 		 20693540 
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. 		 20506525 
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. 		 19564342 
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. 		 19144703 
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. 		 18829063 
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. 		 18719603 
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. 		 18383394 
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.  		 17343315 
 

Keywords
Lupus, HIV-1, CD4 T Cell, Transcription, Nuclear Factor of Activated T Cells, Macrophage Activation Syndrome, Temporomandibular Joint (TMJ)