Transcriptional regulation of cytokine genes and HIV-1 in primary CD4 T lymphocytes
Research Techniques: Tissue culture, molecular cloning, primary (mouse and human) T cell transfection, transgene preparation, flow cytometry, DNA/RNA and protein analysis, nuclear run-on assays, chromatin immunoprecipitation, DNase I hypersensitive site mapping, luciferase reporter gene assays, HIV-1 infection and monitoring.
Our lab's research interests are focused on the role of transcription factors in human immunodeficiency virus type-1 (HIV-1) and cytokine gene transcription in normal human adult peripheral blood and neonatal CD4 T cells. We are studying the role of nuclear factor of activated T cells (NFAT), and c-Maf transcriptional activator proteins in HIV-1 gene expression, and related cytokine gene expression, in neonates and adults. Regulating the transcriptional machinery of host CD4 T cells may lead to alternative approaches in the therapy of HIV-1 infection.
One clear difference between naïve neonatal and adult CD4 T cells is their ability to express CD40-ligand (CD40L, CD154). This appears to be controlled at the level of transcription, and the lack of NFAT1 proteins in the neonate may contribute to this deficiency in CD40L expression. A large part of our research effort is devoted to understanding the transcriptional regulation of the CD40L gene, particularly as it relates to decreased expression in the neonate and to increased expression in patients with systemic lupus erythematosus (SLE). Understanding the transcriptional mechanisms, which contribute to increased and prolonged expression of CD40L on CD4 T cells from patients with SLE, could lead to novel approaches in the therapy of SLE.
Lab rotation projects for graduate students
1. Role of NFAT1 transcription factor in vivo using conditional transgenic expression.
2. Characterize novel CD40-ligand transcriptional regulatory elements in lupus.
3. Role of the c-maf transcription factor in HIV-1 gene transcription.
4. Analysis of Egr transcription factors in NFAT2 regulation.
Current Lab Personnel
Anna Genin, Research Specialist (M.D., Kiev Medical School, Ukraine)
Michael Brunner, Assistant Member, Stokes Institute (Ph.D., Pennsylvania State University)
Mingce Zhang, Post-doctoral fellow (Ph.D., Peking Union Medical College)
Shyamala Arunachalam, (Ph.D., University of Madras, Guindy Campus)
- Assistant Professor of Pediatrics at University of Pennsylvania School of Medicine (1999 – 2007)
- M.D., Medicine, University of California at Los Angeles (1991)
- Ph.D., Immunology, University of Chicago (1990)
- B.S., Biomedical Sciences, with Honors, University of California at Riverside (1985)
- Hamilton, B.J., Genin, A., Cron, R.Q., and Rigby, W.F.C.. Delineation of a novel pathway that regulates CD154 (CD40 Ligand) expression.. Mol. Cell. Biol.. Vol 23. 2003:510-525.
- Cron, R.Q.. Regulation of CD154 expression in lupus.. Lupus News. Vol 23. 2003:33.
- DeWitt, E.M., Cron, R.Q., Finkel, T.H., and Meyers, K.. Treatment quandary: proliferative glomerulonephritis ? lupus versus hepatitis B infection (abstract).. Pediatric Rheumatology International Meeting. Snowmass, CO, Pediatr. Rheumatol. Online J., in press.. 2003.
- DeWitt, E.M., Kaye, R., Towbin, R., and Cron, R.Q.. Temporomandibular joint corticosteroid injections in juvenile rheumatoid arthritis (abstract).. Pediatric Rheumatology International Meeting. Snowmass, CO, Pediatr. Rheumatol. Online J., in press.. 2003.
- Burnham, J.M., and Cron, R.Q.. Sweet syndrome in a child with lupus and subsequent secondary sjogren syndrome (abstract).. Pediatric Rheumatology International Meeting. Snowmass, CO, Pediatr. Rheumatol. Online J., in press.. 2003.
- Burnham, J.M., Cron, R.Q., Finkel, T.H., and Leonard, M.B.. Osteopenia in juvenile rheumatoid arthritis: altered regulation of osteoclastogenesis (abstract).. Pediatric Rheumatology International Meeting. Snowmass, CO, Pediatr. Rheumatol. Online J., in press.. 2003.
- Cron, R.Q., Brunner, M., and Genin, A.. Regulation of CD154 in pediatric systemic lupus erythematosus (abstract).. Pediatric Rheumatology International Meeting. Snowmass, CO, Pediatr. Rheumatol. Online J., in press. [podium presentation]. 2003.
- Cron, R.Q., Genin, A., and Brunner, M.. Identification of a novel GATA-regulated CD154 transcriptional enhancer (abstract).. Pediatr. Res. (oral presentation). Vol 53. 2003:17A.
- Cron, R.Q., Bandyopadhyay, R., Genin, A., Brunner, M., Kersh, G.J., and Crow, M.K.. Egr-1 regulates CD154 transcription (abstract).. Arthritis Research Conference, Keystone, CO, accepted. [oral presentation]. 2003.
- Hamilton, B.J., Genin, A., Cron, R.Q., and Rigby, W.F.C.. CD154 (CD40 Ligand) expression is regulated through a unique post-transcriptional pathway (abstract).. Arthritis Research Conference, Keystone, CO, accepted. [oral presentation by Dr. Rigby]. 2003.