Overview

Sylvia Christakos received her Ph.D. from the State University of New York (SUNY) at
Buffalo School of Medicine. She completed postdoctoral training at the Roswell Park
Cancer Institute, Buffalo, NY, at SUNY Buffalo School of Medicine Dept. of
Biochemistry and at the University of California, Riverside Dept. of Biochemistry.
She joined UMDNJ? New Jersey Medical School in 1980. She is a Professor in the Dept.
of Biochemistry and Molecular Biology. Dr. Christakos has received continuous
funding from the NIH for the past 30 years. Her laboratory is one of the leading
laboratories in research related to vitamin D, its function and mechanism of action.

Education

PHD, 1973, State University of New York at Buffalo
M.A., 1970, State University of New York at Buffalo
B.S., 1967, College of Mt. St. Vincent

Curriculum Vitae

View CV

Languages

Greek

Relevant Publications

Joshi, S., Pantalena, L. C. Liu, X.K., Gaffen, S. L., Liu, H. Rohowsky-Kochan, C., Ichiyama, K., Yoshimura, A., Steinman, L., Christakos, S. and Youssef, S. 1,25(OH)2D3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol. Cell Biology 31: 3653-69 (2011). (Christakos, S, corresponding author)

Christakos, S. In search of regulatory circuits that control the biological activity of vitamin D. J Biol chem. 292: 17559-17560, (2017)

Dhawan, P. Veldurthy, V., Yehia, G. Hsaio, C. Porta, A. Kim, K-i, Patel, N. Lieben, L. Verlinden, L. Carmeliet , G. Christakos, S. Transgenic expression of the vitamin D receptor restricted to the ileum, cecum and colon of vitamin D receptor knockout mice rescues vitamin D receptor dependent rickets. Endocrinology 158: 3792- 3804, 2017

Wei, R., Dhawan, P., Baiocchi, Ra, Kim, KY, Christakos, S. PU.1 and epigenetic signals modulate 1,25(OH)2D3 and C/EBPalpha regulation of the human cathelicidin antimicrobial peptide gene in lung epithelial cells. J. Cell Physiol. 234, 10345-10539, 2019.

Christakos, S., Dhawan, P., Verstuyf, A., Verlinden, L. and Carmeliet, G. Vitamin D: metabolism, molecular mechanism of action and pleiotropic effects. Physiol Rev 96: 365- 408, 2016

Seth-Vollenweider, T., Joshi, S., Dhawan, P. Sif, S. and Christakos, S. Novel mechanism of negative regulation of 1,25-dihydroxyvitamin D3 induced 25- hydroxyvitamin D3 24-hydroxylase (CYP24a1) transcription: epigenetic modification involving cross talk between protein-arginine methyltransferase 5 and the SWI/SNF complex. J Biol Chem 289: 33958-70, 2014.

Bhatt, K., Rafi, W. Shah, N. Christakos, S. and Salgame, P. 1,25(OH)2D3 treatment alters granulomatous response in M. tuberculosis infected mice. Sci Rep 6: 34469, 2016.

Mady, LJ, Ajibade, DV, Hsaio, C., Teichert, A., Fong, C. Wang, Y. Christakos, S. and Bikle, DD. The transient role for calcium and vitamin D during the developmental hair follicle cycle. J. Invest. Dermatol. 136: 1337-1345, 2016.

Pike, J.W. and Christakos, S. Biology and mechanism of action of the vitamin D hormone. Endocrinol Metab Clin North Am 46: 815-843, 2017.

Bikle, D. and Christakos, S. New aspects of vitamin D metabolism and action addressing the skin as a source and target. Nature Reviews Endocrinology submitted 2019

Areas Of Interest

TRPV6

Vitamin D

calbindin

epigenetics

osteoporosis

transcription

vitamin D and the immune system

Course List

GSND5501Q

Medical Biochem & Genetics

Vitamin D: Function and Regulation

My lab has investigated the mechanisms by which inadequate vitamin D status contributes to osteoporosis (the principal focus of my research) as well as the possible role of vitamin D in cancer, in immunity and in autoimmune diseases.
The actions of 1,25(OH)2D3 are mediated by the VDR which together with coregulatory proteins interacts with vitamin D response elements in the DNA of vitamin D target genes resulting in increased synthesis of proteins involved in the maintaining calcium balance. My lab has shown that tissue and gene specific functions of 1,25(OH)2D3 are mediated by differential recruitment of coregulatory proteins to the VDR as well as to epigenetic control (inheritable changes in gene expression that are not mediated at the DNA sequence level). My lab is currently examining molecular level changes in kidney and intestine that are involved in the dysregulation of calcium homeostasis that occurs with aging. The long term goal is to define molecular pathways of vitamin D action in order to reveal new therapeutic strategies to sustain calcium balance. Identification of the most effective vitamin D analog to prevent or reverse deterioration of calcium homeostasis through transcriptional and epigenomic mechanisms may have long term implications for how bone diseases, particularly osteopenia and osteoporosis, are treated.
Non-classical actions of 1,25(OH)2D3 include effects on the immune system. Recent studies in my lab, in collaboration with the L. Steinman (Stanford University), have shown a direct suppression by 1,25(OH)2D3 of IL-17, a cytokine that has been reported to play a role in the pathogenesis of autoimmune inflammation. We have also shown reversal of paralysis and inhibition of progression of EAE [a murine model of multiple sclerosis (MS)] by 1,25(OH)2D3 which is associated with an inhibition of IL-17. The mechanism of suppression of IL-17 by 1,25(OH)2D3 involves, at least in part, a competition of VDR with NFAT (a transcription factor which activates IL-17). Since clinical trials are being done treating MS patients with high dose vitamin D, we are currently examining the effect of high dose dietary vitamin D (in combination with interferon beta, an approved treatment for MS) on paralysis, on the progression of EAE and on the production of IL-17 and other cytokines. 1,25(OH)2D3 not only regulates adaptive but also innate immunity. 1,25(OH)2D3 induces the antimicrobial peptide cathelicidin, with subsequent killing of bacteria. Recently we found that C/EBPa is a potent enhancer of cathelicidin antimicrobial peptide gene transcription and that C/EBPa functionally cooperates with the VDR to regulate cathelicidin in lung epithelial cells. In collaboration with Dr. Gill Diamond at UMDNJ, we are examining the ability of 1,25(OH)2D3 to defend against lung infections in a mouse model. We also plan to examine global networks regulated by VDR to promote the host response to pathogen.
In conclusion, studies related to mechanisms of 1,25(OH)2D3 action, including genome-wide action, will result in new insight in both skeletal and non-skeletal actions of vitamin D that may suggest therapeutic targets. Although, unlike rickets, there is not a causal link between vitamin D deficiency and certain diseases such as cancer and MS, evidence of beneficial effects of 1,25(OH)2D3 beyond bone is convincing. Findings in animal models may suggest pathways in humans that could lead to new therapies.