John White - Professor & Chair

Research Area:  Cell and Molecular Biology

Research Description:

The White laboratory focuses on the physiological implications of signaling through various ligand-regulated transcription factors, most recently the vitamin D receptor (VDR) and the aryl hydrocarbon receptor (AHR). Vitamin D is obtained naturally from limited dietary sources or photochemical conversion in skin exposed to adequate levels of ultraviolet B radiation. The active form of vitamin D induces DNA binding, and controls transcriptional regulation by the VDR, thus acting as a “gene switch”. The lab was the first to use microarray technology to study gene regulation by vitamin D to investigate the mechanisms underlying its physiological effects. Collectively, this work has identified over 1000 novel target genes of vitamin D signaling. It also opened up the field of study of vitamin D as a regulator of human innate immunity, which has implications for roles of vitamin D sufficiency in protection against upper respiratory tract infections and defects in innate immune homeostasis such as the inflammatory bowel condition Crohn’s disease. The laboratory has also made several seminal contributions to understanding the molecular basis of the putative cancer-preventive activities of vitamin D, work that has been borne out by recent meta-analyses of the results of large-scale RCTs of vitamin D supplementation. More recently, we have been studying the AHR, which functions as an environmental sensor and has emerged as a key regulator of immunity. The AHR can be regulated by ligands produced by the photochemical effects of ultraviolet irradiation, and our recent work has shown that the AHR can be activated systemically by exposure of skin to moderate levels of UV light.

Education: B.Sc., MSc. (Chemistry), Carleton, Ph.D. (Biochemistry), Harvard

Selected Recent Publications:

Tavera-Mendoza, L. and White, J.H. (2007) Cell defenses and the sunshine vitamin. Scientific American. November 297, 62-72.

Tavera-Mendoza, L.E., Quach, T., Dabbas, B., Hudon, J., Liao, X., Palijan, A., Gleason, J.L., and White, J.H. (2008) Incorporation of histone deacetylase inhibition into the structure of a nuclear receptor agonist. Proc. Nat. Acad. Sci. U.S.A. 105, 8250-55.

Wang, T.T, Dabbas, B., Laperriere, D., Bitton, A., Tavera-Mendoza, L.E., Soualhine, H., Dionne, S., Servant, M.J., Bitton, A., Seidman, E., Mader, S., Behr, M. and White, J.H. (2010) Direct and indirect induction by 1,25-dihydroxyvitamin D₃ of the NOD2/CARD15-beta defensin 2 innate immune pathway defective in Crohn’s disease. J. Biol. Chem. 285, 2227 – 2231.

An, B.-S., Tavera-Mendoza, L.E., Dimitrov, V., Wang, X., Calderon, M., Wang, H.-J., and White, J.H. (2010) Stimulation of SIRT1-regulated FoxO protein function by the ligand-bound vitamin D receptor. Mol. Cell. Biol. 30, 4890-4900.

Fisher, J., Wang, T.T., Kaldre, D., Rochel, N., Moras, D., White, J.H.*, Gleason J.L.* (2012) Synthetically accessible non-secosteroidal hybrid molecules combining vitamin D receptor agonism and histone deacetylase inhibition. Chemistry & Biology 19, 963-71.

Salehi-Tabar, R., Nguyen-Yamamoto, L., Tavera-Mendoza, L.E., Quail, T., Dimitrov, V., An, B.-S., Glass, L., Goltzman, D. and White, J.H. (2012) The vitamin D receptor as a master regulator of the cMYC/MXD1 network. Proc. Nat. Acad. Sci. U.S.A. 109, 18827-32.

Verway, M., Bouttier, M., Wang, T.T., Carrier, M., Calderon, M., An, B.-S., Devemy, E., McIntosh, F., Divangahi, M., Behr, M.A. and White, J.H. (2013) Vitamin D induces interleukin-1b expression: Paracrine macrophage-epithelial signaling controls M. tuberculosis infection. PLoS Pathogens 9(6): e1003407. doi:10.1371/journal.ppat.1003407

White, J.H. (2013) Vitamin D and human health: More than just bone. Nature Rev. Endocrinol. 9(10), 623.

Calderon, M. Verway, M., Benslama, R.O., Birlea, M., Bouttier, M., Dimitrov, V., Mader, S., and White, J.H. (2014) Ligand-dependent corepressor contributes to transcriptional repression by C₂H₂ zinc-finger transcription factor ZBRK1 through association with KRAB-associated protein-1. Nucl. Acids Res. 42, 7012-27.

Memari, B., Bouttier, M., Dimitrov, V., Behr, M.A., Fritz, J.H., and White, J.H. (2015) Engagement of aryl hydrocarbon receptor signaling by M. tuberculosis-infected macrophages. J. Immunol. 195, 4479-91.

Bouttier, M., Laperriere, D., Memari, B., Verway, M., Fiore, A, Mitchell, E., Wang, T.T., Sladek, R., Behr, M., Mader, S. and White, J.H. (2016) Alu repeats as transcriptional regulatory platforms in macrophage responses to M. tuberculosis infection. Nucl. Acid. Res. 44, 10571-87.

Dimitrov, V., Bouttier, M., Boukhaled, G., Salehi-Tabar R., Memari, B., Hasaj, B., Krawczyk, C.M. and White, J.H. (2017) Species- and tissue-specific induction of PD-L1 and PD-L2 expression by hormonal vitamin D. J. Biol. Chem. 292, 20657-20668.

Salehi-Tabar, R., Memari, B., Wong, H. Rochel, N. and White, J.H. (2019) The E3 ligase FBW7 and the vitamin D receptor are mutual cofactors in protein turnover and transcriptional regulation. Mol. Cancer Res. 17, 709-719.

Memari, B., Nguyen-Yamamoto, L., Salehi-Tabar, R., Zago, M., Fritz, J., Baglole, C.J., Goltzman, D., and White, J.H. (2019) Endocrine aryl hydrocarbon receptor signaling is induced by moderate cutaneous exposure to ultraviolet light. Sci. Reports 9, 8486. doi.org/10.1038/s41598-019-44862-4

Link to Dr. White's publications