Molecular Pharmacology Program
The Richard Kolesnick Lab
Our laboratory focuses on the role of sphingolipid signaling as a stress response. In this pathway, generation of the second messenger ceramide in response to diverse environmental and pharmacologic stresses (heat, ionizing radiation, ultraviolet light, chemotherapeutic agents, oxidative challenges, etc.) occurs either by degradation of sphingomyelin or by de novo synthesis. The quality and quantity of the ceramide response, in combination with other signals, determines whether adaptation or apoptosis ensues. This pathway is evolutionarily conserved and is obligate for the heat shock response in yeast.
Bodo S, Campagne C, Thin TH, Higginson DS, Vargas HA, Hua G, Fuller JD, Ackerstaff E, Russell J, Zhang Z, Klingler S, Cho H, Kaag MG, Mazaheri Y, Rimner A, Manova-Todorova K, Epel B, Zatcky J, Cleary CR, Rao SS, Yamada Y, Zelefsky MJ, Halpern HJ, Koutcher JA, Cordon-Cardo C, Greco C, Haimovitz-Friedman A, Sala E, Powell SN, Kolesnick R, Fuks Z. Single-dose radiotherapy disables tumor cell homologous recombination via ischemia/reperfusion injury. J Clin Invest. 2018; pii: 97631.
Martin ML, Zeng Z, Adileh M, Jacobo A, Li C, Vakiani E, Hua G, Zhang L, Haimovitz-Friedman A, Fuks Z, Kolesnick R*, Paty PB*. Logarithmic expansion of LGR5+ cells in human colorectal cancer. Cell Signal. 2018; 42:97-105. doi: 10.1016/j.cellsig.2017.09.018. * Equal co-author.
Van Hell AJ, Haimovitz-Friedman A, Fuks Z, Tap WD, Kolesnick R. Gemcitabine kills proliferating endothelial cells exclusively via acid sphingomyelinase activation. Cell Signal. 2017; 34:86-91. doi: 10.1016/j.cellsig.2017.02.021.
Zhang L, Adileh M, Martin ML, Klingler S, White J, Ma X, Howe LR, Brown AM, Kolesnick R. Establishing estrogen-responsive mouse mammary organoids from single Lgr5+ cells. Cell Signal. 2017; 29:41-51. doi: 10.1016/j.cellsig.2016.08.001.
Richard N. Kolesnick, MD
- Physician-scientist Richard Kolesnick studies the role of ceramide signaling in radiation-induced vascular dysfunction and tumor regression.
- MD, University of Chicago School of Medicine
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Richard N. Kolesnick discloses the following relationships and financial interests:
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