Theodore L. Steck, MD Theodore L. Steck
Membrane cholesterol biochemistry and cholesterol homeostasis

Professor Emeritus, Biochemistry and Molecular Biology,
Molecular Genetics and Cell Biology

B.S., Lawrence College, 1960
M.D., Harvard Medical School, 1964

 

Research Summary

My long-term research interest is in membrane biochemistry. Over the years, I have studied the molecular organization of the human red cell membrane and several aspects of the cell biology of the ameba, Dictyostelium discoideum. In addition, the disposition of cell cholesterol has been a recurrent focus. We are currently investigating cellular cholesterol homeostasis: how cells sense their need for this essential plasma membrane lipid and make appropriate adjustments to keep it in balance. We suggest that cells gauge the magnitude of the bulk pool of cholesterol in the plasma membrane by sensing the high activity of the cholesterol in excess of phospholipids. This active excess sets the size of the sterol pool in the endoplasmic reticulum and mitochondria through the flow of cholesterol between the cell surface and intracellular membranes. The endoplasmic reticulum pool then sets the level of activity of several regulatory elements in its membrane that mediate sterol homeostasis while the mitochondria convert cholesterol to oxysterols that serve as messengers of cholesterol excess. The elements of this cholesterol sensing system and how it can be manipulated are under investigation.


Selected Publications

Lange, Y. and Steck, T.L. (2016). Active membrane cholesterol as a physiological effector. Chem Phys Lipids. pii: S0009-3084(16)30015-9. doi: 10.1016/j.chemphyslip.2016.02.003. (PubMed)

Czyz DM, Potluri LP, Jain-Gupta N, Riley SP, Martinez JJ, Steck TL, Crosson S, Shuman HA, Gabay JE. Host-directed antimicrobial drugs with broad-spectrum efficacy against intracellular bacterial pathogens. MBio. 2014; 5(4):e01534-14. (PubMed)

Lange Y, Ye J, Steck TL. Essentially all excess fibroblast cholesterol moves from plasma membranes to intracellular compartments. PLoS One. 2014; 9(7):e98482. (PubMed)

Tietjen GT, Gong Z, Chen CH, Vargas E, Crooks JE, Cao KD, Heffern CT, Henderson JM, Meron M, Lin B, Roux B, Schlossman ML, Steck TL, Lee KY, Adams EJ. Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4. Proc Natl Acad Sci U S A. 2014 Apr 15; 111(15):E1463-72. (PubMed)

Lange Y, Tabei SM, Ye J, Steck TL. Stability and stoichiometry of bilayer phospholipid-cholesterol complexes: relationship to cellular sterol distribution and homeostasis. Biochemistry. 2013 Oct 8; 52(40):6950-9. (PubMed)

Lange, Y., Ye, J., and Steck, T.L. (2012) Activation mobilizes the cholesterol in the late endosomes-lysosomes of Niemann Pick Type C cells. PLoS One 7, e30051. (PubMed)

Steck, T.L., and Lange, Y. (2010) Cell cholesterol homeostasis: Mediation by active cholesterol. Trends in Cell Biology 20, 680-687. (PubMed)

Lange, Y., Ye, J., Duban, M.-E., and Steck, T. L. (2009) Activation of Membrane Cholesterol by 63 Amphipaths. Biochemistry 48, 8505-8515. (PubMed)

Lange, Y., Steck, T. L., Ye, J., Lanier, M. H., Molugu, V., and Ory, D. (2009) Regulation of fibroblast mitochondrial 27-hydroxycholesterol production by active plasma membrane cholesterol. Journal of Lipid Research 50, 1881-1888. (PubMed)

Lange, Y., and Steck, T.L. (2008). Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol. Prog Lipid Res 47, 319-332. (PubMed)

Lange, Y., Ory, D.S., Ye, J., Lanier, M.H., Hsu, F.-F., and Steck, T.L. (2008). Effectors of Rapid Homeostatic Responses of Endoplasmic Reticulum Cholesterol and 3-Hydroxy-3-methylglutaryl-CoA Reductase. J Biol Chem 283, 1445-1455. (PubMed)

Ratajczak, M.K., Ko, Y.T.C., Lange, Y., Steck, T.L., and Lee, K.Y.C. (2007). Cholesterol Displacement from Membrane Phospholipids by Hexadecanol. Biophys J 93, 2038-2047. (PubMed)

Lange Y, Ye J, Steck TL. (2007). Scrambling of phospholipids activates red cell membrane cholesterol. Biochemistry. 46(8):2233-8. (PubMed)

 

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