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