My laboratory is investigating two topics. First, we are investigating the molecular mechanisms involved in lipoprotein uptake by the LDL receptor. This receptor is responsible for the clearance of atherogenic lipoproteins such as LDL, VLDL and VLDL remnants, which are the carriers of so-called "bad" cholesterol in the blood. Current projects are exploring the role of adaptor proteins that mediate LDLR internalization and the mechanisms by which the LDLR releases lipoproteins in endosomes prior to their degradation in lysosomes. The second topic encompasses structural studies of proteins containing repeating amino acid sequences. The purpose of this project is to understand the relationships between sequence, structure and function with the goal of developing designed proteins that can be employed to combat human disease. A current project is developing designed proteins for use in targeting therapeutic agents to atherosclerotic lesions, which are the principal cause of heart attack and stroke.
Protein structure - proteins containing repeating amino acid motifs
RECENT PUBLICATIONS
Garuti R, Jones C, Li WP, Michaely P, Herz J, Gerard RD, Cohen JC, Hobbs HH, "The modular adaptor protein ARH promotes LDLR clustering into clathrin-coated pits" J. Biol. Chem., 280:40996, December 2005
Lee G, Abdi K, Jiang Y, Michaely P, Bennett V, Marszalek PE, "Nanospring behaviour of ankyrin repeats" Nature, 440:246-9, March 2006
Jones C, Garuti R, Michaely P, Li WP, Maeda N, Cohen JC, Herz J, Hobbs HH, "Disruption of LDL but not VLDL clearance in autosomal recessive hypercholesterolemia" J. Clin. Invest., 117:165-74, January 2007
Michaely P, Zhao Z, Li WP, Garuti R, Huang LJ, Hobbs HH, Cohen JC, "Identification of a VLDL-induced, FDNPVY-independent internalization mechanism for the LDLR" EMBO J., 26:3273, July 2007
Yu L, Bharadwaj S, Brown JM, Ma Y, Du W, Davis MA, Michaely P, Liu P, Willingham MC, Rudel LL, "Cholesterol-regulated translocation of NPC1L1 to the cell surface facilitates free cholesterol uptake" J. Biol. Chem., 281:6616-24, March 2006
SIGNIFICANT PUBLICATIONS
Michaely P, Kamal A, Anderson RG, Bennett V, "A requirement for ankyrin binding to clathrin during coated pit budding" J. Biol. Chem., 274:35908-13, October 1999
Michaely P, Tomchick DR, Machius M, Anderson RG, "Crystal structure of a 12 ANK repeat stack from human ankyrinR" EMBO J., 21:6387-96, December 2002
Michaely P, Li WP, Anderson RG, Cohen JC, Hobbs HH., "The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits" J. Biol. Chem., 279:34023-31, August 2004
Lee G, Abdi K, Jiang Y, Michaely P, Bennett V, Marszalek PE, "Nanospring behaviour of ankyrin repeats" Nature, 440:246-9, March 2006
Michaely P, Zhao Z, Li WP, Garuti R, Huang LJ, Hobbs HH, Cohen JC, "Identification of a VLDL-induced, FDNPVY-independent internalization mechanism for the LDLR" EMBO J., 26:3273-82, July 2007
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