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Faculty Detail    
Name JERE P SEGREST
 
Campus Address BDB 630 Zip 0012
Phone  (20-5) -420
E-mail  segrest@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Center  Comprehensive Diabetes Center  Comprehensive Diabetes Center Professor Emeritus
Primary  Medicine  Med-Gerontology/Geriatrics/Palliative Care Professor Emeritus

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Biochemistry and Structural Biology 
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Medical Scientist Training Program 

Biographical Sketch 
Jere P. Segrest (b. 1940) obtained his B.A., M.D. and Ph.D. (Biochemistry) at Vanderbilt Univer­sity. Postdoctoral studies at NIH resulted in elucidation of the hydrophobic a helical transmembrane domain of glycophorin, the first transmembrane protein so characterized, and development of the theory of the arnphipathic a helix. In recent years his lab developed the first detailed molecular models for HDL and for the assembly of apo B-containing lipoproteins and is currently working on a detailed molecular model for LDL. His team approaches these research topics through use of computer-based molecular modeling and dynamics, rational design and syn­thesis of peptide analogs, and over-expression of rationally designed site-directed mutant human apolipoproteins in cells in culture and in transgenic mouse models. He is presently the Director of the Atherosclerosis Research Unit and the Atherosclerois Reversal and Lipid Clinic. Outside inter­ests include reading classical Greek and Roman history and science fiction and bicycling.



Research/Clinical Interest
Title
Structural Biology of Supramolecular Assemblies (Particularly Lipoproteins and Membranes)
Description
Dr. Segrest is a Professor of Medicine, Biochemistry and Molecular Genetics and Pathology, Direc­tor of the Atherosclerosis Research Unit and Director of the Atherosclerosis Reversal and Lipid Clinic. He is the Program Director for an NHLBI Program Project, P01HL34343, “Amphipathic Motifs, Lipoproteins And Atherosclerosis” that focuses on development of a comprehensive theory of the interaction of amphipathic motifs with lipid to: (a) determine the minimal structural features of apoA-I that can prevent and/or reverse atherosclerosis, (b) determine the minimal structural fea­tures of apoB that are involved in both the biosynthesis of apoB-containing lipoproteins and the structure, function and properties of LDL, and (c) apply this knowledge to understand mechanisms involved in prevention and reversal of atherosclerosis and potentially for the development of phar­macological agents. Proteins that insert into membrane lipids are fundamental to biology and medicine. Dr. Segrest’s research goals have been guided by a recognition that lipid-water interfaces leave a signature in those proteins evolutionarily adapted to interact with lipids. Two "lipid signatures" have been discovered by his research program, the amphipathic ? helix (1) and the amphipathic ? sheet (2). These two "lipid signatures" are being used in three separate studies of the structural biology of plasma lipoproteins. i)He developed the first detailed molecular model for HDL and is currently testing the model by site-directed mutagenesis and molecular dynamics simulations. ii) He developed a molecular model for the assembly of apoB-containing particles and is currently testing the model by site-directed mutagenesis and molecular modeling. iii) Finally, he is in the process of developing a detailed molecular model for LDL. His team approaches these research topics through use of computer-based molecular modeling and dynamics, rational design and synthesis of peptide analogs, and over-expression of rationally designed site-directed mutant human apolipoproteins in E. coli, in mammalian cells in culture, and in transgenic mouse models of atherosclerosis.

Selected Publications 
Publication PUBMEDID
Dashti, N., Gandhi, M., Liu, X., Lin, X., and Segrest, J. P. (2002). The N-terminal 1000 residues of apolipoprotein B associate with microsomal triglyceride transfer protein to create a lipid transfer pocket required for lipoprotein assembly. Biochemistry 41, 6978-87.  12033930 
Segrest, J. P., Jones, M. K., De Loof, H., and Dashti, N. (2001). Structure of apolipoprotein B-100 in low density lipoproteins. J Lipid Res 42, 1346-67.  11518754 
Garber, D. W., Datta, G., Chaddha, M., Palgunachari, M. N., Hama, S. Y., Navab, M., Fogelman, A. M., Segrest, J. P., and Anantharamaiah, G. M. (2001). A new synthetic class A amphipathic pep­tide analogue protects mice from diet-induced atherosclerosis. J Lipid Res 42, 545-552.  11290826 
Segrest, J. P., Li, L., Anantharamaiah, G. M., Harvey, S. C., Liadaki, K. N., and Zannis, V. (2000). Structure and function of apolipoprotein A-I and high-density lipoprotein. Curr Opin Lipidol 11, 105-15.  10787171 
Segrest, J. P., Jones, M. K., Klon, A. E., Sheldahl, C. J., Hellinger, M., De Loof, H., and Harvey, S. C. (1999). A detailed molecular belt model for apolipoprotein A-I in discoidal high density lipopro­tein. J Biol Chem 274, 31755-8.  10542194 
Segrest, J. P., Jones, M. K., and Dashti, N. (1999). N-terminal domain of apolipoprotein B has structural homology to lipovitellin and microsomal triglyceride transfer protein: a "lipid pocket" model for self-assembly of apob-containing lipoprotein particles. J Lipid Res 40, 1401-16.  10428976 
Hristova, K., Wimley, W. C., Mishra, V. K., Anantharamiah, G. M., Segrest, J. P., and White, S. H. (1999). An amphipathic alpha-helix at a membrane interface: a structural study using a novel X-ray diffraction method. J Mol Biol 290, 99-117.  10388560 
Segrest, J. P., Jones, M. K., Mishra, V. K., and Anantharamaiah, G. M. (2002). Experimental and computational studies of the interactions of amphipathic peptides with lipid surfaces. Current Top­ics in Membranes 52, 391-429.