Department of Pathology, Microbiology, and Immunology

  

  Larry L. Swift, Ph.D.

 

 

   Professor

   Dept of Pathology, Microbiology and Immunology

   Director, Investigative Pathology

 

  

  Contact Information

 

 

Office Location:

CC-3327 MCN

Office:  CC-3327 MCN

Phone: 615-343-2646       

E-mail:  larry.swift@vanderbilt.edu

 

Campus Mail address:

Pathology, Microbiology and Immunology-3rd Fl

C-3321 MCN (2561)

 

US Mailing address:

Vanderbilt University School of Medicine

Pathology, Microbiology and Immunology-3rd Fl

C-3321 MCN

Nashville, TN 37232-2561

 

 

 

Education

 

 

Ph.D., Vanderbilt University, Nashville, TN
B.S., Indiana Central College, Indianapolis, IN

 

 

Research Keywords

 

 

Lipid/Lipoprotein Metabolism and Lipoprotein Assembly

 

 

Research Description

 

 

The major interest of the laboratory is the assembly and secretion of plasma very low density lipoproteins (VLDL) by the liver. VLDL transport triglyceride to peripheral tissues for storage and/or utilization. They are the sole precursors of plasma low density lipoproteins (LDL), which have been positively correlated with risk for atherosclerotic heart disease. The assembly of VLDL is a complex process which is initiated in the rough ER, but the steps in the association of apolipoprotein (apo) B, an extremely hydrophobic protein and the major structural protein of VLDL, with lipid are unclear. The goal of our work is to define the steps in the assembly process specifically the mechanisms by which lipid is added to the maturing particle.

A second area of research in our laboratory focuses on apoE, a protein associated with nearly all plasma lipoprotein classes. ApoE mediates the uptake of a number of lipoprotein classes via receptors on the cell surface. It is our hypothesis that some apoE escapes degradation and is recycled, i.e., re-secreted from the cell. Our studies are designed to investigate cell entry points required for recycling, the intracellular pathways involved in recycling, and the physiologic relevance of this process.

 

 

Publications

 

 

Berglund, ED, Kang, L, Lee-Young, RS, Hasenour, CM, Lustig, DG, Lynes, SE, Donahue, EP, Swift, LL, Charron, MJ, Wasserman, DH. Glucagon and lipid interactions in the regulation of hepatic AMPK signaling and expression of PPARalpha and FGF21 transcripts in vivo. Am J Physiol Endocrinol Metab, 299(4), E607-14, 2010

Shearer, J, Coenen, KR, Pencek, RR, Swift, LL, Wasserman, DH, Rottman, JN. Long Chain Fatty Acid Uptake In Vivo: Comparison of [(125)I]-BMIPP and [ (3)H]-Bromopalmitate. Lipids, 43(8), 703-11, 2008

Stafford, JM, Yu, F, Printz, R, Hasty, AH, Swift, LL, Niswender, KD. Central nervous system neuropeptide Y signaling modulates VLDL triglyceride secretion. Diabetes, 57(6), 1482-90, 2008

Lo, CM, Nordskog, BK, Nauli, AM, Zheng, S, Vonlehmden, SB, Yang, Q, Lee, D, Swift, LL, Davidson, NO, Tso, P. Why does the gut choose Apolipoprotein B48 but not B100 for chylomicron formation. Am J Physiol Gastrointest Liver Physiol, 2007

Mohler, PJ, Zhu, MY, Blade, AM, Ham, AJ, Shelness, GS, Swift, LL. Identification of a novel isoform of microsomal triglyceride transfer protein. J Biol Chem, 282(37), 26981-8, 2007

Buchowski, MS, Swift, LL, Akohoue, SA, Shankar, SM, Flakoll, PJ, Abumrad, N. Defects in postabsorptive plasma homeostasis of fatty acids in sickle cell disease. JPEN J Parenter Enteral Nutr, 31(4), 263-8, 2007

Fan, D, Qiu, S, Overton, CD, Yancey, PG, Swift, LL, Jerome, WG, Linton, MF, Fazio, S. Impaired secretion of apolipoprotein E2 from macrophages. J Biol Chem, 2007

Dove, DE, Su, YR, Swift, LL, Linton, MF, Fazio, S. ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages. Atherosclerosis, 186(2), 267-274, 2006

Braun, NA, Mohler, PJ, Weisgraber, KH, Hasty, AH, Linton, MF, Yancey, PG, Su, YR, Fazio, S, Swift, LL. Intracellular trafficking of recycling apolipoprotein E in Chinese hamster ovary cells. J Lipid Res, 47(6), 1176-86, 2006

Dove, DE, Su, YR, Zhang, W, Jerome, WG, Swift, LL, Linton, MF, Fazio, S. ACAT1 deficiency disrupts cholesterol efflux and alters cellular morphology in macrophages. Arterioscler Thromb Vasc Biol, 25(1), 128-34, 2005

Zhu, MY, Hasty, AH, Harris, C, Linton, MF, Fazio, S, Swift, LL. Physiological relevance of apolipoprotein E recycling: studies in primary mouse hepatocytes. Metabolism, 54(10), 1309-15, 2005

Swift, LL, Kakkad, B, Boone, C, Jovanovska, A, Jerome, WG, Mohler, PJ, Ong, DE. Microsomal triglyceride transfer protein expression in adipocytes: a new component in fat metabolism. FEBS Lett, 579(14), 3183-9, 2005

Swift, LL, Jovanovska, A, Kakkad, B, Ong, DE. Microsomal triglyceride transfer protein expression in mouse intestine. Histochem Cell Biol, 123(4-5), 475-82, 2005

Hasty, AH, Plummer, MR, Weisgraber, KH, Linton, MF, Fazio, S, Swift, LL. The recycling of apolipoprotein E in macrophages: influence of HDL and apolipoprotein A-I. J Lipid Res, 46(7), 1433-9, 2005

Ma, Li-Jun, Mao, Su-Li, Taylor, Kevin L, Kanjanabuch, Talerngsak, Guan, YouFei, Zhang, YaHua, Brown, Nancy J, Swift, Larry L, McGuinness, Owen P, Wasserman, David H, Vaughan, Douglas E, Fogo, Agnes B. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes, 53(2), 336-46, 2004

Farkas, MH, Weisgraber, KH, Shepherd, VL, Linton, MF, Fazio, S, Swift, LL. The recycling of apolipoprotein E and its amino-terminal 22 kDa fragment: evidence for multiple redundant pathways. J Lipid Res, 45(8), 1546-54, 2004

Nobuhiko, A, Suganuma, E, Babaev, VR, Fogo, A, Swift, LL, Linton, MF, Fazio, S, Ichikawa, I, Kon, V. Angiotensin II amplifies macrophage-driven atherosclerosis. Arterioscler Thromb Vasc Biol, 24(11), 2143-8, 2004

Farkas, Monica H, Swift, Larry L, Hasty, Alyssa H, Linton, MacRae F, Fazio, Sergio, . The recycling of apolipoprotein E in primary cultures of mouse hepatocytes. Evidence for a physiologic connection to high density lipoprotein metabolism.. J Biol Chem, 278, 9412-7, 2003

Swift, Larry L., Zhu, Mei-Ying, Kakkad, Bharati, Jovanovska, Aneta, Neely, M. Diana, Valyi-Nagy, Klara, Roberts, Richard L., Ong, David E., Jerome, W. Gray, . Subcellular localization of microsomal triglyceride transfer protein (MTP).. J Lipid Res, 45, 1546-1554, 2003

Valyi-Nagy, Klara, Harris, Carla, Swift, Larry L, . The assembly of hepatic very low density lipoproteins: evidence of a role for the Golgi apparatus.. Lipids, 37, 879-84, 2002

Bassett, Casey N, Swift, Larry L, Montine, Kathleen S, Markesbery, William R, Montine, Thomas J. Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentration. J Alzheimers Dis, 4(1), 19-30, 2002

Reich, E E, Markesbery, W R, Roberts, L J, Swift, L L, Morrow, J D, Montine, T J. Brain regional quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease. Am J Pathol, 158(1), 293-7, 2001

Swift, L L, Farkas, M H, Major, A S, Valyi-Nagy, K, Linton, M F, Fazio, S. A recycling pathway for resecretion of internalized apolipoprotein E in liver cells. J Biol Chem, 276(25), 22965-70, 2001

Reich, E E, Markesbery, W R, Roberts, L J, Swift, L L, Morrow, J D, Montine, T J. Quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease. Adv Exp Med Biol, 500, 253-6, 2001

Swift, L L, Valyi-Nagy, K, Rowland, C, Harris, C. Assembly of very low density lipoproteins in mouse liver: evidence of heterogeneity of particle density in the Golgi apparatus. J Lipid Res, 42(2), 218-24, 2001

Fazio, S, Major, A S, Swift, L L, Gleaves, L A, Accad, M, Linton, M F, Farese, R V. Increased atherosclerosis in LDL receptor-null mice lacking ACAT1 in macrophages. J Clin Invest, 107(2), 163-71, 2001

Reich, E E, Montine, K S, Gross, M D, Roberts, L J, Swift, L L, Morrow, J D, Montine, T J. Interactions between apolipoprotein E gene and dietary alpha-tocopherol influence cerebral oxidative damage in aged mice. J Neurosci, 21(16), 5993-9, 2001

Fazio, S, Linton, M F, Swift, L L. The cell biology and physiologic relevance of ApoE recycling. Trends Cardiovasc Med, 10(1), 23-30, 2000

Neely, MD, Swift, LL, Montine, TJ. Human, but not bovine, oxidized cerebral spinal fluid lipoproteins disrupt neuronal microtubules. Lipids, 35(11), 1249-57, 2000

Bassett, C N, Montine, K S, Neely, M D, Swift, L L, Montine, T J. Cerebrospinal fluid lipoproteins in Alzheimer's disease. Microsc Res Tech, 50(4), 282-6, 2000

Fazio, S, Linton, M F, Hasty, A H, Swift, L L. Recycling of apolipoprotein E in mouse liver. J Biol Chem, 274(12), 8247-53, 1999

Bassett, C N, Neely, M D, Sidell, K R, Markesbery, W R, Swift, L L, Montine, T J. Cerebrospinal fluid lipoproteins are more vulnerable to oxidation in Alzheimer's disease and are neurotoxic when oxidized ex vivo. Lipids, 34(12), 1273-80, 1999

Hasty, A H, Linton, M F, Swift, L L, Fazio, S. Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance. J Lipid Res, 40(8), 1529-38, 1999

Montine, TJ, Montine, KS, Olson, SJ, Graham, DG, Roberts, LJ, Morrow, JD, Linton, MF, Fazio, S, Swift, LL. Increased cerebral cortical lipid peroxidation and abnormal phospholipids in aged homozygous apoE-deficient C57BL/6J mice. Exp Neurol, 158(1), 234-41, 1999

Montine, K S, Bassett, C N, Ou, J J, Markesbery, W R, Swift, L L, Montine, T J. Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins. J Lipid Res, 39(12), 2443-51, 1998

Morrow, JD, Roberts, LJ, Daniel, VC, Awad, JA, Mirochnitchenko, O, Swift, LL, Burk, RF. Comparison of formation of D2/E2-isoprostanes and F2-isoprostanes in vitro and in vivo--effects of oxygen tension and glutathione. Arch Biochem Biophys, 353(1), 160-71, 1998

Hada, T, Swift, LL, Brash, AR. Discovery of 5R-lipoxygenase activity in oocytes of the surf clam, Spisula solidissima. Biochim Biophys Acta, 1346(2), 109-19, 1997

Montine, TJ, Montine, KS, Swift, LL. Central nervous system lipoproteins in Alzheimer''s disease. Am J Pathol, 151(6), 1571-5, 1997

Sindelar, DK, Chu, CA, Rohlie, M, Neal, DW, Swift, LL, Cherrington, AD. The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog. Diabetes, 46(2), 187-96, 1997

Swift, L L. Role of the Golgi apparatus in the phosphorylation of apolipoprotein B. J Biol Chem, 271(49), 31491-5, 1996

Swift, L L. Assembly of very low density lipoproteins in rat liver: a study of nascent particles recovered from the rough endoplasmic reticulum. J Lipid Res, 36(3), 395-406, 1995

Longmire, AW, Swift, LL, Roberts, LJ, Awad, JA, Burk, RF, Morrow, JD. Effect of oxygen tension on the generation of F2-isoprostanes and malondialdehyde in peroxidizing rat liver microsomes. Biochem Pharmacol, 47(7), 1173-7, 1994

Moore, MC, Pagliassotti, MJ, Swift, LL, Asher, J, Murrell, J, Neal, D, Cherrington, AD. Disposition of a mixed meal by the conscious dog. Am J Physiol, 266(4 Pt 1), E666-75, 1994

Swift, LL, Hill, JO, Peters, JC, Greene, HL. Plasma lipids and lipoproteins during 6 d of maintenance feeding with long-chain, medium-chain, and mixed-chain triglycerides. Am J Clin Nutr, 56(5), 881-6, 1992

Awazu, M, Yared, A, Swift, LL, Hoover, RL, Ichikawa, I. Dietary fatty acid modulates glomerular atrial natriuretic peptide receptor. Kidney Int, 42(2), 265-71, 1992

Atkinson, JB, Swift, LL, Virmani, R. Watanabe heritable hyperlipidemic rabbits. Familial hypercholesterolemia. Am J Pathol, 140(3), 749-53, 1992

Greene, HL, Swift, LL, Knapp, HR. Hyperlipidemia and fatty acid composition in patients treated for type IA glycogen storage disease. J Pediatr, 119(3), 398-403, 1991

Pavlou, SN, Brewer, K, Farley, MG, Lindner, J, Bastias, MC, Rogers, BJ, Swift, LL, Rivier, JE, Vale, WW, Conn, PM. Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido. J Clin Endocrinol Metab, 73(6), 1360-9, 1991

Atkinson, JB, Swift, LL. Nifedipine reduces atherogenesis in cholesterol-fed heterozygous WHHL rabbits. Atherosclerosis, 84(2-3), 195-201, 1990

Jackowski, MM, Swift, LL, Cohen, S, McKanna, JA. Morphologic changes in human carcinoma cells (A-431) stimulated by epidermal growth factor: effect of cholesterol and low-density lipoproteins on the ruffling response. J Cell Physiol, 142(3), 458-68, 1990

Hill, JO, Peters, JC, Swift, LL, Yang, D, Sharp, T, Abumrad, N, Greene, HL. Changes in blood lipids during six days of overfeeding with medium or long chain triglycerides. J Lipid Res, 31(3), 407-16, 1990

Swift, LL, Hill, JO, Peters, JC, Greene, HL. Medium-chain fatty acids: evidence for incorporation into chylomicron triglycerides in humans. Am J Clin Nutr, 52(5), 834-6, 1990

Atkinson, JB, Hoover, RL, Berry, KK, Swift, LL. Cholesterol-fed heterozygous Watanabe heritable hyperlipidemic rabbits: a new model for atherosclerosis. Atherosclerosis, 78(2-3), 123-36, 1989

Harrison, JC, Swift, LL, LeQuire, VS. Identification of lipoprotein-binding proteins in rat liver Golgi apparatus membranes. J Lipid Res, 29(11), 1439-49, 1988

Swift, LL, Gray, ME, LeQuire, VS. Intestinal lipoprotein synthesis in control and hypercholesterolemic rats. Biochim Biophys Acta, 962(2), 186-95, 1988