.

Department of Pathology, Microbiology, and Immunology

 

 

  Virginia L. Shepherd, Ph.D.

 

 

  Professor

  Dept of Pathology, Microbiology and Immunology 
 

 

  Contact Information
 


  Office Location and 
US Mailing address:

Vanderbilt University School of Medicine

806 Light Hall

Nashville, TN 37232

 

Phone: 615-327-4751 ext 5499  

E-mail: virginia.l.shepherd@vanderbilt.edu

 

 

 

Education

 

 

Ph.D., University of Iowa, Iowa City, Iowa
M.S., University of Iowa, Iowa City, Iowa
B.S., University of Iowa, Iowa City, Iowa

 

 

Research Keywords

 

 

Macrophage biology, Host defense, Lectins, Biochemistry, Immunology, Infectious disease, Microbiology, Pathology, Pulmonary, Receptor, Tyrosine phosphorylation

 

 

Research Description

 

 

The focus of research in our laboratory is the study of the function of macrophage receptors that are involved in control of inflammation and host defense. Two mannose-specific lectins that are localized to the lung are the membrane-associated mannose receptor (MR) and the soluble protein surfactant-associated protein A (SP-A). The MR binds directly to pathogens and extracellular glycoproteins and mediates internalization and delivery of ligand to the phagolysosomal compartment. SP-A binds to extracellular pathogens and glycoproteins, then these complexes interact with a specific macrophage surface receptor (SP-AR) that then mediates internalization. Expression of each of these receptors, the MR and the SP-AR, is dependent on the functional state of the macrophage. Activated macrophages and undifferentiated monocytes express predominantly the SP-AR, while deactivated macrophages express the MR. We have been studying the MR for the past several years, and have determined that its expression is regulated transcriptionally, translationally, and posttranslationally. Work is now underway to delineate the mechanisms involved at each of these levels. The work of SP-AR regulation is just beginning with the cloning of the SP-AR cDNA.

A second major research area involves the role that the MR and SP-A/SP-AR play in pathogen clearance by macrophages. We are using both Mycobacterium and Candida albicans as model systems to investigate the direct binding of lectin and pathogen, to study the role of each receptor in internalization, and to determine if binding of pathogen to these receptors results in signaling for subsequent cytokine production. A component of this study is to examine the effect of HIV-derived proteins and mycobacteria-derived products on MR and SP-AR expression, and to determine if these products alter receptor expression and cytokine production by human macrophages.

 

 

Publications

 

 

Caldwell, R.L., Gadipatti, R., Lane, K.L., and Shepherd, V.L.. HIV-1 TAT REPRESSES TRANSCRIPTION OF THE BONE MORPHOGENIC PROTEIN RECEPTOR-2 IN MACROPHAGES. J. Leukocyte Biol., In press

Lopez, JP, Vigerust, DJ, Shepherd, VL. Mitogen-activated protein kinases and NFkappaB are involved in SP-A-enhanced responses of macrophages to mycobacteria. Respir Res, 10, 60, 2009

McCombs, GB, Ufnar, JA, Shepherd, VL. The Virtual Scientist: connecting university scientists to the K-12 classroom through videoconferencing. Adv Physiol Educ, 31(1), 62-6, 2007

Vigerust, DJ, Shepherd, VL. Virus glycosylation: role in virulence and immune interactions. Trends Microbiol, 15(5), 211-8, 2007

Edelson, BT, Stricker, TP, Li, Z, Dickeson, SK, Shepherd, VL, Santoro, SA, Zutter, MM. Novel collectin/C1q receptor mediates mast cell activation and innate immunity. Blood, 107(1), 143-50, 2006

Caldwell, RL, Lane, KB, Shepherd, VL. HIV-1 Tat interaction with cyclin T1 represses mannose receptor and the bone morphogenetic protein receptor-2 transcription. Arch Biochem Biophys, 449(1-2), 27-33, 2006

Caldwell, RL, Gadipatti, R, Lane, KB, Shepherd, VL. HIV-1 TAT represses transcription of the bone morphogenic protein receptor-2 in U937 monocytic cells. J Leukoc Biol, 79(1), 192-201, 2006

Vigerust, DJ, Egan, BS, Shepherd, VL. HIV-1 Nef mediates post-translational down-regulation and redistribution of the mannose receptor. J Leukoc Biol, 77(4), 522-34, 2005

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

Egan, BS, Abdolrasulnia, R, Shepherd, VL. IL-4 modulates transcriptional control of the mannose receptor in mouse FSDC dendritic cells. Arch Biochem Biophys, 428(2), 119-30, 2004

Greaton, CJ, Lane, KB, Shepherd, VL, McLaughlin, BJ. Transcription of a single mannose receptor gene by macrophage and retinal pigment epithelium. Ophthalmic Res, 35(1), 42-7, 2003

Lopez, Joseph P, Clark, Emily, Shepherd, Virginia L. Surfactant protein A enhances Mycobacterium avium ingestion but not killing by rat macrophages. J Leukoc Biol, 74(4), 523-30, 2003

Shepherd, Virginia L, . Distinct roles for lung collectins in pulmonary host defense.. Am J Respir Cell Mol Biol, 26, 257-60, 2002

Shepherd, Virginia L, . Pulmonary surfactant protein D: a novel link between innate and adaptive immunity.. Am J Physiol Lung Cell Mol Physiol, 282, L516-7, 2002

Lopez, J.P. and Shepherd, V.L. MITOGEN-ACTIVATED PROTEIN KINASES AND NF-i?

Shepherd, V.L. Distinct roles for lung collectins in pulmonary host defense. Am. J. Respir. Cell Mol. Biol., 26, 257-260, 2002

Hickman-Davis, JM, Fang, FC, Nathan, C, Shepherd, VL, Voelker, DR, Wright, JR. Lung surfactant and reactive oxygen-nitrogen species: antimicrobial activity and host-pathogen interactions. Am J Physiol Lung Cell Mol Physiol, 281(3), L517-23, 2001

Shepherd, V.L., and Lopez, J.P . The role of surfactant-associated protein A in pulmonary host defense. Immunol. Res. , 23, 111-120, 2001

Shepherd, V L, Lopez, J P, . The role of surfactant-associated protein A in pulmonary host defense.. Immunol Res, 23, 111-20, 2001

Hickman-Davis, J.M., Fang, F.C., Nathan, C., Shepherd, V.L., Voelker, D.R., and Wright, J.R. Lung surfactant and reactive oxygen-nitrogen species: antimicrobial activity and host-pathogen interactions. Am. J. Physiol. Lung Cell Mol. Physiol. , 281, L517-L523, 2001

Caldwell, R L, Egan, B S, Shepherd, V L, . HIV-1 Tat represses transcription from the mannose receptor promoter.. J Immunol, 165, 7035-41, 2000

Weikert, LF, Lopez, JP, Abdolrasulnia, R, Chroneos, ZC, Shepherd, VL. Surfactant protein A enhances mycobacterial killing by rat macrophages through a nitric oxide-dependent pathway. Am J Physiol Lung Cell Mol Physiol, 279(2), L216-23, 2000

Barr, FE, Pedigo, H, Johnson, TR, Shepherd, VL. Surfactant protein-A enhances uptake of respiratory syncytial virus by monocytes and U937 macrophages. Am J Respir Cell Mol Biol, 23(5), 586-92, 2000

Weikert, L., Lopez, J.P., Abdolrasulnia, R., Chroneos, Z.C., and Shepherd, V.L. Surfactant protein A enhances mycobacterial killing by rat macrophages through a nitric oxide-dependent pathway. Am. J. Physiol., 279, L216-L223, 1999

Egan, B.S., Lane, K.B., and Shepherd, V.L. PU.1 and USF are required for macrophage-specific mannose receptor promoter activity. J. Biol. Chem., 274, 9098-9107, 1999

Egan, BS, Lane, KB, Shepherd, VL. PU.1 and USF are required for macrophage-specific mannose receptor promoter activity. J Biol Chem, 274(13), 9098-107, 1999

Lane, KB, Egan, B, Vick, S, Abdolrasulnia, R, Shepherd, VL. Characterization of a rat alveolar macrophage cell line that expresses a functional mannose receptor. J Leukoc Biol, 64(3), 345-50, 1998

Hartshorn, L.K., Crouch, E., White, M.R., Colamusi, M.L., Kakkanatt, A., Tauer, B., Shepherd, V.L., Sastry, K.N. Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacterial. Am J Physiol., 274, L958-969, 1998

Borron, P., McCormack, F.X., Elhalwagi, B.M., Chroneos, Z.C., Lewis, J.F., Zhu, S., Wright, J.R., Shepherd, V.L., Possmayer, F., Inchle, K., Frahler, L.J. Surfactant protein A inhibits T cell proliferation via its collagen- like tail and a 210-kDa receptor. Am J Physiol., 275: (Lung Cell Mol Physiol. 4 pt 1), L679-686, 1998

Borron, P, McCormack, FX, Elhalwagi, BM, Chroneos, ZC, Lewis, JF, Zhu, S, Wright, JR, Shepherd, VL, Possmayer, F, Inchley, K, Fraher, LJ. Surfactant protein A inhibits T cell proliferation via its collagen-like tail and a 210-kDa receptor. Am J Physiol, 275(4 Pt 1), L679-86, 1998

Weikert, LF, Edwards, K, Chroneos, ZC, Hager, C, Hoffman, L, Shepherd, VL. SP-A enhances uptake of bacillus Calmette-Gu??rin by macrophages through a specific SP-A receptor. Am J Physiol, 272(5 Pt 1), L989-95, 1997

Shepherd, VL, Lane, KB, Abdolrasulnia, R. Ingestion of Candida albicans down-regulates mannose receptor expression on rat macrophages. Arch Biochem Biophys, 344(2), 350-6, 1997

Hartshorn, K.L., White, M.R., Shepherd, V., Reid, K., Jensenius, J., Crouch, E. Mechanisms of anti-influenze activity of surfactant proteins A and D: comparison with serum collectins. Am J Physiol, 273: (Lung Cell Mol Physiol. 6 pt 1), L1156-L1166, 1997

Lane, K.B., Egan, B., Vick, S., Abdolrasulnia, R., Shepherd, V.L. Characterization of a rat alveolar macrophage cell line that expresses a functional mannose receptor. J. Leuk Biol., 64, 345-350, 1997

Chroneos, Z.C., Abdolrasulnia, R., Whitsett, J.A., Rice, W.J., and Shepherd, V.L. Purification of a cell surface receptor for surfactant protein A. . J. Biol. Chem., 271, 16375-16383, 1996

Chroneos, ZC, Abdolrasulnia, R, Whitsett, JA, Rice, WR, Shepherd, VL. Purification of a cell-surface receptor for surfactant protein A. J Biol Chem, 271(27), 16375-83, 1996

Yan, F, Lutz, DA, Shepherd, VL, Boyle, D, McLaughlin, BJ. Characterization of rod outer segment plasma membrane proteins which bind to the mannose receptor. Curr Eye Res, 14(6), 465-71, 1995

P??rez-P??rez, GI, Shepherd, VL, Morrow, JD, Blaser, MJ. Activation of human THP-1 cells and rat bone marrow-derived macrophages by Helicobacter pylori lipopolysaccharide. Infect Immun, 63(4), 1183-7, 1995

Chroneos, Z, Shepherd, VL. Differential regulation of the mannose and SP-A receptors on macrophages. Am J Physiol, 269(6 Pt 1), L721-6, 1995

Cowan, H.B., Abdolrasulnia, R., Vick, S., Shepherd, V.L. Dexamethasone blocks the interferon \0-mediated down-regulation of the macrophage mannose receptor. Arch Biochem Biophys., 312, 367-374, 1994

Shepherd, VL, Cowan, HB, Abdolrasulnia, R, Vick, S. Dexamethasone blocks the interferon-gamma-mediated downregulation of the macrophage mannose receptor. Arch Biochem Biophys, 312(2), 367-74, 1994

Rinaldo, J.E., Clark, M., Parrinello, J., Shepherd, V.L. Nitric oxide inactivates xanthine dehydrogenase and xanthine oxidase in interferon-\0-stimulated macrophages. Am J Respir Cell Mol Biol., 11, 625-630, 1994

Abdolrasulnia, R, Shepherd, VL. Purification of type I and type II tumor necrosis factor receptors from human lung tissue. Am J Respir Cell Mol Biol, 7(1), 42-8, 1992

Haas, DW, Shepherd, VL, Hagedorn, CH. Lipopolysaccharide stimulates phosphorylation of eukaryotic initiation factor-4F in macrophages and tumor necrosis factor participates in this event. Second Messengers Phosphoproteins, 14(3), 163-71, 1992

Cowan, HB, Vick, S, Conary, JT, Shepherd, VL. Dexamethasone up-regulates mannose receptor activity by increasing mRNA levels. Arch Biochem Biophys, 296(1), 314-20, 1992

Tanner, WG, Welborn, MB, Shepherd, VL. Tumor necrosis factor-alpha and interleukin-1 alpha synergistically enhance phorbol myristate acetate-induced superoxide production by rat bone marrow-derived macrophages. Am J Respir Cell Mol Biol, 7(4), 379-84, 1992

Christman, JW, Blackwell, TR, Cowan, HB, Shepherd, VL, Rinaldo, JE. Endotoxin induces the expression of macrophage inflammatory protein 1 alpha mRNA by rat alveolar and bone marrow-derived macrophages. Am J Respir Cell Mol Biol, 7(4), 455-61, 1992

Shepherd, VL, Tarnowski, BI, McLaughlin, BJ. Isolation and characterization of a mannose receptor from human pigment epithelium. Invest Ophthalmol Vis Sci, 32(6), 1779-84, 1991

Christman, JW, Abdolrasulnia, R, Shepherd, VL, Rinaldo, JE. Paradoxical regulation by PGE-2 on release of neutrophil chemoattractants by rat bone marrow macrophages. Prostaglandins, 41(3), 251-62, 1991

Christman, JW, Christman, BW, Shepherd, VL, Rinaldo, JE. Regulation of alveolar macrophage production of chemoattractants by leukotriene B4 and prostaglandin E2. Am J Respir Cell Mol Biol, 5(3), 297-304, 1991

Shepherd, V.L., Abdolrasulnia, R., Garrett, M.G., Cowan, H.B. Down-regulation of mannose receptor activity in macrophages following treatment with lipopolysaccharide and phorbol esters. J Immunol., 145, 1530-1536, 1990

Shepherd, V.L., Hoidal, J. Clearance of neutrophil-derived myeloperoxidase by the macrophage mannose receptor . Am J Respir Cell Mol Biol., 2, 335-340, 1990

Shepherd, V.L., Abdolrasulnia, R., Stephenson, J., Crenshaw, C. Modulation of mannose receptor activity by proteolysis. Biochem J., 270, 771-776, 1990

Shepherd, VL, Abdolrasulnia, R, Garrett, M, Cowan, HB. Down-regulation of mannose receptor activity in macrophages after treatment with lipopolysaccharide and phorbol esters. J Immunol, 145(5), 1530-6, 1990

Shepherd, VL, Abdolrasulnia, R, Stephenson, J, Crenshaw, C. Modulation of mannose receptor activity by proteolysis. Biochem J, 270(3), 771-6, 1990

Bozeman, PM, Hoidal, JR, Shepherd, VL. Oxidant-mediated inhibition of ligand uptake by the macrophage mannose receptor. J Biol Chem, 263(3), 1240-7, 1988

Bozeman, P., Hoidal, J., Shepherd, V.L. Oxidant-mediated inhibition of ligand uptake by the macrophage mannose receptor. J Biol Chem., 263, 1240-1247, 1988

Tarnowski, BI, Shepherd, VL, McLaughlin, BJ. Expression of mannose receptors for pinocytosis and phagocytosis on rat retinal pigment epithelium. Invest Ophthalmol Vis Sci, 29(5), 742-8, 1988

Lennartz, MR, Cole, FS, Shepherd, VL, Wileman, TE, Stahl, PD. Isolation and characterization of a mannose-specific endocytosis receptor from human placenta. J Biol Chem, 262(21), 9942-4, 1987

Stephenson, JD, Shepherd, VL. Purification of the human alveolar macrophage mannose receptor. Biochem Biophys Res Commun, 148(2), 883-9, 1987

Stephenson, J.D., Shpherd, V.L. Purification of the human alveolar macrophage mannose receptor. Biochem Biophys Res Comm., 148, 883-889, 1987

Shepherd, VL. The role of the respiratory burst of phagocytes in host defense. Semin Respir Infect, 1(2), 99-106, 1986

Shepherd, VL, Konish, MG, Stahl, P. Dexamethasone increases expression of mannose receptors and decreases extracellular lysosomal enzyme accumulation in macrophages. J Biol Chem, 260(1), 160-4, 1985

Shepherd, V.L., Konish, M.G., Stahl, P.D. Dexamethasone increases expression of mannose receptors and decreases extracellular lysosomal enzyme accumulation in macrophages. J Biol Chem., 260, 160-164, 1985

Shepherd, V., Stahl, P., Bernd, P., Rabinovitch, M. Receptor-mediated entry of ?-glucuronidase into the parasitophororous vacuoles of macrophages infected with Leishmania mexicana amazonesis. J. Exp. Med., 157, 1471-1482, 1983

Shepherd, VL, Stahl, PD, Bernd, P, Rabinovitch, M. Receptor-mediated entry of beta-glucuronidase into the parasitophorous vacuoles of macrophages infected with Leishmania mexicana amazonensis. J Exp Med, 157(5), 1471-82, 1983

Shepherd, V.L., Campbell, E., Senior, R., Stahl, P.D. Characterization of the mannose/fucose receptor in human mononuclear phagocytes. J. Reticuloendothel.Soc., 32, 423-431, 1982

Shepherd, VL, Campbell, EJ, Senior, RM, Stahl, PD. Characterization of the mannose/fucose receptor on human mononuclear phagocytes. J Reticuloendothel Soc, 32(6), 423-31, 1982

Shepherd, VL, Lee, YC, Schlesinger, PH, Stahl, PD. L-Fucose-terminated glycoconjugates are recognized by pinocytosis receptors on macrophages. Proc Natl Acad Sci U S A, 78(2), 1019-22, 1981