Download BIOGRAPHICAL SKETCH Santambrogio, Laura

Principal Investigator/Program Director (Last, first, middle):
Santambrogio, Laura
BIOGRAPHICAL SKETCH
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NAME
POSITION TITLE
Laura Santambrogio
Associate Professor
eRA COMMONS USER NAME
paolo6
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Perugia University, School of Medicine,
Padua University, School of Medicine, Italy
Positions and Honors
DEGREE
(if applicable)
YEAR(s)
M.D.
Ph.D.
1987
1993
FIELD OF STUDY
Medicine
Immunology
1987-89
1989-91
Intern in Medicine, Department of Internal Medicine, Perugia University, Italy
Research in Immunology & Molecular Biology, FIDIA Research Laboratory, Abano
Terme, Padua, Italy
1991-94
Research Scientist, Department of Pathology, NYU Medical Center, New York, NY
1996-2003
Instructor of Pathology, Harvard Medical School, Boston, MA
2003-2006
Assistant Professor of Pathology, Albert Einstein College of Medicine, NY
2006-present Associate Professor of Pathology, Albert Einstein College of Medicine, NY
Honors
2003
Irene Diamond Professorship of Immunology
License:
1994
E.C.F.M.G. certified
Selected peer-reviewed publications (in chronological order 36 out of 56).
Ciuffetti G, Mercuri M, Rizzo MT, Lombardini R, Santambrogio L (1988) Risk factors for ischaemic brain
infarction. BMJ. 297:69.
Mercuri M, Santambrogio L, Ciuffetti G, Lombardini R (1989) Rheological behavior of white blood cells.
Stroke. 20:826-8
Ciuffetti G, Mercuri M, Lombardini R, Maragoni G, Santambrogio L, Mannarino E (1989) Leucocyte
behaviour in controlled ischaemia of the calves. J Clin Pathol. 42:1083-1087.
Santambrogio L, Bellomo G, Mercuri M, Paltriccia R, Ciuffetti G, Mannarino E. (1991) Sympathetic
vascular function in patients with central dysautonomia. J Neural Transm Suppl. 33:111-114.
Bellomo G, Santambrogio L, Fiacconi M, Scarponi AM, Ciuffetti G. (1999) Plasma profiles of
adrenocorticotropic hormone, cortisol, growth hormone and prolactin in patients with untreated Parkinson's
disease. J Neurol. 238:19-22.
Santambrogio L, Lipartiti M, Bruni A, Dal Toso R. (1993) Dopamine receptors on human T- and Blymphocytes. J Neuroimmunol. 45:113-119.
Santambrogio L, Lees MB, Sobel RA. (1998) Altered peptide ligand modulation of experimental allergic
encephalomyelitis: immune responses within the CNS. J Neuroimmunol. 81:1-13.
Santambrogio, L., G.M. Hochwald, B. Saxena, C-H. Leu, J. E. Martz, J. A. Carlino, N. H. Ruddle, M.
A.Palladino, and G.J. Thorbecke. 1993. Studies on the mechanisms by which transforming growth factor-β
(TGF-β) protects against allergic encephalomyelitis. J. Immunol. 151:1116-1127.
Santambrogio, L., M. Benedetti, M. V. Chao, K. Kulig, N. Gabellini, and G.M. Hochwald. 1994. Nerve
growth factor production by lymphocytes. J. Immunol. 153: 4488-4495.
PHS 398/2590 (Rev. 09/04, Reissued 4/2006)
Biographical Sketch Fomat Page
Principal Investigator/Program Director (Last, first, middle):
Santambrogio, Laura
Santambrogio, L., G.M. Crisi, 3. Lu, G.M. Hochwald, T. Ryan, and G.J. Thorbecke. 1995. Tolerogenic
forms of autoantigens and cytokines in the induction of resistance to experimental allergic encephalomyelitis. J.
Neuroimmunol. 58:211-222.
Crisi, G.M., L. Santambrogio, G.M. Hochwald, S. R. Smith, 3. A. Carlino, and G.J. Thorbecke. 1996.
Staphylococcal enterotoxin B and TNF α induced relapses of experimental allergic encephalomyelitis:
protection by TGF-β and IL-10. Eur.J. Immunol. 25:3035-3040.
Santambrogio L., M. Pakaski, M.L. Wong, B. Cipriani, R.A. Sobel, C.F. Brosnan, M.B. Lees, M. Dorf.
1999. Antigen presenting capacity of brain microvasculature in altered peptide ligand modulation of
experimental allergic encephalomyelitis. J. Neuroimmunol. 93: 81-89.
Santambrogio L., A.K. Sato, F.R. Fisher, M.E. Dorf, L.J. Stern. 1999. Abundant Empty Class II MHC
Molecules on the Surface of Immature Dendritic Cells. Proc.Natl.Acad.Sci. USA 96: 15050-15055
Santambrogio L., A.K. Sato, G.J. Carven, S.L. Belyanskaya, J.L. Strominger, L.J. Stern. 1999.
Extracellular antigen Processing and Presentation by Immature Dendritic Cells. Proc.Natl.Acad.Sci. USA . 96:
15056-15061
Falk K., O. Rotzschke, L. Santambrogio, M.E. Dorf, C. Brosnan, J.L. Strominger. 2000. Enhanced in vivo
potency of oligomerized encephalitogenic T cell epitopes: induction and prevention of an autoimmune disease.
J. Exp. Med. 191: 717-730.
Fischer F.R, L. Santambrogio, Y. Luo, M.A. Berman, W.W. Hancock, M.E. Dorf. 2000. Modulation of
Experimental Autoimmune Encephalomyelitis: Effect of Altered Peptide Ligand on Chemokine and Chemokine
Receptor Expression. J. Neuroimmunol. 110: 195-208.
F. R. Fischer, M. Luo, Y. Luo, L. Santambrogio, M.E. Dorf. 2001. RANTES Induced Chemokine Cascade
In Immature Dendritic Cells. J. Immunol. 167(3):1637-43.
Santambrogio L., S. L. Belyanskaya, F.R. Fischer, B. Cipriani, C. F. Brosnan, P. Ricciardi-Castagnoli, L. J.
Stern, J. L. Strominger, R. Riese. 2001. Developmental Plasticity of Central Nervous System Microglia.
Proc.Natl.Acad.Sci. USA . 98: 6295-6300.
K. Falk, J.M. Lau, L. Santambrogio, V. M. Esteban, F. Puentes, O. Rotzschke, J. L. Strominger 2002.
Small-molecular H-bond donors as catalysts of ligand exchange reactions of MHC class II molecules. J. Biol.
Chem. 277: 2709-2715.
Storm van’s Gravesande K., M.D. Layne, Q. Ye, L. Le, M.A. Perrella, L. Santambrogio, E.S. Silverman,
R. J. Riese. 2002. Interferon Regulatory Factor-1 Regulates Interferon γ-dependent Cathepsin S Expression. J.
Immunol. 168:4489-4494
Fridkis-Hareli, M., L. Santambrogio, J. N. H. Stern, L. Fugger, C. Brosnan, J. L. Strominger. 2002 Novel
Synthetic amino acid copolymers that inhibit autoantigen-specific T cell responses and suppress experimental
allergic encephalomyelitis. I. Clin. Invest.109:1635-1643.
F. Re, S. L. Belyanskaya, R. Riese, B. Cipriani, F.R. Fischer, F. Granucci, P. Ricciardi-Castagnoli, C. F.
Brosnan, L. J. Stern, J. L. Strominger, L. Santambrogio. 2002. GM-CSF induces an expression program in
neonatal microglia that primes them for antigen presentation. J.Immunol 169:2264-2273.
I. Potolicchio, L. Santambrogio & J.L. Strominger. 2003. Macrophage Migration Inhibitory Factor (MIF)
exert its Thioredoxin Activity on HLA Class II-bound peptides and interacts with HLA-DP molecules. J. Biol.
Chem. 278: 30889-30895
Granucci F., F. Petralia, S. Citterio, M. Urbano, F. Di Tota, L. Santambrogio, P. Ricciardi-Castagnoli.
2003. The Scavenger receptor MARCO mediates cytoskeleton rearrangements in Dendritic Cells and
Microglia. Blood 102:2940-2947
Carven GJ, S. Chitta, I. Hilgert, M.M. Rushe, R.F. Baggio, M. Palmer, J.E. Arenas, J.L. Strominger, V.
Horejsi, L. Santambrogio, L.J. Stern. 2004. Monoclonal antibodies specific for the empty conformation of
HLA-DR1 reveal the conformational change associated with peptide binding. J. Biol. Chem. 279: 16561-70.
Stern J.N.H., Z. Illes, J. Reddy, L. Santambrogio, D.K. Keskin, E. Sheu, H. Nishimura, M. Fridkis-Hareli, S.
Egorova, C. Goodman, C. Brosnan, V.K. Kuchroo, J.L. Strominger. (2004). Amelioration of PLP 139-151induced EAE by novel synthetic amino acid copolymers and their mechanisms. Proc. Natl. Acad. Sci. USA
101(32):11743-8.
Illes Z., J.N.H. Stern, J. Reddy, H. Waldner, M. Mycko, C. F. Brosnan, S. Ellmerich, D.M. Altmann, L.
Santambrogio, J.L. Strominger, V.K. Kuchroo. (2004) Novel synthetic amino acid copolymer suppress MBP
85-99-induced EAE in humanized double-transgenic mice through different effects on T cell responses.
Proc.Natl.Acad.Sci. USA. 101(32):11749-54.
PHS 398/2590 (Rev. 09/04, Reissued 4/2006)
Biographical Sketch Fomat Page
Principal Investigator/Program Director (Last, first, middle):
Santambrogio, Laura
Wong SH, L. Santambrogio , and J.L. Strominger. Caspases and nitric oxide broadly regulate dendritic
cell maturation and surface expression of class II MHC proteins. 2004 Proc.Natl.Acad.Sci. USA. 101: 1778317788
Potolicchio I, G.J Carven, R. J.Riese, X. Xu, C S. Stipp, L.J. Stern, L. Santambrogio. Proteomics of
microglial-cell derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptides catabolism.
J.Immunol. 175:2237-2243
Santambrogio, L., I. Potolicchio, S. Fessler, S-H Wong, G. Raposo and J.L. Strominger. Role of caspasecleaved and intact AP-1 complex during endosomal remodeling in maturing dendritic cells. 2005 Nature
Immunol. 6:1020-1028.
Potolicchio, I., S. Chitta, X. Xu, D. Fonseca, G. Crisi, J. Strominger, G. Raposo, V. Horejsi, L.J. Stern, L.
Santambrogio. Conformational variation of surrace MHC II proteins during myeloid dendritic cell
differentiation accompanies structural changes in MHC class II compartments. (2005) J.Immunol. 175:49354947.
Illes Z., J.N.H. Stern, D. B. Keskin, J. Reddy, C.F. Brosnan, H. Waldner, L. Santambrogio, V. K. Kuchroo,
J.L. Strominger. (2005) Effects of amino acid copolymers on microglia and T cells within the CNS. Eur. J.
Immunol. 35:3683-3693.
Stern, L..J., I Potolicchio, L. Santambrogio. Structure, development and cell biology of antigen processing
compartments. (2006). Current Opinion in Immunology. 18 (1):64-9.
Sun J, Soos T, Kewalramani VN, Osiecki K, Zheng JH, Falkin L, Santambrogio L, Littman DR, Goldstein
H. (2006). CD4-Specific Transgenic Expression of Human Cyclin T1 Markedly Increases Human
Immunodeficiency Virus Type 1 (HIV-1) Production by CD4+ T Lymphocytes and Myeloid Cells in Mice
Transgenic for a Provirus Encoding a Monocyte-Tropic HIV-1 Isolate. J Virol. 80(4):1850-62.
Santambrogio L., J.L. Strominger. The Ins and Outs of MHC Class II Proteins in Dendritic Cells. (2006).
Immunity 6:857-9.
Follenzi A., L. Santambrogio, A. Annoni. Immune Responses to Lentiviral vectors. (2007). Current Opinion
in Gene Therapy. 5:306-15
S. Chitta, L. Santambrogio, L.J. Stern. GMCSF in the absence of other cytokines
sustains human
dendritic cell precursors with T cell regulatory activity and capacity to differentiate into functional dendritic
cells. (2008). Immunol Lett. 116(1):41-54.
Tallóczy Z., J. Martinez, D. Joset, Y. Ray, A. Gácser, S. Toussi, N. Mizushima, J. Nosanchuk, H. Goldstein,
J. Loike, D. Sulzer, L. Santambrogio. Methamphetamine Inhibits Antigen Processing, Presentation, and
Phagocytosis (2008). PLoS Pathog. 4 (2).
R. Maitra, C.C. Clement, G.M. Crisi, N. Cobelli, L. Santambrogio. Immunogenecity of modified alkane
polymers is mediated through TLR1/2 activation. (2008) PLOS ONE 18;3(6):e2438.
L. Shi, P.C. Albuquerque, X. Wang, L. Santambrogio, A. Gácser, and J. D. Nosanchuk. A monoclonal
antibody to Histoplasma capsulatum alters the intracellular fate of the fungus in macrophages. (2008) Eukaryot
Cell. 7(7):1109-17
A. Bunbury, I. Potolicchio, L. Santambrogio Calcium regulated lysosomal exocytosis in human monocytes
mediates surface MHC class II expression. (2009) FASEB J. Jan;23(1):164-71. Epub 2008 Sep 24.
Omari K.M., S. Lutz, L. Santambrogio, S. Lira, C. Raine. Neuroprotection and remyelination in
experimental autoimmune encephalomyelitis mice inducibly over-expressing CXCL1. Am. J. Pathology (2009)
Jan;174(1):164-76. Epub 2008 Dec 18.
Nour AM, Yeung YG, Santambrogio L, Boyden ED, Stanley ER, Brojatsch . Anthrax lethal toxin triggers
the formation of a membrane-associated inflammasome complex in murine macrophages. J. Infect. Immun.
(2009) Mar;77(3):1262-71. Epub 2009 Jan 5.
Completed research support:
“Antigen and Superantigens in EAE: modulation towards a TH1 and Th2 phenotype”
Principal Investigator: Laura Santambrogio
Agency: National Multiple Sclerosis Society
Period: 01/01/1996 – 01/01/1997
PHS 398/2590 (Rev. 09/04, Reissued 4/2006)
Biographical Sketch Fomat Page
Principal Investigator/Program Director (Last, first, middle):
Santambrogio, Laura
“Mechanisms of Experimental Allergic Encephalomyelitis protection by T cell receptor altered
peptide ligands”
Principal Investigator: Laura Santambrogio
Agency: Italian Multiple Sclerosis Society
Period: 01/01/1996 – 01/01/1999
“Role of Exosomes in HIV release from multivesicular bodies in CNS microglial cells”
Principal Investigator: Laura Santambrogio
Agency: NIH (CFAR Pilot Project)
Period: 08/01/2004-12/31/2005 ($ 35,000)
The objective of this research is to evaluate the role of exosomes, derived from microglial cells, as carrier of
HIV in the CNS.
“Empty Class II MHC on dendritic cells and microglia”
Principal Investigator: Laura Santambrogio (100% effort)
Agency: NIH R01 AI48833 ($ 1,555,000)
Period: 01/29/2001-3/31/2008
The long-term objective of this research is to characterize the physiological role and relevance in the
immunological response of an alternative pathway of antigen processing and presentation, known to be
active in immature dendritic cells and possibly in central nervous system microglia. Such alternative
pathway relay on abundant cell surface expression of empty class II MHC protein and H2-DM for
peptide loading and antigen presentation and on secreted dendritic cells proteases for processing of
intact proteins into antigenic peptides.
“Caspases regulation of endosomal trafficking of the AP-1 tetrameric complex”
Principal Investigator: Laura Santambrogio
Agency: Irene Diamond Foundation Professorship in Immunology
Period: 09/01/2003-08/31/2006 ($ 500.000)
The long term objective of this research is to evaluate the role of Caspase cleavage occurring during
DC maturation on the assembly of the AP-1 complex and evaluate the ability of Cleaved adaptins to
bind regulatory proteins important for clathrin budding and vesicle transport.
Active Research Support:
“Non-apoptotic role of caspase 3 in endosomal remodeling”
Principal Investigator: Laura Santambrogio
Agency: NIH; 1R56AI072667 ($ 250,000)
Period; 4/1/07-3/31/09 $250,000
The overall objective of this proposal is to determine the role of caspase in the maturation of dendritic cells.
The specific hypothesis to be tested is that caspase acting in a non-apoptotic pathway, control the processing
of molecules required for the delivery to the cell membrane of proteins involved in antigen presentation.
The long term objective of this research is to evaluate the role of Caspase cleavage occurring during DC
maturation on the assembly of the AP-1 complex and evaluate the ability of Cleaved adaptins to bind
regulatory proteins important for clathrin budding and vesicle transport.
Mechanisms of Antigen Processing and Presentation in Aging Dendritic Cells
Principal Investigator: Laura Santambrogio/Ana Maria Cuervo
Project 2 and Director Core B
Agency: NIH; PO1 AG031782 ($1,500,000)
Period: 2/1/09-1/31/14
In this proposal we plan to study the antigen processing and presentation capacity of DC and MΦisolated from
3, 12 and 22 month old mice. The specific hypothesis to be tested is that a reduction in the efficiency of antigen
processing and presentation is a major contributing factor in the development of immunosenescence
associated with aging.
PHS 398/2590 (Rev. 09/04, Reissued 4/2006)
Biographical Sketch Fomat Page