INBRE

Andrea Ferrante

Assistant Professor

University of Alaska Fairbanks
Institute of Arctic Biology
PO Box 757000
Fairbanks, AK 99775
 
 
 
 
 
Affiliations
 
● INBRE
   (IDeA Network of Biomedical Research Excellence)
●  Institute of Arctic Biology (UAF)
●  Department of Biology and Wildlife (UAF)

Education
 Diploma di Maturita' Scientifica  1995 
   Liceo Scientifico "G.P. Vieusseux" - Imperia, Italy
● M.D. 2003 Diploma di Laurea in Medicina e Ghirurgia
   University of Genoa Medical School, Italy
● Internal Medicine Board Certification
   S. Martino Hospital, Genoa Medical School, Italy
● Ph.D. 2005 Molecular Genetics
   Blood REsearch Institute, Blood Center of Wisconsin, Milwaukee
 
Current Research Projects

Molecular Basis of Immune Recognition

The study of histocompatibility in man and in other vertebrates has led to the understanding of the mechanisms of immune recognition and to the discovery of novel molecules and cells involved in these processes, including class I and class II proteins encoded in the major histocompatibility complex (MHC) of all vertebrates examined and T cell receptors. The normal human response to bacterial and viral infection involves these molecules and results in either the generation of T helper cells and antibodies or of cytotoxic T-lymphocytes. In addition, many important human autoimmune diseases are linked to particular alleles of the class I and class II proteins.

In particular, the recognition by CD4+ T cells of peptides bound to class II MHC (MHCII) and exposed on the surface of antigen presenting cells initiates an adaptive immune response. Antigen presentation is a multistep process involving the intracellular fragmentation of protein antigens, followed by binding of the derived peptide epitopes to MHCII with the participation of the peptide-editing molecule DM, and subsequent transport to the surface for recognition. Our long-term goal is to sufficiently characterize the stages of this process so that we can predict T cell responses.

My laboratory is currently focused on three main projects:

  ●  The biochemical and biophysical bases of binding of antigenic peptides to MHC II molecules and the correlation between binding thermodynamics, structure and biology of the peptide/MHCII complex.

●  The mechanism by which DM skews the repertoire of peptide/MHCII complexes presented to CD4+ T cells in favor of the most stable complexes.

●  Developing an in silico binding prediction algorithm based on the in vitro observations, with specific clinical application, such as development of inhibitors in Hemophilia A patients.

 
PUBLICATIONS
1.   Nocera A, Tagliamacco A, De Palma R, Del Galdo F, Ferrante A, Fontana I, Barocci S, Ginevri F, Rolla D, Ravetti J.L., Valente U. (2004). Cytokine mRNA expression in chronically rejected human renal allografts. Clinical Transplantation,18:564-570. PMID: 15344961
 
2.   Nocera A, Tagliamacco A, Ferrante A, Fontana I, Rolla D, De Palma R, Del Galdo F, Ginevri F, Barocci S, Valente U. (2005). Cytotoxic molecule mRNA expression in chronically rejected human kidney allografts. Transplant Proc., 37(6):2476-8. PMID: 16182715
 
3.   Ferrante,A. & Gorski,J. (2007). Cooperativity of hydrophobic "anchor" interactions: evidence for epitope selection by MHC class II as a folding process. J. Immunol. 178(11): 7181-7189. PMID: 17513767
 
4.   Ferrante A, Anderson MW, Klug CS, Gorski J. (2008). HLA-DM Mediates Epitope Selection by a “Compare-Exchange” Mechanism when a Potential Peptide Pool Is Available. PLoS ONE 3(11) PMID: 19005572
 
5.   Baumgartner CK, Ferrante A, Nagaoka M, Gorski J, Malherbe LP. (2010) Peptide-MHC class II complex stability governs CD4 T cell clonal selection. J Immunol. 184(2):573-81. PMID: 20007533
 
6.   Ferrante A, Gorski J. (2010) Cutting edge: HLA-DM-mediated peptide exchange functions normally on MHC class II-peptide complexes that have been weakened by elimination of a conserved hydrogen bond. J Immunol. 184(3):1153-8. PMID: 20038641
 
7.   Yassai M, Bosenko D, Unruh M, Zacharias G, Reed E, Demos W, Ferrante A, Gorski J. (2011) Naïve T cell repertoire skewing in HLA-A2 individuals by a specialized rearrangement mechanism results in public memory clonotypes. J. Immunol.186(5):2970-7 PMID: 21282510
 
8.   Ferrante A , Gorski J. (2012) Entropy-enthalpy compensation as the thermodynamic foundation of permissive specificity in epitope selection by MHCII. Journal Molecular Biology.
 
9.   Ferrante A, Gorski J. (2012) A peptide/MHCII conformer generated in the presence of exchange peptide is the substrate for HLA-DM editing. Nature Scientific Reports, under revision
 
10. Ferrante A, (2012) For many but not for all: how the conformational flexibility of the peptide/MHCII complex shapes epitope selection, Springer Science & Business Media
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