John J. Monaco , PhD

Bachelor's Degree: Massachusetts Institute of Technology Cambridge, MA, USA, 1977 (Life Sciences (Biology))

Doctoral degree: Stanford University Stanford, CA, USA, 1983 (Medical Microbiology (Immunology))

Postdoctoral Fellowship: Stanford University Stanford, CA, , 1985

Cells of higher vertebrates have evolved mechanisms enabling them to display on their surfaces a sampling of their intracellular contents, in the form of peptides bound to major histocompatibility complex MHC class I molecules. Such complexes are required not only for the recognition and destruction of cells harboring intracellular pathogens, or cells containing altered forms of self proteins, such as oncogenes, but also for the positive and negative selection of T cells during their development in the thymus. It is therefore important to determine how these peptide-MHC complexes are generated. Moreover, recent data suggest that not all peptides of a given antigen which can bind to a particular MHC class I molecule are in fact produced under normal circumstances, and that polymorphism in antigen processing may alter the repertoire of peptides presented to T cells in different individuals. Thus, it is important to determine whether and to what extent the specificity of, and potential polymorphism in, their generation affects the repertoire of peptides that are presented to T cells. Despite their critical importance, the mechanisms by which peptides relevant to presentation to T cells are produced in normal cells are incompletely understood. Recent evidence implicates a large intracellular structure called the LMP complex, or proteasomes, in this process. We aim to define the proteolytic specificity of this complex, and to delineate the effect of known allelic structural variation in this complex on its proteolytic activity and specificity. This information should aid in the identification of T cell epitopes in infectious and in autoimmune disease and may ultimately improve vaccine design. The results of these studies may also have important implications for individual differences in immune responsiveness, the genetic basis of MHC-linked predisposition to disease, and MHC-class I matched and non-matched transplantation.

1985 -1992 Assistant Professor of Microbiology & Immunology, Virginia Commonwealth University, Richmond, VA

1992 -1993 Associate Professor of Microbiology & Immunology, Virginia Commonwealth University, Richmond, VA

1993 -To Present Professor of Molecular Genetics, Biochemistry & Microbiology, University of Cincinnati, Cincinnati, OH

1994 -2001 Investigator, Howard Hughes Medical Institute, University of Cincinnati

Grant: #R56 AI023695 Investigators:Miller, William; Monaco, John; Weiss, Alison 08-01-2008 -07-31-2009 National Institute of Allergy and Infectious Diseases Biologic Activities of the Pertusis Toxin B-Pentamer Role:Collaborator $351,000.00 Closed Level:Federal

Grant: #2 R01 AI023695-20A1 Investigators:Miller, William; Monaco, John; Weiss, Alison 09-01-2009 -08-31-2012 National Institute of Allergy and Infectious Diseases Biologic Activities of the Pertusis Toxin B-Pentamer Role:Collaborator $706,500.00 Closed Level:Federal

Grant: #R21 AI107244 Investigators:Monaco, John 04-01-2014 -03-31-2016 National Institute of Allergy and Infectious Diseases Proteasome subunit beta5t and thymus-specific peptides in T cell selection Role:PI $237,750.00 Awarded Level:Federal

Peer Reviewed Publications

Rockwell, Cheryl E; Monaco, John J; Qureshi, Nilofer (2012. ) A critical role for the inducible proteasomal subunits LMP7 and MECL1 in cytokine production by activated murine splenocytes.Pharmacology, , 89 (3-4 ) ,117-26 More Information

Reis, Julia; Hassan, Ferdaus; Guan, Xiu Qin; Shen, Jing; Monaco, John J; Papasian, Christopher J; Qureshi, Asaf A; Van Way, Charles W; Vogel, Stefanie N; Morrison, David C; Qureshi, Nilofer (2011. ) The immunoproteasomes regulate LPS-induced TRIF/TRAM signaling pathway in murine macrophages.Cell biochemistry and biophysics, , 60 (1-2 ) ,119-26 More Information

Deverson, Edward V; Gow, Irene R; Coadwell, W John; Monaco, John J; Butcher, Geoffrey W; Howard, Jonathan C (2008. ) MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters. 1990. Journal of immunology (Baltimore, Md. : 1950), , 180 (5 ) ,2729-32

Monaco, John J; Cho, Sungae; Attaya, Michelle (2008. ) Transport protein genes in the murine MHC: possible implications for antigen processing. 1990. Journal of immunology (Baltimore, Md. : 1950), , 180 (5 ) ,2725-8

Li, Xiaotao; Amazit, Larbi; Long, Weiwen; Lonard, David M; Monaco, John J; O'Malley, Bert W (2007. ) Ubiquitin- and ATP-independent proteolytic turnover of p21 by the REGgamma-proteasome pathway.Molecular cell, , 26 (6 ) ,831-42 More Information

Deol, Parampal; Zaiss, Dietmar M W; Monaco, John J; Sijts, Alice J A M (2007. ) Rates of processing determine the immunogenicity of immunoproteasome-generated epitopes. Journal of immunology (Baltimore, Md. : 1950), , 178 (12 ) ,7557-62

Pang, Ken C; Sanders, Megan T; Monaco, John J; Doherty, Peter C; Turner, Stephen J; Chen, Weisan (2006. ) Immunoproteasome subunit deficiencies impact differentially on two immunodominant influenza virus-specific CD8+ T cell responses. Journal of immunology (Baltimore, Md. : 1950), , 177 (11 ) ,7680-8

Basler, Michael; Moebius, Jacqueline; Elenich, Laura; Groettrup, Marcus; Monaco, John J (2006. ) An altered T cell repertoire in MECL-1-deficient mice. Journal of immunology (Baltimore, Md. : 1950), , 176 (11 ) ,6665-72

Caudill, Christy M; Jayarapu, Krupakar; Elenich, Laura; Monaco, John J; Colbert, Robert A; Griffin, Thomas A (2006. ) T cells lacking immunoproteasome subunits MECL-1 and LMP7 hyperproliferate in response to polyclonal mitogens. Journal of immunology (Baltimore, Md. : 1950), , 176 (7 ) ,4075-82

Barton, Lance F; Runnels, Herbert A; Schell, Todd D; Cho, Yunjung; Gibbons, Reta; Tevethia, Satvir S; Deepe, George S; Monaco, John J (2004. ) Immune defects in 28-kDa proteasome activator gamma-deficient mice. Journal of immunology (Baltimore, Md. : 1950), , 172 (6 ) ,3948-54

Lili?, Mirjana; Popmihajlov, Zoran; Monaco, John J; Vukmanovi?, Stanislav (2004. ) Association of beta2-microglobulin with the alpha3 domain of H-2Db heavy chain.Immunogenetics, , 55 (11 ) ,740-7 More Information

Wenderfer, Scott E; Monaco, John J (2004. ) Exon trapping for positional cloning and fingerprinting.Methods in molecular biology (Clifton, N.J.), , 256 ,7-20 More Information

De, Mita; Jayarapu, Krupakar; Elenich, Laura; Monaco, John J; Colbert, Robert A; Griffin, Thomas A (2003. ) Beta 2 subunit propeptides influence cooperative proteasome assembly.The Journal of biological chemistry, , 278 (8 ) ,6153-9 More Information

Barton, Lance F; Cruz, Miguel; Rangwala, Reshma; Deepe, George S; Monaco, John J (2002. ) Regulation of immunoproteasome subunit expression in vivo following pathogenic fungal infection. Journal of immunology (Baltimore, Md. : 1950), , 169 (6 ) ,3046-52

Beyette, J R; Hubbell, T; Monaco, J J (2001. ) Purification of 20S proteasomes. Methods in molecular biology (Clifton, N.J.), , 156 ,1-16

Runnels, H A; Watkins, W A; Monaco, J J (2000. ) LMP2 expression and proteasome activity in NOD mice.Nature medicine, , 6 (10 ) ,1064-5; author reply More Information

Fang, C H; Li, B G; Fischer, D R; Wang, J J; Runnels, H A; Monaco, J J; Hasselgren, P O (2000. ) Burn injury upregulates the activity and gene expression of the 20 S proteasome in rat skeletal muscle. Clinical science (London, England : 1979), , 99 (3 ) ,181-7

Nelson, J E; Loukissa, A; Altschuller-Felberg, C; Monaco, J J; Fallon, J T; Cardozo, C (2000. ) Up-regulation of the proteasome subunit LMP7 in tissues of endotoxemic rats.The Journal of laboratory and clinical medicine, , 135 (4 ) ,324-31 More Information

Griffin, T A; Slack, J P; McCluskey, T S; Monaco, J J; Colbert, R A (2000. ) Identification of proteassemblin, a mammalian homologue of the yeast protein, Ump1p, that is required for normal proteasome assembly.Molecular cell biology research communications : MCBRC, , 3 (4 ) ,212-7 More Information

Wenderfer, S E; Slack, J P; McCluskey, T S; Monaco, J J (2000. ) Identification of 40 genes on a 1-Mb contig around the IL-4 cytokine family gene cluster on mouse chromosome 11.Genomics, , 63 (3 ) ,354-73 More Information

Elenich, L A; Nandi, D; Kent, A E; McCluskey, T S; Cruz, M; Iyer, M N; Woodward, E C; Conn, C W; Ochoa, A L; Ginsburg, D B; Monaco, J J (1999. ) The complete primary structure of mouse 20S proteasomes. Immunogenetics, , 49 (10 ) ,835-42

Hobler, S C; Williams, A; Fischer, D; Wang, J J; Sun, X; Fischer, J E; Monaco, J J; Hasselgren, P O (1999. ) Activity and expression of the 20S proteasome are increased in skeletal muscle during sepsis. The American journal of physiology, , 277 (2 Pt 2 ) ,R434-40

Ma, J F; Ochsner, U A; Klotz, M G; Nanayakkara, V K; Howell, M L; Johnson, Z; Posey, J E; Vasil, M L; Monaco, J J; Hassett, D J (1999. ) Bacterioferritin A modulates catalase A (KatA) activity and resistance to hydrogen peroxide in Pseudomonas aeruginosa. Journal of bacteriology, , 181 (12 ) ,3730-42

Hermel, E; Han, M; Hague, B; Kindt, T; Monaco, J J (1999. ) Isolation and mapping of the rabbit DM genes. Immunogenetics, , 49 (4 ) ,295-302

Russell, H I; York, I A; Rock, K L; Monaco, J J (1999. ) Class II antigen processing defects in two H2d mouse cell lines are caused by point mutations in the H2-DMa gene. European journal of immunology, , 29 (3 ) ,905-11

Grandea, A G; Comber, P G; Wenderfer, S E; Schoenhals, G; Früh, K; Monaco, J J; Spies, T (1998. ) Sequence, linkage to H2-K, and function of mouse tapasin in MHC class I assembly. Immunogenetics, , 48 (4 ) ,260-5

Chianese-Bullock, K A; Russell, H I; Moller, C; Gerhard, W; Monaco, J J; Eisenlohr, L C (1998. ) Antigen processing of two H2-IEd-restricted epitopes is differentially influenced by the structural changes in a viral glycoprotein. Journal of immunology (Baltimore, Md. : 1950), , 161 (4 ) ,1599-607

Kulig, K; Nandi, D; Bacik, I; Monaco, J J; Vukmanovi?, S (1998. ) Physical and functional association of the major histocompatibility complex class I heavy chain alpha3 domain with the transporter associated with antigen processing. The Journal of experimental medicine, , 187 (6 ) ,865-74

Griffin, T A; Nandi, D; Cruz, M; Fehling, H J; Kaer, L V; Monaco, J J; Colbert, R A (1998. ) Immunoproteasome assembly: cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits. The Journal of experimental medicine, , 187 (1 ) ,97-104

Nandi, D; Marusina, K; Monaco, J J (1998. ) How do endogenous proteins become peptides and reach the endoplasmic reticulum. Current topics in microbiology and immunology, , 232 ,15-47

Cruz, M; Elenich, L A; Smolarek, T A; Menon, A G; Monaco, J J (1997. ) DNA sequence, chromosomal localization, and tissue expression of the mouse proteasome subunit lmp10 (Psmb10) gene.Genomics, , 45 (3 ) ,618-22 More Information

Nandi, D; Woodward, E; Ginsburg, D B; Monaco, J J (1997. ) Intermediates in the formation of mouse 20S proteasomes: implications for the assembly of precursor beta subunits.The EMBO journal, , 16 (17 ) ,5363-75 More Information

Marusina, K; Iyer, M; Monaco, J J (1997. ) Allelic variation in the mouse Tap-1 and Tap-2 transporter genes. Journal of immunology (Baltimore, Md. : 1950), , 158 (11 ) ,5251-6

Cruz, M; Nandi, D; Hendil, K B; Monaco, J J (1997. ) Cloning and characterization of mouse Lmp3 cDNA, encoding a proteasome beta subunit. Gene, , 190 (2 ) ,251-6

Baldeón, M E; Neece, D J; Nandi, D; Monaco, J J; Gaskins, H R (1997. ) Interferon-gamma independently activates the MHC class I antigen processing pathway and diminishes glucose responsiveness in pancreatic beta-cell lines. Diabetes, , 46 (5 ) ,770-8

Marusina, K; Reid, G; Gabathuler, R; Jefferies, W; Monaco, J J (1997. ) Novel peptide-binding proteins and peptide transport in normal and TAP-deficient microsomes.Biochemistry, , 36 (4 ) ,856-63 More Information

Jiang, H; Monaco, J J (1997. ) Sequence and expression of mouse proteasome activator PA28 and the related autoantigen Ki. Immunogenetics, , 46 (2 ) ,93-8

Kasai, M; Hirokawa, K; Kajino, K; Ogasawara, K; Tatsumi, M; Hermel, E; Monaco, J J; Mizuochi, T (1996. ) Difference in antigen presentation pathways between cortical and medullary thymic epithelial cells.European journal of immunology, , 26 (9 ) ,2101-7 More Information

Nandi, D; Jiang, H; Monaco, J J (1996. ) Identification of MECL-1 (LMP-10) as the third IFN-gamma-inducible proteasome subunit. Journal of immunology (Baltimore, Md. : 1950), , 156 (7 ) ,2361-4

Marusina, K; Monaco, J J (1996. ) Peptide transport in antigen presentation. Current opinion in hematology, , 3 (1 ) ,19-26

Nandi, D; Iyer, M N; Monaco, J J (1996. ) Molecular and serological analysis of polymorphisms in the murine major histocompatibility complex-encoded proteasome subunits, LMP-2 and LMP-7. Experimental and clinical immunogenetics, , 13 (1 ) ,20-9

Monaco, J J (1995. ) Pathways for the processing and presentation of antigens to T cells. Journal of leukocyte biology, , 57 (4 ) ,543-7

Monaco, J J; Nandi, D (1995. ) The genetics of proteasomes and antigen processing.Annual review of genetics, , 29 ,729-54 More Information

Woodward, E C; Monaco, J J (1995. ) Characterization and mapping of the gene encoding mouse proteasome subunit DELTA (Lmp19). Immunogenetics, , 42 (1 ) ,28-34

Hermel, E; Yuan, J; Monaco, J J (1995. ) Characterization of polymorphism within the H2-M MHC class II loci. Immunogenetics, , 42 (2 ) ,136-42

Hermel, E; Monaco, J J (1995. ) RT1.DMa and RT1.DMb: the rat homologues of H2-DMa and H2-DMb. Immunogenetics, , 42 (5 ) ,446-7

Morris, P; Shaman, J; Attaya, M; Amaya, M; Goodman, S; Bergman, C; Monaco, J J; Mellins, E (1994. ) An essential role for HLA-DM in antigen presentation by class II major histocompatibility molecules.Nature, , 368 (6471 ) ,551-4 More Information

Patel, S D; Monaco, J J; McDevitt, H O (1994. ) Delineation of the subunit composition of human proteasomes using antisera against the major histocompatibility complex-encoded LMP2 and LMP7 subunits. Proceedings of the National Academy of Sciences of the United States of America, , 91 (1 ) ,296-300

Kishi, F; Suminami, Y; Monaco, J J (1993. ) Genomic organization of the mouse Lmp-2 gene and characteristic structure of its promoter. Gene, , 133 (2 ) ,243-8

Driscoll, J; Brown, M G; Finley, D; Monaco, J J (1993. ) MHC-linked LMP gene products specifically alter peptidase activities of the proteasome.Nature, , 365 (6443 ) ,262-4 More Information

Martinez, C K; Monaco, J J (1993. ) Post-translational processing of a major histocompatibility complex-encoded proteasome subunit, LMP-2. Molecular immunology, , 30 (13 ) ,1177-83

Brown, M G; Driscoll, J; Monaco, J J (1993. ) MHC-linked low-molecular mass polypeptide subunits define distinct subsets of proteasomes. Implications for divergent function among distinct proteasome subsets. Journal of immunology (Baltimore, Md. : 1950), , 151 (3 ) ,1193-204

Monaco, J J (1993. ) Structure and function of genes in the MHC class II region. Current opinion in immunology, , 5 (1 ) ,17-20

Brown, M G; Monaco, J J (1993. ) Biochemical purification of distinct proteasome subsets. Enzyme & protein, , 47 (4-6 ) ,343-53

Aldrich, C J; Waltrip, R; Hermel, E; Attaya, M; Lindahl, K F; Monaco, J J; Forman, J (1992. ) T cell recognition of QA-1b antigens on cells lacking a functional Tap-2 transporter. Journal of immunology (Baltimore, Md. : 1950), , 149 (12 ) ,3773-7

van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O (1992. ) Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes. Proceedings of the National Academy of Sciences of the United States of America, , 89 (23 ) ,11594-7

Monaco, J J (1992. ) Not so groovy after all? .Current biology : CB, , 2 (8 ) ,433-5

Gaskins, H R; Monaco, J J; Leiter, E H (1992. ) Expression of intra-MHC transporter (Ham) genes and class I antigens in diabetes-susceptible NOD mice. Science (New York, N.Y.), , 256 (5065 ) ,1826-8; author reply

Monaco, J J (1992. ) A molecular model of MHC class-I-restricted antigen processing.Immunology today, , 13 (5 ) ,173-9 More Information

Attaya, M; Jameson, S; Martinez, C K; Hermel, E; Aldrich, C; Forman, J; Lindahl, K F; Bevan, M J; Monaco, J J (1992. ) Ham-2 corrects the class I antigen-processing defect in RMA-S cells.Nature, , 355 (6361 ) ,647-9 More Information

Monaco, J J (1992. ) Genes in the MHC that may affect antigen processing. Current opinion in immunology, , 4 (1 ) ,70-3

Monaco, J J (1992. ) Major histocompatibility complex-linked transport proteins and antigen processing. Immunologic research, , 11 (2 ) ,125-32

Martinez, C K; Monaco, J J (1991. ) Homology of proteasome subunits to a major histocompatibility complex-linked LMP gene.Nature, , 353 (6345 ) ,664-7 More Information

Cho, S G; Attaya, M; Monaco, J J (1991. ) New class II-like genes in the murine MHC.Nature, , 353 (6344 ) ,573-6 More Information

Kelly, A P; Monaco, J J; Cho, S G; Trowsdale, J (1991. ) A new human HLA class II-related locus, DM.Nature, , 353 (6344 ) ,571-3 More Information

Brown, M G; Driscoll, J; Monaco, J J (1991. ) Structural and serological similarity of MHC-linked LMP and proteasome (multicatalytic proteinase) complexes.Nature, , 353 (6342 ) ,355-7 More Information

Cho, S; Attaya, M; Brown, M G; Monaco, J J (1991. ) A cluster of transcribed sequences between the Pb and Ob genes of the murine major histocompatibility complex. Proceedings of the National Academy of Sciences of the United States of America, , 88 (12 ) ,5197-201

Monaco, J J; Cho, S; Attaya, M; Brown, M G Molecular genetics of the K end of the murine MHC. Research in immunology, , 142 (5-6 ) ,389-91

Monaco, J J; Cho, S; Attaya, M (1990. ) Transport protein genes in the murine MHC: possible implications for antigen processing. Science (New York, N.Y.), , 250 (4988 ) ,1723-6

Deverson, E V; Gow, I R; Coadwell, W J; Monaco, J J; Butcher, G W; Howard, J C MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters.Nature, , 348 (6303 ) ,738-41 More Information

Monaco, J J; McDevitt, H O (1986. ) The LMP antigens: a stable MHC-controlled multisubunit protein complex. Human immunology, , 15 (4 ) ,416-26

Monaco, J J; McDevitt, H O H-2-linked low-molecular weight polypeptide antigens assemble into an unusual macromolecular complex. Nature, , 309 (5971 ) ,797-9

Monaco, J J; McDevitt, H O (1982. ) Identification of a fourth class of proteins linked to the murine major histocompatibility complex. Proceedings of the National Academy of Sciences of the United States of America, , 79 (9 ) ,3001-5

Boos, S C; Monaco, J J; Gottlieb, P D (1978. ) Production of congenic Anti-Lyt-3.1 sera.Immunogenetics, , 7 (1 ) ,165-8 More Information

Millen, Scott H; Schneider, Olivia D; Miller, William E; Monaco, John J; Weiss, Alison A (2013. ) Pertussis toxin B-pentamer mediates intercellular transfer of membrane proteins and lipids.PloS one, , 8 (9 ) ,e72885 More Information

1995 Eli Lilly & Co. Research Award ASM's oldest and most prestigious prize, it rewards fundamental research of unusual merit in microbiology or immunology by an individual on the threshold of his or her career. See: http://www.asm.org/index.php/awards/10-awards-a-grants/awards/36-eli-lilly-and-company-research-award American Society for Microbiology Status:Recipient Level:International

1997 Pharmingen Investigator Award This award recognizes an early-career investigator who has made outstanding contributions to the field of immunology See: http://www.aai.org/awards/Career/index.html American Association of Immunologists Status:Recipient Level:National

Antigen processing, Proteasomes,Proteolysis,Enzyme Complex,Immunogenetics,Immunoregulation,Laboratory Mouse,Molecular Cloning,Peptide Structure, Major Histocompatibility Complex,Tissue Culture,Antigen Presentation,Genetic Polymorphism,Protein Purification,Nucleic Acid Sequence,Cytotoxic T Lymphocyte, MALDI-TOF, mass spectrometry

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john.monaco@uc.edu