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Faculty Detail    
Name JOHN D MOUNTZ
  
Campus Address SHEL 307 Zip 2182
Phone  (205) 934-8909
E-mail  jdmountz@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Med - Immunology/Rheumatology  Med - Immunology/Rheumatology Professor
Secondary  Med - Div of Human Gene Therapy  Gene Therapy Center Professor
Secondary  Med-Gerontology/Geriatrics/Palliative Care  Med-Gerontology/Geriatrics/Palliative Care Professor
Secondary  Microbiology  Microbiology Professor
Secondary  Pathology Chair Office  Pathology Chair Office Professor
Center  Biomatrix Eng Regen Med (BERM) Ctr  Biomatrix Eng Regen Med (BERM) Ctr Professor
Center  Cell Adhesion & Matrix Research Center  Cell Adhesion & Matrix Research Center Professor
Center  Center for AIDS Research  Center for AIDS Research Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Ctr for Exercise Medicine (Org Ret)  Ctr for Exercise Medicine (Org Ret) Professor
Center  Integrative Center for Aging Research  Integrative Center for Aging Research Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Immunology 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Mountz is a Professor of Medicine and Director of the UAB Recombinant Inbred Strain Facility. Dr. Mountz is the Co-Director of the UAB Bone Center, the UAB Center for Aging, Basic Biology Component, and is a Physician at the Birmingham Veterans Administration Medical Center. Dr. Mountz is the recipient of the J. W. & Virginia Goodwin-Warren D. Blackburn, Jr. Research Chair in Rheumatology (2002) and recipient of the Max Cooper Award for Excellence in Research (2003). Dr. Mountz was designated one of 50 Arthritis Foundation ˇ§Heroesˇ¨for outstanding contributions for research in Rheumatology (2002). Dr. Mountz was Co-Chair of the National Institutes on Aging Task Force on Immunology and Aging and Co-Chair of the ˇ§Leukocyte Trafficking in Inflammatory Diseaseˇ¨ symposium at the 2004 annual meeting of the American Association of Immunologists. Dr. Mountz received a Ph.D. in High Energy Physics and graduated Summa Cum Laude before carrying out a post-doctoral fellowship in the area of biophysics studying bilayer lipid membranes. Dr. Mountz then received an MD from Ohio State University and carried out an internship of residency and a one-year fellowship in Internal Medicine in Rheumatology. Dr. Mountz was a research staff fellow at the National Institutes of Health for five years and also an Assistant Professor of Medicine at the Naval Bethesda Medical Center. During this time, Dr. Mountz was the first investigator to identify that Onco genes were elevated in autoimmune mice and humans. Dr. Mountz became an Assistant Professor of Medicine at The University of Alabama at Birmingham in 1987, where he produced the first transgenic mouse expressing Fas in T cells and ameliorated the lymphoproliferative autoimmune disease in /lpr (Fas mutant mice). Dr. Mountz then identified the Fas mutation in MRL-lpr/lpr mice as being an insertion of the Etn retrotransposon. Dr. Mountz also was the first investigator to study clono-deletion and energy induction in PCR transgenic mice on the lpr/lpr background. Dr. Mountz continues an active research program in lupus, arthritis, molecular nuclear imaging, immune response to virus and poxvirus and gene therapy, as well as T-cell senescence in aging in both mice and humans.



Research/Clinical Interest
Title
autoimmunity, immune senescence, gene therapy
Description
The major focus of the laboratory is analysis of immune regulation of autoantibody production. The BXD2 recombinant inbred strain of mouse produces multireactive pathogenic autoantibodies that can cause arthritis and glomerulonephritis. The T cell defects, including upregulation of IL-17 and T follicular helper cell factors, and their effects on B cell development and immunoglobulin somatic hypermutation and class-switch recombination are being investigated. One underlying key mechanism leading to the development of spontaneous germinal centers (GCs) in BXD2 mice is a rapid loss of a protective barrier, called marginal zone macrophages (MZMs), in the spleen of BXD2 mice. These MZMs express scavenger receptors and act as the major phagocytic cells to clear apoptotic debris derived from the circulation and the spleen. We have identified that loss of MZMs in the spleen is associated with defective clearance of apoptotic debris, upregulation of type I interferons (IFNs), and development of spontaneous GCs in BXD2 mice. We have identified that type I IFN-stimulated follicular migration of marginal zone (MZ) B cells exhibits an important pathogenic impact on BXD2 mice through the loss of close interactions between MZMs and MZ B cells in the spleen marginal zone. Such close contact is important to upregulate a mechanosensitive signal called megakaryoblastic leukemia 1 (MKL1) that is important to mainatain the normal phagocytic function and survival of MZMs. Defective expression of MKL1 in BXD2 mice as a result of type I IFN stimulation has promoted the loss of MZMs in the MZ. We have further identified that IgG immune complex (IC) stimulation exhibits an important effect to convert the otherwise tolerogenic MZMs to inflammatory MZMs during the course of autoimmune disease initiation in BXD2 mice. The molecular mechanism that is associated with the IgG-IC-induced MZM defects is the upregulation of Bruton tyrosine kinase (Btk). We are testing the possibility to tolerize MZMs via a small molecule liposome delivery strategy to specifically suppress the activity of Btk in MZMs of BXD2 mice. A third focus of my laboratory is the investigation of the positive feedback loop between inflammatory macrophages and effector CD4 T cells in the pathogenesis of rheumatoid arthritis (RA). We are employing novels strategies to selectively block the inflammatory M1 macrophage or the Th17 polarization process to reshape immune regulation in RA. A potential inhibitor that can convert inflammatory macrophages to anti-inflammatory macrophages is a small molecular inhibitor that can specifically block terminal fucosyltransferases (FUTs). We have identified these terminal FUTs are selectively expressed by inflammatory M1 but not anti-inflammatory M2 macrophages. We currently study the molecular mode of action of terminal fucosylation in M1 lineage development.

Selected Publications 
Publication PUBMEDID
Li H, Hsu H-C, Wu Q, Yang PA, Li J, Cua D, Oukka M, Grizzle, Steele III CH, WE, and Mountz JD. IL-23 Promotes TCR-mediated Thymocyte Negative Selection through the Upregulation of IL-23 Receptor and RORgammat (In Press, Nature Communications)   
Ding Y, Li J, Yang P, Zajac A, Hsu H-C, Mountz JD. IL-21 promotes germinal center reaction by regulating Tfr/Tfh in autoimmune BXD2 mice. Arthritis Rheumatol. 2014 Jun 6. doi: 10.1002/art.38735. [Epub ahead of print]  24909430  
Li J, Yang PA, Wu Q, Li, H, Ding Y, Hsu H-C, and Mountz JD. Inhibition of terminal fucosylation reshapes human and mouse M1 macrophages and suppresses collagen II-induced arthritis. 2014 May 16. doi: 10.1002/art.38711. [Epub ahead of print]  24838610  
Ding Y, Li J, Wu Q, Yang P, Luo B, Xie S, Druey KM, Zajac AJ, Hsu H-C, and Mountz JD. IL-17RA is essential for optimal localization of follicular T helper cells in the germinal center light zone to promote autoantibody-producing B cells. J Immunol 191:1614-1624, 2013   23858031  
Wang JH, New JS, Xie S, Yang PA, Wu Q, Li J, Luo B, Ding Y, Druey KM, Hsu H-C, and Mountz JD. Extension of the germinal center stage of B-cell development promotes autoantibodies in BXD2 mice. Arthritis & Rheum 65(10), 2703-2712, 2013, PMC3979745.  23818250 
Li J, Yang PA, Wu Q, Li, H, Ding Y, Hsu H-C, Spalding DM, and Mountz JD. TRA-8 depletes low-SHP-1-associated inflammatory IRF5+IL-23+ macrophages and GM-CSF+IL-17+ CD4 T cells in viable motheaten mice and subjects with rheumatoid arthritis. Arthritis & Rheum 65(10), 2594-2605, 2013, PMC3993980  23818173  
Li H, Wu Q, Li J, Yang P, Zhu Z, Luo B, Hsu H-C, and Mountz JD. Cutting Edge: Defective follicular exclusion of apoptotic antigens due to marginal zone macrophage defects in autoimmune BXD2 mice. J Immunol 190(9):4465-9, 2013. PMC3656168.  23543760  
Li J, Hsu HC, Yang P, Wu Q, Li H, Edgington LE, Bogyo M, Kimberly RP, Mountz JD. Treatment of arthritis by macrophage depletion and immunomodulation: Testing an apoptosis-mediated therapy in a humanized death receptor mouse model. Arthritis Rheum. 64(4): 1098–1109, 2012. PMC3596268  22006294  
Hsu H-C, Yang PA, Wu Q, Wang J, Godwin J, Guentert T, Li J, Stockard CR, Le T, Chaplin DD, Grizzle WE, and Mountz, JD. Inhibition of the catalytic function of activation-induced cytidine deaminase (AICDA) promotes apoptosis of germinal center B cells. Arthritis Rheum, 2011 Jan 21. doi: 10.1002/art.30257  21305519  
Wang JH, Wu Q, Yang PA, Li H, Li J, Mountz JD and Hsu H-C. Type I IFN-dependent CD86high marginal zone-precursor B cells are potent T-cell costimulators. Arthritis Rheum. 2011 Apr;63(4):1054-64.  21225691  
Hsu HC, Mountz JD. Metabolic syndrome, hormones and maintenance of T cells during aging. Curr Opin Immunol 22: 541-548, 2010.   20591642  
He D, Li H, Yusuf N, Elmets CA, Li J, Mountz JD, Xu H. IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells. J Immunol 184: 2281-8, 2010.   20118280  
Xie S, Wang J, Wu Q, Li H, Li J, Hsu H-C, Smythies LE, and Mountz JD. IL-17 activates the canonical NF-kB signaling pathway in autoimmune B cells of BXD2 mice to upregulate the expression of regulators of G-protein signaling 16. J Immunol 184:2289-96, 2010.  20118280  
Wang JH, Li J, Wu Q, Yang P, Pawar RD, Xie S, Timares L, Raman C, Chaplin DD, Lu L, Mountz JD, Hsu HC. Marginal zone precursor B cells as cellular agents for Type I IFN-promoted antigen transport in autoimmunity. J Immunol, Epub ahead of print, November 30, 2009.   19949066  
Chen J, Li J, Lim FC, Wu Q, Douek DC, Scott DK, Ravussin E, Hsu HC, Jazwinski SM, Mountz JD, The Louisiana Healthy Aging Study. Maintenance of naïve CD8 T cells in nonagenarians by leptin, IGFBP3 and T3. Mech Ageing Dev 131(1):29-37, 2010.   19941883  
Chen J, Li J, Lim FC, Wu Q, Douek DC, Scott DK, Ravussin E, Hsu HC, Jazwinski SM, Mountz JD; for The Louisiana Healthy Aging Study. Maintenance of naïve CD8 T cells in nonagenarians by leptin, IGFBP3 and T3. Mech Ageing Dev 131(1):29-37, 2010.  19941883  
Wang X, Fujita M, Prado, R, Tousson A, Hsu H-C, Ynonne YL, Kelly DR, Yang PA, Wu Q, Chen J, Xu H, Elemets CA, Mountz JD and Edwards CKIII. X. Visualizing CD4 T cell Migration into Inflamed Skin and Its Inhibition by CCR4/CCR10 Blockades using in vivo Imaging Model. Br J Dermatol. 2009 Oct 15  19832835  
Xu X, Hsu H-C, Grizzle WE, Chatham WW, Wu Q, Stockard CR, Yang PA, Tunmire D, Holers M and Mountz JD. Increased expression of activation-induced cytidine deaminase (AID) is associated with anti-CCP and rheumatoid factor (RF) in rheumatoid arthritis (RA). Scan J Immunol 70:309-316, 2009.   19703021 
Matthews QL, Yang P, Wu Q, Belousova N, Rivera AA, Stoff-Khalili MA, Waehler R, Hsu HC, Li Z, Li J, Mountz JD, Wu H, Curiel DT. Optimization of capsid-incorporated antigens for a novel adenovirus vaccine approach. Virol J 5:98, 2008.   18718011  
Hsu H-C, Yang PA, Wang J, Wu Q, Myers R, Chen J, Yi J, Guentert T, Tousson A, Stanus AL, Le TV, Lorenz RG, Xu H, Kolls JK, Carter RH, Chaplin DD, Lu L, Williams RW and Mountz JD. Interleukin 17–producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol 9:166-175, 2008.  18157131  
Hsu HC, Wu Y, Yang P, Wu Q, Job G, Chen J, Wang J, Accavitti-Loper MA, Grizzle WE, Carter RH, Mountz JD. Overexpression of activation-induced cytidine deaminase in B cells is associated with production of highly pathogenic autoantibodies. J Immunol 178:5357-5365, 2007.   17404321  
Hsu H-C, Zhou T, Kim H, Barnes S, Yang PA, Wu Q, Zhou J, Freeman BA, Luo M, Mountz JD: Production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice causes glomerulonephritis and arthritis. Arthritis Rheum 54(1):343-355, 2005.  16385526  
 

Keywords
type I IFNs, IL-23, germinal centers, marginal zone macrophages, inflammatory macrophages, rheumatoid arthritis, lupus