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John Cambier PhD

Distinguished Professor and Chairman of the Integrated Department of Immunology

 

 John Cambier

 

 

Ida and Cecil Green Distinguished Professor and Chairman,
Integrated Department of Immunology
University of Colorado Denver and
National Jewish Health
Phone: (303) 398-1325
E-mail:cambierj@NJHealth.org
Dr. Cambier's National Jewish Health webpage

 

Development, growth and differentiation of cells of the immune system is regulated by myriad environmental queues which take the form of soluble or cell associated ligands that bind cell surface or intracellular receptors.  Proper function of  these pathways assures the generation of protective innate and adaptive immunity. Failure of these systems can lead to immunode-ficiency and autoimmunity.  The overarching interest of my laboratory is in understanding how immune responses are orchestrated at the level of receptor signaling, and translating this knowledge to understand  and treat immune abnormality in humans.

 

Our work is currently focused on six specific problems related to tolerance and autoimmunity:  1) the basis of antigen unresponsiveness of anergic B cells, and mechanisms underlying loss of  anergy leading to autoimmunities such as Lupus, Type 1 Diabetes and Rheumatoid Arthritis, 2) the role of autoantigen avidity and affinity in determining alternate molecular bases of anergy, 4) the mechanism of signal regulation by feedback mechanisms and inhibitory receptors such as FcRIIB, 5) basis of aging-associated defects in B cell poiesis and function, and 6) the function of STING/MPYS, a recently described innate signaling adaptor cloned in our laboratory.

 

We are currently most excited about our studies involving isolation and functional analysis of autoantigen-specific B cells from healthy and autoimmune mice and humans. Our initial studies have focused on the status of insulin-specific B cells Type 1 Diabetes, and indicate that in both mice and humans anergy to this autoantigen is lost long before onset of disease, but regained in humans within one year of diagnosis. These studies suggest an important role for environmental factors such as infection and injury in predisposing individuals to autoimmunity. Future work in this area will expand studies to other autoimmunities, and define signaling mechanisms that maintain anergy, and fail during development of autoimmunity. Parallel studies seek to understand whether and how environment factors such as infection and injury defeat tolerance mechanisms.  

 

  • Jordan MB, Mills DM, Kappler J, Marrack P and Cambier JC. 2004. Promotion of B cell Immune responses via an alum-induced myeloid cell population. Science. Jun 18;304(5678):1808-10. *Recommended as “must read” by Faculty of 1000.

  • Gauld SB, Benschop R, Merrell K and Cambier JC. 2005. Maintenance of B Cell Anergy Requires Constant Antigen Receptor Occupancy and Signaling. Nat Immunol. Nov;6(11):1160-7

  • Merrell KT, Benschop RJ, Gauld SB, Aviszus K, Decote D, Wysocki LJ and Cambier JC. 2006. Identification of anergic B cells within a wild-type repertoire. Immunity Dec:25(6):953-962. *Previewed by F. Melchers, Anergic B Cells Caught in the Act Dec:25(6):864-867. Recommended as “must read” by Faculty of 1000 Biology. New finding Factor 6.0. E. Charles Snow: Faculty of 1000 Biology, 26 Jan 2007.

  • Brauweiler A, Merrell K, Gauld SB and Cambier JC. 2007. Cutting Edge: Acute and chronic exposure of immature B cells to antigen leads to impaired homing and SHIP1-dependent reduction in stromal cell-derived factor-1 responsiveness. J Immunol Mar 15 178(6):3353-7. *Recommended as “must read” by Faculty of 1000 Biology. New finding factor 3.0. E. Charles Snow: Faculty of 1000 Biology. http://www.f1000biology.com/article/id/1070954/evaluation.

  • Cambier JC, Gauld SB, Merrell KT, and Vilen BJ. 2007. B-cell anergy: from transgenic models to naturally occurring anergic B cells. Nat Rev Immunol. Aug;7(8):633-43 

  • Guerrettaz LM, Johnson SA and Cambier JC. 2008. Acquired Hematopoietic Stem Cell Defects Determine B Cell repertoire Changes Associated with Aging. Proc Natl Acad Sci U S A Aug 19;105(33):11898-902.

  • Cady CT, Powell MS, Harbeck RJ, Giclas PC, Murphy JR, Katial RK, Weber RW, Hogarth PM, Johnson S, Bonvini E, Koenig S,  Cambier JC. 2010. IgG antibodies produced during subcutaneous allergen immunotherapy mediate inhibition of basophil activation via a mechanism involving both FcgRIIA and FcgRIIB. Immunol Lett. May 4;130(1-2):57-65.

  • Jin L, Lenz LL, Cambier JC. 2010. Cellular reactive oxygen species inhibit MPYS induction of IFNb. PloS ONE. (accepted)

  • Khalil Ashraf M, Cambier JC and Shlomchik MJ. 2012. B cell signal transduction is short-circuited by increased phosphatase activity in germinal center B cells inhibits B cell signal transduction. Science. 2012 May 3.

  • Waterman PM, Marschner S, Brandl E and Cambier JC. 2012. The inositol 5-phosphatase SHIP-1 and adaptors Dok-1 and 2 play central roles in CD4-mediated inhibitory signaling. Immunol Lett. 2012 Mar 30;143:122-30

  • Xu, L, Jin L, Zhang B, Akerlund JL, Shu HB and Cambier JC. 2012. VISA is required for B cell expression of TLR7. J. Immunol. Jan 1;188:248-58

  • O’Neill SK, Getahun A, Gauld SB, Merrell KT, Tamir I, Smith MJ, Dal Porto JM, Quan-Zhen L and Cambier JC. 2011. Monophosphorylation of CD79a and b ITAMs initiates a SHIP-1-mediated inhibitory signaling cascade required for B cell anergy. Immunity. Nov 23;35:746-56

  • Jin L, Hill KK, Filak H, Mogan J, Knowles H, Zhang B, Perraud AL,Cambier JC, Lenz LL. 2011. MPYS is required for IFN response factor 3 activation and type 1 IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. J Immunol. 2011 Sep 1;187:2595-601
  • Jin L, Xu L, Yang IV, Davidson EJ, Schwartz DA, Wurfel MM and Cambier JC. 2011. Identification and Characterization of a Loss-of-Function Human MPYS Variant. Genes Immun. 2011 Jun;12:263-9.
  • Jin L, Lenz LL, Cambier JC. 2010. Cellular reactive oxygen species inhibit MPYS induction of IFNb. PloS ONE. 2010 December  Volume 5, Issue 12, e15142 pages 1-7


View of Recent Publications in PubMed

 Currrent Trainees  Lab Member since Date of Current Degree Granting Inst. Title of Project
Akerlund, Linda Jane 2008 2006-B.S. University of Oregon  Biochemical basis of SHIP-1 and Dok in the maintenance of B cell anergy
Getahun, Andrew 2007 2005-PhD

Uppsala U, Sweden 

Effects of infection and other innate signals on  B cell responsiveness and anergy 

Hardy, Ian 2008 2010-PhD U. of Colorado
SOM		  Anti-CD79 as a therapeutic for autoimmunity
Hinman, Rochelle 2010 2009-PhD

U. of Texas Southwestern, Dallas

  The microbiome and B cell autoimmunity
Jin, Lei 2004 2004-PhD Tufts Univ Cloning and functional analysis the innate Sensor MPYS/STING/MITA/TMEM173
Kogut, Igor 2010 2010-PhD

U. of Colorado
SOM

 Development and use of induced pluripotent stem (iPS) cells immunosenscenece and tumor therapy
O’Neill, Shannon 2007 2005-PhD Rush Univ Autoantigen specific B cell function in human and murine Type 1 Diabetes
VandenBroeck, Arnaud 2009 2009-PhD U. of Grenoble France Epigenetic changes in aging stem cells
Xu, Liang Guo 2008 PhD Beijing University VISA/MAVS/IPSI/ function in TLR signaling 
Yarkoni, Yuval 2005 2004-PhD Hebrew Univ. Function of STIM1 in BCR signaling 

Active Grant Funding

P01 AI022295 PI Marrack Antigen Recognition by Lymphocytes

5R01 AI062739 PI Cambier) NKIP signaling and function

JDRF 1-2008-994 Gottlieb, Cambier co-PIs Autoantigen Specific B Cells in the Development of Human Type 1 Diabetes

R21 AI078207 PI Cambier B Cell Development in Aging

R01 AG013983 PI Cambier B Cells and Autoimmunity

R01 AI077597 PI Cambier Infectious Agents and B Cell Anergy