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School of Medicine Departments
 

John Cambier, Ph.D.

Distinguished Professor & Cahirman of the Department of Immunology & Microbiology


Contact
   Phone: TBD
   E-mail: john.cambier@ucdenver.edu

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.  

 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