Gender	Female
E-mail	julie.blander@mssm.edu
Education and Training	Ph.D., University of Pittsburgh School of Medicine
	B.S., American University of Beirut
	Postdoctoral Fellowship, Yale University School of Medicine
	Internship, University of California
Awards	2010 - 2014 Hirschl Scholar Award Irma T. Hirschl/Monique Weill-Caulier
	2009 Thorbecke Award
	2007 - 2010 Searle Scholar
	2003 - 2005 J.V. Satterfield Award Arthritis Foundation

Education and Training	Ph.D., University of Pittsburgh School of Medicine
	B.S., American University of Beirut
	Postdoctoral Fellowship, Yale University School of Medicine
	Internship, University of California

Specific Clinical/Research Interest: Toll-Like Receptors and control of innate and adaptive immunity

Current Students: Priyanka Nair, Ariel Bulua.

Postdoctoral Fellows: Johan Garaude, Ph.D., Leif E. Sander, M.D., Ph.D., Corinna Brereton, Ph.D., Lara Manganaro, Ph.D.

Current work in the laboratory is directed towards the following areas:

Control of cross-presentation by TLRs.  Cross-presentation is the process of presentation of exogenous phagocytosed antigens by major histocompatibility complex (MHC) class I molecules.  We focus on antigens acquired by dendritic cells through phagocytosis, a primary means by which DCs internalize and degrade not only microorganisms but also apoptotic cells.  We have shown that TLRs control phagosome maturation and presentation of antigens by MHC class II molecules.  Here we ask: 1) Do TLRs control cross-presentation, and if so, what is the molecular basis for this control?  2) Is provision of CD4 T cell help to cross-presented antigen regulated by signals from TLRs?  Our studies here have implications in viral and anti-tumor immunity.

Mobilizing the helper immune response against tumors.  Having been derived from self and lacking microbial structures, tumors are poor at inducing activation of the adaptive immune response.  We have shown that the physical presence of phagocytosed antigen and TLR ligands within the same phagosome results in optimal antigen presentation within MHC class II molecules, and successful activation of CD4 T cells.  We have thus engineered transplantable tumor cells that express TLR ligands with the prediction that these cells would induce potent CD4 T cell help to tumor-specific CD8 T cells.  We have found that TLR ligand bearing tumors fail to develop within syngeneic mice.  We are now characterizing the nature of the immune response responsible for rejecting these tumors.  Our studies should pave the way to improved tumor immunotherapeutic strategies.

The immune response to infected and uninfected apoptotic cells.  The immunosuppressive nature of apoptotic cell clearance must sometimes coexist with the necessarily inflammatory nature of infection.  We have found that pathogens particularly adept at triggering apoptosis preferentially induce T helper 17 (TH17) mediated immunity.  We have assigned an important role to phagocytosis of infected apoptotic cells in contributing signals for the development of TH17 cells.  We are now investigating the pathways of innate recognition of infected apoptotic cells.  Given that infected apoptotic cells comprise signals derived from both self and non-self, we also seek to define the regulatory mechanisms that prevent activation of TH17 cells with specificities to apoptotic cell derived self antigens.  Our work should reveal the reasons behind the preferential association of TH17 cells with autoimmunity.

Molecular basis for the superiority of viable vaccines.  Vaccination induces a state of immune preparedness by exposing the host to signature components from select pathogens.  Although some vaccine preparations can induce protective immunity, there is room for improvement, as certain poorly characterized aspects of natural infection (not incorporated in most vaccines) are particularly effective in inducing the right combination of signals for generating protective immunity.  We are working to define the nature of these signals, and delineate the unique receptors and innate immune pathways that they trigger.  We hope this knowledge will guide us towards significantly improved vaccine design strategies.

 

 

 

Torchinsky MB, Garaude J, Blander JM. Infection and apoptosis as a joint inflammatory trigger. Current Opinion in Immunology 2009;.

Sander LE, Blander JM. Innate immune cells cast an eye on DNA. Molecular Cell Biology 2009; 10: 1093.

Blander JM, Amsen D. Amino acid addiction. Science 2009; 324: 1282-1283.

Sander LE, Blander JM. Inflammasome and Toll-like receptor 9:partners in crime in toxic liver injury. Hepatology 2009; 49: 2119-2121.

Torchinsky MB, Garaude J, Martin A, Blander JM. Innate Immune recognition of infected apoptotic cells directs TH17 cell differentiation. Nature 2009;: in press.

Blander JM. Analysis of the TLR/NF-( *B pathway in antigen-presenting cells in malignancies promoted by inflammation. Methods Mol Biol 2009; 512: 99-117.

Blander JM. Phagocytosis and antigen presentation: a partnership initiated by Toll-like receptors [review]. Ann Rheum Dis 2008 Dec; 67(Suppl 3): iii44-iii49.

Blander JM, Medzhitov R. Toll-like receptors and phagosome maturation. Nat Immunol 2007; 8: 217-218.

Blander JM. Signalling and phagocytosis in the orchestration of host defence. [review]. Cell Microbiol 2007 February; 9(2): 290-299.

Blander JM. Coupling Toll-like receptor signaling with phagocytosis: potentiation of antigen presentation [review]. Trends Immunol 2007 January; 28(1): 19-25.

Blander JM. On phagosome maturation and antigen presentation. Nat Immunol 2006 October; 7(10): 1029-1035.

Blander JM, Medzhitov R. Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 2006 Apr 6; 440(7085): 808-812.

Blander JM, Medzhitov R. Regulation of phagosome maturation by signals from toll-like receptors. Science 2004 May 14; 304(5673): 1014-1018.

Amsen D, Blander JM, Lee GR, Tanigaki K, Honjo T, Flavell RA. Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell 2004 May 14; 117(4): 515-526.