Julie Magarian Blander, Ph.D.
GLADYS AND ROLAND HARRIMAN PROFESSOR OF IMMUNOLOGY
Investigates the mechanisms of innate and adaptive immune responses particularly to microbial infection and cell death.
The Blander Lab studies the fundamental principles of innate immunity and inflammation, and their application to human disease. Our research is on the function of phagocytes in infection, cancer, and chronic inflammation. Our goal is to inform new treatments and vaccines against disease.
The Blander laboratory is located at Weill Cornell Medicine, within The Jill Roberts Institute for Research in Inflammatory Bowel Disease
The Department of Microbiology and Immunology
The Sandra and Edward Meyer Cancer Center
Major achievements
Life and death of individual cells are at the core of multicellular existence: homeostatic apoptosis is necessary for replacement of cells and organogenesis, whereas cell death during infection signals serious threats to the host organism. Guided by this paradigm, we have studied the regulation of phagocytosis, a process of internalization and degradation of microbes or dying cells by professional phagocytes. We described ‘phagosome autonomy’ to define phagosomes as autonomous information-processing units irrespective of the phagocyte activation state. Phagosomes carrying microbes are favored for the presentation of microbial antigens because they engage Toll-like receptors, which alert the innate immune system. Phagosome autonomy has inspired the design of vaccine carriers that co-deliver antigens and adjuvants to the same subcellular compartment within antigen-presenting cells. We have used this knowledge to prime anti-tumor immunity in mice by targeting to phagosomes a bacterial protein within internalized tumor cells.
Our work showed that the phagocytosis of infected dying cells generates a dual inflammatory and anti-inflammatory milieu, which instructs T helper-17 immunity –best suited for host defense and tissue repair. We delineated the immunosuppressive genetic programs in phagocytes following internalization of cells dying by homeostatic apoptosis, and found that many of the genes comprising these programs are associated with susceptibility for a chronic inflammatory disease.
We discovered the ability of the innate immune system to discriminate between live and dead microbes by sensing signature molecules of microbial viability, which we have named vita-PAMPs. Vita-PAMPs mobilize distinct and highly inflammatory immune responses not warranted for dead microbes. We found vita-PAMPs to be responsible for the efficacy of live vaccines over their dead counterparts, and linked innate detection of bacterial messenger RNA, a vita-PAMP, to the differentiation of follicular T helper cells, which heighten the antibody response. Our work has prompted the design of adjuvants incorporating vita-PAMPs in inactivated or subunit vaccines to replicate the efficacy of live vaccines in mobilizing long-lasting protective immunity.