NIBR
POSTDOCTORAL PROGRAM

JenniferMatarazaJennifer Mataraza, PhD
Exploratory Immuno-Oncology
Cambridge, Massachusetts, United States


Programmed death-1 (PD-1) is one of the most well-characterized immune checkpoint cell surface receptors. PD-1 is expressed on activated CD4 and CD8 T cells and T regs and regulates the adaptive immune response. Engagement of PD-1 by its ligands, PD-L1 and PD-L2, transduces a signal that inhibits T-cell proliferation, cytokine production, and cytolytic function. PD-1 is upregulated on effector T cells in settings of cancer or chronic viral infection, leading to a stage of exhaustion/dysfunction, while PD-L1 is expressed at high levels on many types of tumors. Blockade of the PD-1 pathway can reverse and prevent the inhibition of effector T cell function, thereby promoting a robust anti-tumor response. A number of agents targeting the PD-1 pathway are in clinical development, and clinical trial data has shown durable responses in patients in multiple cancer types.

There is a strong rationale to combine agents targeting immune checkpoints with various therapeutic modalities such as small molecule inhibitors, vaccines and CAR T cells. These combinations have the potential to optimize different aspects of the immune response: triggering an anti-tumor immune response that will be enhanced by the immune checkpoint blockade; decreasing the tumor-induced immunosuppression to facilitate the activated immune response; or specifically increasing the immune-checkpoint target expression on tumor cells to boost efficacy. Recent studies demonstrating the synergistic effects of anti-PD-1 and anti-CTLA-4 co-blockade in clinical trials in a number of indications illustrates the potential for increased potency with combination therapy. Our group is interested in investigating the potential of these combinations using in vitro and in vivo model systems.

Selected Publications

IQGAP1 stimulates proliferation and enhances tumorigenesis of human breast epithelial cells.
Jadeski L, Mataraza JM, Jeong HW, Li Z, Sacks DB.
J Biol Chem. 2008 Jan 11;283(2):1008-17

Disruption of cyclin D3 blocks proliferation of normal B-1a cells, but loss of cyclin D3 is compensated by cyclin D2 in cyclin D3-deficient mice.
Mataraza JM, Tumang JR, Gumina MR, Gurdak SM, Rothstein TL, Chiles TC.
J Immunol. 2006 Jul 15;177(2):787-95.

IQGAP1 promotes cell motility and invasion.
Mataraza JM, Briggs MW, Li Z, Entwistle A, Ridley AJ, Sacks DB.
J Biol Chem. 2003 Oct 17;278(42):41237-45.

Click here for additional publications.