"The most encouraging advance in the field of immunology today is the realization that we can leverage T cells as therapeutics against cancer. It is extremely exciting to be working at the forefront of cancer immunotherapy research in such a vibrant and collaborative scientific community as Genentech."
I have been interested in studying mechanisms that regulate immune cell function since I started my graduate work in the laboratory of Christian Münz, first at the Rockefeller University in NYC, and then at the University of Zurich. Characterizing the immunological synapse between dendritic cells and natural killer cells became the starting point for my scientific interest on understanding how immune cells are regulated in their response against cancer. I started my postdoctoral work at the Institut Pasteur in Paris and moved to Genentech in 2015, where I continued working with Matthew Albert and Ira Mellman, in the department of Cancer Immunology. My work focused on discerning druggable pathways that govern immune cell migration into tumors.
I became a Senior Scientist in the Department of Cancer Immunology in 2021. My group works to translate observations from immunotherapy clinical trials into research hypotheses with the aim of discovering and validating novel therapeutic targets. I am extremely fortunate to collaborate with many exceptionally talented scientists across Genentech, that inspire me every day.
In revision at Nature Immunology.
Nat Immunol, 20:257-264
Nat Immunol 8:850-8.
Immunotherapy agents, such as inhibitors of the immune checkpoint Programmed cell death protein 1 (PD-1) or its ligand PD-L1, potentiate cytotoxic CD8 T cell responses against tumor cells and have been approved for the treatment of many cancer types. However, we also recognize that tumors evolve to evade the immune system, motivating us to discover and develop novel ways to achieve sustained anti-tumor immunity.
During my time as a postdoctoral fellow at Genentech, I studied mechanisms that regulate leukocyte migration into tumors with the goal of modulating these pathways in a manner that improves anti-tumor immunity. Specifically, we demonstrated that the key proinflammatory chemokine CXCL10 is altered through post-translational modifications that compromise its function, thus affecting cytotoxic CD8 T cell migration to tumors. Pharmacological inhibition of the extracellular enzyme Dipeptidylpeptidase 4 (DPP4), which truncates CXCL10, restores chemokine function and enhances T cell migration into tumors. My postdoctoral work further elucidated a similar role for DPP4 in limiting eosinophil migration in cancer through the truncation of the chemokine CCL11. Lastly, we described the function the intracellular enzyme Glutaminyl-peptide cyclotransferase-like (QPCTL) in protecting monocyte chemoattractants from inactivation by DPP4. QPCTL inhibition limited monocyte migration into tumors and thereby reshaped the myeloid cell infiltrate to enhance anti-tumor immunity.
My research group in the department of Cancer Immunology investigates mechanisms that impact patient’s responses to cancer immunotherapies, such as checkpoint inhibition, with the goal of discovering new immunoregulatory targets. This reverse translation approach aims to spur research efforts from our plentiful clinical trial data thus enabling next generation immunotherapies.