Scientists / Our Scientists

Avi Ashkenazi

Distinguished Fellow, Cancer Immunology

Postdoc Mentor

"I believe that the most important purpose of science is to advance knowledge toward practical applications that can transform human life."

Years at Genentech

174

Publications at Genentech

Awards & Honors

I came to Genentech to pursue postdoctoral training because I valued the company’s scientific excellence and its foundational philosophy of integrating basic research and medical translation. My postdoc studies on neurotransmitter receptors led to papers in Science, Nature and Cell, and earned the 1988 Boeringer Ingelheim Award. I joined the department of Molecular Biology as Scientist in 1989, and my lab helped establish a technology to fuse biologically important proteins to antibody molecules. This approach is now widely implemented in biological research and biotech drugs.

In the 1990’s, the Human Genome Project inspired my team to discover several novel members of the TNF cytokine superfamily, most notably, Apo2L/TRAIL and its "death" and "decoy" receptors. This led us to investigate a cell-suicide process called Apoptosis—which has important roles in normal physiology as well as in disease. Our contributions to elucidating the mechanisms of apoptosis led to clinical investigation of a novel class of molecules called Pro-Apoptotic Receptor Agonists, and aided in the advancement of apoptosis-promoting cancer medicines such as venclexta. In separate work, my team identified a set of secreted proteins overexpressed in the tumor microenvironment, and developed antibodies to block their cognate receptors for therapeutic gain.

More recently, we’ve turned our attention to an intracellular signaling network dubbed the unfolded protein response (UPR). The UPR normally helps secretory cells to resolve issues with 3D shaping of newly synthesized proteins. UPR dysregulation can promote diseases such as cancer, autoimmunity and neurodegeneration. We have discovered that the key UPR enzyme IRE1 is hijacked by certain cancer cells to avert apoptosis and resist proteotoxic stress. Our research further revealed that inhibiting IRE1 activity in cancer-surveilling dendritic cells augments anti-tumor immunity. These studies identify IRE1 as a potential therapeutic target for cancer.

Postdoctoral Mentor

To date I have mentored over 30 postdoctoral fellows, who made many key contributions to our lab’s success. Most have gone on to obtain competitive scientific positions in industry or academia. Our postdocs enjoy significant autonomy: They learn how to (1) identify, define and address key biological questions with scientific rigor and elegance; (2) unite intellectual independence with collaborative teamwork; and (3) integrate basic and translational science to discover and develop transformative new medicines.

Featured Publication

Decoding non-canonical mRNA decay by the endoplasmic-reticulum stress sensor IRE1α.

Nat Commun 12, 7310 (2021).

Le Thomas, A., et al.

View Abstract

We are currently developing strategies that aim to kill cancer cells by directly disrupting their inherent stress-adaptation mechanisms or by augmenting the anti-tumor immune response.

Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay

Nature Communications, ISSN: 20411723

Fátima Cairrão; Cristiana C. Santos; Adrien Le Thomas; Scot A. Marsters; Avi Ashkenazi; Pedro M. Domingos

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Avi Ashkenazi

Distinguished Fellow, Cancer Immunology

Featured Publication

Decoding non-canonical mRNA decay by the endoplasmic-reticulum stress sensor IRE1α.

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