Proteolytic Degradation in Immuno-Oncology

Principal Investigator: 
Antonio Marzio, Ph.D.

The focus of the Marzio laboratory is to elucidate how deregulation of the ubiquitin-proteasome system (UPS) promotes cancer progression, with a particular emphasis on the DNA damage response (DDR) and antitumor immunity. To date, despite the rapid increase in interest in the role of the UPS in regulating immune responses, there has been rather limited progress in understanding how deregulation of E3 ubiquitin ligases (E3s) participate in antitumor immunity. To address these questions, we use multidisciplinary approaches including biochemistry, cell signaling, mouse models of tumorigenesis, and pharmacotherapy. The ultimate goal of these efforts is to understand the underlying molecular drivers of tumorigenesis in order to leverage these genetic and biochemical alterations for therapeutic applications.

The Marzio lab has recently identified a molecular mechanism by which deregulation of the E3 ubiquitin ligase KEAP1 controls fundamental aspects of anti-tumor immunity and DDR in the context of non-small cell lung cancer (NSCLC) (Marzio et al., Cell 2022). Understanding the role of KEAP1, and its substrates, has the potential to have a profound impact on our understanding of the immune response NSCLC, and to improve the success of therapy for this tumor type. The laboratory also studies how overexpression of the chromatin regulator EMSY modulates DDR pathways, and how this contributes to tumorigenesis.

Active Projects

  • The role of the tumor suppressor KEAP1 in antitumor immunity
  • UPS components activity in innate immunity (and tumor immunosurveillance)
  • The oncogenic activity of EMSY in cancer development and progression


PI: Antonio Marzio, PhD
United States Department of Defense

PI: Alessandra Ferri, PhD
American Italian Cancer Foundation

Additional Key Academic Personnel

Sachith De Silva
Post Doc
Alessandra Ferri
Post Doc

Contact Information

Antonio Marzio, PhD
Assistant Professor of Pathology and Laboratory Medicine
Weill Cornell Medicine

Belfer Research Building, 15th Floor
413 E 69th St.
New York, NY 10021

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700