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Matthew D. Weitzman, PhD
Matthew D. Weitzman Headshot
Co-Director, Division of Protective Immunity

Dr. Weitzman's research program aims to understand host responses to virus infection, and the cellular environment encountered and manipulated by viruses. He studies multiple viruses in an integrated experimental approach that combines biochemistry, molecular biology, genetics, and cell biology.

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Bio

Dr. Weitzman's research addresses how viruses create conditions conducive to their reproduction by shaping host cell environments, particularly with regards to genome interactions. He discovered cellular antiviral defenses, and identified viral strategies to manipulate these host processes. His work addresses the dynamic interactions between viruses and host cells when their genomes are in conflict.

He investigates the interplay between viral genetic material and host defense strategies. He has used proteomic approaches to probe the interactions taking place on viral and cellular genomes during infection, and has uncovered ways that viruses manipulate chromatin and DNA damage responses as they take control of cellular processes.

The pathways illuminated are key to fighting viral infection, provide insights into fundamental processes that maintain genome instability, and have implications for developing viral vectors for gene therapy. The confrontation between viral and host genomes provides a battleground that provides lessons in genome protection, and which will help guide therapeutic strategies to fight infection and cancer.

Among his notable career highlights, Dr. Weitzman:

  • Discovered that host DNA repair machinery recognizes the genomes of DNA viruses and can act as intrinsic barrier to virus infection.
  • Identified the MRN complex as the mammalian sensor of DNA breaks and viral genomes in the nucleus and its role in activation of damage signaling pathways.
  • Defined strategies for viruses to exploit ubiquitination to degrade key mediators of host pathways or redirect cellular processes to promote infection.
  • Discovered how a core basic viral protein disrupts host nuclear architecture and gets incorporated into cellular chromatin where it retains an alarmin danger signal to affect immune responses.
  • Demonstrated that the human APOBEC3A protein inhibits replication of DNA viruses and can modify the host genome, causing DNA damage and cell cycle arrest, but also presenting a vulnerability for targeting cancer cells.

Education and Training

BS, University of Leeds (Genetics), 1987

PhD, Institute of Virology & Oxford Polytechnic (Molecular Virology), 1991

Titles and Academic Titles

Co-Director, Division of Protective Immunity

Professor of Pathology and Laboratory Medicine

Professor of Pediatrics

Professor of Microbiology

Professional Memberships

American Society for Gene and Cell Therapy

American Society for Virology

American Society for Microbiology

Professional Awards

Young Investigator Award, American Society for Gene Therapy, 2004

Innovation Grant recipient, the Salk Institute Innovation Fund, 2008

Pioneer Developmental Chair, Salk Institute, 2008-2011

Harold S Ginsberg Lecture, America Society for Virology Annual Meeting, 2010

Foerderer Award, Children's Hospital of Philadelphia, 2013

CHOP Faculty Mentor Award, 2016

CHOP Award for Excellence in Mentoring Research Trainees, 2017

Publication Highlights

Reyes RD, Kulej K, Akhtar LN, Avgousti DC, Pancholi NJ, Kim ET, Bricker D, Koniski S, Seeholzer SH, Isaacs SN, Garcia BA, and Weitzman, MD. Identifying host factors associated with DNA replicated during virus infection. Mol Cell Proteomics. 2017 Dec; 16(12):2079-2097. PMID: 28972080
Green AM, Budagyan K, Hayer KE, Reed MA, Savani MR, Wertheim GB and Weitzman, MD. Cytosine deaminase APOBEC3A sensitizes leukemia cells to inhibition of the DNA replication checkpoint. Cancer Res. 2017 Nov; 77(17):4579-4588. PMID: 28655787
Avgousti DC, Herrmann C, Sekulic N, Kulej K, Petrescu J, Molden RC, Pancholi NJ, Reyes ED, Seeholzer SH, Black BE, Garcia BA and Weitzman, MD. A core viral protein binds host nucleosomes to sequester immune danger signals. Nature. 2016 Jul; 535(7610):173-7. PMID: 27362237
Chaurushiya MS, Lilley CE, Aslanian A, Meisenhelder J, Scott DC, Landry S, Ticau S, Boutell C, Yates JR, Schulman BA, Hunter T and Weitzman, MD. Viral E3 ubiquitin-mediated degradation of a cellular E3: viral mimicry of a cellular phosphorylation mark targets the RNF8 FHA domain. Mol Cell. 2012 Apr; 46(1):79-90. PMID: 22405594
Stracker TH, Carson CT, and Weitzman MD. Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Nature. 2002 Jul; 418(6895):348-52. PMID: 12124628

Links of Interest