Mark Manzano

Start Date: January 1, 2027

Assistant Professor of Virology, Immunology & Microbiology

Research Interest

The long-term goal of our laboratory is to understand how viruses interact with host cells and how these contribute to viral persistence, viral replication, and cancer development. We combine genome-scale CRISPR screens with molecular and cellular biology to uncover the underlying mechanisms of these biological processes. We are interested in three broad research questions:

1. Chromatin Regulation by Long Non-coding RNAs: How is viral latency established and maintained? 

Herpesviruses evade immune clearance by establishing latency, a transcriptionally restricted state in which only a small subset of viral genes is expressed from the viral dsDNA genome. Our laboratory uses the Kaposi’s sarcoma-associated herpesvirus (KSHV) as a model to study viral latency. Using a CRISPR/Cas13d tiling library designed to systematically knockdown viral transcripts, we identified a viral long non-coding RNA required for maintenance of the latency program. We are studying how this lncRNA regulates the viral chromatin and gene expression to establish and maintain latency.

2. Viral Oncogenesis and Cell Biology: How do oncogenic viruses cause cancer? 

KSHV is the causative agent of several malignancies in people living with HIV, including Kaposi sarcoma and primary effusion lymphoma. Unlike many human cancers, these viral tumors lack recurrent driver mutations. As a result, transformation depends on the constitutive manipulation of cellular pathways by the virus. We previously performed genome-wide CRISPR screens to identify host genes and pathways required by these viral tumor cells. We study the functions of these cellular pathways in promoting cellular survival by inhibiting cell death processes (apoptosis and ferroptosis) and through metabolic reprogramming. 

3. Host Determinants of Viral Infection: Which host factors promote or restrict viral replication?

In collaboration with other virology groups, we use CRISPR screens to identify host pathways that regulate infection by evolutionarily distinct viruses. We primarily use murine gammaherpesvirus 68 and human orthoreovirus as models of DNA and RNA viruses, respectively. By comparing host requirements across unrelated viral families, we seek to distinguish broadly conserved host-virus interactions from mechanisms that are unique to specific pathogens.