Mark Irvin Manzano, PhD

Research Program: Cancer Biology Faculty Rank: Assistant Professor Campus: University of Arkansas for Medical Sciences College: College of Medicine Department: Microbiology & Immunology Faculty

Cancer Research Interest

• Research Keywords: B cell lymphoma, primary effusion lymphoma, tumor virus, genomics
• Research Interest Statement: My lab uses functional genomics to study host-pathogen interactions and biological processes. Functional genomics (in our case, using CRISPR screens) allows for the simultaneous interrogation of the contribution of each gene in the human genome to a particular phenotype. Simply put, this bridges genotype to phenotype on a genome-wide scale in one experiment. We are interested in studying primary effusion lymphoma (PEL), an aggressive B cell cancer caused by the Kaposi’s sarcoma-associated herpesvirus or human herpesvirus 8 (KSHV/HHV8). PEL tumor cells rely on the constitutive expression of virally encoded genes that globally reprogram host gene expression to create a conducive environment optimal for tumor cell proliferation and survival. We previously performed genome-wide CRISPR/Cas9 screens and identified 210 host genes that are required for tumor cell proliferation and survival. Our over-all goal is to understand the functions of these host genes in B cell lymphoma. Using CRISPR/Cas9, CRISPRi and CRISPRa-based synthetic lethality and rescue screens, we aim to identify functional genetic interactions of these host genes. We anticipate that this unbiased approach will uncover novel and underappreciated insights into the biology of these host genes. We will furthermore leverage these host genetic dependencies by testing the efficacy of small molecule inhibitors against PEL in vitro and in vivo. Lastly, we are developing a CRISPR-Cas13 system to screen for coding and non-coding transcripts from KSHV that are essential for tumor cell proliferation and survival. Together, our research program will provide a better understanding of the oncogenic processes driven by the tumor virus KSHV, uncover new biology of host genes, and develop new therapeutics for this aggressive malignancy.

Contact Information

• Email Address: MMANZANO@UAMS.EDU
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Active Grants

• NIH/Nat. Cancer Institute – 1R21CA285135
  “Role of a latent OriLyt RNA in KSHV latency in primary effusion lymphoma”
  Principal Investigator
  8/1/2023 – 7/31/2025

Recent Publications

• Kuehnle N, Osborne SM, Liang Z, [et al., including Manzano M]. CRISPR screens identify novel regulators of cFLIP dependency and ligand-independent, TRAIL-R1-mediated cell death. Cell death and differentiation. 2023. PMID: 36801923. PMCID: PMC10154404.
• Dunham D, Viswanathan P, Gill J, Manzano M. Expression Ratios of the Antiapoptotic BCL2 Family Members Dictate the Selective Addiction of Kaposi's Sarcoma-Associated Herpesvirus-Transformed Primary Effusion Lymphoma Cell Lines to MCL1. Journal of virology. 2022 96(23):e0136022. PMID: 36416587. PMCID: PMC9749474.
• Manzano M, Günther T, Ju H, [et al.]. Kaposi's Sarcoma-Associated Herpesvirus Drives a Super-Enhancer-Mediated Survival Gene Expression Program in Primary Effusion Lymphoma. mBio. 2020 11(4). PMID: 32843547. PMCID: PMC7448273.