# Project 2 - Uncovering Mechanisms of the Lymphoid Oncogenesis of Epstein-Barr Virus and Kaposi's Sarcoma

> **NIH NIH P01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $413,682

## Abstract

PROJECT 2 – PROJECT SUMMARY/ABSTRACT
Project 2. Uncovering Mechanisms of the Lymphoid Oncogenesis of Epstein-Barr Virus and Kaposi’s
Sarcoma Herpesvirus
Bill Sugden, Project Leader; Paul Lambert and Eric Johannsen, Co-Leaders
EBV causes several lymphoid cancers; EBV and KSHV together cause Primary Effusion Lymphomas (PELs).
We have uncovered previously unrecognized cellular drivers of Burkitt Lymphomas (BL) caused by EBV with
screens using CRISPR/Cas9 and sgRNAs to all human genes in early passage BL cells. PEL and BL are AIDS-
defining malignancies. We have developed a new approach to inhibit EBV in these early passage BL cells after
the comprehensive CRISPR screen and identified cellular genes which EBV must regulate for the lymphomas
to be maintained. These approaches have worked and ensure that our collaboration with Dr. Johannsen to
screen EBV+ DLBCLs in Project 4 will be informative. We are examining our newly developed co-transformation
of peripheral and tonsillar B-cells with EBV and KSHV to elucidate it mechanistically. We focus on EBV because
its causal role in PEL was formerly unappreciated. We are collaborating with Dr. Paul F. Lambert (Project 1), to
define EBV’s and KSHV's roles in PEL tumorigenesis studying co-transformed cells as xenografts in NSG mice.
These cells grow better in the peritoneal cavities of NSG mice than do cells infected only with EBV and express
genes characteristic of bona fide PELs. We are testing contributions of the peritoneal cavity to the tumor-growth
of co-transformed cells and PEL cell lines.

## Key facts

- **NIH application ID:** 10837988
- **Project number:** 2P01CA022443-46A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** WILLIAM M. SUGDEN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $413,682
- **Award type:** 2
- **Project period:** 1997-02-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10837988

## Citation

> US National Institutes of Health, RePORTER application 10837988, Project 2 - Uncovering Mechanisms of the Lymphoid Oncogenesis of Epstein-Barr Virus and Kaposi's Sarcoma (2P01CA022443-46A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10837988. Licensed CC0.

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