# Rational Translation of EZH2 Targeted Therapy in Germinal Center B-cell Lymphoma

> **NIH NIH K08** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $171,180

## Abstract

This proposal describes a 5-year training program designed to enable the applicant to develop an independent
research career in the field of lymphoma biology and experimental therapeutics. The applicant is a pediatric
oncologist at Weill Cornell Medical College (WCMC) who is committed to an academic career studying disease
mechanisms in lymphoma and exploiting these mechanisms to develop novel therapies. Her current research
focuses on targeting the histone methyltransferase EZH2 in B-cell lymphoma. The candidate’s immediate
career goals are to gain further training in experimental design and develop expertise in epigenomics. Her
long-term career goals are to establish independent laboratory space, lead a team of researchers, and make
scientific contributions that allow her develop into a national/international leader in the field. To enable these
goals this proposal outlines the following career development objectives: 1) formal training in experimental
design, drug development, and statistical genomics; 2) coursework in epigenetic dysregulation, 3) regular
meetings with an advisory committee composed of distinguished clinicians, scientists, and institutional leaders;
4) formal and informal professional development in leadership, management skills, public speaking and
grantsmanship. The applicant’s mentors, Dr. Ethel Cesarman and Dr. Ari Melnick, are both tenured professors
at WCMC and are international leaders in the study of viral-related lymphomas and epigenetic mechanisms in
lymphoma respectively. Dr. Cesarman and Dr. Melnick have an extensive track record of collaboration
including multiple joint grant awards and joint mentorship of trainees. The research proposal focuses on the
rational translation of EZH2 targeted therapy in germinal center (GC) B-cell lymphomas. GC B-cell lymphomas
are aggressive tumors that occur in pediatrics and adults. Relapsed/refractory disease represents an unmet
need with most treatments failing to induce durable remissions. GC B-cell lymphomas are dependent on EZH2
which is a lineage factor for germinal center B-cells. EZH2 may play a unique role in EBV+ lymphoma where it
contributes to restricted EBV viral latency that allows immune evasion. Small molecule inhibitors of EZH2 are
currently in clinical development, including GSK126, which is being studied in a phase I trial that the applicant
is conducting in collaboration with GSK. The unique mechanism and time course of epigenetic therapy
requires careful consideration for effective clinical deployment. The overarching goal of this proposal is to
develop a rational approach for the clinical use of EZH2i in lymphoma. The specific aims are 1) Define the
epigenetic and transcriptional background of lymphomas that respond to EZH2 inhibition (EZH2i); 2) Determine
the kinetics of response to EZH2i and the point of maximum vulnerability to combination therapy; 3) Determine
the impact of EZH2i on the vulnerability of EBV + lymphomas to immune mediated therapy. Overall ...

## Key facts

- **NIH application ID:** 9989804
- **Project number:** 5K08CA219473-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Lisa Giulino Roth
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $171,180
- **Award type:** 5
- **Project period:** 2017-07-06 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989804

## Citation

> US National Institutes of Health, RePORTER application 9989804, Rational Translation of EZH2 Targeted Therapy in Germinal Center B-cell Lymphoma (5K08CA219473-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989804. Licensed CC0.

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