# Oncogenic programs driven by notch signaling in B-cell lymphoma

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $113,778

## Abstract

PROJECT SUMMARY / ABSTRACT
Despite advances in the clinical treatment of B-cell lymphoma, patients with certain high-risk genetic lesions
continue to have poor outcomes with current therapies. Recurrent gain-of-function mutations in genes
encoding Notch receptors are associated with aggressive disease and decreased survival in chronic
lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The oncogenic effects of altered Notch
signaling are likely mediated through activation of gene regulatory targets by the Notch transcription factor
complex, but the specific targets of altered Notch signaling in B-cell lymphoma are largely unknown, limiting
our ability to devise rational treatment strategies for these patients. I recently used genome-wide epigenetic
profiling to identify lymphoma subtype-specific enhancers and enhancer-associated genomic rearrangements
in primary tumor samples from diverse B-cell lymphoma subtypes (Cancer Discovery, 2015), linking
transcription factor-mediated enhancer activation to specific oncogene programs. I will extend this approach in
primary CLL and MCL specimens, as well as physiologically relevant in vitro and in vivo models, to uncover the
specific gene targets of Notch signaling and identify cooperating pathways. I will use this improved biological
understanding of the role of Notch in B-cell lymphomas to design and pre-clinically test novel strategies for the
treatment of Notch-driven lymphomas.
I am a hematopathologist with a strong research interest in the role of altered transcriptional regulatory genes
in the biology of B-cell lymphoma. My primary career objective in the coming years is to obtain a tenure-track
position at an academic medical center as a research laboratory Principal Investigator. I am seeking K08
support for mentored research in the laboratory of Dr. Bradley Bernstein at Massachusetts General Hospital /
Broad Institute, with co-mentorship from Dr. Jon Aster at Brigham and Women’s Hospital and Dana-Farber
Cancer Institute. A K08 award would give me protected time to advance my research program, to develop
additional skills in the biological analysis of genome-wide data sets, and to pursue specialized training and
experience in the use of physiologically relevant mouse models for the study of lymphoma. I will devote at least
80% of my time to a focused research investigation into the mechanisms of Notch signaling and transcriptional
regulation in B cell lymphomas, with up to 20% of my time devoted to the clinical diagnosis of hematological
malignancies, as well as teaching and training pursuits. Massachusetts General Hospital, Broad Institute of
MIT and Harvard University, Brigham and Women’s Hospital, and Dana-Farber Cancer Institute are institutions
of international renown in the fields of biomedical research and research training, and host the laboratories of
many highly accomplished experts in lymphoid malignancy, transcriptional and epigenetic regulation, and
experimental therapeutics. T...

## Key facts

- **NIH application ID:** 9991764
- **Project number:** 5K08CA208013-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** RUSSELL James Hubbard RYAN
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $113,778
- **Award type:** 5
- **Project period:** 2017-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991764

## Citation

> US National Institutes of Health, RePORTER application 9991764, Oncogenic programs driven by notch signaling in B-cell lymphoma (5K08CA208013-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9991764. Licensed CC0.

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