# Gene Regulation and Cell Proliferation Program

> **NIH NIH P30** · COLD SPRING HARBOR LABORATORY · 2020 · $41,073

## Abstract

Gene Regulation and Cell Proliferation Program
Program Leader: David L. Spector
Program Co-leader: Christopher R. Vakoc
Project Summary
Alterations in the regulation of gene expression and promiscuous entry into the cell cycle are defining
characteristics of human cancer cells. The Gene Regulation and Cell Proliferation Program (GR) represents an
interdisciplinary program with the central aim focused on understanding the regulation of gene expression and
cell proliferation in cancer cells. The program has three main focus areas: (1) RNA Biology, (2) Cancer
Epigenetics, and (3) Cell Proliferation. Research in this Program over the past five years has produced major
advances in our understanding of cancer promoting pathways and has led to the discovery of novel therapeutic
strategies now under investigation in, or moving toward, human clinical trials. In the area of RNA biology,
researchers in the GR Program have shown that machineries that regulate alternative pre-mRNA splicing
reactions include a major class of oncoproteins in human breast and skin cancers. In addition, long non-coding
RNAs have been causally linked to the differentiation and metastatic programs in breast cancer, thus
motivating the evaluation of anti-sense oligonucleotide (ASO)-based therapeutics in pre-clinical models and in
human clinical trials. Researchers investigating small RNA pathways have obtained insight into how cancer
cells communicate with their microenvironment using exosomes and evade sensitivity to kinase-targeted
therapeutics. An epigenetics focus of this program has led to the discovery that hematological malignancies
exploit bromodomain-containing proteins to sustain oncogenic enhancer landscapes. This has led to a
rationale to target specific bromodomains in cancer, an approach that is now under investigation in ealy stage
clinical trials. Epigenomic profiling of mammary gland cell types is also revealing how a woman's risk for
developing breast cancer can be modulated by transient signaling events during pregnancy. Studies in the
area of DNA replication are focused on the mechanisms of origin recognition proteins and replicative DNA
helicases, including those utilized by tumor-causing papillomaviruses. Technology development continues to
be a major focus of the GR program. A novel CRISPR-based functional genomics strategy is revealing core
gene regulatory circuitries that sustain the cancer cell state and is also identifying strategies to bolster blood
stem cell self-renewal. High throughput screening of ASOs targeting long non-coding RNAs is leading to the
identification of targetable vulnerabilites in breast cancers. A continued effort that balances basic research into
molecular mechanisms with therapeutic development will lead to continued synergies among members of the
Program that is fostered by the Cancer Center. Since 9/1/10, the GR Program published 126 cancer-related
research articles, 30 (24%) involved multiple Cancer Center members; 11 (9%) from i...

## Key facts

- **NIH application ID:** 9975723
- **Project number:** 5P30CA045508-33
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** DAVID L SPECTOR
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $41,073
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975723

## Citation

> US National Institutes of Health, RePORTER application 9975723, Gene Regulation and Cell Proliferation Program (5P30CA045508-33). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9975723. Licensed CC0.

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