# Control of cell proliferation and differentiation by the Retinoblastoma tumor suppressor pathway

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $570,160

## Abstract

PROJECT SUMMARY/ABSTRACT
Inactivation of the retinoblastoma (Rb) tumor suppressor pathway is an early obligatory event in human
cancer. One of the key targets of the Rb pathway is the family of E2F transcription factors, which regulate
cell proliferation and apoptosis. Overlapping and redundant functions of mammalian members of the E2F
and Rb tumor suppressor protein (pRB) families is a major hurdle in identification of their in vivo function.
Model organisms such as Drosophila provide attractive alternatives to complement studies in mammalian
systems due to high conservation of the Rb pathway and the amenability of flies to genetic analysis. Our
research program is aimed at addressing two fundamental questions: what are the essential functions of
the Rb pathway in development, and how do Rb pathway mutations affect different cell types in the
tissue? To address these questions, we are using genetic, genomic and single-cell RNA-Seq approaches.
We have identified adult skeletal muscle where E2F and Rb proteins regulate growth and
myofibrillogenesis, to be important for viability. We will determine how the Rb pathway regulates gene
expression and cellular metabolism during muscle development, and will investigate the systemic effects
inferred by E2F deficiency in specific tissues such as adult skeletal muscle and the fat body. We have
adapted Drop-Seq, a single-cell RNA-sequencing technology, to determine the effect of Rb pathway
mutations in heterogeneous tissue. We have established the feasibility of this approach by building the
first cell atlas of the Drosophila wild-type eye imaginal disc. Profiling of Rb mutants by Drop-Seq revealed
elevated intracellular acidification in a small cell population that makes them uniquely sensitive to
apoptosis. The link between apoptosis and acidification will be evaluated further. Among other questions
to be addressed with Drop-seq is the investigation of why inactivation of the Hippo pathway induces
dedifferentiation of Rb mutant photoreceptors. Collectively, the proposed research will enhance our
knowledge of pRB and its functions during animal development.

## Key facts

- **NIH application ID:** 10396992
- **Project number:** 5R35GM131707-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Maxim Frolov
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $570,160
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396992

## Citation

> US National Institutes of Health, RePORTER application 10396992, Control of cell proliferation and differentiation by the Retinoblastoma tumor suppressor pathway (5R35GM131707-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10396992. Licensed CC0.

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