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

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2023 · $34,043

## 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, which is 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:** 10794727
- **Project number:** 3R35GM131707-05S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Maxim Frolov
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $34,043
- **Award type:** 3
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10794727

## Citation

> US National Institutes of Health, RePORTER application 10794727, Control of cell proliferation and differentiation by the Retinoblastoma tumor suppressor pathway (3R35GM131707-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10794727. Licensed CC0.

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