# Cell Signaling and Cell Decisions

> **NIH NIH R35** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $1,013,610

## Abstract

PROJECT SUMMARY/ABSTRACT
Mammalian cells must move and proliferate to maintain and regenerate tissues and defend themselves against
pathogens, but mutations that increase movement or proliferation can also cause cancer. Stem, progenitor, and
differentiated cells are often non-motile and quiescent but keep integrating cell-cell contacts, cell-matrix contacts,
and receptor inputs, and make two distinct decisions (that are often connected) whether they should start to
move and start to proliferate if needed. Several challenges have prevented an understanding of these two
decision processes. Genetic approaches in animals cannot readily tackle the co-regulation of large numbers of
signaling processes while biochemical analysis of cultured cells often leads to inconclusive results due to the
difficulty to synchronize cells and resolve when and where in a cell signaling occurs. Only single cell analysis
can resolve the spatial and temporal signaling feedbacks controlling these complex decisions. Our laboratory
has developed critically needed fluorescent single-cell activity reporters, rapid perturbation strategies, and
automated microscopy and analysis methods to investigate these two fundamental decision processes.
 To understand the decision to polarize and move, we will use the new tools we developed to explore how
external receptor tyrosine kinase signals and cell-cell and cell-matrix contacts synergistically control the initiation
and maintenance of gradients in cell signaling and actin organization, and how cells locally direct the signaling
gradients and movement. To understand the decision to proliferate, we will investigate the competition
mechanism that determines how these same signal inputs at the plasma membrane control the activation of two
cyclin-Cdk kinase activities in the nucleus, explore how cells control a proliferation decision process that can still
be reversed for many hours before cells commit to proliferate much later, and resolve how this same decision
process coordinates the licensing of origins of replication and DNA replication to prevent genome instability and
cell death. The outcome of our work will be a quantitative, molecular, and mechanistic understanding of how
mammalian cells integrate signals to make decisions to start to move and proliferate, and how mutations that
dysregulate these proliferation and migration decisions can cause cancer and other diseases.

## Key facts

- **NIH application ID:** 10832460
- **Project number:** 5R35GM127026-08
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** TOBIAS MEYER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,013,610
- **Award type:** 5
- **Project period:** 2018-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832460

## Citation

> US National Institutes of Health, RePORTER application 10832460, Cell Signaling and Cell Decisions (5R35GM127026-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10832460. Licensed CC0.

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