# Systems analysis of phenotypic switch in control of cancer invasion

> **NIH NIH U54** · YALE UNIVERSITY · 2020 · $1,798,772

## Abstract

PROJECT SUMMARY/ABSTRACT: Overall
Over 90% of cancer related mortality is linked to invasive and metastatic spread of cancer cells from the
primary tumor. This spread can be catastrophically fast in the cases of particularly aggressive, high grade
melanomas and gliomas (i.e., glioblastoma multiforme (GBM)), leading to uniformly poor prognosis and short
life expectancy in these cancers. In spite of the crucial importance of invasive cancer phenotype, we still have
only fragmentary knowledge and understanding of the mechanisms leading to transition from proliferative to
aggressive, migratory behavior of cancer cells (referred here as the P-A phenotypic switch). Increasing
evidence suggests that this switch is a reflection of inherent capacity of cancer cells to adopt both proliferative
and migrator phenotypes, with the probability and rate of switching between these two phenotypes controlled
by the cell genome, environmental conditions and cell-cell interactions. To address the problem of regulation of
invasive cancer spread and, more specifically the P-A phenotypic switch, we propose to establish the Yale
Cancer Systems Biology Center (Y-CSBC). The Center will based on the existing organization and
infrastructure of the recently founded Yale Systems Biology Institute (YSBI) on the Yale West Campus,
leveraging the extensive existing shared resources and juxtaposition of the labs within the same recently
renovated, state of the art research space. The Center will bring together researchers from 7 Yale departments
based at Yale schools of Arts and Science, Engineering and Applied Science and Medicine and Emory
University, in close collaboration with Yale Cancer Institute (physically adjacent to YSBI), Yale Cancer Center,
Yale skin cancer SPORE, and Yale Neurosurgery department. The work at the proposed Center will be initially
based on the Proposed tightly knit two Research Projects and two support shared resource Cores, initially
focused on the analysis of glioblastoma and melanoma cells, and normal cells of various species modeling
invasive growth behavior and phenotypic switching. With time, the emphasis on these two cancers may
broaden with new members expanding the scope and the aims. The proposed research already reflects the
diversity and innovative nature of the work pursued by the participating labs within YSBI and collaborative labs,
with the combination of techniques and approaches as diverse as synthetic biology, nano-scale
bioengineering, evolutionary biology, high throughput genomics, mathematical modeling, novel animal models,
all combined into a integrated research program. The work will be supported by the Administrative Core and
the results disseminated through various mechanisms mediated by the Outreach and Education Core. The
orthogonal and unconventional approaches proposed in the application and characteristic of the highly
collaborative use of cutting edge, innovative approaches, many of which are being pioneered here, will pro...

## Key facts

- **NIH application ID:** 10003175
- **Project number:** 5U54CA209992-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Andre Levchenko
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,798,772
- **Award type:** 5
- **Project period:** 2016-08-08 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003175

## Citation

> US National Institutes of Health, RePORTER application 10003175, Systems analysis of phenotypic switch in control of cancer invasion (5U54CA209992-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10003175. Licensed CC0.

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