# DEFINING THE ROLE OF CELL MIGRATION IN HUMAN NK CELL DIFFERENTIATION

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $434,976

## Abstract

PROJECT SUMMARY
This proposal aims to define the poorly understood yet critical relationship between human NK cell migration
and differentiation. By integrating our validated system of human NK cell differentiation and highly quantitative
imaging and image analysis, we will 1) define the requirement for migration in human NK cell differentiation,
and 2) dissect the molecular interactions between NK cell developmental intermediates and stromal cells.
Natural killer (NK) cells are required for our body's defense against viral infection and malignancy; they also
shape the outcome and success of transplantation. Despite their documented requirement in human health,
NK cell development and acquisition of function is poorly understood. Interactions with accessory cells such as
lymphoid stromal cells are required for human NK cell development, yet the molecular biology behind these
cell-cell interactions is not known and has never been visualized. Using in vitro differentiation of human NK
cells and quantitative imaging, we have described the contacts formed between developing NK cells and
stromal cells, which we termed the developmental synapse. In addition, we have defined distinct migratory
phenotypes associated with the progressive maturation of human NK cells on stromal cells. To dissect the
relationship between NK cell development and migration on stromal cells, we will pursue the following specific
aims: 1) determine the requirement for migration on stroma in human NK cell development; using both
mechanical restraint and NK precursors from patients with rare mutations that impair NK cell migration, we will
quantitatively measure the effect of inhibiting cell migration on human NK cell differentiation. To further
delineate the role that adhesion and migration plays in human NK cell development, we will: 2) define the
physical contribution of stromal cells to NK cell development. This will include the evaluation alternative
substrates to determine the contribution of adhesiveness and substrate stiffness on NK cell development.
Finally, we will 3) define the structural and functional relationship between the NK cell uropod and
developmental synapse. This will delineate the mechanism of signal transduction that occurs in cells
conjugated through the developmental synapse and define how this is related to the uropod formed in
migrating cells. This final aim will be performed in situ and in vitro to correlate the physiological developmental
synapse with that formed in culture.
Through these aims we will advance our knowledge of the contact-dependent requirements for human NK cell
development, a field in which few scientific advances have been made in the past ten years. Our ultimate goal
is to identify necessary and sufficient mechanical and biochemical signals required to recapitulate human NK
cell development to efficiently generate therapy cells without the use of stromal cell feeders. By understanding
the requirement for cell migration in this proc...

## Key facts

- **NIH application ID:** 9970182
- **Project number:** 5R01AI137073-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Emily Margaret Mace
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $434,976
- **Award type:** 5
- **Project period:** 2018-07-02 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970182

## Citation

> US National Institutes of Health, RePORTER application 9970182, DEFINING THE ROLE OF CELL MIGRATION IN HUMAN NK CELL DIFFERENTIATION (5R01AI137073-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9970182. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*