# Investigating the molecular basis of context-dependent STAT3 function in NK cells

> **NIH NIH K99** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $114,722

## Abstract

PROJECT SUMMARY/ABSTRACT
RESEARCH: Natural Killer (NK) cells are crucial for the immediate defense against virus infections. To exert
their function, NK cells need to receive signals through activating receptors and cytokines. Cytokines
mediate their function via STAT transcription factors. We could previously show that STAT1, STAT2, STAT4
and STAT5 are all required for NK cell expansion in murine cytomegalovirus (MCMV) infection. Studying the
role of STAT3 in NK cells, I found that STAT3 plays a context-dependent role. In regular-dose infection,
STAT3 augmented proliferation of NK cells. However, in high-dose infection STAT3 appeared to impair NK
cell expansion. This suggests that our model can be used to study the context-dependent role of STAT3,
which has broad relevance for the fields of immunology and cancer biology. In this proposal, I seek to answer
1) how are different upstream signals altering the role of STAT3 for NK cell function and 2) how are identified
downstream targets of STAT3 contributing to the context-specific role of STAT3.
CANDIDATE: I am a postdoctoral fellow in the lab of Dr. Joseph Sun at Memorial Sloan Kettering Cancer
Center (MSKCC). Prior to this position, I studied the differentiation of CD8+ T cells and NK cells. My interest
is the mechanistic study of immune cell differentiation and function during viral infection. I joined the Sun
lab as one of the leading groups studying the molecular mechanisms underlying NK cell function. Through
the work outlined in this proposal I will 1) acquire technical expertise available in my current lab with a focus
on the study of transcription factors, 2) develop a network of scientists that enable the collaborative type of
research I seek to participate in and 3) develop skills necessary for career development such as mentoring,
data presentation and grantsmanship skills. I have assembled an excellent Advisory Committee that is
committed and capable to guide me on my path to independence: Dr. Rudensky for technical support, Dr.
Leslie for mentorship in computational biology and Dr. Ivashkiv as an expert in cytokine and STAT biology.
With the support of my mentor and Advisory Committee I will be able to acquire the necessary knowledge
and expertise during the K99 phase to launch my own independent career.
ENVIRONMENT: The Immunology Program at MSKCC is part of the Tri-Institutional network composed of
MSKCC, Rockefeller University and Weill Cornell University. The highly collaborative culture promotes
scientific exchange and has provided me with crucial technological support. Furthermore, I could begin to
form a network with multiple groups at our campus. Regular presentations by renowned senior scientists
enable me to expand the scope of my scientific questions. Weekly lab meetings and frequent personal
meetings with my mentor Joseph Sun, who has successfully guided multiple former trainees in launching
their own academic career, make my environment ideal for starting my path to inde...

## Key facts

- **NIH application ID:** 10985381
- **Project number:** 1K99AI180360-01A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Simon Grassmann
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $114,722
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985381

## Citation

> US National Institutes of Health, RePORTER application 10985381, Investigating the molecular basis of context-dependent STAT3 function in NK cells (1K99AI180360-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10985381. Licensed CC0.

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