# Tissue Dependent Megakaryocyte Functions

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2022 · $509,139

## Abstract

Our concepts of platelet and megakaryocyte (Mk) origins and functions continue to expand. Mks are found in
extramedullary tissues, including the lungs and spleen. We have shown that platelets initiate, accelerate, and
regulate all phases of the immune responses and have now discovered that Mks have immune plasticity and
functions that are dependent on their tissue environment. This includes our discovery that lung Mks take up,
process, and present pathogen derived antigens to T cells. Our studies lead us to now hypothesize that: Mk
differentiation is responsive to, and dictated by, environmental pathogens and/or stimuli. Our data also
presents questions related to extramedullary Mk origins and differentiation. We will leverage the unique
expertise of our collaborative team by using disease relevant in vitro and in vivo mouse model systems to explore
this novel research inquiry.
Proposed studies in this application will explore whether Mks differentiate from hematopoietic stem cells outside
the bone marrow, determine the environmental regulators of Mk phenotype plasticity, and potential roles for
extramedullary Mks in all phases of the immune responses. These studies will establish that tissue resident Mks
have environmentally regulated roles in immune responses, changing how we view Mk and platelet functions,
thereby impacting our understanding of major causes of morbidity and mortality. This includes infectious
diseases such as bacterial pneumonias or viral infections (examples; influenza and coronavirus). To accomplish
these paradigm shifting goals, we will pursue the following Aims:
Aim #1. To demonstrate mechanisms of tissue dependent Mk differentiation.
Aim #2. To demonstrate megakaryocyte immune regulatory roles.

## Key facts

- **NIH application ID:** 10337469
- **Project number:** 1R01HL160610-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** CRAIG N MORRELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $509,139
- **Award type:** 1
- **Project period:** 2022-02-08 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337469

## Citation

> US National Institutes of Health, RePORTER application 10337469, Tissue Dependent Megakaryocyte Functions (1R01HL160610-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10337469. Licensed CC0.

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