# Molecular mechanisms of megakaryocyte differentiation and maturation during inflammation

> **NIH NIH K01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $119,772

## Abstract

PROJECT SUMMARY/ABSTRACT
Candidate. My Ph.D. thesis, under the direction of Dr. Alisa Wolberg (Associate Professor, University of North
Carolina at Chapel Hill), entailed the application of cellular and molecular biology, confocal microscopy,
biochemistry, and murine models of thrombosis to identify the role of elevated plasma coagulation factor levels
(hypercoagulability) in the pathophysiology of thrombotic disorders. My post-doctoral research in Dr. Joseph
Italiano’s laboratory (Associate Professor, Harvard University), has added to my repertoire a number of
specialized cell biology techniques including fluorescence, high-content, and electron microscopy, live cell
imaging, retroviral infection, cell culture of primary megakaryocytes, and transgenic mouse models to study
megakaryocyte maturation and platelet production. These projects have provided me with the necessary
expertise to meet my career goals by familiarizing me with cell biological processes and signaling pathways
that orchestrate hematopoietic stem cell differentiation and megakaryocyte maturation.
Environment. Dr. Italiano’s laboratory has offered unequalled access to an extensive network of exceptionally
talented megakaryocyte and platelet researchers whose input and experience have helped guide my research
and allowed me to markedly expand my arsenal of analytical, management, writing, and oratory skills. Dr.
Italiano has also made available to me a range of highly specialized equipment, armed me with a number of
molecular biology techniques that are complementary to my research goals, and provided me with dedicated
mentorship that has enabled me to become an accomplished megakaryocyte biologist and microscopist. The
opportunity to train at an institute that is world-renowned for its megakaryocyte research has allowed me to
establish meaningful collaborative relationships with experts worldwide. My joint appointment at Harvard
Medical School and Brigham and Women’s Hospital has afforded me access to a multitude of courses, internal
training programs, departmental seminars, and career development and educational programs that have made
me a better scientist and supported my career trajectory toward independent investigator.
Research. My interests lay in investigating the mechanisms of megakaryocyte differentiation for the purpose of
understanding how and why platelets are made, and ultimately developing targeted therapies to enhance or
repress megakaryocyte differentiation and maturation. The ability to control megakaryocyte maturation in vivo
will result in the ability to regulate platelet count in thrombocytopenia and thrombocytosis. My short-term goal
is to investigate the role of the cytokine CCL5 and its receptor CCR5 in hematopoiesis and megakaryocyte
maturation, for which a research plan comprising three specific aims is proposed. I hypothesize that in times of
inflammation, the cytokine CCL5 signals through its receptor, CCR5. This may work to 1) increase the number
of h...

## Key facts

- **NIH application ID:** 9936178
- **Project number:** 5K01DK111515-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Kellie Rae Machlus
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $119,772
- **Award type:** 5
- **Project period:** 2016-09-14 → 2020-11-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936178

## Citation

> US National Institutes of Health, RePORTER application 9936178, Molecular mechanisms of megakaryocyte differentiation and maturation during inflammation (5K01DK111515-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9936178. Licensed CC0.

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