# Inflammation-mediated platelet hyperreactivity and thrombosis

> **NIH NIH K99** · BLOODWORKS · 2024 · $210,724

## Abstract

Project Summary/Abstract
The Candidate is an assistant professor in pediatrics and a young physician-scientist dedicated
to developing an academic career focused on investigating the intersection of inflammation and
thrombosis through the study of the mechanisms by which inflammation promotes platelet
hyperreactivity. With a strong background in inflammation, megakaryocyte, and platelet biology,
the candidate looks to develop new expertise in autophagy and metabolism to determine their
contribution to platelet hyperreactivity and thrombosis. The Career Development Plan described
in the proposal outlines 2 years of mentored training, including technical skill training and career
development activities, to promote the successful transition to independence and future funding.
The Candidate’s Mentors and Co-Mentors have proven track-records of excellent translational
research productivity and successful mentorship. The Research Plan: Inflammation contributes
to the development of cardiovascular disease (CVD) and promotes platelet hyperreactivity and
thrombosis in older humans (aging) and patients with rheumatoid arthritis (RA). The thrombotic
events experienced by these groups are characterized by platelet-rich arterial clots denoting that
platelet hyperreactivity is central for the elevated morbidity and mortality in these populations.
The central hypothesis of this application is that chronic inflammation promotes platelet
hyperreactivity and thrombosis through the reprogramming of key platelet metabolic pathways.
The work proposed in this application is set to elucidate the mechanisms by which chronic
inflammation promotes platelet hyperreactivity through dysregulation of critical metabolic
regulators of platelet function such as autophagy (aim 1) and the pentose phosphate pathway
(PPP, [aim 2]) in older humans and in patients with rheumatoid arthritis (aim3). For this purpose,
I have integrated multidisciplinary mentoring and advisory teams of world-known experts in
autophagy (Andrew Thorburn, Ph.D.), metabolomics (Angelo D’Alessandro Ph.D.), and platelet
biology (Matthew Rondina, MD) to guide the successful completion of the proposed work. The
mentoring, skills, and tools developed throughout the K99 phase of this award will lay down a
solid foundation to establish my independent research program focused on the study of the
platelet metabolic determinants for hyperreactivity and thrombosis. Finally, and most important,
discoveries from our research have the potential to improve the care and outcomes not only for
older individuals and patients with RA but also children with chronic inflammatory conditions such
as Juvenile Idiopathic Arthritis (JIA) and sickle cell disease.

## Key facts

- **NIH application ID:** 11063033
- **Project number:** 7K99HL156058-04
- **Recipient organization:** BLOODWORKS
- **Principal Investigator:** Pavel Davizon-Castillo
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $210,724
- **Award type:** 7
- **Project period:** 2021-03-05 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11063033

## Citation

> US National Institutes of Health, RePORTER application 11063033, Inflammation-mediated platelet hyperreactivity and thrombosis (7K99HL156058-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11063033. Licensed CC0.

---

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