# Platelet Exocytosis and Endocytosis in Thrombosis and Immunity

> **NIH NIH R35** · UNIVERSITY OF KENTUCKY · 2024 · $912,539

## Abstract

Abstract
Surprisingly, platelets are capable of bidirectional interactions with their microenvironment
through basic cellular processes that are largely unexplored. In this R35 proposal, we expand on
our active research themes: one unraveling the mechanistic role of exocytosis in hemostasis and
the other investigating endocytosis as an entry pathway to define the role of platelets in innate
immunity. By linking these two areas, we can gain deeper insights into how platelet interact with
their microenvironments. Despite advances in understanding signaling from vascular damage
detection, our view of how activated platelets execute the steps needed for clot formation is
limited. We have probed the mechanisms of platelet secretion and how it affects hemostasis,
using genetically altered models, and determined that modulating secretion controls thrombus
growth without compromising hemostasis. To build on that advance, a better understanding of
platelet exocytosis is clearly needed so logical therapeutic strategies can be developed. Our work
on platelet endocytosis, endo-lysosomal trafficking, and processing of endocytosed cargo led to
the discovery that platelets take up pathogens, e.g., viruses, and are activated. Increasingly,
platelets are being associated with immune responses, yet the mechanisms underlying these
non-hemostatic functions are largely unknown. Very little is known about platelet endocytosis
and next to nothing is known about how platelets traffic and process endocytosed material. Our
R35 research program seeks to fill these gaps in knowledge by taking a holistic approach to the
study of platelet “cell biology”. Building on our innovative past work (>50 publications), we will
further define platelet membrane trafficking (endocytosis, exocytosis, cargo sorting/processing,
etc.). We hypothesize that bidirectional trafficking processes, endo- and exocytosis, are essential
for platelet-specific functions, specifically thrombosis and innate immune responses. To address
this hypothesis, we will examine platelet exocytosis and endocytosis at mechanistic and
physiological levels using an extensive suite of reagents, transgenic mouse strains, and
technologies. Going forward, we will use these powerful tools and approaches to define how
platelet membrane trafficking (both exo- and endocytosis) affects hemostasis/thrombosis and
immune responses at molecular and organismal levels. The data generated are directly
applicable to the understanding and treatment of human disease, especially thrombotic diseases
which accounts for 1 in 4 deaths world-wide and chronic viremia, e.g., AIDS/HIV1, which
increases CVD risk.

## Key facts

- **NIH application ID:** 10815725
- **Project number:** 5R35HL150818-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** SIDNEY Waldo WHITEHEART
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $912,539
- **Award type:** 5
- **Project period:** 2020-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10815725

## Citation

> US National Institutes of Health, RePORTER application 10815725, Platelet Exocytosis and Endocytosis in Thrombosis and Immunity (5R35HL150818-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10815725. Licensed CC0.

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