# Uncovering the Role of Platelets in Anti-Aspergillus Immune Defense

> **NIH NIH F31** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $36,501

## Abstract

PROJECT SUMMARY/ABSTRACT.
 This proposal describes a mentored two-year training plan that will provide the applicant with broad
training in fungal pathogenesis, platelet biology, cellular immunology, and microscopy to develop a career as an
investigator in infectious disease research. The sponsor’s and co-sponsor’s broad clinical and laboratory
expertise in modeling and analyzing immune responses to microbial pathogens, the inclusion of a training
committee with expertise in platelet biology, the dedicated training plan, and institutional strengths in immunology
and microbial pathogenesis all contribute to an outstanding training environment and high likelihood of success.
 Aspergillus fumigatus is a filamentous mold and opportunistic human pathogen. Every day, humans
inhale hundreds of airborne A. fumigatus conidia or vegetative spores. In immune competent hosts, innate
immune cells, such as neutrophils, are recruited to the lungs, and clear the infection. In immune compromised
hosts, conidia can escape inactivation, germinate into tissue-invasive hyphae and cause invasive aspergillosis
(IA). Because standard of care treatment still results in high mortality, there is an unmet medical need to
understand the host response to infection. Beyond the established roles of neutrophils, thrombocytopenia has
recently been identified as a risk factor for IA. The in vivo role of platelets in the context of the antifungal immune
response remains an open question.
 The Hohl lab is particularly well equipped for me to train in this area and to address this question. My
preliminary data suggests that thrombocytopenia impairs host survival in two independent mouse models. In
addition, thrombocytopenia increases tissue damage and impacts the antifungal activities of neutrophils by
reducing conidial uptake. My training and research objective is to integrate the role of platelets in the context
of the pulmonary antifungal immune response and to acquire training in the technical disciplines needed for
these studies. I hypothesize that platelets are necessary for murine survival due to their functions in maintaining
hemostasis, tissue integrity, and regulating phagocyte function and microbicidal activity.
 Specific Aim 1 of the proposed research will define the roles of platelets in anti-Aspergillus host defence
at a cellular level. By using complementary models of thrombocytopenia and fluorescent labeling of platelets, I
will uncover the relative contributions of platelet interactions, platelet cross-talk with immune effector cells, and
platelet-mediated tissue integrity to host survival. Specific Aim 2 of the proposed will identify molecular
mechanisms of platelet-mediated host defence. Using candidate-gene and unbiased approaches, I will uncover
novel regulators of platelet-driven anti-Aspergillus immunity. The implications of these studies will lead to novel
therapeutic approaches for invasive aspergillosis.

## Key facts

- **NIH application ID:** 9908591
- **Project number:** 1F31HL147468-01A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Benjamin Yona Tischler
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $36,501
- **Award type:** 1
- **Project period:** 2020-02-10 → 2020-10-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908591

## Citation

> US National Institutes of Health, RePORTER application 9908591, Uncovering the Role of Platelets in Anti-Aspergillus Immune Defense (1F31HL147468-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9908591. Licensed CC0.

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