# Pathogenesis of thrombotic microangiopathies

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $508,688

## Abstract

PROJECT SUMMARY
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare but potentially fatal blood disorder, resulting
from autoantibodies against ADAMTS13, a plasma metalloprotease that cleaves endothelial von Willebrand
factor. Despite progresses being made in past decades, major gap remains in our understanding the
pathogenesis of iTTP. The proposed study will test the hypotheses that: 1) distinct molecular signatures in the
complementarity determining region (CDR)-3 and the VDJ rearrangements in the variable regions of
immunoglobulins (Ig) against ADAMTS13 determine their functionalities (e.g., the inhibitory vs. activating) in
patients with iTTP; 2) the abnormalities in ANKRD26 and 36 gene family, initially identified to associate with
hereditary thrombocytopenia, may also play a role in pathogenesis of iTTP, likely through disruption of
megakaryocytopoiesis and enhanced immune inflammatory responses. The proposed study will use various
cutting-edge tools and animal models to test these hypotheses. The results of the proposed study will shed
new light on pathogenesis of iTTP and other immune thrombotic disorders. The findings may help develop
novel strategies for therapeutic interventions for such disorders.

## Key facts

- **NIH application ID:** 10904634
- **Project number:** 5R01HL164016-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** X. Long Zheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $508,688
- **Award type:** 5
- **Project period:** 2023-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904634

## Citation

> US National Institutes of Health, RePORTER application 10904634, Pathogenesis of thrombotic microangiopathies (5R01HL164016-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10904634. Licensed CC0.

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