# Standardized Monitoring of Cellular Adhesion to Improve Clinical Care in Sickle Cell Disease

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $393,231

## Abstract

PROJECT SUMMARY
The sickle hemoglobin mutation afflicts millions of people worldwide and is associated with considerable
morbidity and mortality. The pathophysiology of Sickle Cell Disease (SCD) is a consequence of abnormal
deoxygenated sickle hemoglobin polymerization and its deleterious effects on Red Blood Cell (RBC)
membrane, shape, density, deformability, and adhesion. The original powerful observation that sickle red cells
show abnormal adhesion to endothelial cells has since been deepened and expanded to describe a complex
pathophysiology in which abnormal white blood cell (WBC) adhesion also plays an important role. These
studies led to clinical trial development utilizing targeted anti-adhesion therapy. Despite the remarkable insights
about abnormal cellular adhesion in SCD that have been made, there remain gaps in knowledge about these
complex adhesive interactions. There is no established `atlas' of abnormal adhesive events, examined
longitudinally and in a standardized manner in a large heterogeneous population of SCD patients under a
range of clinical circumstance and with and without treatment. Neither the topography of adhesive events for
an individual patient, nor for the SCD population as a whole is known. Better knowledge of the nature and
scope of abnormal adhesive events is critical to the goals of establishing associations with clinical outcomes
and successfully identifying therapeutic targets in clinical trials.
We have developed a novel microfluidic assay that allows rapid, preprocessing free, and standardized
interrogation of RBC and WBC adhesion in whole blood. In our ongoing experiments, high levels of HbF are
associated with lesser adhesion, while greater adhesion is associated with hemolysis. In preliminary
longitudinal studies, we find that RBC adhesion drops with initiation of treatment, and that levels of adhesion
are stable in stably treated patients. Given our preliminary findings, we hypothesize that, in SCD: (1) changes
in RBC or WBC adhesion will reflect the subjects' clinical state and treatment response, and (2) that the
adhesive profile will change with age, and will differ between children and adults during vaso-occlusive crises
(VOCs).
To test these hypotheses, we propose the following distinct but interrelated Specific Aims: Aim 1: To
standardize the simultaneous baseline evaluation of multiple cellular adhesive properties in a large population
of asymptomatic adults and children (at more than one center and longitudinally); Aim 2: To determine the
change from baseline in cellular adhesive properties that are present during vaso-occlusive crises, and to
analyze these in adult and pediatric populations; and Aim 3: To examine changes in cellular adhesive
properties before and after therapeutic interventions, including transfusions, hydroxyurea, and targeted anti-
adhesion therapy. Our studies will afford the more precise characterization of abnormal adhesive events in a
given individual and a more accurate ...

## Key facts

- **NIH application ID:** 9975877
- **Project number:** 5R01HL133574-05
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Umut A. Gurkan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,231
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975877

## Citation

> US National Institutes of Health, RePORTER application 9975877, Standardized Monitoring of Cellular Adhesion to Improve Clinical Care in Sickle Cell Disease (5R01HL133574-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9975877. Licensed CC0.

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