# Development of an Ultrasensitive Microdevice for the Investigation of Sphingosine Kinase Activity in Single Cells

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $5,318

## Abstract

Project Summary
Multiple myeloma (MM) is a deadly disease characterized by a shortage of red blood cells, white blood cells,
and platelets in the blood.1,2 The disease has a grim prognosis, as it is estimated that in 2018 there were
30,770 new cases and 12,770 deaths resulting from MM.3 In the past decade there have been significant
strides made in the development of new drugs and implementation of combination therapies, but variability in
treatment response between patients has kept median survival approximately 5 years and MM remains
an incurable disease.1,2,4 MM has not only been shown to be a highly heterogenous disease from patient-to-
patient, but patients have also exhibited intra-tumor clonal heterogeneity.4–8 For this reason, personalized
therapies are highly desirable, particularly those targeted at specific signaling pathways exhibiting
aberrant behavior in a given patient.1,2,9,10 Presently, cytogenetic and molecular markers are used to inform
personalized therapies; however, these assays do not directly investigate specific biochemical activity i.e. the
target for most pharmacologic interventions. It is well-accepted that the enzyme sphingosine kinase (SK) plays
a crucial function in MM initiation, progression, and drug resistance.11–20 This knowledge, in combination with
the increasing number of single-cell studies in MM highlighting that the heterogeneity of the malignancy from
patient-to-patient and intra-tumor clonal heterogeneity affects MM cell sensitivity to various drugs, suggests
that measurements of metabolic activity in the sphingolipid pathway will improve MM treatment
response and decrease the frequency of relapse.4–7,21,22
Biochemical investigations of the sphingolipid pathway have traditionally relied on bulk cell assays, which only
reflect a population average of cell behavior.23–26 Single-cell assays have been developed, but even highly
automated assays have been low throughput and technically complex.27–29 I aim to address the limitations of
existing SK assays by creating an increased-throughput, highly parallelizable, simple-to-use chemical
separations platform that incorporates a chemical sensor or reporter for enzyme activity measurement.
The analytical chemistry technology proposed in this research will facilitate measurements of SK activity within
samples of primary MM cells, providing insights into the efficacy of SK inhibitors as part of a therapy regimen
on a patient-by-patient basis. The central hypothesis of this research is that MM cells analyzed on the
proposed novel single-cell analysis platform will exhibit heterogeneity in SK activity and diversity in responding
to SK inhibitors. It is important to note that while this proposal limits its scope to investigating SK activity in MM
cells, the platform can easily be adapted to investigate essentially any metabolic pathway for any disease,
provided that chemical probes are available. This urgently needed novel technology will provide researchers
with an ea...

## Key facts

- **NIH application ID:** 10197043
- **Project number:** 5F31CA243312-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Luke Austin Gallion
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $5,318
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-08-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197043

## Citation

> US National Institutes of Health, RePORTER application 10197043, Development of an Ultrasensitive Microdevice for the Investigation of Sphingosine Kinase Activity in Single Cells (5F31CA243312-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10197043. Licensed CC0.

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