Summary of Study ST003291
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002043. The data can be accessed directly via it's Project DOI: 10.21228/M8J52B This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST003291 |
Study Title | Atopic dermatitis and STAT3 double null mutant skin biopsies during healing. |
Study Summary | To do this we developed a matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) workflow for high throughput lipid analysis of cutaneous biopsies as well as a cell culture model of wound healing. A total of 51 samples taken from normal and healing tissue in healthy and AD participants were analyzed using this workflow. The goal of our study was to (a) elucidating a broader understanding of the metabolic pathways initiated during wound healing, with a specific interest in lipid signatures, and (b) identify potential therapeutic targets for patients with barrier deficiencies or impaired healing. |
Institute | National Institutes of Health |
Last Name | Ratley |
First Name | Grace |
Address | 9000 Rockville Pike, Bethesda, MD, 20814, USA |
grace.ratley@nih.gov | |
Phone | 8507371782 |
Submit Date | 2024-06-18 |
Num Groups | 3 |
Total Subjects | 58 |
Raw Data Available | Yes |
Raw Data File Type(s) | imzML |
Analysis Type Detail | MALDI |
Release Date | 2024-07-25 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
Project ID: | PR002043 |
Project DOI: | doi: 10.21228/M8J52B |
Project Title: | Imaging mass spectrometry evaluation of wound healing in patients with atopic dermatitis with and without STAT3 dominant negative mutations. |
Project Summary: | Frequent injury due to environmental challenges requires constant restoration of the skin barrier. Specific defects in ceramide lipid metabolism have been associated with inflammatory skin diseases such as atopic dermatitis (AD). The goal of this study was to characterize the lipid landscape and biosynthetic pathways activated during epidermal repair using MALDI imaging mass spectrometry (IMS). A keratinocyte culture model of wound healing confirmed that glycerophospholipids and glycosphingolipids are impacted during cell proliferation and that sialic acid supplementation can decrease wound closure time. In skin biopsies of healing tissue taken from healthy volunteers, specific phospholipids were upregulated, including phosphatidylcholine and sphingolipids, which play critical roles in membrane repair and cell signaling. Comparing controls to patients with AD, we again identified defects in ceramide-related lipid metabolism with specific defects in lysophosphatidylcholine (Lyso PC) 18:1. Topical application of LysoPC 18:1 provided modest clinical improvement in a mouse model of AD. We then applied this workflow to samples taken from patients with eczematous phenotypes due to STAT3 dominant negative hyper IgE syndrome and identified metabolic disruption of thiamine and phosphatidylinositol metabolism. Overall, the results indicate MALDI imaging can be used to characterize changes in lipid metabolism during wound healing and may indicate an underappreciated role of LysoPC 18:1 during tissue repair. |
Institute: | National Institutes of Health |
Department: | National Institute of Allergy and Infectious Disease |
Laboratory: | Epithelial Therapeutics Unit, |
Last Name: | Ratley |
First Name: | Grace |
Address: | 9000 Rockville Pike, Bethesda, MD, 20814, USA |
Email: | grace.ratley@nih.gov |
Phone: | 8507371782 |
Subject:
Subject ID: | SU003411 |
Subject Type: | Human |
Subject Species: | Homo sapiens |
Taxonomy ID: | 9606 |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
mb_sample_id | local_sample_id | Group | Skin Biopsy | Sample source |
---|---|---|---|---|
SA356522 | ad-9-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356523 | ad-20-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356524 | ad-19-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356525 | ad-18-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356526 | ad-17-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356527 | ad-16-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356528 | ad-15-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356529 | ad-14-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356530 | ad-13-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356531 | ad-12-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356532 | ad-11-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356533 | ad-10-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356534 | ad-1-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356535 | ad-8-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356536 | ad-4-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356537 | ad-7-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356538 | ad-2-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356539 | ad-6-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356540 | ad-3-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356541 | ad-5-baseline | Atopic dermatitis | baseline | Skin Biopsy |
SA356542 | ad-1-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356543 | ad-20-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356544 | ad-19-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356545 | ad-18-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356546 | ad-17-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356547 | ad-3-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356548 | ad-16-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356549 | ad-2-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356550 | ad-15-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356551 | ad-6-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356552 | ad-7-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356553 | ad-4-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356554 | ad-9-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356555 | ad-10-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356556 | ad-8-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356557 | ad-12-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356558 | ad-5-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356559 | ad-14-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356560 | ad-13-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356561 | ad-11-healing | Atopic dermatitis | healing | Skin Biopsy |
SA356562 | hv-12-baseline | Control | baseline | Skin Biopsy |
SA356563 | hv-20-baseline | Control | baseline | Skin Biopsy |
SA356564 | hv-14-baseline | Control | baseline | Skin Biopsy |
SA356565 | hv-15-baseline | Control | baseline | Skin Biopsy |
SA356566 | hv-16-baseline | Control | baseline | Skin Biopsy |
SA356567 | hv-17-baseline | Control | baseline | Skin Biopsy |
SA356568 | hv-18-baseline | Control | baseline | Skin Biopsy |
SA356569 | hv-19-baseline | Control | baseline | Skin Biopsy |
SA356570 | hv-23-baseline | Control | baseline | Skin Biopsy |
SA356571 | hv-21-baseline | Control | baseline | Skin Biopsy |
SA356572 | hv-22-baseline | Control | baseline | Skin Biopsy |
SA356573 | hv-24-baseline | Control | baseline | Skin Biopsy |
SA356574 | hv-25-baseline | Control | baseline | Skin Biopsy |
SA356575 | hv-27-baseline | Control | baseline | Skin Biopsy |
SA356576 | hv-28-baseline | Control | baseline | Skin Biopsy |
SA356577 | hv-29-baseline | Control | baseline | Skin Biopsy |
SA356578 | hv-30-baseline | Control | baseline | Skin Biopsy |
SA356579 | hv-26-baseline | Control | baseline | Skin Biopsy |
SA356580 | hv-13-baseline | Control | baseline | Skin Biopsy |
SA356581 | hv-11-baseline | Control | baseline | Skin Biopsy |
SA356582 | hv-2-baseline | Control | baseline | Skin Biopsy |
SA356583 | hv-4-baseline | Control | baseline | Skin Biopsy |
SA356584 | hv-6-baseline | Control | baseline | Skin Biopsy |
SA356585 | hv-3-baseline | Control | baseline | Skin Biopsy |
SA356586 | hv-7-baseline | Control | baseline | Skin Biopsy |
SA356587 | hv-8-baseline | Control | baseline | Skin Biopsy |
SA356588 | hv-5-baseline | Control | baseline | Skin Biopsy |
SA356589 | hv-9-baseline | Control | baseline | Skin Biopsy |
SA356590 | hv-10-baseline | Control | baseline | Skin Biopsy |
SA356591 | hv-1-baseline | Control | baseline | Skin Biopsy |
SA356592 | hv-28-healing | Control | healing | Skin Biopsy |
SA356593 | hv-1-healing | Control | healing | Skin Biopsy |
SA356594 | hv-4-healing | Control | healing | Skin Biopsy |
SA356595 | hv-2-healing | Control | healing | Skin Biopsy |
SA356596 | hv-26-healing | Control | healing | Skin Biopsy |
SA356597 | hv-29-healing | Control | healing | Skin Biopsy |
SA356598 | hv-25-healing | Control | healing | Skin Biopsy |
SA356599 | hv-3-healing | Control | healing | Skin Biopsy |
SA356600 | hv-11-healing | Control | healing | Skin Biopsy |
SA356601 | hv-30-healing | Control | healing | Skin Biopsy |
SA356602 | hv-23-healing | Control | healing | Skin Biopsy |
SA356603 | hv-27-healing | Control | healing | Skin Biopsy |
SA356604 | hv-24-healing | Control | healing | Skin Biopsy |
SA356605 | hv-22-healing | Control | healing | Skin Biopsy |
SA356606 | hv-16-healing | Control | healing | Skin Biopsy |
SA356607 | hv-21-healing | Control | healing | Skin Biopsy |
SA356608 | hv-12-healing | Control | healing | Skin Biopsy |
SA356609 | hv-13-healing | Control | healing | Skin Biopsy |
SA356610 | hv-14-healing | Control | healing | Skin Biopsy |
SA356611 | hv-8-healing | Control | healing | Skin Biopsy |
SA356612 | hv-15-healing | Control | healing | Skin Biopsy |
SA356613 | hv-10-healing | Control | healing | Skin Biopsy |
SA356614 | hv-7-healing | Control | healing | Skin Biopsy |
SA356615 | hv-20-healing | Control | healing | Skin Biopsy |
SA356616 | hv-17-healing | Control | healing | Skin Biopsy |
SA356617 | hv-5-healing | Control | healing | Skin Biopsy |
SA356618 | hv-9-healing | Control | healing | Skin Biopsy |
SA356619 | hv-19-healing | Control | healing | Skin Biopsy |
SA356620 | hv-18-healing | Control | healing | Skin Biopsy |
SA356621 | hv-6-healing | Control | healing | Skin Biopsy |
Collection:
Collection ID: | CO003404 |
Collection Summary: | 2mm biopsies were taken from the forearm and 3mm biopsies were taken over the same spots 3 days later. Biopsies were embedded in OCT freezing media and flash frozen using liquid nitrogen. Samples were sent to histoserv for sectioning on intelislides (Bruker Daltonik) and stored in a -80 C freezer for later use. |
Sample Type: | Skin |
Storage Conditions: | -80℃ |
Treatment:
Treatment ID: | TR003420 |
Treatment Summary: | No treatments were performed. The study was purely observational. |
Sample Preparation:
Sampleprep ID: | SP003418 |
Sampleprep Summary: | Patient biopsies were embedded in OCT freezing media and flash frozen using liquid nitrogen. Samples were sent to histoserv for sectioning on intelislides (Bruker Daltonik) and stored in a -80 C freezer for later use. |
Combined analysis:
Analysis ID | AN005390 |
---|---|
Analysis type | MS |
Chromatography type | None (Direct infusion) |
Chromatography system | none |
Column | none |
MS Type | MALDI |
MS instrument type | timsTOF |
MS instrument name | Bruker MALDI timsTOF fleX |
Ion Mode | POSITIVE |
Units | Intensity |
Chromatography:
Chromatography ID: | CH004086 |
Instrument Name: | none |
Column Name: | none |
Column Temperature: | none |
Flow Gradient: | none |
Flow Rate: | none |
Solvent A: | none |
Solvent B: | none |
Chromatography Type: | None (Direct infusion) |
MS:
MS ID: | MS005117 |
Analysis ID: | AN005390 |
Instrument Name: | Bruker MALDI timsTOF fleX |
Instrument Type: | timsTOF |
MS Type: | MALDI |
MS Comments: | Mass spectrometry was carried out in positive ion mode with an m/z range of 20 to 2,000 and a spatial resolution of 200 μm. The TIMS settings were as follows: 1/K0 Start of 0.70 V*s/cm^2, 1/K0 End 1.89 V*s/cm^2, Ramp time 200 ms, Accu.time 20 ms, Duty cycle 10%. The transfer settings were: MALDI plate offset 30V, Deflection 1 Delta 70V, Funnel 1 RF 500 Vpp, isCID energy 0eV, Funnel 2 RF 500 Vpp, Multipole RF 600 Vpp. Collisional energy was 10 eV and Collisional RF was 3000 Vpp. Quadrapole Ion energy was 5 eV and Low Mass was 100m/z. Transfer time was 120us and pre pulse storage was 10us. |
Ion Mode: | POSITIVE |