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.

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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.

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Study IDST003291
Study TitleAtopic dermatitis and STAT3 double null mutant skin biopsies during healing.
Study SummaryTo 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 NameRatley
First NameGrace
Address9000 Rockville Pike, Bethesda, MD, 20814, USA
Emailgrace.ratley@nih.gov
Phone8507371782
Submit Date2024-06-18
Num Groups3
Total Subjects58
Raw Data AvailableYes
Raw Data File Type(s)imzML
Analysis Type DetailMALDI
Release Date2024-07-25
Release Version1
Grace Ratley Grace Ratley
https://dx.doi.org/10.21228/M8J52B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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
SA356522ad-9-baselineAtopic dermatitis baseline Skin Biopsy
SA356523ad-20-baselineAtopic dermatitis baseline Skin Biopsy
SA356524ad-19-baselineAtopic dermatitis baseline Skin Biopsy
SA356525ad-18-baselineAtopic dermatitis baseline Skin Biopsy
SA356526ad-17-baselineAtopic dermatitis baseline Skin Biopsy
SA356527ad-16-baselineAtopic dermatitis baseline Skin Biopsy
SA356528ad-15-baselineAtopic dermatitis baseline Skin Biopsy
SA356529ad-14-baselineAtopic dermatitis baseline Skin Biopsy
SA356530ad-13-baselineAtopic dermatitis baseline Skin Biopsy
SA356531ad-12-baselineAtopic dermatitis baseline Skin Biopsy
SA356532ad-11-baselineAtopic dermatitis baseline Skin Biopsy
SA356533ad-10-baselineAtopic dermatitis baseline Skin Biopsy
SA356534ad-1-baselineAtopic dermatitis baseline Skin Biopsy
SA356535ad-8-baselineAtopic dermatitis baseline Skin Biopsy
SA356536ad-4-baselineAtopic dermatitis baseline Skin Biopsy
SA356537ad-7-baselineAtopic dermatitis baseline Skin Biopsy
SA356538ad-2-baselineAtopic dermatitis baseline Skin Biopsy
SA356539ad-6-baselineAtopic dermatitis baseline Skin Biopsy
SA356540ad-3-baselineAtopic dermatitis baseline Skin Biopsy
SA356541ad-5-baselineAtopic dermatitis baseline Skin Biopsy
SA356542ad-1-healingAtopic dermatitis healing Skin Biopsy
SA356543ad-20-healingAtopic dermatitis healing Skin Biopsy
SA356544ad-19-healingAtopic dermatitis healing Skin Biopsy
SA356545ad-18-healingAtopic dermatitis healing Skin Biopsy
SA356546ad-17-healingAtopic dermatitis healing Skin Biopsy
SA356547ad-3-healingAtopic dermatitis healing Skin Biopsy
SA356548ad-16-healingAtopic dermatitis healing Skin Biopsy
SA356549ad-2-healingAtopic dermatitis healing Skin Biopsy
SA356550ad-15-healingAtopic dermatitis healing Skin Biopsy
SA356551ad-6-healingAtopic dermatitis healing Skin Biopsy
SA356552ad-7-healingAtopic dermatitis healing Skin Biopsy
SA356553ad-4-healingAtopic dermatitis healing Skin Biopsy
SA356554ad-9-healingAtopic dermatitis healing Skin Biopsy
SA356555ad-10-healingAtopic dermatitis healing Skin Biopsy
SA356556ad-8-healingAtopic dermatitis healing Skin Biopsy
SA356557ad-12-healingAtopic dermatitis healing Skin Biopsy
SA356558ad-5-healingAtopic dermatitis healing Skin Biopsy
SA356559ad-14-healingAtopic dermatitis healing Skin Biopsy
SA356560ad-13-healingAtopic dermatitis healing Skin Biopsy
SA356561ad-11-healingAtopic dermatitis healing Skin Biopsy
SA356562hv-12-baselineControl baseline Skin Biopsy
SA356563hv-20-baselineControl baseline Skin Biopsy
SA356564hv-14-baselineControl baseline Skin Biopsy
SA356565hv-15-baselineControl baseline Skin Biopsy
SA356566hv-16-baselineControl baseline Skin Biopsy
SA356567hv-17-baselineControl baseline Skin Biopsy
SA356568hv-18-baselineControl baseline Skin Biopsy
SA356569hv-19-baselineControl baseline Skin Biopsy
SA356570hv-23-baselineControl baseline Skin Biopsy
SA356571hv-21-baselineControl baseline Skin Biopsy
SA356572hv-22-baselineControl baseline Skin Biopsy
SA356573hv-24-baselineControl baseline Skin Biopsy
SA356574hv-25-baselineControl baseline Skin Biopsy
SA356575hv-27-baselineControl baseline Skin Biopsy
SA356576hv-28-baselineControl baseline Skin Biopsy
SA356577hv-29-baselineControl baseline Skin Biopsy
SA356578hv-30-baselineControl baseline Skin Biopsy
SA356579hv-26-baselineControl baseline Skin Biopsy
SA356580hv-13-baselineControl baseline Skin Biopsy
SA356581hv-11-baselineControl baseline Skin Biopsy
SA356582hv-2-baselineControl baseline Skin Biopsy
SA356583hv-4-baselineControl baseline Skin Biopsy
SA356584hv-6-baselineControl baseline Skin Biopsy
SA356585hv-3-baselineControl baseline Skin Biopsy
SA356586hv-7-baselineControl baseline Skin Biopsy
SA356587hv-8-baselineControl baseline Skin Biopsy
SA356588hv-5-baselineControl baseline Skin Biopsy
SA356589hv-9-baselineControl baseline Skin Biopsy
SA356590hv-10-baselineControl baseline Skin Biopsy
SA356591hv-1-baselineControl baseline Skin Biopsy
SA356592hv-28-healingControl healing Skin Biopsy
SA356593hv-1-healingControl healing Skin Biopsy
SA356594hv-4-healingControl healing Skin Biopsy
SA356595hv-2-healingControl healing Skin Biopsy
SA356596hv-26-healingControl healing Skin Biopsy
SA356597hv-29-healingControl healing Skin Biopsy
SA356598hv-25-healingControl healing Skin Biopsy
SA356599hv-3-healingControl healing Skin Biopsy
SA356600hv-11-healingControl healing Skin Biopsy
SA356601hv-30-healingControl healing Skin Biopsy
SA356602hv-23-healingControl healing Skin Biopsy
SA356603hv-27-healingControl healing Skin Biopsy
SA356604hv-24-healingControl healing Skin Biopsy
SA356605hv-22-healingControl healing Skin Biopsy
SA356606hv-16-healingControl healing Skin Biopsy
SA356607hv-21-healingControl healing Skin Biopsy
SA356608hv-12-healingControl healing Skin Biopsy
SA356609hv-13-healingControl healing Skin Biopsy
SA356610hv-14-healingControl healing Skin Biopsy
SA356611hv-8-healingControl healing Skin Biopsy
SA356612hv-15-healingControl healing Skin Biopsy
SA356613hv-10-healingControl healing Skin Biopsy
SA356614hv-7-healingControl healing Skin Biopsy
SA356615hv-20-healingControl healing Skin Biopsy
SA356616hv-17-healingControl healing Skin Biopsy
SA356617hv-5-healingControl healing Skin Biopsy
SA356618hv-9-healingControl healing Skin Biopsy
SA356619hv-19-healingControl healing Skin Biopsy
SA356620hv-18-healingControl healing Skin Biopsy
SA356621hv-6-healingControl healing Skin Biopsy
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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
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