Biology subjects

Katz, P.

Publications and source records attributed to Katz, P..

4 recordsLinked to original sources

bioRxiv2025

Transcriptomic analysis reveals immune signatures associated with specific cutaneous manifestations of lupus in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) presents with diverse heterogenous cutaneous manifestations. However, the molecular and immunologic pathways driving specific cutaneous manifestations of SLE are poorly understood. Here, we leverage transcriptomics from a large well-phenotyped longitudinal cohort of SLE patients to map molecular pathways linked to ten distinct SLE-related rashes. Through whole blood and immune cell-sorted bulk RNA sequencing, we identified immune signatures specific to cutaneous subtypes of SLE. Subacute cutaneous lupus (SCLE) exhibited broad upregulation of interferon, TNF-, and IL6-JAK-STAT3 pathways suggesting potential unique therapeutic responses to JAK and type I interferon inhibition. While interferon signaling is prominent in SCLE, discoid lupus, and acute lupus, it is unexpectedly attenuated in patients with skin and mucosal ulcers. Pathway and cell-type enrichment analysis revealed unexpected roles for CD14+ monocytes in photosensitivity of SLE and NK cells in alopecia, mucosal ulceration, and livedo reticularis. These findings illuminate the immune heterogeneity of rashes in SLE, highlighting subtype-specific mechanistic targets, and presenting opportunities for precision therapies for SLE-associated skin phenotypes.

bioinformatics↗

bioRxiv2024

GDNF family receptor alpha-like (GFRAL) expression is restricted to the caudal brainstem

The TGF-{beta} cytokine, growth differentiation factor 15 (GDF15) is a critical mediator of the physiologic response to a range of cellular stresses. While circulating levels of GDF15 are normally very low, these levels increase substantially under a number of acute and chronic pathogenic states including mycotoxin exposure, infection and cancer. GDF15 controls a range of physiologic outputs including reduced appetite, gastric motility, hyperalgesia, emesis, energy expenditure and immune cell function via the GDNF family receptor alpha-like (GFRAL). While the area postrema and nucleus of the solitary tract (AP/NTS) within the caudal brainstem are the only known sites of Gfral-expressing cells, Gfral may also be expressed in other cell types. We therefore utilized single molecule in-situ hybridizations and genetic mouse models to label Gfral-expressing cells from development to adult mouse. With both approaches, we found Gfral-labelled cells in the brainstem and extremely rare Gfral-labelled cells in peripheral tissues in the mouse under normal physiological conditions. Confirming these findings, single nucleus RNA-sequencing of human tissues demonstrated nearly undetectable levels of Gfral mRNA in sites outside the AP/NTS. Our findings confirm AP/NTS neurons are the major site of Gfral expression.

molecular biology↗

bioRxiv2020

Ethnicity-specific transcriptomic variation in immune cells and correlation with disease activity in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease in which outcomes vary among different racial groups. The aim of this study is to leverage large-scale transcriptomic data from diverse populations to better sub-classify SLE patients into more clinically actionable groups. We leverage cell sorted RNA-seq data (CD14+ monocytes, B cells, CD4+T cells, and NK cells) from 120 SLE patients (63 Asian and 57 White individuals) and apply a four tier analytical approach to identify SLE subgroups within this multiethnic cohort: unsupervised clustering, differential expression analyses, gene co-expression analyses, and machine learning. K-means clustering on the individual cell type data resulted in three clusters for CD4 and CD14, and two clusters for B cells and NK cells. Correlation analysis revealed significant positive associations between the transcriptomic clusters of each immune cell and clinical parameters including disease activity and ethnicity. We then explored differentially expressed genes between Asian and White groups for each cell-type. The shared differentially expressed genes across the four cell types were involved in SLE or other autoimmune related pathways. Co-expression analysis identified similarly regulated genes across samples and grouped these genes into modules. Samples were grouped into White-high, Asians-high (high disease activity defined by SLEDAI score >=6) and White-low, Asians-low (SLEDAI < 6). Random forest classification of disease activity in the White and Asian cohorts showed the best classification in CD4+ T cells in White. The results from these analyses will help stratify patients based on their gene expression signatures to enable precision medicine for SLE.

bioinformatics↗

bioRxiv2019

Accelerated clearing and molecular labeling of large tissue samples using magnetohydrodynamic force

Here we report a strategy to efficiently render opaque biological tissues transparent and demonstrate that this approach can be modified to rapidly label intact samples with antibodies for large volume fluorescence microscopy. This strategy applies a magnetohydrodynamic (MHD) force to accelerate the removal of lipids from and the introduction of antibodies into tissue samples as large as an intact adult mouse brain. This strategy complements a growing array of tools that enable high-resolution 3-dimensional anatomical analyses in intact tissues using fluorescence microscopy. MHD-accelerated clearing and MHD-accelerated antibody labeling are fast, reliable, inexpensive, and compatible with existing strategies for high-quality fluorescence microscopy of intact tissues.

neuroscience↗