Molecular Signature Associated With Acute Rejection in Vascularized Composite Allotransplantation.

Background: A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens.

Methods: Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling.

LINE-1 retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5' single-cell RNA-Seq.

LINE-1 retrotransposons are sequences capable of copying themselves to new genomic loci via an RNA intermediate. New studies implicate LINE-1 in a range of diseases, especially in the context of aging, but without an accurate understanding of where and when LINE-1 is expressed, a full accounting of its role in health and disease is not possible. We therefore developed a method-5' scL1seq-that makes use of a widely available library preparation method (10x Genomics 5' single cell RNA-seq) to measure LINE-1 expression in tens of thousands of single cells.

Super-Resolution Imaging of Fas/CD95 Reorganization Induced by Membrane-Bound Fas Ligand Reveals Nanoscale Clustering Upstream of FADD Recruitment.

Signaling through the TNF-family receptor Fas/CD95 can trigger apoptosis or non-apoptotic cellular responses and is essential for protection from autoimmunity. Receptor clustering has been observed following interaction with Fas ligand (FasL), but the stoichiometry of Fas, particularly when triggered by membrane-bound FasL, the only form of FasL competent at inducing programmed cell death, is not known. Here we used super-resolution microscopy to study the behavior of single molecules of Fas/CD95 on the plasma membrane after interaction of Fas with FasL on planar lipid bilayers.

Decreased cytotoxic T cells and TCR clonality in organ transplant recipients with squamous cell carcinoma.

T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ transplant recipients (TSCC in OTR) are unclear. We developed an analytical method to define tumor infiltrating lymphocyte (TIL) phenotype in cSCC from immune competent and immune suppressed patients using single-cell TCR sequencing and gene expression data. TSCC exhibits reduced proportions of cytotoxic and naïve TILs and similar numbers of regulatory TILs.

Beyond Cell Death: New Functions for TNF Family Cytokines in Autoimmunity and Tumor Immunotherapy.

Originally discovered as an inducer of apoptosis, the TNF-family receptor Fas (CD95, APO-1, TNFRSF6) has more recently been found to have functions beyond cell death, including T cell co-stimulation and promoting terminal differentiation of CD4 and CD8 T cells. Other TNF family members also discovered as apoptosis inducers, such as TRAIL (APO-2L, TNFSF10), can promote inflammation through caspase-8. Surprisingly, non-apoptotic signaling through Fas can protect from the autoimmunity seen in Fas deficiency independently from the cell death inducing functions of the receptor.

Designing a ruggedisation lab to characterise materials for harsh environments.

Designing products for use in developing countries presents a unique set of challenges including harsh operating environments, costly repairs and maintenance, and users with varying degrees of education and device familiarity. For products to be robust, adaptable and durable, they need to be ruggedised for environmental factors such as high temperature and humidity as well as different operational conditions such as shock and chemical exposure. The product characterisation and ruggedisation processes require specific expertise and resources that are seldom available outside of large corporations and elite national research labs.