Publications by authors named "C J Hull"

Background: Patients with Alzheimer's Disease (AD) frequently suffer from comorbidities such as type 2 diabetes mellitus (T2DM), accompanied by shared common pathologies such as increased inflammation and impaired glucose homeostasis. Beta-secretase 1 (BACE1), the rate limiting enzyme in AD associated beta-amyloid (Aβ) production, is also implicated in metabolic dysfunction and can increase central and peripheral protein levels of protein tyrosine phosphatase 1B (PTP1B). PTP1B is a validated target in diabetes and obesity, and is a neuroinflammatory regulator involved in degenerative processes.

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NKG2D ligands (NKG2DLs) are broadly expressed in cancer. To target these, we describe an adaptor chimeric antigen receptor (CAR) termed NKG2D/Dap10-12. Herein, T cells are engineered to co-express NKG2D with a fusion protein that comprises Dap10 joined to a Dap12 endodomain.

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Spinocerebellar ataxia type 7 (SCA7) is a genetic neurodegenerative disorder caused by a CAG-polyglutamine repeat expansion. Purkinje cells (PCs) are central to the pathology of ataxias, but their low abundance in the cerebellum underrepresents their transcriptomes in sequencing assays. To address this issue, we developed a PC enrichment protocol and sequenced individual nuclei from mice and patients with SCA7.

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Introduction: Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells has proven transformative in the management of B cell and plasma cel derived malignancies. However, solid tumors have largely proven to be resistant to this therapeutic modality. Challenges include the paucity of safe target antigens, heterogeneity of target expression within the tumor, difficulty in delivery of CAR T cells to the site of disease, poor penetration within solid tumor deposits and inability to circumvent the array of immunosuppressive and biophysical barriers imposed by the solid tumor microenvironment.

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