CXCR4-Targeted Macrophage-Derived Biomimetic Hybrid Vesicle Nanoplatform for Enhanced Cancer Therapy through Codelivery of Manganese and Doxorubicin.

Immune-cell-derived membranes have garnered significant attention as innovative delivery modalities in cancer immunotherapy for their intrinsic immune-modulating functionalities and superior biocompatibilities. Integrating additional parental cell membranes or synthetic lipid vesicles into cellular vesicles can further potentiate their capacities to perform combinatorial pharmacological activities in activating antitumor immunity, thus providing insights into the potential of hybrid cellular vesicles as versatile delivery vehicles for cancer immunotherapy. Here, we have developed a macrophage-membrane-derived hybrid vesicle that has the dual functions of transporting immunotherapeutic drugs and shaping the polarization of tumor-associated macrophages for cancer immunotherapy.

Protein interaction networks in the vasculature prioritize genes and pathways underlying coronary artery disease.

Population-based association studies have identified many genetic risk loci for coronary artery disease (CAD), but it is often unclear how genes within these loci are linked to CAD. Here, we perform interaction proteomics for 11 CAD-risk genes to map their protein-protein interactions (PPIs) in human vascular cells and elucidate their roles in CAD. The resulting PPI networks contain interactions that are outside of known biology in the vasculature and are enriched for genes involved in immunity-related and arterial-wall-specific mechanisms.

Vaccines for immune tolerance against autoimmune disease.

The high prevalence and rising incidence of autoimmune diseases have become a prominent public health issue. Autoimmune disorders result from the immune system erroneously attacking the body's own healthy cells and tissues, causing persistent inflammation, tissue injury, and impaired organ function. Existing treatments primarily rely on broad immunosuppression, leaving patients vulnerable to infections and necessitating lifelong treatments.

Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia.

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons.

Induction of T-helper-17-cell-mediated anti-tumour immunity by pathogen-mimicking polymer nanoparticles.

The effectivity of cancer immunotherapies is hindered by immunosuppressive tumour microenvironments that are poorly infiltrated by effector T cells and natural killer cells. In infection and autoimmune disease, the recruitment and activation of effector immune cells is coordinated by pro-inflammatory T helper 17 (T17) cells. Here we show that pathogen-mimicking hollow nanoparticles displaying mannan (a polysaccharide that activates T17 cells in microbial cell walls) limit the fraction of regulatory T cells and induce T17-cell-mediated anti-tumour responses.

The Effects of pH and Excipients on Exenatide Stability in Solution.

Exenatide, a glucagon-like peptide-1 receptor agonist, is the active pharmaceutical ingredient in Byetta and Bydureon, two type 2 diabetes drug products that have generics and multiple follow-up formulations currently in development. Even though exenatide is known to be chemically and physically unstable at pH 7.5, there lacks a systematic evaluation of the impact of pH and excipients on the peptide solution stability.

Genoppi is an open-source software for robust and standardized integration of proteomic and genetic data.

Combining genetic and cell-type-specific proteomic datasets can generate biological insights and therapeutic hypotheses, but a technical and statistical framework for such analyses is lacking. Here, we present an open-source computational tool called Genoppi (lagelab.org/genoppi) that enables robust, standardized, and intuitive integration of quantitative proteomic results with genetic data.

GeNets: a unified web platform for network-based genomic analyses.

Functional genomics networks are widely used to identify unexpected pathway relationships in large genomic datasets. However, it is challenging to compare the signal-to-noise ratios of different networks and to identify the optimal network with which to interpret a particular genetic dataset. We present GeNets, a platform in which users can train a machine-learning model (Quack) to carry out these comparisons and execute, store, and share analyses of genetic and RNA-sequencing datasets.

Integrated Bayesian analysis of rare exonic variants to identify risk genes for schizophrenia and neurodevelopmental disorders.

Background: Integrating rare variation from trio family and case-control studies has successfully implicated specific genes contributing to risk of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASD), intellectual disability (ID), developmental disorders (DDs), and epilepsy (EPI). For schizophrenia (SCZ), however, while sets of genes have been implicated through the study of rare variation, only two risk genes have been identified.

Methods: We used hierarchical Bayesian modeling of rare-variant genetic architecture to estimate mean effect sizes and risk-gene proportions, analyzing the largest available collection of whole exome sequence data for SCZ (1,077 trios, 6,699 cases, and 13,028 controls), and data for four NDDs (ASD, ID, DD, and EPI; total 10,792 trios, and 4,058 cases and controls).

N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth.

Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms.

Early auditory processing evoked potentials (N100) show a continuum of blunting from clinical high risk to psychosis in a pediatric sample.

Background: The N100 is a negative deflection in the surface EEG approximately 100 ms after an auditory signal. It has been shown to be reduced in individuals with schizophrenia and those at clinical high risk (CHR). N100 blunting may index neural network dysfunction underlying psychotic symptoms.