Abstract: Described and featured herein are antibodies that specifically bind to a phosphorylated S104 amino acid residue in a CARD9 polypeptide and methods of using such antibodies to identify subjects vulnerable to fungal infection, including fungal infections caused by Candida spp.

Abstract: Methods and compositions capable of obtaining paired transcriptome and genotype information from single cells in high throughput are provided. Disclosed methods and compositions obtain paired transcriptome and genotype information from single cells in a manner that is highly sensitive, capable of detecting even very low-level transcripts in single cells, and associating such low-level transcripts and abundance information with associated genotypes, within a single cell.

Abstract: An atlas of intestinal epithelial cells, intestinal epithelial stem cells and intestinal immune cells identifies new cell populations, markers, networks, and responses to stimuli. Intestinal epithelial cell sub-types are also found in the trachea. Accordingly, disclosed are methods of modulating epithelial cell differentiation, maintenance and/or function, related methods for the treatment of disease, including IBD and asthma. Also disclosed are methods and kits for identifying cell types, their differentiation, homeostasis and activation.

Abstract: The present disclosure provides compounds of Formula (I), (II), and (III). The provided compounds are able to bind protein kinases (e.g., SIK) and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase (e.g., SIK, (e.g., SIK1, SIK2, or SIK3)) in a subject or cell. The provided compounds may be useful in treating or preventing a disease (e.g., proliferative disease, musculoskeletal disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.

Abstract: The present disclosure provides compounds of Formula (I), (II), and (III). The provided compounds are able to bind protein kinases (e.g., SIK) and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase (e.g., SIK, (e.g., SIK1, SIK2, or SIK3)) in a subject or cell. The provided compounds may be useful in treating or preventing a disease (e.g., proliferative disease, musculoskeletal disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.

Abstract: A system and method for prediction of immunodominant epitopes is provided herein. MHCII peptidomics was used to discover complex bacterial epitopes and host antigen processing pathways. Novel insights into the features of antigenicity are leveraged to build an algorithm for prediction of immunodominant epitopes. Use of immunodominant epitopes is described.

Abstract: T cell responses are exquisitely antigen-specific and directed against peptide epitopes displayed by human leukocyte antigen (HLA) on the surface of presenting cells. In particular, class II HLA (HLA-II) is remarkably polymorphic, which allows for presentation of diverse peptide antigens to T cells, but also forms the basis for genetic associations with diverse immunopathologies across the spectrum of infectious disease and autoimmunity. Here, Applicants employ monoallelic immunopeptidomics to retrieve over 200,000 unique peptides presented by 41 HLA-II heterodimers covering major alleles across diverse ancestries. Applicants leveraged this expansive dataset to develop computational models that predict peptide antigens based on HLA-II binding properties and infer informative features of the protein antigens from which these peptides derive.

Abstract: The development of new immunoregulatory small molecules represents a significant advance in immunotherapy. Provided herein are compounds, such as compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, and compositions, methods, uses, and kits that may be used in immunotherapy. The compounds provided herein are responsible for immunomodulatory signaling through the TLR2 receptor and are therefore useful for the treatment and/or prevention of various diseases (e.g., metabolic diseases, inflammatory diseases, immune disorders, or proliferative diseases).

Abstract: An atlas of intestinal epithelial cells, intestinal epithelial stem cells and intestinal immune cells identifies new cell populations, markers, networks, and responses to stimuli. Intestinal T cells drive intestinal epithelial cell differentiation and activity. Accordingly, disclosed are methods of modulating intestinal epithelial cell differentiation, maintenance and/or function, related methods for the treatment of disease, including IBD. Also disclosed are methods and kits for identifying cell types, their differentiation, homeostasis and activation.

Abstract: Microbes expressing cholesterol oxidoreductase (COR) proteins, methods of engineering the microbes expressing COR proteins, compositions and methods of using the microbes are provided.

Abstract: The present disclosure provides methods of treating and/or preventing osteoporosis using salt-inducible kinase (SIK) inhibitors. Also provided are methods of using SIK inhibitors for increasing the function of osteocytes, increasing the number of osteoblasts, increasing the activity of osteoblasts, inhibiting the resorption of a bone, decreasing the number of osteoclasts, inhibiting the activity of osteoclasts, increasing the mass of a bone, down-regulating the expression of the gene SOST, and/or inhibiting the activity of sclerostin. The SIK inhibitors may be combined with Src inhibitors or CSF1R inhibitors.

Abstract: The present invention provides for a human cell atlas of the colon from healthy and diseased subjects. The atlas was obtained by single sequencing of about 117,000 cells. The present invention discloses novel markers for cell types. Moreover, genes associated with disease are identified in the colon and colon specific cell types. The invention provides for diagnostic assays based on gene markers and cell composition, as well as target cell types that express genes associated with disease. Finally, disclosed are novel cell types and methods of quantitating, detecting and isolating the cell types.

Abstract: Described in several exemplary embodiments are Bifidobacterium longum subspecies, microorganisms and formulations thereof. Described in several exemplary embodiments are formulations, such as synthetic formulations, that contain one or more of the Bifidobacterium longum subspecies microorganisms. Described in several embodiments herein is use of the Bifidobacterium longum subspecies microorganisms and formulations thereof, such as in an infant and/or young child.

Abstract: The present invention provides for cross-neutralizing SARS-COV2 antibodies. The antibodies can be used to treat SARS-CoV2 and variants thereof.

Abstract: The present invention provides antigen binding domains that bind phosphorylated versions of CREB-regulated transcription coactivator 3 (CRTC3), polynucleotides encoding them, vectors, host cells, and methods of making and using them.

Abstract: Small molecule inhibitors of salt inducible kinases (SIKs) are provided. In particular, compounds of formula (II) and compounds of formula (III), and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof are provided. Also provided are pharmaceutical compositions containing the compounds, methods of preparing the compounds, and methods of using the compounds for inhibiting SIKs, such as SIK1 and SIK2, and methods of treating diseases mediated by SIKs.

Abstract: Small molecule inhibitors of salt inducible kinases (SIKs) are provided. In particular, compounds of formula (I), and tautomers, stereoisomers, pharmaceutically acceptable salts and solvates thereof are provided. Also provided are pharmaceutical compositions containing the compounds, methods of preparing the compounds, and methods of using the compounds for inhibiting SIKs, such as SIK1 and SIK2, and methods of treating diseases mediated by SIKs.

Abstract: The subject matter disclosed herein is generally directed to pathogenic Th1 cells whose phenotype is dependent on IL-23R signaling. Th1 cell specific therapeutic targets and gene programs are disclosed herein. In particular, inhibition of CD160 reduces Th1 cell pathogenicity.

Abstract: Microbes expressing cholesterol oxidoreductase (COR) proteins, methods of engineering the microbes expressing COR proteins, compositions and methods of using the microbes are provided.

Abstract: This application provides for methods of treatment for IBD, especially in subjects who have R. gnavus species or R. gnavus group IBD strains as a component of their microbiome. The application also provides for methods of diagnosing IBD, as well as kits for use in the claimed methods.