Abstract: The present invention includes CSNK1A1 inhibitors that are useful in treating or preventing a cancer in a subject. In certain embodiments, the cancer comprises a hematological cancer, such as but not limited to acute myeloid leukemia (AML) and/or MDS (myelodysplastic syndrome, including 5q-MDS). In other embodiments, the cancer comprises colon cancer.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of EGLN1-dependent cancers. In particular, the instant disclosure provides for identification of a cancer as EGLN1-dependent, and selection and/or administration of an inhibitor of EGLN1 or VHL (Von Hippel-Lindau Tumor Suppressor) as a therapeutic agent for such a cancer and/or subject having or at risk of developing such a cancer.

Abstract: The present disclosure relates to compositions, methods, and kits for increasing the viability of bacteria that have been subjected to freeze-drying/lyophilization. In particular, the disclosure relates to compositions and methods for increasing the viability of living medicines (e.g.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: Disclosed is an in situ method for detecting spatial proximity relationships between nucleic acid sequences, such as DNA, in a cell. The method includes: providing a sample of one or more cells comprising nucleic acids; fragmenting the nucleic acids present in the cells that leaves 5? overhanging ends; filling in the overhanging ends with at least one labeled nucleotide; joining the filled in end of the fragmented nucleic acids that are in close physical proximity to create one or more end joined nucleic acid fragments having a junction; isolating the one or more end joined nucleic acid fragments using the labeled nucleotide; and determining the sequence at the junction of the one or more end joined nucleic acid fragments.

Abstract: The invention provides methods for generating pools of variants of DNA templates, and methods of using pools of variants to identify sequences involved in conferring sensitivity or resistance to environmental factors.

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers that exhibit elevated expression and/or amplification of the ABCB1 (MDR1) transporter, optionally for reasons related to development of chemotherapeutic resistance having occurred during treatment with an initial chemotherapeutic drug. In particular, the instant disclosure provides for identification of a cancer as possessing elevated ABCB1 expression and/or exhibiting resistance to a non-tepoxalin chemotherapeutic drug, and selecting and/or administering tepoxalin, a tepoxalin derivative and/or metabolite thereof as a therapeutic agent for such a cancer and/or subject having or at risk of developing such a cancer. Methods and compositions for therapies that combine such tepoxalin or tepoxalin-related compounds with other cancer therapies and/or chemotherapeutic agents are also provided.

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.

Abstract: Provided herein are compounds useful for the treatment of diseases caused by infections of T. gondii, and closely related parasites. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compositions including veterinary compositions and may be used in methods of treatment and/or prophylaxis of disease.

Abstract: A system and method for isolating target substrates includes a microfluidic chip, comprising a plurality of processing units, each processing unit comprising: an inlet port, a plurality of first chambers connected to the inlet port by a fluid channel, the fluid channel comprising a plurality of valves, a plurality of second chambers, each of the second chambers connected to a respective first chamber by a fluid channel, each fluid channel including a controllable blocking valve, and a plurality of respective outlet ports, each outlet port in fluid communication with a respective one of said second chambers and each outlet port including a blocking valve. A magnet is adjacent the microfluidic chip and is movable relative to the microfluidic chip. A valve control is capable of actuating certain ones of the controllable blocking valves in response to a control signal.

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.

Abstract: In one aspect, the invention features a method for identifying a drug-modulated polypeptide substrate of cereblon (CRBN). In another aspect, the invention features a method of identifying a polypeptide target of a modulator of CRBN. In yet another aspect, the invention provides methods of monitoring or characterizing the sensitivity of a subject to a modulator of CRBN.

Abstract: The present invention includes methods of treating patients with acute myeloid leukemia across a range of genetic subtypes with DHODH inhibitors, such as 6-fluoro-2-(2?-fluoro-[1,1?-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid).

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit elevated expression of FOXA1 and/or FOXA1 gene targets, such as certain breast, liver and/or prostate cancers, including luminal and/or ER-positive forms of breast cancer. Three previously identified adenosine receptor antagonists, CGS-15943, MRS-1220 and SCH-58261, as well as furan ring moiety-possessing derivatives of CGS-15943 are specifically provided for killing cancer cells in a manner that appears to involve activation of the aryl hydrocarbon receptor (AHR) by such compounds. The instant disclosure therefore provides for selecting and/or administering CGS-15943, MRS-1220, SCH-58261 and/or a furan-possessing derivative of CGS-15943, MRS-1220 and/or SCH-58261 as a therapeutic agent to target a cancer cell and/or subject having or at risk of developing a cancer.

Abstract: 3D cell cultures and devices for 3D cell culture, and methods of use thereof are provided. In some embodiments, the 3D cell culture comprise pancreatic ? cells and can be generated in multi-well plates, allowing for high throughput assays on the cell culture.

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit elevated expression of SLC26A2, such as certain ovarian, endometrial, brain, bone, and lung cancers, as well as melanoma. A previously identified vanadium-containing compound, bis(maltolato)oxovanadium(IV) (BMOV), specifically provided for killing of SLC26A2 expressing cancer cells in a SLC26A2-dependent manner. The instant disclosure therefore provides for selecting and/or administering BMOV and related vanadium-containing compounds as a therapeutic agent to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided.

Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit arm-level loss of chromosome 16q, focal copy loss of 16q13 and/or low expression of metallothionein proteins, such as certain uterine, ovarian, gastroesophageal and lung cancers. Three known drugs, disulfiram, elesclomol and thiram, as well as certain disulfiram metabolites, are specifically provided for killing cancer cells characterized by arm-level loss of chromosome 16q, focal copy loss of 16q13 and/or low expression of metallothioneins. The instant disclosure therefore provides for selecting and/or administering disulfiram, elesclomol and thiram and/or active metabolites or derivatives of disulfiram, elesclomol and thiram as a therapeutic agent(s) to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided.

Abstract: Chromatin 3D structure modulating agents in the context of the present invention are intended to interfere or manipulate the function of loop anchor motifs, such as CTCF motifs. In certain example embodiments, the present invention may block formation of an loop anchor or chromatin domain or induce formation of a loop anchor or chromatin domain at a targeted genomic location. For instance, a loop anchor motif can be altered, such as by mutating (including inverting) a binding motif so as to remove such a motif, or by adding new binding motifs in new locations within a loop domain, so as to reduce the size of an existing loop, so as to modify the size of an existing loop, or combinations thereof. Alternatively, the chromatin 3D structure modulating agent may bind a target region and mask a loop anchor motif, thereby preventing a loop anchor or chromatin domain from forming. The chromatin 3D structure modulating agent may bind a target region and cause a loop anchor of chromatin domain to form.

Abstract: A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a RAF inhibitor and a second inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a RAF inhibitor and an effective amount of a second inhibitor, wherein the second inhibitor is a MEK inhibitor, a CRAF inhibitor, a CrkL inhibitor or a TPL2/COT inhibitor. A method of identifying a kinase target that confers resistance to a first inhibitor is also provided.