Abstract: Disclosed are compositions and methods for engineered peptide inhibitors of NLRP3 infiammasome and methods of their use in the treatment of Myelodysplastic Syndromes. In one aspect, disclosed herein are engineered inhibitors of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome comprising a Helix 2 of POP1 comprising one or more substitutions at residues 18, 21, 22, 25, 26, 28, 29, and/or 30 of POP1 as set forth in SEQ ID NO:1.

Abstract: Disclosed herein is a chimeric polypeptide, comprising at least a portion of the TIM3 receptor ectodomain and a fusion moiety for solubilizing the TIM3 receptor. Also disclosed is a method for treating a hematological cancer in a subject that involves administering to the subject a therapeutically effective amount of the disclosed chimeric polypeptide. Also disclosed is a method for enhance hematopoiesis in a subject, comprising administering to the subject a therapeutically effective amount of the disclosed chimeric polypeptide.

Abstract: Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in de15q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Ac?, or a combination thereof, and a toll like receptor-9 (TLR9) targeting ligand. The molecule can also contain lenalidomide, or an analogue or derivative thereof. Also disclosed is a composition comprising the disclosed molecule in a pharmaceutically acceptable carrier. Also disclosed is a method for treating non-del(5q) myelodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition.

Abstract: Disclosed herein are small molecule pyrin-domain targeted NLRP3 inflammasome inhibitors.

Abstract: The present disclosure relates to a method for diagnosing in a subject the progression from myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML). Also disclosed are methods of treating AML in a subject diagnosed by the disclosed methods.

Abstract: Disclosed are compositions and methods for targeted treatment of TLR9-expressing cancers. In particular, disclosed herein are molecules or conjugates containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, and a cytotoxic nanoparticle that targets TLR9-expressing malignant cells. Also disclosed is a pharmaceutical composition comprising a molecule disclosed herein in a pharmaceutically acceptable carrier. Also disclosed is a method for treating a TLR9-positive cancer in a subject that involves administering to the subject a therapeutically effective amount of a disclosed pharmaceutical composition.

Abstract: Disclosed are compositions and methods for targeted treatment of cancers, such as TLR9-expressing cancers. In particular, molecules containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, that target lytic peptides to TLR9-expressing malignant cells are disclosed.

Abstract: The present disclosure relates to a method for diagnosing in a subject the progression from myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML). Also disclosed are methods of treating AML in a subject diagnosed by the disclosed methods.

Abstract: Peptides useful as inflammasome inhibitors are disclosed and can comprise an H2 helix of a pyrin domain, wherein at least two non-consecutive amino acids of the H2 helix are covalently linked. Methods of treating a subject with a disease comprising administering to the subject the disclosed peptides are also disclosed. Further, disclosed herein are methods of inhibiting binding between a first polypeptide comprising a pyrin domain and a second polypeptide comprising a pyrin domain, the method comprising contacting either the first polypeptide or the second polypeptide with the disclosed peptides.

Abstract: Disclosed herein is a chimeric polypeptide, comprising at least a portion of the TIM3 receptor ectodomain and a fusion moiety for solubilizing the TIM3 receptor. Also disclosed is a method for treating a hematological cancer in a subject that involves administering to the subject a therapeutically effective amount of the disclosed chimeric polypeptide. Also disclosed is a method for enhance hematopoiesis in a subject, comprising administering to the subject a therapeutically effective amount of the disclosed chimeric polypeptide.

Abstract: Disclosed are derivatives of icariin. Disclosed are compounds having Formula I-VIII as defined herein. Methods of using these compounds for the treatment of cancer and inflammation are also disclosed.

Abstract: Disclosed are methods for treating a meylodysplastic syndrome (MDS) in a subject that involves administering to the subject a therapeutically effective amount of an inflammasome inhibitor. Also disclosed are methods for diagnosing a myelodysplastic syndrome (MDS) in a subject. In some embodiments, the method involves assaying a sample from the subject to detect inflammasome activation, wherein an increase in inflammasome activation in the sample compared to a control is an indication of MDS in the subject. In some embodiments, the method involves assaying a sample from the subject to detect s100A9 protein levels, wherein an increase in s100A9 protein levels in the sample compared to a control is an indication of MDS in the subject. The disclosed methods can further involve treating the subject for MDS if an increase in inflammasome activation and/or s100A9 levels are detected.

Abstract: Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in del5q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Ac?, or a combination thereof, and a toll like receptor-9 (TLR9) targeting ligand. The molecule can also contain lenalidomide, or an analogue or derivative thereof. Also disclosed is a composition comprising the disclosed molecule in a pharmaceutically acceptable carrier. Also disclosed is a method for treating non-del(5q) meylodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition.

Abstract: Disclosed are derivatives of icariin. Disclosed are compounds having Formula I-V as defined herein. Methods of using these compounds for the treatment of cancer and inflammation are also disclosed.

Abstract: Disclosed herein is a method of using erythroid expression levels of RNF41 as a predictive biomarker for responsiveness to lenalidomide (LEN) in patients with non-del(5q) MDS.

Abstract: Disclosed are compositions and methods for targeted treatment of cancers, such as TLR9-expressing cancers. In particular, molecules containing a TLR9 targeting ligand, such as a CpG oligodeoxynucleotide, that target lytic peptides to TLR9-expressing malignant cells are disclosed.

Abstract: Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in del5q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Ac?, or a combination thereof, and a toll like receptor-9 (TLR9) targeting ligand. The molecule can also contain lenalidomide, or an analogue or derivative thereof. Also disclosed is a composition comprising the disclosed molecule in a pharmaceutically acceptable carrier. Also disclosed is a method for treating non-del(5q) meylodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition.

Abstract: Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in del5q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Ac?, or a combination thereof, and a toll like receptor-9 (TLR9) targeting ligand. The molecule can also contain lenalidomide, or an analogue or derivative thereof. Also disclosed is a composition comprising the disclosed molecule in a pharmaceutically acceptable carrier. Also disclosed is a method for treating non-del(5q) meylodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition.

Abstract: Disclosed herein is a method of using erythroid expression levels of RNF41 as a predictive biomarker for responsiveness to lenalidomide (LEN) in patients with non-del(5q) MDS.

Abstract: Disclosed are methods for treating a meylodysplastic syndrome (MDS) in a subject that involves administering to the subject a therapeutically effective amount of an inflammasome inhibitor. Also disclosed are methods for diagnosing a myelodysplastic syndrome (MDS) in a subject. In some embodiments, the method involves assaying a sample from the subject to detect inflammasome activation, wherein an increase in inflammasome activation in the sample compared to a control is an indication of MDS in the subject. In some embodiments, the method involves assaying a sample from the subject to detect s100A9 protein levels, wherein an increase in s100A9 protein levels in the sample compared to a control is an indication of MDS in the subject. The disclosed methods can further involve treating the subject for MDS if an increase in inflammasome activation and/or s100A9 levels are detected.