MLL3 (KMT2C), MLL4, PA1, UTX And PTIP Antibodies for the Treatment of Development Diseases and Cancers

This technology includes polyclonal antibodies against MLL3 (KMT2C), MLL4, PA1, UTX And PTIP for the development of treatments for development diseases and cancer. Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for H3K4me1/2 on enhancers remain elusive. Furthermore, how these enzymes function on enhancers to regulate cell-type-specific gene expression is unclear.

PPTN as a Selective P2Y14 Receptor Antagonist for the Discovery of Treatments of Inflammatory Disorders

This technology includes PPTN which can be used to study treatments of inflammatory diseases. PPTN is currently a useful pharmacological probe that many labs in the field of purinergic signaling are interested in obtaining. The availability of PPTN as a research tool will stimulate basic advances in the field and possibly eventually lead to new treatments. However, PPTN itself is unsuitable for therapeutic applications. Separately, we are working on new and improved antagonists of the P2Y14 receptor.

Mouse Models for the Study of Male Fertility

This technology includes two mouse models to be used in studying male sterility. One mouse is deficient in the full-length protein for STAMP/TtH5. The second is a conditional mutant STAMP mouse that can be used to produce tissues/organs that are deficient in full length STAMP. STAMP represents an intriguing new protein in the study of male fertility. More detailed future studies should identify the precise defect(s) leading to male sterility and may identify other behavioral and developmental consequences, such as a role in the immune system that is suggested by the microarray studies.

Mouse Model for the Study of Glycosphingolipid Storage Disorders

This technology includes a conventional knockout mice: beta- 1,4-N-acetylgalactosaminyl transferase 1 (GM2 Synthase) KO; B4galntltm1Rlp for the study of glycosphingolipid storage disorders. The glycosphingolipid (GSL) storage diseases are caused by genetic disruption in the lysosomal degradation pathway of GSLs, and include Tay-Sachs disease, Sandhoff's disease, Gaucher's disease, Fabry's disease, Krabbe's disease, and several others. In most of these diseases, GSLs accumulate to massive levels in cells, particularly in neurons, causing neurodegeneration and a shortened life span.

Treatment and Prevention of Neuropathic Pain with P2Y14 Antagonists

This technology includes the use of selective antagonist for the P2Y14 receptor for the treatment and prevention of neuropathic pain. Neuropathic pain conditions arising from injuries to the nervous system due to trauma, disease or neurotoxins are exceedingly difficult to treat. Clinicians and patients are often left to manage neuropathic pain with opioids, but these approaches are limited by the eventual loss in opioid efficacy with developing tolerance, the occurrence of severe adverse side effects and the strong potential for their abuse.

Sphingosine-1-phosphate 1 (S1P1) Receptor Signaling Mouse for Therapeutic Development

This technology includes a mouse model for studying SiP1 receptor signaling for development of therapeutics for a variety of conditions. The S1P1 receptor locus of the mouse has been modified by gene targeting to encode a fusion of the S1P1 receptor and the tetracycline-controlled activator protein (tTA) connected by a Tobacco Etch Virus (TEV) cleavage sequence, internal ribosome initiation sequence (IRES), followed by a beta-arrestin-Tobacco Etch Virus (TEV) protease fusion protein. When activated, the modified S1P1 receptor binds the beta-arrestin-TEV protease fusion, which cleaves the tTA.

Truncated (N)-Methanocarba Nucleosides as Al Adenosine Receptor Agonists and Partial Agonists: Receptor Docking and Potent Anticonvulsant Activity for the Treatment of Various Conditions

This technology includes A1AR-selective agonists which are full or partial agonists of the A1AR and are being considered for treatment of various conditions: seizures, stroke, diabetes, pain, cardio-protection and arrhythmias. A1AR agonists are highly neuroprotective in ischemic and epileptic models. A1AR agonists are also being explored for antidepressant, antianxiety, and other neuropsychiatric effects, due to their presynaptic action to decrease the release of excitatory amino acids in the brain.

Phenotypic Screening for Treating Chronic Neuropathic Pain: Focus on 2-Arylethynyl Substitution of A3 Adenosine Agonists

This technology includes (N)-methanocarba derivatives that are selective agonists of the A3 receptor to be used for the treatment of chronic neuropathic pain. This class of compounds produced full agonists of the human A3AR of nanomolar affinity that were consistently highly selective (>1000-fold vs. A1AR and A2AAR). The selectivity at mouse A3 receptors is smaller, but the compounds are still effective in vivo in reducing or preventing development of neuropathic pain.

Eukaryotic Transposase Mutants and Transposon End Compositions for Modifying Nucleic Acids and Methods for Production and Use in the Generation of Sequencing Libraries

This technology includes novel hyperactive Hermes Transposase mutants and their encoding genes. These transposases are easily purified in large quantity after expression in bacteria. The modified Hermes Transposases are soluble and stable and exist as smaller active complexes compared to the native enzyme. The consensus target DNA recognition sequence is the same as the native enzyme and shows minimal insertional sequence bias.

MiR-193b and MiR-365-1 are Not Required for the Development and Function of Brown Fat in the Mouse

This technology includes the discovery that two specific microRNAs are not required for the development and function of brown fat in mice. Effects of inactivating microRNAs in cell culture in vitro have not always been reproduced in vivo. The paper tests the effect of inactivating two microRNAs, miR-193b and miR-365-1 on the differentiation, function and development of brown adipose tissue. In contrast to positive results previously observed in vitro, the mouse in vivo studies failed to demonstrate significant effects.