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This technology includes a class of A3AR-selective agonists to be used therapeutically to treat a variety of conditions, including chronic pain, cancer, and inflammatory diseases. 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.

This technology includes antibodies to apolipoprotein L1 (ApoL 1) to be used in basic science laboratory studies. ApoL 1 is a protein that is present within cells and circulates as component of high-density lipoprotein. Its functions are not well understood. Recently APOL 1 genetic variants have been shown to be highly associated with kidney disease in African Americans.

This technology includes mouse models for both mild and severe Gaucher disease. Gba-L444P and Gba-L444P A456P mice, respectively, carry common gene mutations for milder or severe Gaucher disease, a lysosomal storage disease. Gaucher Disease is caused by mutations in the lysosomal enzyme, glucocerebrosidase. Deficiency of enzyme activity leads to the accumulation of glucosylceramide in liver, spleen, bone, and in the most severe cases, the central nervous system.

This technology includes a knockout mouse model for Sphingosine kinase 2 (Sphk2) to be used in neurobiology and immunology research studies. Sphingosine kinase 1 and 2 are enzymes that produce sphingosine-1-phosphate, a potent bioactive compound that activates a family of G-protein coupled receptors known as Edg or S1P receptors. Triggering these receptors on cells may have important effects related to inflammation, immunity, cancer, angiogenesis, cell proliferation, adhesion, cardiovascular function, nervous system function and injury responses.

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.

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.

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.

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.

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.

This technology includes a transgenic mouse model which can be used to study perinatal oocyte dynamics. In the first two days after birth, the number of primordial ovarian follicles and their germ cells undergo a major decrease. The mechanism for this decrease was studied. Ablation of FIGLA (Factor in the germline, alpha), a basic helix-loop-transcription factor, results in massive perinatal oocyte loss. A transgenic mouse line was established, Figla-EGFP /Cre, in which EGFP and Cre recombinase are expressed just before birth in germ cells.