Prematurely-Graying Mouse Line Demonstrates Regulation of Melanocyte Stem Cell Development by SOX10 (Sry-Related HMG-Box) Transcription Factor for Use in Regenerative Medicine

This technology includes transgenic mice to be used in the study of melanocyte stem cells (MSCs) for utilization in regenerative medicine. Using the melanocyte system as a model, we investigated establishment of MSCs in the hair bulge - the stem cell compartment of the hair. During embryogenesis, all melanoblasts express SOX10, but this expression is downregulated during hair follicle morphogenesis and MSC differentiation. To further study the role of SOX10, we generated transgenic mice overexpressing SOX10 in melanoblasts.

Nucleoside Agonists of Adenosine Receptors as Cardio- and Cerebroprotective Agents

This technology includes a compound for use as a selective agonist of the A1 adenosine receptor (AR) for therapeutic hypothermia and other conditions. We have examined various synthesized nucleosides in a model of mouse hypothermia, in conjunction with AR knockout mice, to characterize the biological profiles. In trying to identify novel highly selective A1AR agonists that have superior in vivo activities, we have adapted a means of rigidifying the ribose moiety of adenosine in the form of a bicyclic (N)-methanocarba ring.

MicroRNAs for Cell Line Utilization and Future Therapeutic Application

This technology includes microRNAs for use in cell lines for protein production and potentially future treatments of cancer or diseases related to metabolism. Mmu-miR-466h was identified as a major apoptotic regulator in suspension adapted Chinese Hamster Ovary cells. Mmu-miR-466h was found to have the pro-apoptotic activity by targeting some anti-apoptotic genes for degradation during the exposure of CHO-S cells to the nutrients depleted media.

Ionophores as Treatment for Sickle Cell Disease

This technology includes a method using ionophores to reduce sickling in patients with sickle cell disease. Sickle cell disease is caused by polymerization of a hemoglobin mutant, and the only approved treatment acts by replacing sickle hemoglobin with fetal hemoglobin, thereby increasing the delay time prior to polymerization. This drug is only partially successful because it does not induce fetal hemoglobin synthesis in all cells.

Structure-Based Design of A3 Adenosine Receptor-Selective 2-Arylethynyl (N)-methanocarba Nucleosides for Diagnostic and Therapeutic Uses

This technology includes compounds that are selective agonists of the A3 receptor for the treatment of various disorders such as cancer and autoinflammatory diseases. Structurally, these compounds extend the class of (N)-methanocarba derivatives that are selective agonists of the A3 receptor.

Composition and Methods for Modulation of Thyrotropin Releasing Hormone for the Treatment of Cancer-related Fatigue

This technology includes a series of small molecule TRHR agonists for the treatment of cancer-related fatigue. In particular, PTLS-04 and PTLS-11 have shown excellent TRHR agonist activities in mouse and human cells and have improved metabolic profile compared to TRI I and taltirelin. Additional work is being done to further optimize the series by designing and synthesizing additional compounds.

Ribose Derivatives as A3 Adenosine Receptor Modulator for Various Therapeutic Uses

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.

Antibacterial and Antifungal Polyketides from Environmental Amycolatopsis Strains

This technology includes three new chemical entities discovered for antibacterial and antifungal activities. The compounds are novel tetramic acid containing polyketides obtained from two different Amycolatopsis strains. Their planar structures and relative stereochemistry were elucidated by 1D and 2D NMR methods, including 1H-1H and 13C-13C COSY, TOCSY, HSQC, HMBC and ROESY. Whole genome sequencing of these two strains revealed a 158 kb biosynthetic gene cluster (BGC) containing a 23-module, mixed NRPS-PKS pathway responsible for their biosynthesis.