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Exposed collagen in injured blood vessels provides a substrate for platelets to adhere and aggregate initiating the first step in thrombosis, the formation of blood clots inside a blood vessel. Despite the essential role of platelets in vascular injury, excessive platelet aggregation may also result in thrombotic diseases such as stroke and heart attack.

The catalytic subunit of the DNA-dependent protein kinase complex (DNA-PKcs) has been shown to be important in DNA repair and VDJ recombination in lymphocytes. The inventors have discovered that DNA-PKcs also plays novel, important roles in energy regulation and neurological function. The inventors observed that mature DNA-PKcs-deficient mice (also known as SCID mice) have a lower proportion of fat, resist obesity, and have significantly greater physical endurance than wild-type control mice, particularly with increasing age.

Aquaporins, also known as water channels, form pores in cell membranes and selectively transport water in and out of the cell. Aquaporins are involved in regulation of water balance and blood pressure, and thirteen different isoforms have been found in mammals. Aquaporin 2 (AQP2) is located in the collecting duct of the kidney, and is regulated by the peptide hormone vasopressin. AQP2 expression is increased in conditions where there is water retention, such as pregnancy and congestive heart failure, and mutations of AQP2 are associated with nephrogenic diabetes insipidus.

This invention involves the use of inhibitors of alpha-4 beta-7 (a4b7) integrin to inhibit HIV transmission/infection, as a prophylactic to inhibit onset of the acute stage of HIV infection or to treat HIV infection. The a4b7 integrin inhibitors were previously developed for use in other diseases, such as multiple sclerosis or inflammatory bowel disease.

The ubiquitin-proteasome system has recently been recognized to play a central role in tumor biology. Bortezomib, an inhibitor of the chymotrypsin-like activity of the proteasome, has clinical activity in a variety of hematologic malignancies and is FDA approved for use in Multiple Myeloma and Mantle Cell Lymphoma.

NIH inventors, in collaboration with Scott and White Memorial Hospital inventors, have developed new immunotoxins comprising a mutant diphtheria toxin linked to an anti-prostate specific membrane antigen (PSMA) fold-back diabody. The fold-back diabody construct has a shortened linker region between the heavy and light chains of the antibody variable domain. This construct allows interactions between the longer-linked variable domains while preventing interactions between the shorter-linked variable domains.

Available for licensing and commercial development are compositions and methods for the treatment and inhibition of Methicillin-resistant Staphylococcus aureus (MRSA), a dangerous human pathogen. The invention concerns immunogenic peptides that can be used to induce protective immunity against MRSA, including phenol-soluble modulin (PSM) peptides.

Cell-free hemoglobin based oxygen carriers (HBOCs) are blood substitutes and resuscitative agents that can be used to replace whole blood donations, alleviate blood shortages and reduce the risks of infections such as HIV and hepatitis. Stroma-free HBOCs offer the advantages of increased stability, consistency of supply, and reduced immunogenicity over the use of the alternative cell based sources.

Ixodes scapularis is a blood-sucking tick and the principal vector of Lyme disease, a spirochetal illness caused by Borrelia burgdorferi and now the most common vector-borne infection in the United States; more than 50,000 cases have been reported during the last ten years. The salivary gland of I. scapularis has a number of pharmacologically active molecules that help the tick to successfully feed on blood, such as inhibitors of complement system, in addition to coagulation and platelet aggregation inhibitors.

The nucleotide-binding oligomerization domain 2 (NOD2) protein plays a key role in innate immunity as a sensor of muramyl dipeptide (MDP), a breakdown product of bacterial peptidoglycan. Bacterial peptidoglycan promotes the innate immune response through the activation of Toll-like receptor 2 (TLR2), which ultimately provokes inflammation. Activation of NOD2 by MDP negatively regulates the activity of TLR2, and thus reduces inflammation.