The University of New Mexico

University of Kansas

Other

Sanford-burnham Medical Research Institute

Angela Wandinger-Ness

Larry A Sklar

Zurab Surviladze

Jacob Ongudi Agola

Peter C Simons

Tudor Oprea

Tione Buranda

Laurie Hudson

Jennifer Elizabeth Golden

Chad Schroeder

Denise S Simpson

Virginie Bondu

Soumik BasuRay

Scarlett Swanson

Jeffrey Aube

John C Reed

Dayong Zhai

Eric R Prossnitz

Jeffrey Aubé

Mathewos Z Tessema

Tamara Roitbak

Elsa G Romero

Stephen Young

Julica J Noth

The present invention relates to molecules which function as modulators (i.e., inhibitors and agonists) of the Ras-homologous (Rho) family of small GTPases (e.g. Rac, Cdc42 and Rho GTPases) and their use to treat diseases, including cancers (including solid tumors-medulloblastoma, ovarian, breast, head and neck, testicular, prostate among others and hematologic malignancies-B cell lymphoma, where these GTPases are overexpressed or hyperactivated), sporadic and genetic diseases where activation of Rho GTPases plays a pivotal role (Menkes disease, rheumatoid arthritis, atherosclerosis, diabetes (type I), Huntington's disease and Alzheimer's disease) which are mediated through these proteins. Compounds according to the present invention may also be used as a therapy for the treatment ofspp. orspp. infections, especially including

Modulators of GTPases and their use

In one embodiment, the invention provides a method of diagnosing sepsis or a virus-related infection (often a viral hemorrhagic fever infection) in a subject by detecting and measuring the level of a set of sepsis and virus infection-associated-GTPase biomarkers in a sample obtained from the subject using multiplexed flow cytometry. Related kits are also provided. In a preferred embodiment, the invention provides point of care diagnostic methods for determining an early stage sepsis or the severity of a virus infection, especially in a hospital or other setting.

Activated GTPase-based assays and kits for the diagnosis of sepsis and other infections

The present invention is directed to the discovery that RapI-GTP, Rac1-GTP and Flt3-L can be used as Biomarkers for the early detection of sepsis in patients suspected of a bacterial infection which presents as sepsis or is likely to produce sepsis. In particular, the present invention is directed to methods, assays and kits which may be used to distinguish sepsis (infection) from systematic inflammatory response caused by sterile inflammation in trauma patients. The method may be used to diagnose bacteria infection and/or sepsis and monitor therapy of a patient to allow modification of treatment and/or cessation of treatment.

Rap1-Gtp, Rac1-GTP and FMS-like tyrosine kinase 3 ligand (FLT3-L) as biomarkers for early detection of sepsis

The present invention relates to molecules which function as selective modulators (i.e., inhibitors and agonists, preferably inhibitors) of the Ras-homologous (Rho) family of small GTPases, in particular, Cdc42 GTPase and their use to treat diseases, for example cancers, including metastatic cancer, where Cdc42 GTPase is overexpressed or hyperactivated, genetic and acquired diseases where activation of Cdc42 GTPase plays a pivotal role (e.g., neurodegenerative diseases), rheumatoid arthritis, atherosclerosis, diabetes type I, autosomal polycystic kidney diease, cystic kidney disease, precystic kidney disease and microbial infections. Additionally, compounds according to the present invention may be used to inhibit rejection (graft host response) in transplant patients (pursuant to transplantation), to promote immunosuppression, anti-inflammatory response and to mobilize stem cell (migration) in patients in need, among others.

Modulators of GTPase and use in relevant treatment

This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.

Rab7 GTPase inhibitors and related methods of treatment

The present invention relates generally to glutathione derivatized beads which are adapted for use in conjunction with glutathione-S-transferase fusion proteins (generally, GST fusion proteins, which contain a fluorescent label such as fluorescent green protein) for use in flow cytometry. The present invention also relates to methods for detecting and/or quantifying interactions between a GST fusion protein and their binding partners, in particular, labeled binding partners such as fluorescently labeled binding partners. By creating glutathione beads with an appropriate high or increased site density, disadvantages often associated with low affinity systems and quick off-rates in solution may be resolved to provide a workable system and method. Methods of identifying potential agonists, antagonists and regulator compounds of proteins fused to GST from libraries of compounds represents another aspect of the present invention.

Glutathione beads and GST fusion proteins

The present disclosure provides human renal stem cells. Also described are human renal stem cells isolated from the papillary region of the human kidney and methods of isolating the same. Also described are methods for culturing, characterizing, and differentiating the same, including methods for identifying human renal stem cells that are positive for Nestin and CD133, and methods for allowing the cells to differentiate into neurons.

Human renal stem cells

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Albuquerque, NM, United States of America

Angela Wandinger-Ness