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Port Saint Lucie, FL, United States

Torrey Pines Institute for Molecular Studies, also commonly referred to as TPIMS, is a non-profit biomedical research institute "dedicated to the discovery of causes, treatments and cures for a wide variety of diseases and afflictions including heart disease, cancer, AIDS, diabetes, multiple sclerosis, Alzheimer’s, aging-relating conditions, and pain management. Torrey Pines Institute for Molecular Studies is a 501 research center dedicated to conducting basic research to advance the understanding of human disease and the improvement of human health.Torrey Pines' scientists conduct research in fields associated with a wide variety of major medical conditions, including multiple sclerosis, cancer, heart disease, Types I and II diabetes, pain management, Alzheimer’s, inflammatory disorders, AIDS and other infectious diseases, regenerative medicine, obesity, transplant rejection, muscle wasting syndrome, rheumatoid arthritis and new methods for drug discovery.The Institute fosters an innovative research environment, believing that multidisciplinary and collaborative approaches accelerate the discovery process.Techniques created by Torrey Pines Institute include individual compounds arrays, mixture-based synthetic combinatorial libraries, positional scanning deconvolution, biometrical analysis, libraries from libraries, small molecule and heterocyclic compounds, and direct in-vivo testing of mixtures. Wikipedia.

Samad F.,Torrey Pines Institute for Molecular Studies
Blood | Year: 2013

Clinical and epidemiological studies support a connection between obesity and thrombosis, involving elevated expression of the prothrombotic molecules plasminogen activator inhibitor-1 and tissue factor (TF) and increased platelet activation. Cardiovascular diseases and metabolic syndrome-associated disorders, including obesity, insulin resistance, type 2 diabetes, and hepatic steatosis, involve inflammation elicited by infiltration and activation of immune cells, particularly macrophages, into adipose tissue. Although TF has been clearly linked to a procoagulant state in obesity, emerging genetic and pharmacologic evidence indicate that TF signaling via G protein-coupled protease-activated receptors (PAR2, PAR1) additionally drives multiple aspects of the metabolic syndrome. TF-PAR2 signaling in adipocytes contributes to diet-induced obesity by decreasing metabolism and energy expenditure, whereas TF-PAR2 signaling in hematopoietic and myeloid cells drives adipose tissue inflammation, hepatic steatosis, and insulin resistance. TF-initiated coagulation leading to thrombin-PAR1 signaling also contributes to diet-induced hepatic steatosis and inflammation in certain models. Thus, in obese patients, clinical markers of a prothrombotic state may indicate a risk for the development of complications of the metabolic syndrome. Furthermore, TF-induced signaling could provide new therapeutic targets for drug development at the intersection between obesity, inflammation, and thrombosis. Source

Medina-Franco J.L.,Torrey Pines Institute for Molecular Studies
Journal of Chemical Information and Modeling | Year: 2012

Systematic description of structure-activity relationships (SARs) of data sets and structure-property relationships (SPRs) is of paramount importance in medicinal chemistry and other research fields. To this end, structure-activity similarity (SAS) maps are one of the first tools proposed to describe SARs using the concept of activity landscape modeling. One of the major goals of the SAS maps is to identify activity cliffs defined as chemical compounds with high similar structure but unexpectedly very different biological activity. Since the first publication of the SAS maps more than ten years ago, these tools have evolved and adapted over the years to analyze various types of compound collections, including structural diverse and combinatorial sets with activity for one or multiple biological end points. The development of SAS maps has led to general concepts that are applicable to other activity landscape methods such as "consensus activity cliffs" (activity cliffs common to a series of representations or descriptors) and "selectivity switches" (structural changes that completely invert the selectivity pattern of similar compounds against two biological end points). Herein, we review the development, practical applications, limitations, and perspectives of the SAS and related maps which are intuitive and powerful informatics tools to computationally analyze SPRs. © 2012 American Chemical Society. Source

Kumar V.,Torrey Pines Institute for Molecular Studies
Journal of Hepatology | Year: 2013

Natural killer T cells (NKT) are innate-like cells which are abundant in liver sinusoids and express the cell surface receptors of NK cells (e.g., NK1.1 (mouse) or CD161+/CD56+(human)) as well as an antigen receptor (TCR) characteristic of conventional T cells. NKT cells recognize lipid antigens in the context of CD1d, a non-polymorphic MHC class I-like molecule. Activation of NKT cells has a profound influence on the immune response against tumors and infectious organisms and in autoimmune diseases. NKT cells can be categorized into at least two distinct subsets: iNKT or type I use a semi-invariant TCR, whereas type II NKT TCRs are more diverse. Recent evidence suggests that NKT-cell subsets can play opposing roles early in non-microbial liver inflammation in that type I NKT are proinflammatory whereas type II NKT cells inhibit type I NKT-mediated liver injury. © 2013 European Association for the Study of the Liver. Source

Fields G.B.,Torrey Pines Institute for Molecular Studies
Journal of Biological Chemistry | Year: 2013

Interstitial collagen mechanical and biological properties are altered by proteases that catalyze the hydrolysis of the collagen triple-helical structure. Collagenolysis is critical in development and homeostasis but also contributes to numerous pathologies. Mammalian collagenolytic enzymes include matrix metalloproteinases, cathepsin K, and neutrophil elastase, and a variety of invertebrates and pathogens possess collagenolytic enzymes. Components of the mechanism of action for the collagenolytic enzyme MMP-1 have been defined experimentally, and insights into other collagenolytic mechanisms have been provided. Ancillary biomolecules may modulate the action of collagenolytic enzymes. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Source

Kumar V.,Torrey Pines Institute for Molecular Studies | Delovitch T.L.,Robarts Research Institute
Immunology | Year: 2014

Summary: Natural killer T cells (NKT) can regulate innate and adaptive immune responses. Type I and type II NKT cell subsets recognize different lipid antigens presented by CD1d, an MHC class-I-like molecule. Most type I NKT cells express a semi-invariant T-cell receptor (TCR), but a major subset of type II NKT cells reactive to a self antigen sulphatide use an oligoclonal TCR. Whereas TCR-α dominates CD1d-lipid recognition by type I NKT cells, TCR-α and TCR-β contribute equally to CD1d-lipid recognition by type II NKT cells. These variable modes of NKT cell recognition of lipid-CD1d complexes activate a host of cytokine-dependent responses that can either exacerbate or protect from disease. Recent studies of chronic inflammatory and autoimmune diseases have led to a hypothesis that: (i) although type I NKT cells can promote pathogenic and regulatory responses, they are more frequently pathogenic, and (ii) type II NKT cells are predominantly inhibitory and protective from such responses and diseases. This review focuses on a further test of this hypothesis by the use of recently developed techniques, intravital imaging and mass cytometry, to analyse the molecular and cellular dynamics of type I and type II NKT cell antigen-presenting cell motility, interaction, activation and immunoregulation that promote immune responses leading to health versus disease outcomes. © 2014 John Wiley & Sons Ltd. Source

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