Institute for Systems Biology

About: Institute for Systems Biology is a nonprofit organization based out in Seattle, Washington, United States. It is known for research contribution in the topics: Population & Proteomics. The organization has 1277 authors who have published 2777 publications receiving 353165 citations.

Systems cancer medicine: towards realization of predictive, preventive, personalized and participatory (P4) medicine.

Abstract: A grand challenge impeding optimal treatment outcomes for cancer patients arises from the complex nature of the disease: the cellular heterogeneity, the myriad of dysfunctional molecular and genetic networks as results of genetic (somatic) and environmental perturbations. Systems biology, with its holistic approach to understanding fundamental principles in biology, and the empowering technologies in genomics, proteomics, single-cell analysis, microfluidics, and computational strategies, enables a comprehensive approach to medicine, which strives to unveil the pathogenic mechanisms of diseases, identify disease biomarkers and begin thinking about new strategies for drug target discovery. The integration of multi-dimensional high throughput “omics” measurements from tumor tissues and corresponding blood specimens, together with new systems strategies for diagnostics, enables the identification of cancer biomarkers that will enable presymptomatic diagnosis, stratification of disease, assessment of disease progression, evaluation of patient response to therapy, and the identification of reoccurrences. While some aspects of systems medicine are being adopted in clinical oncology practice through companion molecular diagnostics for personalized therapy, the mounting influx of global quantitative data from both wellness and diseases, is shaping up a transformational paradigm in medicine we termed predictive, preventive, personalized, and participatory (P4) medicine, which requires new strategies, both scientific and organizational, to enable bringing this revolution in medicine to patients and to the healthcare system. P4 medicine will have a profound impact on society—transforming the healthcare system, turning around the ever escalating costs of healthcare, digitizing the practice of medicine and creating enormous economic opportunities for those organizations and nations that embrace this revolution

Genetic Divergence of the Rhesus Macaque Major Histocompatibility Complex

Abstract: The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque.

Calcineurin/NFAT Signaling Is Required for Neuregulin-Regulated Schwann Cell Differentiation

Abstract: Schwann cells develop from multipotent neural crest cells and form myelin sheaths around axons that allow rapid transmission of action potentials. Neuregulin signaling through the ErbB receptor regulates Schwann cell development; however, the downstream pathways are not fully defined. We find that mice lacking calcineurin B1 in the neural crest have defects in Schwann cell differentiation and myelination. Neuregulin addition to Schwann cell precursors initiates an increase in cytoplasmic Ca2+, which activates calcineurin and the downstream transcription factors NFATc3 and c4. Purification of NFAT protein complexes shows that Sox10 is an NFAT nuclear partner and synergizes with NFATc4 to activate Krox20, which regulates genes necessary for myelination. Our studies demonstrate that calcineurin and NFAT are essential for neuregulin and ErbB signaling, neural crest diversification, and differentiation of Schwann cells.

A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis.

Abstract: A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis