Nicolai van Oers, Ph.D.

Associate Professor

Department: Immunology, Microbiology, Pediatrics

Graduate Programs: Immunology, Molecular Microbiology

Biography

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Project 1: Stress causes acute and chronic immune system abnormalities.  The thymus, required for the generation of T cells, is especially sensitive to stress.  In fact, pregnancy, malnutrition, surgery, infections, and steroid injections elicit a dramatic cell death of developing T cells in the thymus.  We are characterizing the stress-induced changes in the microRNAs that are expressed in thymus.  MicroRNAs are small, non-coding RNA molecules that control gene expression.  Using a microRNA profiling assay, we uncovered 18 distinct microRNAs in the thymus that exhibit >2-fold differences in expression.  Four microRNAs are being characterized for their contribution to glucocorticoid sensitivity, T cell repertoire selection, T helper cell differentiation, and thymopoiesis, respectively, using a combination of transgenic and knock-out technologies.

Project 2: Patients with primary immunodeficiency diseases (PID) are unable to respond to viral, bacterial, and fungal infections properly.  To better understand the immune system deficiencies in such patients, we are performing a microRNA profiling study for DiGeorge syndrome, hyper-IgM syndrome, and chronic variable immunodeficiency disorders.  The DiGeorge cohort have an intriguing microRNA dysregulation, leading to hyper-variable miR expression levels, and a loss of group miR behavior.  We are characterizing selected miRs and defining their contribution to selected pathologies in the various PIDs.

Project 3: Mycobacterium tuberculosis is estimated to infect 1/4 of the World’s population.  Yet, the majority of infected individuals are unaware of their infection status.  We have a novel, high throughput screening methodology to identify the genetic elements that allow M. tuberculosis to limit innate inflammatory responses in the host (see photos on web site).

Project 4:  The T cells of the immune system expressed a multimeric receptor complex that comprises separate ligand-binding and signaling components.  The signaling components, which are termed the CD3 chains, all share a well-defined signaling domain termed the immunoreceptor tyrosine-based activation motif.  In our studies of these chains, we have discovered a new signaling motif in CD3 zeta and epsilon that we term the basic-rich stretch.  This motif, resembling polybasic clusters, enables both chains to complex phosphoinositides.  For CD3 zeta, the phosphoinositide-binding domain is necessary for the stable formation of the immunological synapse (see images and movies on website).  In the case of CD3 epsilon, the phosphoinositol interaction maintains T cell surface expression at an optimal level (see publications on website).

Education

Graduate School Mcgill University - Canada (1990)

Research Interests

  • Immunology
  • Infectious Diseases
  • microRNAs
  • primary immunodeficiency diseases
  • Protein tyrosine kinases and phosphatases
  • Signal Transduction
  • T cell development

Publications

Featured Publications Legend

Featured Publications

The Membrane-proximal Portion of CD3 {epsilon} Associates with the Serine/Threonine Kinase GRK2

DeFord-Watts, L.A., Young, J. A.,Pitcher, L. A.,van Oers, N. S. J. Biol. Chem. June 2007 282 16126-16134

The CD3 ge/de signaling module provides normal T cell functions in the absence of the TCR z-ITAMs

Pitcher, L.A.,Mathis, M.A.,Young, J. A., DeFord, L.M., Purtic, B., Wulfing, C., van Oers, N.S.C. Eur. J. immunol. December 2005 In Press

Results 1-10 of 12

Professional Associations/Affiliations

  • Federation of clinical immunology societies (2011)
  • American Association of Immunologists (2000)
  • American Association for the Advancement of Science (1998)