Nicolai Van Oers, PhD

Associate Professor
Immunology, Microbiology, Pediatrics
Graduate Program: Immunology
Molecular Microbiology

Contact Information

UT Southwestern Medical Center
5323 Harry Hines Boulevard
Dallas, Texas 75390

Office Phone: 214-648-1236
Office Fax: 214-648-7331

nicolai.vanoers@utsouthwestern.edu

Biography

The antigen specific cells of the immune system, the T and B lymphocytes, express multi-subunit cell surface receptors that are essential for recognizing and responding to pathogens such as viruses, bacteria, and parasites.

We are studying the signal transduction pathways that are triggered following interactions between these receptors and the appropriate target molecules. Receptor stimulation activates a cascade of intracellular signals that are regulated by different families of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases). For T cells, effective receptor signaling will elicit diverse biological outcomes such as lymphokine release and cytotoxic functions.

However, incomplete or attenuated signals may promote T cell death and/or anergy induction, and in the thymus, may be important for the development of the T cell repertoire. The TCR z molecule, a component of the TCR complex, is one of the many tyrosine phosphorylated proteins that develops following TCR ligation. A prevailing hypothesis is that certain phosphorylated intermediates of the TCR z subunit control many of these biological processes.

We have been using mice that are genetically deficient in selected tyrosine phosphorylated intermediates of the TCR z molecule. Our studies of these mice have revealed very surprising and dramatic results concerning the mechanisms of TCR signal transmission.

We are currently pursuing several related questions:

  1. What are the functional roles of the distinct tyrosine phosphorylated intermediates of the TCR z subunit?
  2. How are TCR signaling processes regulated by the different families of protein kinases?
  3. How do differences in the signals generated through the TCR promote very distinct biological outcomes, immune-responsiveness or non-responsiveness?
  4. How does the protein tyrosine phosphatase PTPH1 attenuate TCR signaling processes?

With answers to these questions, we hope to gain a better understanding of the mechanisms of T cell development and T cell effector functions during normal and disease conditions.

 

Education

Graduate SchoolMcgill University - Canada (1990)

Research Interests

Immunology
Infectious Diseases
Protein tyrosine kinases and phosphatases
Signal Transduction
T cell development

Publications

Featured
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):16126-34

Featured
The Constitutive Tyrosine Phosphorylation of CD3{zeta} Results from TCR-MHC Interactions That Are Independent of Thymic Selection

Becker, A. M.,Deford-Watts, L. M.,Wuelfing, C.,van Oers, N. S. , Journal of Immunology , April 2007; (178):4120-8

Selective Expression of the 21-Kilodalton Tyrosine-Phosphorylated Form of TCR {zeta} Promotes the Emergence of T Cells with Autoreactive Potential

Pitcher, L. A.,Mathis, M. A., Subramanian, S., Young, J. A., Wakeland, E. K., Love, P. E.,van Oers, N. S. , J Immunol , May 2005; (174):6071-9

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

T cell receptor (TCR) clustering in the immunological synapse integrates TCR and costimulatory signaling in selected T cells

Purtic, B., Pitcher, L. A., van Oers, N. S., Wulfing, C. , Proc Natl Acad Sci U S A , February 2005; (102):2904-9

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)

The Constitutive Tyrosine Phosphorylation of CD3{zeta} Results from TCR-MHC Interactions That Are Independent of Thymic Selection

Becker, A.M., Deford-Watts, L. M, Wuelfing, C., van Oers, N.S.C. , Journal of Immunology , April 2007; :4120-8178

Professional Associations/Affiliations

American Association for the Advancement of Science

American Association of Immunologists