Nicolai Van Oers, Ph.D.
Associate Professor

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Project 1: Patients with primary immunodeficiency diseases (PID) are unable to respond to viral, bacterial, and fungal infections properly. Patients with one PID called 22q11.2 deletion syndrome can present with a small thymus, hypoparathyroidism, cardiac problems, and for 1/3 who progress to adulthood, schizophrenia. The thymus is required for the generation of the T cells that combat infections. To better understand their immune system problems, we performed a microRNA profiling study of the blood and thymus. MicroRNAs are small, non-coding RNA molecules that control gene expression. We discovered that the 22q11.2 deletion syndrome patients exhibit an intriguing microRNA dysregulation; hyper-variable miR expression values and abnormal group miR behavior. We are studying the developmental abnormalities that occur in these patients, with an emphasis on how microRNAs affect these pathways.

 

Project 2: Stress, elicited by malnutrition, infections, trauma, surgery, alcoholism, steroid injections and even pregnancy, causes acute and chronic immune system abnormalities. The thymus is particularly sensitive to stress, with cell dying, eventually leading to a weakened immune system. Hypoplastic, or small thymii, are very common in the elderly, which leads to their poor responses to vaccines. We identified several distinct microRNAs in the thymus that are either stress-responsive or poorly expressed in hypoplastic tissues.  Our current research efforts are exploring the role of 4 such microRNA (miR-128, miR-181d, miR-185, miR-205). One of these, miR-205, exhibits a stress-responsive, thymic epithelial specific expression pattern. This suggests an important role for this microRNA in epithelial cell function and survival. We are using conditional knockout mice to test this possibility

 

Project 3: Mycobacterium tuberculosis infects 1/3 of the World’s population. Yet, the majority of infected individuals are unaware of their infection status. Vaccines have proven ineffective to date. Using novel gene expression comparison and RNA sequencing approaches, we are uncovering previously unrecognized pathogenic mechanisms deployed by M. tuberculosis (see photos section).  Using this information, our goal is to engineer efficacious vaccines that will benefit mankind. The study is done in collaboration with Dr. Tawanda Gumbo. Towards this goal, we have recently engineered novel mycobacterial expression vectors, the use of which are high-lighted on the cover of the journal, AEM (AEM cover). Some intriguing new discoveries are forthcoming!

Graduate School

Mcgill University - Canada (1990)

• 22q11.2 deletion syndrome
• Immunology
• Infectious Diseases
• Long noncoding RNAs
• microRNAs
• primary immunodeficiency diseases
• T cell development

Featured Publications

RNA sequencing reveals the consequences of a novel insertion in DOCK8

Khan, S, Kuruvilla, M, Hagin, D Wakeland, B. Liang, C. Vishvanathan, K Gatti, R Torgersen, T Abraham, R Wakeland, E van Oers, N de la Morena, M van Oers,N, de la Morena, M JACI 2016

The Haemophilus ducreyi LspA1 Protein Inhibits Phagocytosis By Using a New Mechanism Involving Activation of C-Terminal Src Kinase.

Dodd DA, Worth RG, Rosen MK, Grinstein S, van Oers NS, Hansen EJ MBio 2014 5 3

The CD3 zeta subunit contains a phosphoinositide-binding motif that is required for the stable accumulation of TCR-CD3 complex at the immunological synapse.

DeFord-Watts LM, Dougall DS, Belkaya S, Johnson BA, Eitson JL, Roybal KT, Barylko B, Albanesi JP, Wülfing C, van Oers NS J. Immunol. 2011 Jun 186 12 6839-47

Dynamic modulation of thymic microRNAs in response to stress.

Belkaya S, Silge RL, Hoover AR, Medeiros JJ, Eitson JL, Becker AM, de la Morena MT, Bassel-Duby RS, van Oers NS PLoS ONE 2011 6 11 e27580

Spatiotemporal patterning during T cell activation is highly diverse.

Singleton KL, Roybal KT, Sun Y, Fu G, Gascoigne NR, van Oers NS, Wülfing C Sci Signal 2009 2 65 ra15

Basal and antigen-induced exposure of the proline-rich sequence in CD3e.

de la Cruz J, Kruger T, Parks CA, Silge RL, van Oers NS, Luescher IF, Schrum AG, Gil D J. Immunol. 2011 Feb 186 4 2282-90

A novel missense mutation in the nuclear factor-?B essential modulator (NEMO) gene resulting in impaired activation of the NF-?B pathway and a unique clinical phenotype presenting as MRSA subdural empyema.

Devora GA, Sun L, Chen Z, van Oers NS, Hanson EP, Orange JS, de la Morena MT J. Clin. Immunol. 2010 Nov 30 6 881-5

Invariant NKT cell development requires a full complement of functional CD3 zeta immunoreceptor tyrosine-based activation motifs.

Becker AM, Blevins JS, Tomson FL, Eitson JL, Medeiros JJ, Yarovinsky F, Norgard MV, van Oers NS J. Immunol. 2010 Jun 184 12 6822-32

Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity.

Holst J, Wang H, Eder KD, Workman CJ, Boyd KL, Baquet Z, Singh H, Forbes K, Chruscinski A, Smeyne R, van Oers NS, Utz PJ, Vignali DA Nat. Immunol. 2008 Jun 9 6 658-66

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

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