Biography

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Primary Immunodeficiency Diseases

Patients with primary immunodeficiency diseases (PID) are often unable to respond to viral, bacterial, and fungal infections, leaving them prone to life-threatening conditions. We are interested those patients with hypoplasia’s of the thymus. We are using both patient samples and mouse models pertaining to elucidate the causes of the thymic hypoplasia’s. Our studies focus on individuals with 22q11.2 deletion syndrome (affecting 1/4000 individuals) and a rare group of patients we discovered who harbor compound heterozygous mutations in FOXN1, a key transcription factor required for the formation of the thymus, hair extrusion and nail beds.

 

Developmental and Regenerative Processes

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, undergoing atrophy and reduced T cell development. This causes a weakened immune system. We have identified different noncoding RNAs (miRNAs and lncRNAs) that regulate these stress responses.

 

We seek to delineate the mechanisms by which these noncoding RNAs govern either the development of the thymus (and pituitary) and the regenerative process needed for these tissues to return to normal functionality. Our studies use advanced molecular approaches to characterize the functions of the noncoding RNAs in this process, taking advantage of CRISPR/Ca9s genome editing. Manipulating the formation of key cell populations such as epithelial, mesenchymal, endothelial and precursor thymocytes may allow us to generate a thymus de novo.

 

Infections

Mycobacterium tuberculosis (Mtb) infects 1/3 of the World’s population. We seek to understand the pathogenic mechanisms whereby mycobacteria are able to subvert host immune responses. Using RNA sequencing approaches for small RNAs, we identified several Mtbencoded small noncoding RNAs (sncRNAs) produced in infected cells. These sncRNAs regulate both mycobacterial and mammalian gene expression. The molecular mechanisms leading to gene regulation are under investigation using loss- and gain-of-function techniques.

Education

Graduate School
Mcgill University - Canada (1990)

Research Interest

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

Publications

Featured Publications LegendFeatured Publications

Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations.
Maryoung L, Yue Y, Young A, Newton CA, Barba C, van Oers NS, Wang RC, Garcia CK J. Clin. Invest. 2017 Mar 127 3 982-986
STAT4-mediated transcriptional repression of the IL5 gene in human memory Th2 cells.
Gonzales-van Horn SR, Estrada LD, van Oers NS, Farrar JD Eur. J. Immunol. 2016 Mar
RNA sequencing reveals the consequences of a novel insertion in dedicator of cytokinesis-8.
Khan S, Kuruvilla M, Hagin D, Wakeland B, Liang C, Vishwanathan K, Gatti RA, Torgersen TR, Abraham RS, Wakeland EK, van Oers NS, de la Morena MT J. Allergy Clin. Immunol. 2016 Feb
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
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

Professional Associations/Affiliations

  • American Society of Microbiologists (2015)
  • Federation of clinical immunology societies (2011)
  • American Association of Immunologists (2000)