Nicolai Van Oers, Ph.D.

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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.

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

Mesenchymal cell replacement corrects thymus hypoplasia in murine models of 22q11.2 deletion syndrome.

Bhalla P, Du Q, Kumar A, Xing C, Moses A, Dozmorov I, Wysocki CA, Cleaver OB, Pirolli TJ, Markert ML, de la Morena MT, Baldini A, van Oers NS, J Clin Invest 2022 Sep

Thymus Functionality Needs More Than a Few TECs.

Bhalla P, Su DM, van Oers NSC, Front Immunol 2022 13 864777

Serum IgG Profiling of Toddlers Reveals a Subgroup with Elevated Seropositive Antibodies to Viruses Correlating with Increased Vaccine and Autoantigen Responses.

Pichilingue-Reto P, Raj P, Li QZ, Dozmorov I, Karp DR, Wakeland EK, Nelson M, Gruchalla RS, de la Morena MT, van Oers NSC, J Clin Immunol 2021 Mar

SARS-CoV-2 infection associated with hepatitis in an infant with X-linked severe combined immunodeficiency.

van Oers NSC, Hanners NW, Sue P, Aquino V, Li QZ, Schoggins JW, Wysocki CA, Clin Immunol 2021 Jan 108662

Impact of Bead-Beating Intensity on the Genus- and Species-Level Characterization of the Gut Microbiome Using Amplicon and Complete 16S rRNA Gene Sequencing.

Zhang B, Brock M, Arana C, Dende C, van Oers NS, Hooper LV, Raj P, Front Cell Infect Microbiol 2021 11 678522

Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus.

Raj P, Song R, Zhu H, Riediger L, Jun DJ, Liang C, Arana C, Zhang B, Gao Y, Wakeland BE, Dozmorov I, Zhou J, Kelly JA, Lauwerys BR, Guthridge JM, Olsen NJ, Nath SK, Pasare C, van Oers N, Gilkeson G, Tsao BP, Gaffney PM, Gregersen PK, James JA, Zuo X, Karp DR, Li QZ, Wakeland EK, Genome Biol 2020 Nov 21 1 281

The Genetics and Epigenetics of 22q11.2 Deletion Syndrome

Du,Qiumei de la Morena,M. Teresa van Oers,Nicolai S. C. 2020

Molecular Insights Into the Causes of Human Thymic Hypoplasia With Animal Models

Bhalla,Pratibha Wysocki,Christian A. van Oers,Nicolai S. C. Frontiers in Immunology 2020

sncRNA-1 Is a Small Noncoding RNA Produced by Mycobacterium tuberculosis in Infected Cells That Positively Regulates Genes Coupled to Oleic Acid Biosynthesis

Coskun, Fatma S. Srivastava, Shashikant Raj, Prithvi Dozmorov, Igor Belkaya, Serkan Mehra, Smriti Golden, Nadia A. Bucsan, Allison N. Chapagain, Moti L. Wakeland, Edward K. Kaushal, Deepak Gumbo, Tawanda van Oers, Nicolai S. C. Frontiers in Microbiology 2020 11 1631

MIR205HG Is a Long Noncoding RNA that Regulates Growth Hormone and Prolactin Production in the Anterior Pituitary.

Du Q, Hoover AR, Dozmorov I, Raj P, Khan S, Molina E, Chang TC, de la Morena MT, Cleaver OB, Mendell JT, van Oers NSC, Dev. Cell 2019 Apr

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