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.
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
- Infectious Diseases
- Long noncoding RNAs
- primary immunodeficiency diseases
- T cell development
- 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
- 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
- FOXN1 compound heterozygous mutations cause selective thymic hypoplasia in humans
- Qiumei Du,1 Larry K. Huynh,1 Fatma Coskun,1 Erika Molina,1 Matthew A. King,1 Prithvi Raj,1 Shaheen Khan,1 Igor Dozmorov,1 Christine M. Seroogy,2 Christian A. Wysocki,3,4 Grace T. Padron,5 Tyler R. Yates,6 M. Louise Markert,6,7 M. Teresa de la Morena,8 and Nicolai S.C. van Oers1,3,9 Journal of Clinical Investigation 2019
- MicroRNA-205 maintains T cell development following stress by regulating Forkhead box N1 and selected chemokines.
- Hoover AR, Dozmorov I, MacLeod J, Du Q, de la Morena MT, Forbess J, Guleserian K, Cleaver OB, van Oers NS J. Biol. Chem. 2016 Sep
- 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 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
- 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
- American Society of Microbiologists (2015)
- Federation of clinical immunology societies (2011)
- American Association of Immunologists (2000)