EDUCATION
B.S. summa cum laude (Chemistry) 1984, Free University of Brussels
Ph.D. summa cum laude (Molecular Biology) 1988, Free University of Brussels

EMPLOYMENT

PROFESSIONAL AFFILIATIONS
Adjunct Faculty, Department of Pathology, School of Medicine, University of New Mexico
Infectious Disease and Inflammation Program, Health Sciences Center, University of New Mexico
The American Society for Microbiology
The International Society for Interferon and Cytokine Research
The American Thoracic Society

AREAS OF RESEARCH
     Infection of vertebrates by a virus leads to the production of interferons and other cytokines, which signal the presence of an infection to the organism and orchestrate antiviral defenses. Exposure to interferon-a/b results in the establishment of an antiviral state in uninfected cells, triggers apoptosis in virus-infected cells, and leads to potent modulations of immune responses. The interferon-b gene plays a pivotal role in both initiating and sustaining this response, through its early direct activation in virtually all cell types and through its ability to promote the induction of the family of interferon-a genes.
     The essential nature of the interferon response is best evidenced by the observation that viruses evolved many mechanisms to evade this antiviral defense. These include (a) inhibition of interferon production (e.g., influenza viruses, measles virus, Ebola virus, adenoviruses, papilloma viruses, herpes viruses, poxviruses), (b) inhibition of interferon-dependent signaling (e.g., parainfluenza viruses, mumps virus, adenoviruses, papilloma viruses, herpes viruses, pox viruses) and (c) inhibition of the antiviral activity induced by interferons (e.g., poliovirus, hepatitis C virus, influenza viruses, adenoviruses, herpes viruses, pox viruses).
     Our laboratory is focused on the mechanisms by which respiratory viruses evade the interferon response. Identification of the viral protein(s) that allows escape from antiviral defenses makes it possible to (a) rationally design avirulent mutants, which could be used for vaccination, (b) use the virulence factor as a bait to identify the cellular protein(s) through which it acts, (c) use the interaction between the virulence factor and its cellular target as the basis for screening molecular libraries to indentify therapeutic drugs, and (d) use the virulence factor to probe virus- and interferon-dependent signaling.
     More than 99% of the area of the lungs exposed to the environment is composed of alveolar epithelial cells, but there is no satisfying in vitro culture system for these cells. Our laboratory is devoted to establishing a 3-dimensional culture system for primary human type I and type II alveolar epithelial cells to study replication of respiratory viruses.

ACCESS THIS AUTHOR'S PUBLICATIONS IN PUBMED

 

REPRESENTATIVE PUBLICATIONS

1. Wathelet, M. G., I. M. Clauss, C. B. Nols, J. Content and G. A. Huez: New Inducers Revealed by the Promoter Sequence Analysis of Two Interferon-Activated Human Genes. Eur. J. Biochem. 169(2): 313-321, 1987.

    

2. Kruys V., M. G. Wathelet and G. A. Huez: Identification of a Translation Inhibitory Element (TIE) in the 3' Untranslated Region of the Human Interferon-b mRNA. Gene 72(1-2): 191-200, 1988.

    

3. Wathelet, M. G., I. M. Clauss, J. Content and G. A. Huez: Regulation of Two Interferon-Inducible Human Genes by Interferon, Poly(rI)·Poly(rC) and Viruses. Eur. J. Biochem. 174(2): 323-329, 1988.

    

4. Wathelet, M. G., I. M. Clauss, F. C. Paillard and G. A. Huez: 2-Aminopurine Selectively Blocks the Transcriptional Activation of Cellular Genes by Virus, Double-Stranded RNA and Interferons in Human Cells. Eur. J. Biochem. 184(3): 503-509, 1989.

    

5. Clauss, I. M., B. Vandenplas, M. G. Wathelet, C. Dorval, A. Delforge, J. Content, P. Stryckmans and G. A. Huez: Analysis of Interferon-Inducible Genes in Cells of Chronic Myeloid Leukemia Patients Responsive or Resistant to an Interferon-a Treatment. Blood 76(11): 2337-2342, 1990.

    

6. Horisberger, M. A., G. K. McMaster, H. Zeller, M. G. Wathelet, J. Dellis and J. Content: Cloning and Sequence Analyses of cDNAs for Interferon- and Virus-Induced Human Mx Proteins Reveal that they Contain Putative Guanine Nucleotide-Binding Sites: Functional Study of the Corresponding Gene Promoter. J. Virol. 64(3): 1171-1181, 1990.

    

7. Deblandre, G. A., O. Leo, G. A. Huez and M. G. Wathelet: CD69 is Expressed on Daudi Cells in Response to Interferon-a. Cytokine 4(1): 36-43, 1992.

    

8. Wathelet, M. G., P. M. Berr and G. A. Huez: Regulation of Gene Expression by Cytokines and Virus in Human Cells Lacking the Type-I Interferon Locus. Eur. J. Biochem. 206(3): 901-910, 1992.

    

9. Deblandre, G. A., O. P. Marinx, S. S. Evans, S. Majjaj, O. Leo, D. Caput, G. A. Huez and M. G. Wathelet: Expression Cloning of an Interferon-Inducible 17-kDa Membrane Protein Implicated in the Control of Cell Growth. J. Biol. Chem. 270(40): 23860-23866, 1995.

    

10. Maniatis, T., J. V. Falvo, T. H. Kim, T. K. Kim, C. H. Lin, B. S. Parekh and M. G. Wathelet: Structure and Function of the Interferon-b Enhanceosome. Cold Spring Har. Symp. Quant. Biol. 63: 609-620, 1998.

     

11. Wathelet, M. G., C. H. Lin, B. S. Parekh, L. V. Ronco, P. M. Howley and T. Maniatis: Virus Infection Induces the Assembly of Coordinately Activated Transcription Factors on the IFN-b Enhancer In Vivo. Mol. Cell 1(4): 507-518, 1998.

     

12. Yang, H., C. H. Lin, G. Ma, M. Orr, M. O. Baffi and M. G. Wathelet: Transcriptional Activity of Interferon Regulatory Factor (IRF)-3 Depends on Multiple Protein-Protein Interactions. Eur. J. Biochem. 269(24): 6142-6151, 2002.

     

13. Yang, H., C. H. Lin, G. Ma, M. O. Baffi and M. G. Wathelet: Interferon Regulatory Factor-7 Synergizes with Other Transcription Factors Through Multiple Interactions with p300/CBP Coactivators. J. Biol. Chem. 278(18): 15495-15504, 2003.

     

14. Yang, H., G. Ma, C. H. Lin, M. Orr and M. G. Wathelet: Mechanism for Transcriptional Synergy Between Interferon Regulatory Factor (IRF)-3 and IRF-7 in Activation of the Interferon-b Gene Promoter. Eur. J. Biochem. 271(18): 3693-3703, 2004.

     

15. Zakrzewska, A., P. O. Schnell, J. B. Striet, A. Hui, J. R. Robbins, M. Petrovic, L. Conforti, D. Gozal, M. G. Wathelet and M. F. Czyzyk-Krzeska: Hypoxia-Activated Metabolic Pathway Stimulates Phosphorylation of p300 and CBP in Oxygen-Sensitive Cells. J. Neurochem. 94(5): 1288-1296, 2005.

     

16. Wathelet, M. G., M. Orr, M. B. Frieman and R. S. Baric: Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated Strain. J. Virol. 81(21): 11620-11633, 2007.

     

17. Prescott, J., P. Hall, M. Acuna-Retamar, C. Ye, M. G. Wathelet, H. Ebihara, H. Feldman and B. Hjelle: New World Hantaviruses Activate IFNl Production in Type I IFN-Deficient Vero E6 Cells. PLoS One 5(6): e11159, 2010.