Education and Professional Standing
PhD University of Toronto
Fellow of the American Academy of Microbiology
Fellow of the Canadian College of Microbiology
The major focus of our research is the pathophysiology of acute respiratory infections caused by specific viruses (influenza, RSV) and bacteria (Chlamydia pneumoniae, P. aeruginosa and C. difficile). One of the major focuses of the laboratory is the development of new antimicrobial agents for both respiratory viruses and bacteria. The laboratory has developed peptide mimetics that target protein-protein interactive domains (20-30 amino acids) and prevent protein interactions which are inhibitory to pathogenic replication. Antimicrobial resistance to peptide therapeutics occurs at a reduced frequency that resistance to small molecular inhibitors. We have developed an influenza peptide mimetic that blocks viral transcription and have tested it against 13 different subtypes of influenza virus including high pathogenicity avian influenza virus. More recently we have developed an inhibitor of pediatric RSV infection. The second major research interest of the laboratory is the characterization of proteins of the type III secretion system of Chlamydia and elucidating how these proteins interact to form the secretion apparatus. The goal is first to identify novel drug targets and second to develop peptidomimetics that will inhibit type III secretion preventing bacterial replication. We have recently been successful with this approach and have developed type III secretion inhibitors for C. pneumoniae, C. trachomatis, and Pseudomonas aeruginosa (a major respiratory pathogen in CF and COPD patients) and have shown that these peptides inhibit bacterial cell invasion. We are now extending these studies to develop peptide therapeutics that block quorum sensing in methicillin-resistant S. aureus (MRSA) and C. difficile both of which are major bacterial infections in hospitalized patients across North America.
Clinical Research Areas
In addition to the development of novel therapeutics the other focus of our clinical research is in the areas of diagnostics. Following the development of a multiplex PCR that detects 19 different respiratory virus types in a single test (FDA cleared test that is being sold around the world) we have developed novel multiplex PCR assays for the detection, subtyping and antiviral resistance profiles of emerging viral infections such as such as pandemic H1N1 influenza. Our laboratory is pioneering the development and implementation of viral load assays to monitor shedding of influenza virus in patients receiving oseltamivir antiviral treatment. We have recently developed a quantitative rhinovirus RT-PCR assay and used this assay to detect the rhinovirus load in nasopharyngeal specimens in various patient populations. This assay will be used to evaluate the efficacy of novel anti-rhinovirus drugs. The therapeutic peptides for influenza and RSV are being evaluated in animal models leading up to their optimal formulation for delivery to the airways via inhalation. Pilot experiments have been completed for the delivery of therapeutic peptides using probiotic bacteria that secrete various antimicrobial peptides.
Teaching within the Faculty of Health Sciences includes the following: Residents in the Medical Microbiology/ Infectious Diseases and Pathology Residency Training Programs, Graduate Course in Clinical Virology (MS763), Graduate students thesis supervision in my laboratory, and Supervisory Committee member for six graduate students in medical Sciences.
Graduate Students: Chris Stone, David Bulir, Tiffany Leighton, Rob Clayden, Alex Ruyter, Andrea Granados
Undergraduate Students: Amit Bhatia, Jessica Tsalikis
Research Assisants: Sylvia Chong
Local Collaborators: Drs Mark Loeb, Jenny Johnstone, Marek Smieja, Param Nair
International Collaborators: Peter Timms (Brisbane), Peter Wark, Phil Hansbro (Newcastle, Australia), Lee Ann Campbell (Seattle), Theo Moraes (Toronto)
Industrial Collaborators: Luminex Molecular Diagnostics, Qiagen, Pro-Lab
Stone, C.B., Bulir, D.C., Gilchrist, J.D., Toor, R.K., Mahony, J.B. 2010. Interactions between flagellar and type III secretarion proteins in Chlamydia pneumoniae. BMC Microbiol., 2010 Jan 22;10(1):18.
Smieja, M., Castriciano, S., Carruthers, S., So, G., Chong, S., Luinstra, K., Mahony, J.B., Petrich, A., Chernesky, M., Savarese, M., Triva, D. 2010. Development and evaluation of a flocked nasal mid-turbinate swab for self collected respiratory virus diagnostic testing. J. Clin. Microbiol.,2010 48:3340-3342.
Mahony, J.B. Detection of respiratory viruses. McGraw Hill – Yearbook of Science Technology – Detection of respiratory viruses, 2010, pp. 98-100.
Elit, L., Levine, M., Julian, JA., Sellors, J., Lytwn, A., Gu, C., Finch, T., Zeferino, L., Roth, P., Bentley, J., Russomano, FB., Bates, S., Chong, S., Mahony, J. Expectant management versus immediate treatment for low-grade cervical intraepithelial neoplasia: a randomized trial in Canada and Brazil. Cancer, 2010, 117(7):1438-1445.
Salit, I.E., Lytwyn, A., Raboud, J., Sano, M., Chong, S., Diong, C., Chapman, W., Mahony, J., Tinmouth, J. The role of cytology (Pap tests) and human papillomavirus testing in anal cancer screening. AIDS, 2010, 24:1307-1313.
Mahony J.B., Chong, S., Luinstra, K., Petrich, A., Smieja, M. Development of a novel bead-based multiplex PCR assay for combined subtyping and oseltamivir resistance genotyping (H275Y) of seasonal and pandemic H1N1 influenza A viruses. J Clin Virol 2010, 49:277-282.
Mahony, J.B., Nucleic acid amplification-based diagnosis of respiratory virus infections. Expert Reviews of Anti-infective Therapy 2010, 8: 1273-1292.
Stone, C.B., Emdin, C.A., Pirie, R.M., Bulir, D. C., Porfilio, E.A., Slootstra, J.W., Mahony, J.B. C. pneumoniae CdsL regulates CdsN ATPase activity and disruption with a peptide mimetic prevents bacterial invasion. Frontiers in Cellular and Infection Microbiology, 2011, 2:21-30.
Monkman, K., Mahony, JB, Lazo-Langer, A., Chin-Yee, B., Minuk, L. The Pandemic H1N1 Influenza Vaccine Results in Low Rates of Seroconversion for patients with Hematological Malignancies. Leukemia & Lymphoma. 2011, 52(9):1736-1741.
Luinstra, K., Petrich, A., Castriciano, S., Ackerman, M., Chong, S., Carruthers, S., Ammons, B., Mahony, JB., Smieja, M. Evaluation and clinical Validation of an Alcohol-Based Transport Medium for Preservation and Inactivation of Respiratory Viruses. Journal of Clinical Virology. 2011, 49:2138-42.
Stone, C.B., Sugiman-Marangos, S., Bulir, DC., Clayden, RC., Leighton, TL., Slootstra, JW., Junop, MS., Mahony, JB. Biochemical characterization and crystallographic analysis of the type III secretion needle-tip protein of Chlamydia pneumoniae and its interaction with host cell components. PLOS One, Pub Jan 17 2012, 7(1):e30220.
Johnstone, J., Hanna, S., Nicolle, L., Drebot, M., Neupane, B., Mahony, J., Loeb, M. Prognosis of West Nile Virus Associated Acute Flaccid Paralysis: A Case Series. Journal of Medical Case Reports. 2011, 5:395-400.
Toor RK, Stone CB, Gilchrist, JD, Mahony JB. Chlamydia pneumoniae CdsQ functions as a multi-cargo transport protein, delivering chaperone-effector complexes to CdsN the type III secretion ATPase. Translational Biomedicine. 2012, 3(1-2), doi 10.3823/430.
Mahony J, Smieja M, Petrich A. Molecular diagnostics for viral respiratory infections. Critical Reviews in Clin Lab Sci. 2011, 48 (5-6):217-249.