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Greg Matlashewski

Professor and Program Leader;
Virology/Parasitology

Human Leishmania infection

Research for the Elimination of Visceral Leishmaniasis
Tropical Diseases Research (TDR)
World Health Organization
Avenue Appia 20
1211 Geneva 27
Switzerland
greg [dot] matlashewski [at] mcgill [dot] ca (Email)
Link to Dr. Matlashewski profile

Interview in the Reporter: Pummelling parasites

 

Professor Greg Matlashewski, previous Chairman of the Department of Microbiology and Immunology at McGill University, has been involved in field research on leishmaniasis in Peru for over 10 years. He has recently taken a leave of absence from McGill to lead a WHO program to eliminate visceral leishmaniasis from Northern India, Nepal and Bangladesh.

Leishmaniasis is the second most deadly parasitic infectious disease after malaria and is a member of the neglected tropical diseases (NTDs) that include other infections of poverty including trypanosomiasis, filariasis, schistosomiasis, onchocerciasis, and others. NTDs are largely confined to rural areas of the developing world and are chronic, disabling and often stigmatizing conditions that contribute to global health disparities between rich and poor countries. More than one billion people, one sixth of the world population, are affected by NTDs. While there is no shortage of high-quality research on NTDs, the translation of basic scientific discoveries into therapeutic interventions has been disappointing. Although not optimal, there do exist diagnostics, treatments, and vector control measures for many of these diseases including leishmaniasis. Professor Matlashewski argues that until better treatments and vaccines are available, the immediate priority must be to establish how to effectively use existing interventions on the ground level. Successful implementation with existing interventions requires close collaboration between public health scientists, local health care providers and their respective governments and funding agencies including NGOs.

There are over 500,000 visceral leishmaniasis cases per year and 70% of the cases are clustered in Northern India (Bihar State), Southern Nepal and Bangladesh. Professor Matlashewski argues that considering the unique epidemiological features of the disease in this endemic region, including (i) humans are the only reservoir (ii) there is only one vector sandfly species (Phlebotomus argentipes) that is amenable to control and (iii) the Geographic distribution is limited and highly clustered, the control of visceral leishmaniasis in this part of the world is a realistic goal. Implementation research with existing interventions is required to provide evidence-based and cost-effective strategies for control while empowering the local health system personnel to engage in the development and sustainability of the control measures. The result will be a dramatic reduction in the number of visceral leishmaniasis infections and saved lives.

Professor Matlashewski is delighted that the WHO has provided him with the responsibility to coordinate the implementation research on the ground level. He spends a considerable amount of time organizing efforts on the ground in the endemic regions, and when not in the field, he is at the WHO head quarters in Geneva and still makes routine visits to his lab at McGill where he maintains a strong basic research program funded by CIHR and the Gates Foundation.

Research Orientations

Human papillomavirus and cervical cancer
Human papillomaviruses (HPV) are the major etiological agents for the development of cervical cancer. Cervical cancer is the second most common form of cancer among women on a world-wide basis. We have previously identified several oncogenes within the genome of HPV and our focus is now to define how these viral oncogenes are involved in malignant transformation.

Our current emphasis is on the HPV E6 oncogene product which is capable of binding to and inactivating the cellular tumour suppressor protein p53. My laboratory is currently defining the biochemical and biological consequences of the E6/p53 interaction.

We are also studying how a polymorphism in the p53 gene may predispose women to HPV associated cervical cancer. Defining the molecular basis for viral oncogenesis in this manner may define strategies for disrupting viral transforming activities and will provide information on malignant transformation in general.

My laboratory is also involved in basic research to define the involvement of p53 in cell programed death and how this may be applied toward the development of new anticancer treatments.

Human Leishmania infection
Leishmania is a protozoan which is transmitted to humans by the sandfly vector and causes leishmaniasis which is often fatal, particularly in children of developing countries. Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization.

We are currently cloning and characterizing virulence genes from Leishmania. In this manner, we are attempting to define novel targets for treatment of this infection. Attempts are underway to develop a live attenuated vaccine for this infection using gene targeting to delete virulence genes from the Leishmania genome.

Studies are also underway to test various macrophage activating compounds as potential chemotherapeutic compounds against leishmaniasis.

Professor Matlashewski is currently on leave of absence from McGill and is working for the World Health Organization (WHO) in Geneva. He will not be accepting new students until his return in Sept. 2011.

Selected Recent Publications

Miranda-Verastegui C., Tulliano G., Gyorkos TW., Calderon W., Rahme E., Ward B., Cruz M., Llanos-Cuentas A., Matlashewski G. "First-line therapy for human cutaneous leishmaniasis in Peru using the TLR7 agonist imiquimod in combination with pentavalent antimony." PLoS Negla Trop Dis 2009 Jul28;3(7):3491.

Ainsworth, J., Thomas, M., Banks, L., Coutlee, F., and Matlashewski, G. "Comparison of p53 and the PDZ domain containing protein MAGI-3 regulation by the E6 protein from high-risk human papillomaviruses." Virol. J. 5: 67, 2008.

Zhang W., Peacock, C. and Matlashewski, G. "A genomic based approach combining in vivo selection in mice to identify a novel virulence gene in Leishmania." PLoS-NTD 2: e248, 2008.

Zhang W., and Matlashewski, G. "Immunization with Toll-like receptor 7/8 agonist vaccine adjuvants increases protective immunity against Leishmania major in BALB/c mice." Infect. Immun. 76: 3777-3783, 2008.

Gregory, D., Sladek, R., Olivier, M., and Matlashewski, G. "Comparison of the effects of Leishmania major and Leishmania donovani infection on macrophage gene expression." Infect. Immun. 76: 1186-1192, 2008.

Arevalo, I., Tulliano, G., Quispe, A., Spaeth, G., Matlashewski, G., Llanos-Cuentas, A., and Pollack, H. "Role of imiquimod and parental meglumine antimoniate in the treatment of cutaneous leishmaniasis." Clin. Infect. Dis. 44: 1549-1554, 2007.

Nascimento M, Zhang WW, Ghosh A, Houston DR, Berghuis AM, Olivier M, Matlashewski G. "Identification and characterization of a protein tyrosine phosphatase in Leishmania; involvement in virulence." J Biol Chem. 2006.

Khouadri S, Villa LL, Gagnon S, Koushik A, Richardson H, Ferreira S, Tellier P, Simao J, Matlashewski G, Roger M, Franco EL, Coutlee F. "Human papillomavirus type 33 polymorphisms and high-grade squamous intraepithelial lesions of the uterine cervix." J Infect Dis. 2006. 194: 886-894.

Zhang WW, Miranda-Verastegui C, Arevalo J, Ndao M, Ward B, Llanos-Cuentas A, Matlashewski G. "Development of a genetic assay to distinguish between Leishmania viannia species on the basis of isoenzyme differences." Clin Infect Dis. 2006. 42: 801-809.

Koushik A, Ghosh A, Duarte-Franco E, Forest P, Voyer H, Matlashewski G, Coutlee F, Franco EL; Biomarkers of Cervical Cancer Risk (BCCR) Study Team "The p53 codon 72 polymorphism and risk of high-grade cervical intraepithelial neoplasia." Cancer Detect Prev. 2005. 29: 307-316.

Stewart D, Ghosh A, Matlashewski G. "Involvement of nuclear export in human papillomavirus type 18 E6-mediated ubiquitination and degradation of p53." J Virol. 2005. 79: 8773-8783.

Miranda-Verástegui C., Arévalo I., Llanos-Cuentas A., Ward B., and Matlashewski G. "Randomized, double blind clinical trial of topical treatment 5% imiquimod (Aldara) with parental meglumine antimonate (Glucantime) in the treament of cutaneous leishmaniasis in Peru." Clin. Inf. Dis. 2005. 40: 1395-403.

Ghosh, D., Stewart, D., and Matlashewski, G. "Regulation of human p53 activity and cell localization by alternative splicing." Mol. Cell. Biol. 2004. 24: 7987-7997.

Zhang W., and Matlashewski G. "In vivo selection for Leishmania donovani miniexon genes that increase virulence in Leishmania major." Mol. Microbiol. 2004. 54: 1051-1062.

Stewart D., Kazemi S., Li S., Massimi P., Banks L., Koromilas A., and Matlashewski G. "Ubiquitination and proteasome degradation of Human papillomavirus types 11 and 18 E6 proteins." J. Gen. Virol. 2004. 85: 1419-1426.

Zhang W., Mendez S., Ghosh A., Myler P., Ivens A., Clos J., Sacks S., and Matlashewski G. "Comparison of the A2 gene locus in L. donovani and L. major and its control over cutaneous leishmaniasis." J. Biol. Chem. 2003. 278: 35508-35515.

Ghosh A., Labrecque S., and Matlashewski G. "Protection against Leishmania donovani infection by DNA vaccination: increased DNA vaccination efficiency through inhibiting the cellular p53 response." Vaccine 2001. 19: 3169-3178.

Buates S., and Matlashewski G. "Treatment of experimental leishmaniasis with the immunomodulator imiquimod and S-28463; efficacy and mode of action." J. Inf. Dis. 1999. 179: 1485-1494.

Storey A., Thomas M., Kalita A., Harwood C., Gardiol D., Mantovani F., Breuer J., Matlashewski G*., and Banks L*. "Role of a p53 polymorphism in the development of human papillomavirus-associated cancer." Nature 1998. 393: 229-234.