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Monica
R
Mugnier
,
PhD

Assistant Professor

Monica Mugnier, PhD, studies how African trypanosomes, which cause African sleeping sickness, evade the immune system.

Contact Info

615 N. Wolfe Street, Room E3632
Baltimore
Maryland
21205
US        

Research Interests

antigenic variation; T. brucei; kinetoplastid; host-pathogen interactions; bioinformatics; genomics

Experiences & Accomplishments
Education
PhD
Rockefeller University
2016
BS
Tufts University
2009
Overview

Antigenic variation in T. brucei
African sleeping sickness, or human African trypanosomiasis, is a devastating human disease affecting sub-Saharan Africa. It is fatal if left untreated, existing drugs are extremely toxic, and the economic burden of sleeping sickness, along with its zoonotic counterpart, nagana, is estimated to be at least 1.5 billion USD per year. The causative agent of both human and animal trypanosomiasis is Trypanosoma brucei, a protozoan parasite covered by a dense variant surface glycoprotein (VSG) coat. The highly antigenic VSG is so densely packed on the parasite cell surface that it effectively obscures all other antigens from immune recognition. Under normal circumstances, this would ensure quick recognition and clearance of the parasite, but T. brucei has evolved a mechanism for antigenic variation during infection in which the parasite can turn on and off VSG-encoding genes from a genomic repertoire of ~2000 different genes. As the VSG expressed by a population of parasites is recognized by the immune system and then cleared, a minority of parasites will “switch” their VSG coat, turning on a new, and likely antigenically distinct, VSG. These “switchers” will then be recognized by the immune system, but not before another set of parasites will have turned on another VSG and escaped immune clearance. This pattern results in periodic waves of parasitemia characteristic of T. brucei infection.

In textbook depictions of antigenic variation, each of these waves is typically represented as a single or limited number of VSGs, suggesting that infection proceeds through the ordered expression of individual variants. Recent work (Hall et al., 2013; Mugnier et al., 2015) has shown, however, that T. brucei parasites express a huge diversity of VSGs at any given time during an infection. These findings suggest that the parasite's genome-encoded VSG repertoire is insufficient to maintain the sometimes years-long infections observed in the wild. Instead, diversification of the genomic VSG repertoire, both through the mutation of individual VSGs and recombination among sets of VSGs, is critical to sustaining a chronic infection.

With this in mind, our goal is to use bioinformatics and other high-throughput approaches to better understand the dynamics of antigenic variation and the mechanisms driving VSG diversification in vivo.

Some questions we are currently studying:
• What determines VSG switching order?
• What role do extravascular parasites play in antigenic variation and immune evasion?
• How do mosaic VSGs form, and how often?
• Can point mutations in VSGs play a role in parasite immune evasion?

Honors & Awards

NIH Early Independence Award, 2016

Select Publications

Select publications reflecting the interests of our lab:

  • Monica R. Mugnier, George A. M. Cross, F. Nina Papavasiliou. (2015) The in vivo dynamics of antigenic variation in Trypanosoma brucei. Science. 347(6229):1470-1473.

  • Jaime So, Sarah Sudlow, Abeeer Sayeed, Tanner Grudda, Stijn Deborggraeve, Dieudonné Mumba Ngoyi, Didier Kashiama Desamber, Bill Wickstead, Veerle Lejon, Monica R. Mugnier. (2022) VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal Domains. mBio. Nov 10:e0255322. doi: 10.1128/mbio.02553-22.

  • Alexander Beaver, Nathan P. Crilly, Jill M.C. Hakim, Bailin Zhang, Bryce Bobb, Filipa Rijo-Ferreira, Luisa Figueiredo, Monica R. Mugnier. (2022) Extravascular spaces are reservoirs of antigenic diversity in Trypanosoma brucei infection. bioRxiv. https://doi.org/10.1101/2022.06.27.497797

  • Jill MC Hakim, Andreea Waltmann, Freddy Tinajeros, Oksana Kharabora, Edith Malaga Machaca, Maritza Calderon, Maria del Carmen Menduina, Jeremy Wang, Daniel Rueda, Mirko Zimic, Manuela Verastegui, Jonathan J Juliano, Monica R. Mugnier, Natalie M. Bowman, Chagas Working Group. (2022) Amplicon sequencing reveals complex infection in infants congenitally infected with Trypanosoma cruzi and informs the dynamics of parasite transmission. bioRxiv. https://doi.org/10.1101/2022.11.16.516746

  • Nathan P. Crilly and Monica R. Mugnier. (2021) Thinking outside the blood: Perspectives on tissue-resident Trypanosoma brucei. PLOS Pathogens. Sep 16;17(9):e1009866.