Departmental Affiliations
Monica Mugnier, PhD, studies how African trypanosomes, which cause African sleeping sickness, evade the immune system.
Contact Info
Research Interests
antigenic variation; T. brucei; kinetoplastid; host-pathogen interactions; bioinformatics; genomics
Additional Links
Experiences & Accomplishments
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.
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 role do extravascular parasites play in antigenic variation and immune evasion?
- How does the VSG repertoire diversify?
- What are the specificities and dynamics of the antibody response to VSG?
Host-pathogen interactions in Chagas disease
In collaboration with Bob Gilman (Department of International Health), we have also begun studying Trypanosoma cruzi, the causative agent of Chagas disease. These projects similarly use high-throughput, computational approaches to understand how T. cruzi causes disease. Some questions we are currently studying:
- Why do ~30% of patients infected with T. cruzi develop cardiomyopathy?
- What are the mechanisms of congenital transmission of T. cruzi?
- How does parasite genetics influence/explain the clinical heterogeneity of T. cruzi infection?
Honors & Awards
Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease, 2024
NIH Early Independence Award, 2016
Select Publications
Select publications reflecting the interests of our lab:
Smith JE, Wang KJ, Kennedy EM, Hakim JMC, So J, Beaver AK, Magesh A, Gilligan-Steinberg SD, Zheng J, Zhang B, Moorthy DN, Akin EH, Mwakibete L, Mugnier MR. DNA damage drives antigen diversification through mosaic Variant Surface Glycoprotein (VSG) formation in Trypanosoma brucei. bioRxiv [Preprint]. 2024 Aug 30:2024.03.22.582209. doi: 10.1101/2024.03.22.582209.
Duque C, So J, Castro-Sesquen YE, DeToy K, Gutierrez Guarnizo SA, Jahanbakhsh F, Malaga Machaca E, Miranda-Schaeubinger M, Chakravarti I, Cooper V, Schmidt ME, Adamo L, Marcus R, Talaat KR, Gilman RH, Mugnier MR; Chagas Working Group. Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional study. Lancet Reg Health Am. 2025 Apr 17;45:101090. doi: 10.1016/j.lana.2025.101090.
Beaver AK, Keneskhanova Z, Cosentino RO, Weiss BL, Awuoche EO, Smallenberger GM, Buenconsejo GY, Crilly NP, Smith JE, Hakim JMC, Zhang B, Bobb B, Rijo-Ferreira F, Figueiredo LM, Aksoy S, Siegel TN, Mugnier MR. Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei. Nature. 2024 Dec;636(8042):430-437. doi: 10.1038/s41586-024-08151-z.
Hakim JMC, Waltmann A, Tinajeros F, Kharabora O, Machaca EM, Calderon M, Del Carmen Menduiña M, Wang J, Rueda D, Zimic M, Verástegui M, Juliano JJ, Gilman RH, Mugnier MR, Bowman NM; Chagas Working Group. Amplicon Sequencing Reveals Complex Infection in Infants Congenitally Infected With Trypanosoma Cruzi and Informs the Dynamics of Parasite Transmission. J Infect Dis. 2023 Sep 15;228(6):769-776. doi: 10.1093/infdis/jiad125.
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.
Mugnier MR, Cross GA, Papavasiliou FN. The in vivo dynamics of antigenic variation in Trypanosoma brucei. Science. 2015 Mar 27;347(6229):1470-3. doi: 10.1126/science.aaa4502.