A FATTY BUSINNESS.

Trypanosoma brucei colonizes multiple organs including brain, adipose tissue and skin. Our lab showed that parasites metabolically adapt to the the tissue environemnt and slow down parasite replicaton, which could have important implictions for pathology, diagnostics and treatment strategies. Our current research focuses on elucidating the fundamental mechanisms that facilitate the parasite’s traversal of the vasculature, tissue colonization, and environmental adaptation. Additionally, we are exploring the severe consequences of adipose tissue colonization on the host, where animals can lose up to 60% of their fat mass within eight days due to activated lipolysis. Our lab aims to identify the signals triggering this dramatic loss, understand the remodeling of adipose tissue during infection, and assess the overall physiological impact on the infected host.

CHANGING COATS.

To persist within its host, Trypanosoma brucei employs a sophisticated strategy of immune evasion by periodically switching its antigenic coat, composed of Variant Surface Glycoproteins (VSG). Our research has delved into the complex molecular machinery that governs this antigenic variation, focusing on the roles of chromatin remodeling and RNA modifications, including N6-methyladenosine (m6A). Currently, we are expanding our scope to explore the broader impacts of RNA modifications and the dynamics of polyadenylation in the regulation of gene expression within the parasite.

While our motivation is to conduct discovery research, we do not neglect research lines that could provide potential targets for therapeutic intervention.

“la Caixa” Foundation, Health Research (2025-2027): CrossTryp

Fundação para a Ciencia e Tecnologia (2025-2026): TrypObese

Main past projects:

“la Caixa” Foundation, Health Research (2021-2024)

European Research Council Consolidator grant (2018-2024)

Howard Hughes Medical Institute, International Scholar (2012-2017)

Beaver AK, Keneskhanova Z, ROC, 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 (2024) Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei. Nature doi: 10.1038/s41586-024-08151-z

Trindade S, De Niz M, Costa-Sequeira M, Bizarra-Rebelo T, Bento F, Dejung M, Narciso MV, López-Escobar L, Ferreira J, Butter F, Bringaud F, Gjini E, Figueiredo LM. (2022) Slow growing behavior in African trypanosomes during adipose tissue colonization. Nature Communications 13(1):7548. doi: 10.1038/s41467-022-34622-w.

De Niz M, Brás D, Ouarné M, Pedro M, Nascimento AM, Henao Misikova L, Franco CA, Figueiredo LM. (2021) Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulence. Cell Reports 21;36(12):109741

Machado H, Hofer P, Zechner R, Smith TK & Figueiredo LM. (2023) Adipocyte lipolysis protects mice against Trypanosoma brucei infection. Nature Microbiology 8(11):. 2020–2032

Viegas IJ, de Macedo JP, Serra L, De Niz M, Temporão A, Silva Pereira S, Mirza AH, Bergstrom E, Rodrigues JA, Aresta-Branco F, Jaffrey SR, Figueiredo LM. (2022) N6-methyladenosine in poly(A) tails stabilize VSG transcripts. Nature 604(7905):362-370.

Guegan F, Rajan KS, Bento F, Pinto-Neves D, Sequeira M, Gumińska N, Mroczek S, Dziembowski A, Cohen-Chalamish S, Doniger T, Galili B, Estévez AM, Notredame C, Michaeli S, Figueiredo LM. (2022) A long non-coding RNA controls parasite differentiation in African trypanosomes. Science Advances 17;8(24):eabn2706.

Machado H, Bizarra-Rebelo T, Costa-Sequeira M, Trindade S, Carvalho T, Rijo-Ferreira F, Rentroia-Pacheco B, Serre K, Figueiredo LM. (2021) Trypanosoma brucei triggers a broad immune response in the adipose tissue. PLoS Pathog 15;17(9):e1009933

Rijo-Ferreira F, Carvalho T, Afonso C, Sanches-Vaz M, Costa RM, Figueiredo LM* and Takahashi JS*. (2018) Sleeping sickness is a circadian disorder. Nature Communications; 9: 62

Rijo-Ferreira F, Pinto-Neves D, Barbosa-Morais NL, Takahashi J* & Figueiredo LM*. (2017) Trypanosoma brucei metabolism is under circadian control. Nature Microbiology; 2:17032

Trindade S & Rijo-Ferreira F, Carvalho T, Pinto-Neves D, Guegan F, Aresta-Branco F, Bento F, Young SA, Pinto A, Van Den Abbeele J, Ribeiro RM, Dias S, Smith TK, Figueiredo LM*. (2016) Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice. Cell Host and Microbe; 19 (6): 837–848.

2024    Honorable mention in the Scientific Prizes of the University of Lisbon / Caixa Geral de Depósitos

2023    EMBO member

2010    Prémio Crioestaminal

Find the lab on Bluesky!