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Dr Joana Sa Pessoa Da Graca Santos

Assistant Professor

United Kingdom

My PhD work focused on characterising the relationship between structure and function of carboxylate transporters in different model organisms (Saccharomyces cerevisiae, Escherichia coli and Aspergillus nidulans) and successfully demonstrating critical residues for transporter function by combining biochemical, functional and byophisical studies. I then switched gears to host-pathogen interactions and pursued a postdoc under Prof. Jose Bengoechea (Queen's University Belfast, UK) where I provided novel mechanistic insights into Klebsiella pneumoniae modification of host proteins by post-translational modifications to impair innate immune responses. On the sequence of my work with Prof. Bengoechea I have been awarded a BBSRC research grant as a Researcher Co-Investigator to determine how K. pneumoniae exploits an effector protein with a eukaryotic domain to antagonize host defences. 

Affiliations

Department of Infection Biology
Faculty of Infectious and Tropical Diseases

Teaching

I have directly supervised 7 MRes and MSc projects and 3 BSc students in their research placement including daily one to one mentoring on project development, planning and time management, practical demonstration, troubleshooting and provision of theoretical knowledge, development of presentation skills and thesis preparation including correction.

I have mentored over 30 undergraduate, Master’s, PhD’s and research technicians within the lab over my academic career; setting, supervising, and assessing projects and ensuring their full integration into the laboratory setting. 

I have collaborated in the development of a module in “Generic Laboratory Skills for life scientists” to Queen's University Belfast PhD students annually delivering a lecture on Western Blotting. I was also regularly involved in the marking of BSc final dissertations and research presentations while at Queen's University Belfast.

I was also actively involved in the design of short post-graduate courses at the University of Minho from 2010 to 2013, designing and delivering lectures as well as practical demonstrations. 

 

 

Research

My work focuses on the infection biology of Gram-negative bacteria. I focus on deciphering interactions between innate host immunity and infection caused by the Gram-negative bacterium Klebsiella pneumoniae. Respiratory infections including bacterial pneumonia are a global health burden and Gram-negative bacteria such as K. pneumoniae infections are a major contributor, having been singled out as an ‘urgent threat to human health’ by the World Health Organization.

My work involves a multidisciplinary approach interfacing cellular microbiology, immunology and molecular biology to uncover mechanisms utilised by K. pneumoniae to manipulate host pathways for successful infection. I have uncovered a sophisticated strategy employed by Klebsiella to subvert the activation of immune defences by controlling the modification of host proteins by post-translational modifications (SUMOylation and NEDDylation). Klebsiella also inhibits Cullin-1 NEDDylation through the formation of mitochondrial reactive oxygen species (mtROS) and activation of the mitochondria-located receptor NLRX1. This is a consequence of an influx of calcium into the mitochondria induced by the trans-kingdom T6SS effector VgrG4.

I have also contributed to determine the anti-immunology strategies employed by this pathogen in endothelial cells, epithelial cells and macrophages and to work on the infection biology of other Gram-negative bacteria causing respiratory infections including Acinetobacter baumannii.

Research Area
Bacteriology
Innate immunity
Molecular biology
Biochemistry
Cell biology
Disease and Health Conditions
Pneumonia
Sepsis
Country
United Kingdom

Selected Publications

<i>Klebsiella pneumoniae</i>
disrupts vasodilation by targeting eNOS post translational modifications via the type VI secretion system and the capsule polysaccharide
Rehman, S; Sa Pessoa, J; Buckley, C; Lancaster, R; Ross, C; Zhang, X; McCarron, JG; Curtis, TM; Bengoechea, JA;
2025
openRxiv
Klebsiella pneumoniae emerging anti-immunology paradigms: from stealth to evasion.
Sá-Pessoa, J; Calderón-González, R; Lee, A; BENGOECHEA, JA;
2025
Trends in microbiology
In vivo single-cell high-dimensional mass cytometry analysis to track the interactions between Klebsiella pneumoniae and myeloid cells.
Calderon-Gonzalez, R; Dumigan, A; Sá-Pessoa, J; Kissenpfennig, A; BENGOECHEA, JA;
2024
PLoS pathogens
PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection.
Baran, M; Feriotti, C; McGinley, A; Carlile, SR; Jiang, Z; Calderon-Gonzalez, R; Dumigan, A; Sá-Pessoa, J; Sutton, CE; Kearney, J; McLoughlin, RM; Mills, KH G; Fitzgerald, KA; Bengeochea, JA; Bowie, AG;
2023
Cell reports
A trans-kingdom T6SS effector induces the fragmentation of the mitochondrial network and activates innate immune receptor NLRX1 to promote infection.
Sá-Pessoa, J; López-Montesino, S; Przybyszewska, K; Rodríguez-Escudero, I; Marshall, H; Ova, A; Schroeder, GN; Barabas, P; Molina, M; Curtis, T; Cid, VJ; BENGOECHEA, JA;
2023
Nature communications
Modelling the Gastrointestinal Carriage of Klebsiella pneumoniae Infections.
Calderon-Gonzalez, R; Lee, A; Lopez-Campos, G; Hancock, SJ; Sa-Pessoa, J; Dumigan, A; McMullan, R; Campbell, EL; BENGOECHEA, JA;
2023
mBio
Visualisation of Host-Pathogen Communication.
Dumigan, A; Gonzalez, RC; Morris, B; Sá-Pessoa, J;
2023
Advances in experimental medicine and biology
In vivo single-cell transcriptomics reveal Klebsiella pneumoniae skews lung macrophages to promote infection.
Dumigan, A; Cappa, O; Morris, B; Sá Pessoa, J; Calderon-Gonzalez, R; Mills, G; Lancaster, R; Simpson, D; Kissenpfennig, A; BENGOECHEA, JA;
2022
EMBO molecular medicine
Meeting report - Cell dynamics: host-pathogen interface.
Odendall, C; Sa Pessoa, J; Mesquita, FS;
2022
Journal of cell science
Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity.
Feriotti, C; Sá-Pessoa, J; Calderón-González, R; Gu, L; Morris, B; Sugisawa, R; Insua, JL; Carty, M; Dumigan, A; Ingram, RJ; Kissenpfening, A; Bowie, AG; BENGOECHEA, JA;
2022
Cell reports
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