David Pérez-Morga

• Ph. D.
• Professor at Université Libre de Bruxelles

The trypanosomatid flagellates possess in their single mitochondrion a highly complex kinetoplast (k)DNA, which is composed of interlocked circular molecules of two types. Dozens of maxicircles represent a classical mitochondrial genome, and thousands of minicircles encode guide (g)RNAs, which direct the processive and essential uridine insertion/d...

Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Though MASH is closely tied to metabolic risk factors, the underlying pathogenic mechanisms remain scarcely understood. Recent research has emphasized the importance of the g...

Background and Aims Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Though MASH is closely tied to metabolic risk factors, the underlying pathogenic mechanisms remain scarcely understood. Recent research underscores the importance of the gut-l...

Sphaeropsidins are iso-pimarane diterpenes produced by phytopathogenic fungi that display promising anticancer activities. Sphaeropsidin A, in particular, has been shown to counteract regulatory volume increase, a process used by cancer cells to avoid apoptosis. This study reports the hemi-synthesis of new lipophilic derivatives obtained by modific...

Vertebrate organs require locally adapted blood vessels1,2. The gain of such organotypic vessel specializations is often deemed to be molecularly unrelated to the process of organ vascularization. Here, opposing this model, we reveal a molecular mechanism for brain-specific angiogenesis that operates under the control of Wnt7a/b ligands—well-known...

Human African trypanosomiasis or sleeping sickness, caused by the protozoan parasite Trypanosoma brucei, is characterized by the manipulation of the host’s immune response to ensure parasite invasion and persistence. Uncovering key molecules that support parasite establishment is a prerequisite to interfere with this process. We identified Q586B2 a...

Ru( ii )-Polypyridyl-1,8-naphthalimide Tröger's bases have undergone detailed biological profiling to unravel their mechanism of cellular uptake, cellular trafficking and cellular responses to photoexcitation.

Background The ability to respond to mechanical forces is a basic requirement for maintaining endothelial cell (ECs) homeostasis, which is continuously subjected to low shear stress (LSS) and high shear stress (HSS). In arteries, LSS and HSS have a differential impact on EC autophagy processes. However, it is still unclear whether LSS and HSS diffe...

Apolipoproteins L1 and L3 (APOLs) are associated at the Golgi with the membrane fission factors phosphatidylinositol 4-kinase-IIIB (PI4KB) and non-muscular myosin 2A. Either APOL1 C-terminal truncation (APOL1Δ) or APOL3 deletion (APOL3-KO [knockout]) reduces PI4KB activity and triggers actomyosin reorganization. We report that APOL3, but not APOL1,...

The emergence of antibiotic-resistant S. aureus has become a major public health concern, necessitating the discovery of new antimicrobial compounds. Given that the skin microbiome plays a critical role in the host defence against pathogens, the development of therapies that target the interactions between commensal bacteria and pathogens in the sk...

Medical implants have improved the quality of life of many patients. However, surgical intervention may eventually lead to implant microbial contamination. The aims of this research were to develop an easy, robust, quantitative assay to assess surface antimicrobial activities, especially the anti-nascent biofilm activity, and to identify control su...

Approximately 20% of sleeping sickness patients exhibit respiratory complications, however, with a largely unknown role of the parasite. Here we show that tsetse fly-transmitted Trypanosoma brucei parasites rapidly and permanently colonize the lungs and occupy the extravascular spaces surrounding the blood vessels of the alveoli and bronchi. They a...

Brucellae are facultative intracellular Gram-negative coccobacilli that chronically infect various mammals and cause brucellosis. Human brucellosis is among the most common bacterial zoonoses and the vast majority of cases are attributed to B. melitensis. Using transposon sequencing (Tn-seq) analysis, we showed that among 3369 predicted genes of th...

Patterning of endoderm into lung and thyroid lineages depends upon a correct early expression of a homeobox domain-containing transcription factor, Nkx2-1. However, the gene networks distinguishing the differentiation of those lineages remain largely unknown. In the present work, by using mouse embryonic stem cell lines, single-cell RNA sequencing,...

Mesoderm arises at gastrulation and contributes to both the mouse embryo proper and its extra-embryonic membranes. Two-photon live imaging of embryos bearing a keratin reporter allowed recording filament nucleation and elongation in the extra-embryonic region. Upon separation of amniotic and exocoelomic cavities, keratin 8 formed apical cables co-a...

Background SARS-CoV-2 targets endothelial cells through the angiotensin-converting enzyme 2 receptor. The resulting endothelial injury induces widespread thrombosis and microangiopathy. Nevertheless, early specific markers of endothelial dysfunction and vascular redox status in COVID-19 patients are currently missing. Methods Observational study i...

Background Acute respiratory distress syndrome due to coronavirus disease 2019 (COVID-19) is associated with high mortality. Several studies have reported that the microcirculation responds adequately to hypoxia in COVID-19 patients by increasing oxygen availability, in contrast to the inadequate response observed in patients with bacterial sepsis....

It has been observed in vitro that complete clot lysis is generally preceded by a slow phase of lysis during which the degradation seems to be inefficient. However, this slow regime was merely notified but not yet quantitatively discussed. In our experiments we observed that the lysis ubiquitously occurred in two distinct regimes, a slow and a fast...

Most obese and insulin-resistant individuals do not develop diabetes. This is the result of the capacity of β-cells to adapt and produce enough insulin to cover the needs of the organism. The underlying mechanism of β-cell adaptation in obesity, however, remains unclear. Previous studies have suggested a role for STAT3 in mediating β-cell developme...

It has been observed in vitro that complete clot lysis is generally preceded by a period of latency during which the degradation seems to be inefficient. However, this latency was merely notified but not yet quantitatively discussed. In our experiments we observed that the lysis ubiquitously occurred in two distinct regimes, a slow and a fast lysis...

After implantation, the mouse embryo undergoes gastrulation and forms mesoderm and endoderm. Mesoderm participates in embryonic and extra-embryonic tissues including the amnion, yolk sac, chorion and allantois, the umbilical cord precursor. Extra-embryonic mesoderm is rich in intermediate filaments. Two-photon live imaging of keratin 8-eYFP knock-i...

The mitochondrion is crucial for ATP generation by oxidative phosphorylation, among other processes. Cristae are invaginations of the mitochondrial inner membrane that house nearly all the macromolecular complexes that perform oxidative phosphorylation. The unicellular parasite Trypanosoma brucei undergoes during its life cycle extensive remodeling...

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1–5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accele...

The AMP-activated kinase (AMPK) is a major energy sensor metabolic enzyme that is activated early during T cell immune responses but its role in the generation of effector T cells is still controversial. Using both in vitro and in vivo models of T cell proliferation, we show herein that AMPK is dispensable for early TCR signaling and short-term pro...

A unique feature of the African trypanosome Trypanosoma brucei is the presence of an outer layer made of densely packed variable surface glycoproteins (VSGs), which enables the cells to survive in the bloodstream. Although the VSG coat is critical to pathogenesis, how exactly the glycoproteins are organized at the nanoscale is poorly understood. He...

Human innate immunity to Trypanosoma brucei involves the trypanosome C-terminal kinesin TbKIFC1, which transports internalized trypanolytic factor apolipoprotein L1 (APOL1) within the parasite. We show that TbKIFC1 preferentially associates with cholesterol-containing membranes, and is indispensable for mammalian infectivity. Knockdown of TbKIFC1 d...

The AMP-activated kinase (AMPK) is a major energy sensor metabolic enzyme that is activated early during T cell immune responses but its role in the generation of effector T cells is still controversial. Using both in vitro and in vivo models of T cell proliferation, we show herein that AMPK is dispensable for early TCR signaling and short-term pro...

The C-terminal variants G1 and G2 of apolipoprotein L1 (APOL1) confer human resistance to the sleeping sickness parasite Trypanosoma rhodesiense, but they also increase the risk of kidney disease. APOL1 and APOL3 are death-promoting proteins that are partially associated with the endoplasmic reticulum and Golgi membranes. We report that in podocyte...

The oil-in-water emulsion Adjuvant System 03 (AS03) is one of the few adjuvants used in licensed vaccines. Previous work indicates that AS03 induces a local and transient inflammatory response that contributes to its adjuvant effect. However, the molecular mechanisms involved in its immunostimulatory properties are ill-defined. Upon intramuscular i...

The virulence of Shigella mainly resides in the use of a Type 3 Secretion System (T3SS) to inject several proteins inside the host cell. Three categories of proteins are hierarchically secreted: (1) the needle components (MxiH and MxiI), (2) the translocator proteins which form a pore (translocon) inside the host cell membrane, and (3) the effector...

The primate-specific serum protein apolipoprotein L1 (APOL1) is the only secreted member of a family of cell death promoting proteins (1-4) . APOL1 kills the bloodstream parasite Trypanosoma brucei brucei, but not the human sleeping sickness agents T.b. rhodesiense and T.b. gambiense (3) . We considered the possibility that intracellular members of...

Cell division is a vital part of the cell cycle that is fundamental to all life. Despite decades of intense investigation, this process is still incompletely understood. Previously, the essential GTPase ObgE, which plays a role in a myriad of basic cellular processes (such as initiation of DNA replication, chromosome segregation, and ribosome assem...

Interactions between chronic lymphocytic leukemia B-cells and the bone marrow microenvironment play a major function in the physiopathology of chronic lymphocytic leukemia. Extracellular vesicles, which are composed of exosomes and microparticles, play an important role in cell communication. However, little is known about their role in chronic lym...

The early stages of clot formation in blood vessels involve platelet adhesion–aggregation. Although these mechanisms have been extensively studied, gaps in their understanding still persist. We have performed detailed in vitro experiments, using the well-known Impact-R device, and developed a numerical model to better describe and understand this p...

The microvillus brush border on the renal proximal tubule epithelium allows the controlled reabsorption of solutes that are filtered through the glomerulus and thus participates in general body homeostasis. Here, using the lipid 5-phosphatase Ship2 global knockout mice, proximal tubule-specific Ship2 knockout mice, and a proximal tubule cell model...

Trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human Chagas disease in South America. This parasite undergoes a complex life cycle alternating between non-proliferative and dividing forms. Owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity...

Representative flow cytometry profiles of the TL-488 and Tf-633 signals in T. cruzi. Full representation of Fig 7D experiment (representative experiment) showing the gating and the quadrant plots of the TL signal (ordinate) and the Tf signal (abscissa) from live cells treated under different conditions. UC represents the uncolored cells. (EPS)

List of LC-MS/MS identified proteins of TL- and GSLII-enriched fractions from T. cruzi. Detailed legend is reported on the table. (XLS)

Tsetse flies are the sole vectors of Trypanosoma brucei parasites that cause sleeping sickness. Our knowledge on the early interface between the infective metacyclic forms and the mammalian host skin is currently highly limited. Glossina morsitans flies infected with fluorescently tagged T. brucei parasites were used in this study to initiate natur...

Transmissibility of different T.b.brucei strains in G.m.morsitans tsetse flies. Teneral male tsetse flies were infected with T.b.brucei AnTAR1, AnTat1.1EdsRed or AnTat1.1ETagGFP2 in the presence of 10 mM reduced L-glutathion. Parasite infection in the salivary gland was evaluated by induced probing on pre-warmed microscopy slides. Indicated are the...

Parasite persistence at a late infection time point. Flow cytometry profiles of control mice and mice at 18 dpi following natural infection with two differentially labeled parasite strains (AnTat1.1EdsRed or AnTat1.1ETagGFP2). Mice were exposed to the bites of infected tsetse flies to introduce AnTat1.1EdsRed parasites in the left ear and AnTat1.1E...

Parasite viability in the inoculum. The viability of the DEAE52-purified MCF and BSF parasites was assessed by 7AAD-based staining and flow cytometry analysis in (A) the parasite inoculum and (B) the inoculum approximately 3h after preparation. Percentage viable trypanosomes are indicated in the dot plots. The parasites in this viability analysis c...

Feeding response of flies in function of increasing temperature. Feeding response of 3-day starved flies on an artificial horse blood meal through a silicone membrane. Membrane surface temperatures were set to match the average left infected ear and the right uninfected ear temperatures measured at 8 dpi (25.1°C and 24.0°C respectively) and at a hi...

Parasite retention and proliferation at the dermal infection initiation site. Flow cytometry profiles illustrating the detection of (A) AnTat1.1EdsRed or (B) AnTat1.1ETagGFP2 trypanosomes in the infection initiation site (L ear) and absence in the contralateral side (R ear). Shown events are all singlets in the ear dermal extracts at 90 hpi. These...

Parasite movement inside the dermis. Movement of T.b.brucei AnTat1.1EdsRed parasites recorded by confocal microscopy inside the ear dermal sheets at 90 hpi. Parasites display a typical anterior-posterior movement consistent with a physical constraint inside the dermis. (AVI)

Apolipoproteins L (ApoLs) are Bcl-2-like proteins expressed under inflammatory conditions in myeloid and endothelial cells. We found that Toll-like receptor (TLR) stimuli, particularly the viral mimetic poly(I:C), specifically induce ApoLs7/11 sub-families in murine CD8α(+) dendritic cells (DCs). This induction requires the TLR3/TRIF signaling path...

Plant root-knot nematode interaction studies are performed on several host plant models. Though root-knot nematodes interact with trees, no perennial woody model has been explored so far. Here we show that poplar (Populus tremula x P. alba) grown in vitro is susceptible to Meloidogyne incognita allowing this nematode to penetrate, to induce feeding...

Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is the last identified member of the inositol 1,4,5-trisphosphate 3-kinases family which phosphorylates inositol 1,4,5-trisphosphate into inositol 1,3,4,5-tetrakisphosphate. Although expression and function of the two other family members ITPKA and ITPKB are rather well characterized, similar informat...

African trypanosomes have been the subject of research of our group at the Université Libre de Bruxelles in Belgium for several decades now. The picture immediately suggests the graceful movement of the parasite, showing its streamlined shape exquisitely adapted for its movement in the viscous environment of the blood. The structural and physiologi...

Unlabelled: Programmed cell death (PCD) is an important hallmark of multicellular organisms. Cells self-destruct through a regulated series of events for the benefit of the organism as a whole. The existence of PCD in bacteria has long been controversial due to the widely held belief that only multicellular organisms would profit from this kind of...

Exposure of phosphatidylserine on the cell surface. (A) Concomitant staining of E. coli WM2949 pJAT8-araE carrying pBAD/His A, pBAD/His A-obgE, or pBAD/His A-obgE* with FITC-conjugated annexin V and PI. (B) Concomitant staining of E. coli WM2949 ΔrecA pJAT8-araE carrying pBAD/His A, pBAD/His A-obgE, or pBAD/His A-obgE* with FITC-conjugated annexin...

Expression of ObgE* triggers PCD in a ΔrecA strain. (A) DiBAC4(3) staining as a measure of membrane depolarization. Fluorescence intensity was measured by flow cytometry. (B) Microscopic analysis of induced cells stained with the blue DNA dye DAPI and the red membrane-specific dye FM4-64. Bars, 2 µm. (C) DNA fragmentation was determined using the T...

Expression of ObgE* is bactericidal and leads to loss of membrane integrity. LIVE/DEAD staining with the Live/Dead BacLight bacterial viability kit (ThermoFisher Scientific) was performed at 0, 2, and 4 h after induction of ObgE* expression in an exponential-phase culture. One milliliter of each culture was washed and resuspended in 500 µl phosphat...

The congenital malformation split hand/foot (SHFM) is characterized by missing central fingers and dysmorphology or fusion of the remaining ones. Type-1 SHFM is linked to deletions/rearrangements of the DLX5–DLX6 locus and point mutations in the DLX5 gene. The ectrodactyly phenotype is reproduced in mice by the double knockout (DKO) of Dlx5 and Dlx...

Humans resist infection by the African parasite Trypanosoma brucei owing to the trypanolytic activity of the serum apolipoprotein L1 (APOL1). Following uptake by endocytosis in the parasite, APOL1 forms pores in endolysosomal membranes and triggers lysosome swelling. Here we show that APOL1 induces both lysosomal and mitochondrial membrane permeabi...

Platelet spreading and retraction play a pivotal role in the platelet plugging and the thrombus formation. In routine laboratory, platelet function tests include exhaustive information about the role of the different receptors present at the platelet surface without information on the 3D structure of platelet aggregates. In this work, we develop, a...

Signaling from the primary cilium regulates kidney tubule development and cyst formation. However, the mechanism controlling targeting of ciliary components necessary for cilium morphogenesis and signaling is largely unknown. Here, we studied the function of class II phosphoinositide 3-kinase-C2α (PI3K-C2α) in renal tubule-derived inner medullary c...

Microparticles (MPs), also called microvesicles (MVs) are plasma membrane-derived fragments with sizes ranging from 0.1 to 1μm. Characterization of these MPs is often performed by flow cytometry but there is no consensus on the appropriate negative control to use that can lead to false positive results. We analyzed MPs from platelets, B-cells, T-ce...

Normal human serum (NHS) confers human resistance to infection by the parasite Trypanosoma brucei owing to the trypanolytic activity of apolipoprotein L1 (APOL1), present in two serum complexes termed Trypanolytic Factors (TLF-1 and -2). In order to identify parasite components involved in the intracellular trafficking and activity of TLFs, an indu...

Brucella spp. are facultative intracellular Gram-negative coccobacilli responsible for brucellosis, a worldwide zoonosis. We observed that Brucella melitensis is able to persist for several weeks in the blood of intraperitoneally infected mice and that transferred blood at any time point tested is able to induce infection in naive recipient mice. B...

Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infec...

Humans can survive bloodstream infection by African trypanosomes, owing to the activity of serum complexes that have efficient trypanosome-killing ability. The two trypanosome subspecies that are responsible for human sleeping sickness - Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense - can evade this defence mechanism by expressing...

Multiple phosphatidylinositol (PtdIns) 3-kinases (PI3Ks) can produce PtdIns3P to control endocytic trafficking, but whether enzyme specialization occurs in defined subcellular locations is unclear. Here, we report that PI3K-C2α is enriched in the pericentriolar recycling endocytic compartment (PRE) at the base of the primary cilium, where it regula...

Ectrodactyly, or Split-Hand/Foot Malformation (SHFM), is a congenital condition characterized by the loss of central rays of hands and feet. The p63 and the DLX5;DLX6 transcription factors, expressed in the embryonic limb buds and ectoderm, are disease genes for these conditions. Mutations of p63 also cause the ectodermal dysplasia–ectrodactyly–cle...

Immortal spheroids were generated from fetal mouse intestine using the culture system initially developed to culture organoids from adult intestinal epithelium. Spheroid proportion progressively decreases from fetal to postnatal period, with a corresponding increase in production of organoids. Like organoids, spheroids show Wnt-dependent indefinite...

The African parasite Trypanosoma brucei gambiense accounts for 97% of human sleeping sickness cases. T. b. gambiense resists the specific human innate immunity acting against several other tsetse-fly-transmitted trypanosome species such as T. b. brucei, the causative agent of nagana disease in cattle. Human immunity to some African trypanosomes is...

Supplementary Table 1. Phage content of the isolates recovered from outside and inside the Concordia station. Supplementary material 2

Supplementary Fig. 1. Phylogenetic position of all isolates analyzed during this study among all Paenibacillus species type strains, based on 16S rRNA gene sequence analysis. Bootstrap branch confidence estimates are indicated. Supplementary material 1

Culturable psychrotolerant bacteria were isolated from the top snow on the high Antarctic Plateau surrounding the research station Concordia. A total of 80 isolates were recovered, by enrichment cultures, from two different isolation sites (a distant pristine site [75° S 123° E] and a site near the secondary runway of Concordia). All isolates were...

Flagellar attachment is a visibly striking morphological feature of African trypanosomes but little is known about the requirements for attachment at a molecular level. This study characterizes a previously undescribed membrane protein, FLA3, which plays an essential role in flagellar attachment in Trypanosoma brucei. FLA3 is heavily N-glycosylated...

Knockdown of FLA3 does not affect the growth of procyclic forms of T. brucei. Knock down of residual FLA3 mRNA had no effect on the growth of a cloned FLA3 RNAi procyclic cell line cultured in the presence (○) or absence of tetracycline (•). A decrease in the residual FLA3 transcript level was confirmed by qRT-PCR which gave a relative ratio (induc...

Flagellar pocket region of a detached flagellum. The cells were cultured for 24 h in the presence of tetracycline, fixed and processed for transmission electron microscopy. Panel A. Section through the flagellar pocket of a non induced FLA3 RNAi cell. The flagellum is tightly associated with the neck of the flagellar pocket (FP). After emerging fro...

Analysis of flagellar detachment in FLA3 bloodstream RNAi cells using scanning electron microscopy. The cells were fixed at various times after the induction of the FLA3 dsRNA and processed for analysis by scanning electron microscopy. At the zero time the cells had the typical long slender morphology with the flagellum (black arrow) emerging from...

Detached flagella continued to beat but directional motility was lost. Bloodstream form FLA3 RNAi cells were grown in the presence of tetracycline for 18 h. The images were captured using phase contrast microscopy. (AVI)

Nucleotide sequence of a partial cDNA identified by screening expression libraries with antibodies against a total tomato lectin binding fraction isolated from bloodstream forms of T. brucei. Panel A. The partial cDNA (1,364 bp) identified in a mini-library of cDNAs isolated by screening expression libraries with antibodies generated against a toma...

Flagellar attachment and motility in non induced FLA3 RNAi cells. Bloodstream form FLA3 RNAi cells were grown in the absence of tetracycline. The images were captured using phase contrast microscopy. (AVI)

Domain structure of Tb927.5.4570/4580. Panel A. The full open reading frame (Tb927.5.4580) was identified after interrogation of the geneDB database using the partial cDNA described in Fig.S1. The hydrophobic spans are underlined and the putative N-glycosylation sites shown in red. A basic region located immediately C-terminal to the second putativ...

Sequence of Tb927.8.4050 and alignment with Tb927.5.4580. Panel A. Sequence of Tb927.8.4050 a protein identified by BLAST analysis to be related to Tb927.5.4580/70. two potential membrane spanning regions are underlined and a basic region located immediately C-terminal to the second putative membrane spanning region is boxed. Panel B. A CLUSTAL ali...

A novel way has been proposed to follow the formation of nanocrystalline magnetite. Iron oxide nanoparticles were synthesized by the thermal decomposition of Fe(acac)(3) in the presence of oleic acid and oleylamine surfactants at high temperature. The species produced during the synthetic process are characterized through their effects on the proto...

The MIR396 family, composed of ath‐miR396a and ath‐miR396b in Arabidopsis, is conserved among plant species and is known to target the Growth‐Regulating Factor (GRF) gene family. ath‐miR396 overexpressors or grf mutants are characterised by small and narrow leaves and show embryogenic defects such as cotyledon fusion. Heterologous expression of ath...