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March 2012 - present
January 2007 - December 2012
Publications
Publications (133)
Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross‐species communication has grown rapidly. Parasitic helminths, worm species found in the phyla Nematoda and Platyhelminthes, are well‐recognised manipulators of host immune function and physiology. Emerging evidence supports a role for helminth‐derived E...
Intricate molecular communication between schistosome flatworms and their mammalian host, as well as between paired male and female schistosomes has shaped the secreted proteome of these flatworms. Whereas the schistosome egg is responsible for the disease manifestations of chronic schistosomiasis, the long lived, adult female and male stages also...
Foodborne trematodes (FBTs) have a worldwide distribution (with particular prevalence in south-east Asia) and are believed to infect almost 75 million people, with millions more living at risk of infection. Although mortality due to trematodiasis is low, these infections cause considerable morbidity and some species are associated with the developm...
Intricate molecular communication between the schistosome (flatworms) and its mammalian host, as well as between paired male and female schistosomes has shaped the secreted proteome of these flatworms. Whereas the schistosome egg is responsible for the disease manifestations of chronic schistosomiasis, the long lived, adult female and male stages a...
Diabetes is recognised as the world’s fastest growing chronic condition globally. Helminth infections have been shown to be associated with a lower prevalence of type 2 diabetes (T2D), in part due to their ability to induce a type 2 immune response. Therefore, to understand the molecular mechanisms that underlie the development of T2D-induced insul...
Diabetes is recognised as the world’s fastest growing chronic condition globally. Helminth infections have been shown to be associated with a lower prevalence of type 2 diabetes (T2D), in part due to their ability to induce a type 2 immune response. Therefore, to understand the molecular mechanisms that underlie the development of T2D-induced insul...
Helminth infections impact the health of hundreds of millions of persons globally and also cause important economic losses in livestock farming. Methodological limitations as well as the low attention given to the study of helminths have impacted biological research and, thus, the procurement of accurate diagnosis and effective treatments. Understa...
Inter-phylum transfer of molecular information is exquisitely exemplified in the uptake of parasite extracellular vesicles (EVs) by their target mammalian host tissues. The oriental liver fluke, Opisthorchis viverrini is the major cause of bile duct cancer in people in Southeast Asia. A major mechanism by which O. viverrini promotes cancer is throu...
Recent advances in the field of host immunity against parasitic nematodes have revealed the importance of macrophages in trapping tissue migratory larvae. Protective immune mechanisms against the rodent hookworm Nippostrongylus brasiliensis (Nb) are mediated, at least in part, by IL‐4‐activated macrophages that bind and trap larvae in the lung. How...
Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with bladder cancer. In schistosomes, tetraspanins (TSPs) are abundantly present in different parasite proteomes and could be potential diagnostic candidates due to their accessibility to...
Parasite infections caused by helminths affect hundreds of millions worldwide. Despite their socioeconomic importance and impact on health, there is still an urgent need to develop appropriate control approaches. The recent discovery that helminths, as most eukaryotic organisms, secrete extracellular vesicles (EVs) of different type has opened new...
Helminths secrete a plethora of proteins involved in parasitism-related processes such as tissue penetration, migration, feeding and immunoregulation. Astacins, a family of zinc metalloproteases belonging to the peptidase family M12, are one of the most abundantly represented protein families in the secretomes of helminths. Despite their involvemen...
Background
Sensitive diagnostics are needed for effective management and surveillance of schistosomiasis so that current transmission interruption goals set by WHO can be achieved. We aimed to screen the Schistosoma haematobium secretome to find antibody biomarkers of schistosome infection, validate their diagnostic performance in samples from ende...
Small extracellular vesicles (sEVs), including exosomes, are formed by the endocytic pathway and contain genetic and protein material which reflect the contents of their cells of origin. These contents have a role in vesicle-mediated information transfer, as well as physiological and pathological functions. Thus, these vesicles are of great interes...
Despite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Praziquantel treatment damages the outermost surface...
Soil-transmitted helminths (STH) affect hundreds of millions worldwide and are some of the most important neglected tropical diseases in terms of morbidity. Due to the difficulty in studying STH human infections, rodent models have become increasingly used, mainly because of their similarities in life cycle. Ascaris suum and Trichuris muris have be...
Helminths can interact with their hosts in many different ways, including through the secretion of soluble molecules (such as lipids, glycans and proteins) and extracellular vesicles (EVs). The field of helminth secreted EVs has significantly advanced in recent years, mainly due to the molecular characterisation of EV proteomes and research highlig...
Type 2 diabetes (T2D) is a major health problem and is considered one of the top 10 diseases leading to death globally. T2D has been widely associated with systemic and local inflammatory responses and with alterations in the gut microbiota. Microorganisms, including parasitic worms and gut microbes have exquisitely co-evolved with their hosts to e...
Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host–parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Her...
Helminth parasites have a remarkable ability to persist within their mammalian hosts, which is largely due to their secretion of molecules with immunomodulatory properties. Although the soluble components of helminth secretions have been extensively studied, the discovery that helminths release extracellular vesicles (EVs) has added further complex...
Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host-parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Her...
The ability of the parasitic blood fluke Schistosoma mansoni and other parasitic helminths to manipulate host biology is well recognised, but the mechanisms that underpin these phenomena are not well understood. An emerging paradigm is that helminths transfer their biological cargo to host cells by secretion of extracellular vesicles (EVs). Herein,...
The tegument (outer surface) of Schistosoma mansoni and other trematodes is in intimate contact with the host and plays an important role in host-parasite interactions. It is a complex structure that contains hundreds of proteins implicated in a variety of functions, although, so far, only a few proteins have been well characterized. Indeed, a few...
The human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a...
Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the liver fluke is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor termed liver fluke granulin, a homologue of the human progranulin, which contributes significantly to biliary...
Hookworms cause a major neglected tropical disease, occurring after larvae penetrate the host skin. Neutrophils are phagocytes that kill large pathogens by releasing neutrophil extracellular traps (NETs), but whether they target hookworms during skin infection is unknown. Using a murine hookworm, Nippostrongylus brasiliensis, we observed neutrophil...
Helminth parasites secrete extracellular vesicles (EVs) into their environment that have potential roles in host-parasite communication, and thus represent potentially useful targets for novel control strategies. Here, we carried out a comprehensive proteomic analysis of two different populations of EVs - 15k pellet and 120k pellet EVs - from Schis...
Opisthorchiasis is a serious public health problem in East Asia and Europe. The pathology involves hepatobiliary abnormalities such as cholangitis, choledocholithiasis and tissue fibrosis that can develop into cholangiocarcinoma. Prevention of infection is difficult as multiple social and behavioral factors are involved, thus, progress on a prophyl...
Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Owing to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. These nematodes secrete a multitude of compounds that interact with host tissues where t...
Cholinesterase (ChE) function in schistosomes is essential for orchestration of parasite neurotransmission but has been poorly defined with respect to the molecules responsible. Interrogation of the S. mansoni genome has revealed the presence of three ChE domain-containing genes (Smche)s, which we have shown to encode two functional acetylcholinest...
Opisthorchiasis affects millions of people in Southeast Asia and has been strongly associated with bile duct cancer. Current strategic control approaches such as chemotherapy and health education are not sustainable, and a prophylactic vaccine would be a major advance in the prevention of the disease. Tetraspanins are transmembrane proteins previou...
This article reviews the past and present scientific reports regarding Bithynia spp. focusing on the biology, ecology and life cycle of Bithynia snails and their responses to Opisthorchis viverrini infection. Moreover, new data regarding comparative molecular genomics and proteomic approaches have recently revealed novel molecular components involv...
Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with fish-borne liver flukes is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor, termed liver fluke granulin (Ov-GRN-1), a homologue of the human progranulin (huPGRN). Secreted Ov-G...
Trematode infections are among the most neglected tropical diseases despite their worldwide distribution and extraordinary ability to parasitise many different host species and host tissues. Furthermore, these parasites are of great socioeconomic, medical, veterinary and agricultural importance. During the last 10 years, there have been increasing...
Background:
The liver fluke Opisthorchis viverrini infects several million people in Southeast Asia. Adult flukes live in the bile ducts of humans, where they cause hepatobiliary pathology, including cholangiocarcinoma. Here, we investigated the potential of extracellular vesicles (EVs) secreted by the fluke and defined recombinant proteins derive...
Background:
Schistosomiasis is a neglected disease affecting hundreds of millions worldwide. Of the three main species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. S. haematobium infection can cause different urogential clinical complications, particularly in the bladder, and...
Cholinesterase (ChE) function in schistosomes is essential for orchestration of parasite neurotransmission but has been poorly defined with respect to the molecules responsible. Interrogation of the S. mansoni genome has revealed the presence of three ChE domain-containing genes ( Smche )s, which we have shown to encode two functional acetylcholine...
The Bithynia snails of B. funiculata, B. siamensis siamensis and B. siamensis goniomphalos, are first intermediate hosts of Opisthorchis viverrini. The success of parasitic infection in snails is related to the host species and efficiency of their internal defense system. Parasitic infections in snails exhibited significant variations in the number...
Infection with the food-borne liver fluke Opisthorchis viverrini is the principal risk factor for cholangiocarcinoma (CCA) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. We exploited this link to explore the role of the secreted growth factor termed liver fluke granulin (Ov-grn-1) in pre-malignant lesio...
Background
Schistosomiasis is a neglected disease affecting hundreds of millions worldwide. Of the three main species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. S . haematobium infection can cause different urogential clinical complications, particularly in the bladder, and...
Opisthorchis viverrini resides in bile ducts and could be targeted optimally by vaccination, which induces both mucosal and systemic antibodies, reflecting the migratory path of this liver fluke. Tetraspanins are transmembrane proteins essential for tegument formation of O. viverrini and are efficacious as vaccine antigens for diseases caused by th...
Opisthorchis viverrini resides in bile ducts and could be targeted optimally by vaccination, which induces both mucosal and systemic antibodies, reflecting the migratory path of this liver fluke. Tetraspanins are transmembrane proteins essential for tegument formation of O. viverrini and are efficacious as vaccine antigens for diseases caused by th...
Granulins are a family of growth factors involved in cell proliferation. The liver-fluke granulin, Ov-GRN-1, isolated from a carcinogenic liver fluke Opisthorchis viverrini, can significantly accelerate wound repair in vivo and in vitro. However, it is difficult to express Ov-GRN-1 in recombinant form at high yield, impeding its utility as a drug l...
The human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a...
Infections with several flatworm parasites represent group 1 biological carcinogens, i.e. definite causes of cancer. Infection with the food-borne liver fluke Opisthorchis viverrini causes cholangiocarcinoma (CCA). Whereas the causative agent for most cancers, including CCA in the West, remains obscure, the principal risk factor for CCA in Thailand...
Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Owing to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. The importance of excretory/secretory (ES) products in governing host–parasite interacti...
Gastrointestinal (GI) parasites, hookworms in particular, have evolved to cause minimal harm to their hosts, allowing them to establish chronic infections. This is mediated by creating an immunoregulatory environment. Indeed, hookworms are such potent suppressors of inflammation that they have been used in clinical trials to treat inflammatory bowe...
Prediction of Nippostrongylus brasiliensis extracellular vesicle (EV) miRNA target interactions to murine host genes. Functional map of N. brasiliensis EV miRNAs and their target murine host genes categorized by PantherDB signaling, metabolic, disease, and other pathways. Heat map corresponds to individual targeted genes in the murine host.
Proteomic analysis of extracellular vesicles (EVs) secreted by Nippostrongylus brasiliensis. Details of the identification of the proteins present in the EVs secreted by N. brasiliensis using X!Tandem, Tide, MS-GF+ and OMSSA. All proteins are shown, including contaminants.
Structural (all-vs-all blast) and functional (Blast2GO) comparison of Nippostrongylus brasiliensis- and Trichuris muris-EV proteomes.
Representative images of mouse colons from all the groups examined in the experimental colitis model.
Alluvial diagram depicting interactions between nematode EV miRNAs and mouse host cytokine gene targets. Nippostrongylus brasiliensis (Nb)-EV miRNAs (green), Trichuris muris (Tm)-EV miRNAs (pink), and shared homologs (orange) are presented. Links are colored according to canonical pro- (red) and anti-inflammatory (blue) responses.
Pathway analysis and parsing of Nippostrongylus brasiliensis EV miRNAs and their target murine host genes categorized by PantherDB pathways.
Effects of Trichuris muris secreted fractions in experimental colitis. Mice received a single intraperitoneal injection of 20 µg protein in PBS 1 day prior to intrarectal administration of 2.5 mg of TNBS in 50% ethanol. Data display daily recorded body weight, final clinical examination, colon length, and colon pathology after euthanasia.
Data description on predicted Nippostrongylus brasiliensis miRNA–host target interactions. Table showing the 52 miRNAs identified in the N. brasiliensis extracellular vesicles and their 3′UTR predicted binding sites in the mouse genome.
Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, broadly employed to study the host-dependent mechanisms that govern the evolution of intestinal helminth infections. Resistance against E. caproni homologous secondary infections has been reported in mice and appears to be related to the generation of a local Th2 response...
Introduction: Helminths are multicellular parasites affecting nearly three billion people worldwide. To orchestrate a parasitic existence, helminths secrete different molecules, either in soluble form or contained within extracellular vesicles (EVs). EVs are secreted by most cell types and organisms, and have varied roles in intercellular communica...
Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Owing to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. These nematodes secrete a multitude of compounds that interact with host tissues where t...
The omics technologies have improved our understanding of the molecular events that underpin host–parasite interactions and the pathogenesis of parasitic diseases. In the last decade, proteomics and genomics in particular have been used to characterize the surface and secreted products of the carcinogenic liver fluke Opisthorchis viverrini and reve...
There is a rapidly growing body of evidence that production of extracellular vesicles (EVs) is a universal feature of cellular life. More recently, EVs have been identified in a broad range of both unicellular and multicellular parasites where they play roles in parasite–parasite intercommunication as well as parasite–host interactions. Parasitic h...
Whipworms are parasitic nematodes that live in the gut of more than 500 million people worldwide. Due to the difficulty in obtaining parasite material, the mouse whipworm Trichuris muris has been extensively used as a model to study human whipworm infections. These nematodes secrete a multitude of compounds that interact with host tissues where the...
Parasitic helminth infections in livestock are responsible for significant economic losses particularly in developing and tropical regions of the world. Soil-transmitted helminths affect more than 1.5 billion people causing great socio-economic impact. Among these, hookworms, roundworms and whipworms are of particular importance due to their high e...
Parasitic helminth infections in livestock are responsible for significant economic losses particularly in developing and tropical regions of the world. Soil-transmitted helminths affect more than 1.5 billion people causing great socio-economic impact. Among these, hookworms, roundworms and whipworms are of particular importance due to their high e...
The current strategy for the control of helminth infections relies on chemotherapy. However, resistance appearance is promoting the necessity of developing new drugs against trematodes. Herein, potential trematocidal effects of garlic (Allium sativum) are investigated in the context of intestinal foodborne trematodes, employing the Echinostoma capr...
Granulins are a family of protein growth factors that are involved in cell proliferation. An orthologue of granulin from the human parasitic liver fluke Opisthorchis viverrini, known as Ov-GRN-1, induces angiogenesis and accelerates wound repair. Recombinant Ov-GRN-1 production is complex, and poses an obstacle for clinical development. To identify...
Different reports have highlighted the potential use of helminths and their secretions in the treatment of inflammatory bowel disease (IBD) conditions; however, no reports have investigated their effects at a proteome level. Herein, we characterise the protein expression changes that occur in lamina propria (LP) and the intestinal epithelial cells...