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Living cells as a biological analog of optical tweezers – a non-invasive microrheology approach (2023)
Journal Article
Hardiman, W., Clark, M., Friel, C., Huett, A., Pérez-Cota, F., Setchfield, K., …Tassieri, M. (2023). Living cells as a biological analog of optical tweezers – a non-invasive microrheology approach. Acta Biomaterialia, 166, 317-325. https://doi.org/10.1016/j.actbio.2023.04.039

Microrheology, the study of fluids on micron length-scales, promises to reveal insights into cellular biology, including mechanical biomarkers of disease and the interplay between biomechanics and cellular function. Here a minimally-invasive passive... Read More about Living cells as a biological analog of optical tweezers – a non-invasive microrheology approach.

A mechanoresponsive nano-sized carrier achieves intracellular release of drug on external ultrasound stimulus (2022)
Journal Article
Catania, R., Onion, D., Russo, E., Zelzer, M., Mantovani, G., Huett, A., & Stolnik, S. (2022). A mechanoresponsive nano-sized carrier achieves intracellular release of drug on external ultrasound stimulus. RSC Advances, 12(26), 16561-16569. https://doi.org/10.1039/d2ra02307e

Control over intracellular release of therapeutic compounds incorporated into nano-carriers will open new possibilities for targeted treatments of various diseases including cancer, and viral and bacterial infections. Here we report our study on mech... Read More about A mechanoresponsive nano-sized carrier achieves intracellular release of drug on external ultrasound stimulus.

Synthesis and Antibacterial Evaluation of New Pyrazolo[3,4-d]pyrimidines Kinase Inhibitors (2020)
Journal Article
Greco, C., Catania, R., Balacco, D. L., Taresco, V., Musumeci, F., Alexander, C., …Schenone, S. (2020). Synthesis and Antibacterial Evaluation of New Pyrazolo[3,4-d]pyrimidines Kinase Inhibitors. Molecules, 25(22), Article 5354. https://doi.org/10.3390/molecules25225354

Pyrazolo[3,4-d]pyrimidines represent an important class of heterocyclic compounds well-known for their anticancer activity exerted by the inhibition of eukaryotic protein kinases. Recently, pyrazolo[3,4-d]pyrimidines have become increasingly attracti... Read More about Synthesis and Antibacterial Evaluation of New Pyrazolo[3,4-d]pyrimidines Kinase Inhibitors.

A multi-phenotypic imaging screen to identify bacterial effectors by exogenous expression in a HeLa cell line (2018)
Journal Article
Collins, A., & Huett, A. (2018). A multi-phenotypic imaging screen to identify bacterial effectors by exogenous expression in a HeLa cell line. Scientific Data, 5, Article 180081. https://doi.org/10.1038/sdata.2018.81

We present a high-content screen (HCS) for the simultaneous analysis of multiple phenotypes in HeLa cells expressing an autophagy reporter (mcherry-LC3) and one of 209 GFP-fused proteins from the Crohn’s Disease (CD)-associated bacterium, Adherent In... Read More about A multi-phenotypic imaging screen to identify bacterial effectors by exogenous expression in a HeLa cell line.

Combinatorial actions of bacterial effectors revealed by exploiting genetic tools in yeast (2017)
Journal Article
Huett, A. (2017). Combinatorial actions of bacterial effectors revealed by exploiting genetic tools in yeast. Molecular Systems Biology, 13(1), 911. https://doi.org/10.15252/msb.20167447

While yeast has been extensively used as a model system for analysing protein–protein and genetic interactions, in the context of bacterial pathogenesis, the use of yeast-based tools has largely been limited to identifying interactions between pathog... Read More about Combinatorial actions of bacterial effectors revealed by exploiting genetic tools in yeast.

The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular salmonella typhimurium (2012)
Journal Article
Huett, A., Heath, R. J., Begun, J., Sassi, S. O., Baxt, L. A., Vyas, J. M., …Xavier, R. J. (2012). The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular salmonella typhimurium. Cell Host and Microbe, 12(6), 778-790. https://doi.org/10.1016/j.chom.2012.10.019

Several species of pathogenic bacteria replicate within an intracellular vacuolar niche. Bacteria that escape into the cytosol are captured by the autophagic pathway and targeted for lysosomal degradation, representing a defense against bacterial exp... Read More about The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular salmonella typhimurium.

Tribbles 2 (Trib2) is a novel regulator of toll-like receptor 5 signaling (2012)
Journal Article
Wei, S. C., Rosenberg, I. M., Cao, Z., Huett, A. S., Xavier, R. J., & Podolsky, D. K. (2012). Tribbles 2 (Trib2) is a novel regulator of toll-like receptor 5 signaling. Inflammatory Bowel Diseases, 18(5), 877-888. https://doi.org/10.1002/ibd.22883

Background: Toll-like receptors (TLRs) are expressed by a variety of cells, including intestinal epithelia. However, the full spectrum of regulators modulating innate responses via TLRs has not been delineated. Tribbles (Trib) have been identified as... Read More about Tribbles 2 (Trib2) is a novel regulator of toll-like receptor 5 signaling.

Crohn disease: A current perspective on genetics, autophagy and immunity (2011)
Journal Article
Stappenbeck, T. S., Rioux, J. D., Mizoguchi, A., Saitoh, T., Huett, A., Darfeuille-Michaud, A., …Xavier, R. J. (2011). Crohn disease: A current perspective on genetics, autophagy and immunity. Autophagy, 7(4), 355-374. https://doi.org/10.4161/auto.7.4.13074

Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract.1 Prevalence in western populations is 100-150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any ag... Read More about Crohn disease: A current perspective on genetics, autophagy and immunity.

A systems biology viewpoint on autophagy in health and disease (2010)
Journal Article
Huett, A., Goel, G., & Xavier, R. J. (2010). A systems biology viewpoint on autophagy in health and disease. Current Opinion in Gastroenterology, 26(4), 302-309. https://doi.org/10.1097/MOG.0b013e32833ae2ed

Purpose of review: The field of autophagy is rapidly expanding to encompass many important areas of cell biology, physiology and disease. Recent discoveries and tools allow the connection of the autophagy pathway to other cellular signals and process... Read More about A systems biology viewpoint on autophagy in health and disease.

Human leucine-rich repeat proteins: A genome-wide bioinformatic categorization and functional analysis in innate immunity (2010)
Journal Article
Ng, A. C., Eisenberg, J. M., Heath, R. J., Huett, A., Robinson, C. M., Nau, G. J., & Xavier, R. J. (2011). Human leucine-rich repeat proteins: A genome-wide bioinformatic categorization and functional analysis in innate immunity. Proceedings of the National Academy of Sciences, 108(SUPPL. 1), 4631-4638. https://doi.org/10.1073/pnas.1000093107

In innate immune sensing, the detection of pathogen-associated molecular patterns by recognition receptors typically involve leucine-rich repeats (LRRs). We provide a categorization of 375 human LRR-containing proteins, almost half of which lack othe... Read More about Human leucine-rich repeat proteins: A genome-wide bioinformatic categorization and functional analysis in innate immunity.

Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly (2009)
Journal Article
Lapaquette, P., Glasser, A. L., Huett, A., Xavier, R. J., & Darfeuille-Michaud, A. (2009). Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly. Cellular Microbiology, 12(1), 99-113. https://doi.org/10.1111/j.1462-5822.2009.01381.x

Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to invade and to replicate within intestinal epithelial cells. Recent genome-wide association studies have highlighted the autop... Read More about Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly.

Building complex biological networks based upon model organisms: Mapping the human autophagy interactome via a hybrid yeast-human protein interaction network (2009)
Journal Article
Huett, A., & Xavier, R. (2009). Building complex biological networks based upon model organisms: Mapping the human autophagy interactome via a hybrid yeast-human protein interaction network. Autophagy, 5(6), 876-878. https://doi.org/10.4161/auto.9094

Autophagy is a process whose core machinery is highly conserved from yeast to higher eukaryotes and mammals. However it is becoming clear that multicellular organisms exhibit increased complexity of autophagic regulation and specialization of the non... Read More about Building complex biological networks based upon model organisms: Mapping the human autophagy interactome via a hybrid yeast-human protein interaction network.

Autophagy at the gut interface: Mucosal responses to stress and the consequences for inflammatory bowel diseases (2009)
Journal Article
Huett, A., & Xavier, R. J. (2010). Autophagy at the gut interface: Mucosal responses to stress and the consequences for inflammatory bowel diseases. Inflammatory Bowel Diseases, 16(1), 152-174. https://doi.org/10.1002/ibd.20991

Autophagy is a conserved homeostatic process by which cells degrade and recycle cytoplasmic contents and organelles. Recently, autophagy has come to prominence as a factor in many disease states, including inflammatory bowel diseases. In this review... Read More about Autophagy at the gut interface: Mucosal responses to stress and the consequences for inflammatory bowel diseases.

The cytoskeletal scaffold Shank3 is recruited to pathogen-induced actin rearrangements (2009)
Journal Article
Huett, A., Leong, J. M., Podolsky, D. K., & Xavier, R. J. (2009). The cytoskeletal scaffold Shank3 is recruited to pathogen-induced actin rearrangements. Experimental Cell Research, 315(12), 2001-2011. https://doi.org/10.1016/j.yexcr.2009.04.003

The common gastrointestinal pathogens enteropathogenic Escherichia coli (EPEC) and Salmonella typhimurium both reorganize the gut epithelial cell actin cytoskeleton to mediate pathogenesis, utilizing mimicry of the host signaling apparatus. The PDZ d... Read More about The cytoskeletal scaffold Shank3 is recruited to pathogen-induced actin rearrangements.

A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy (2009)
Journal Article
Huett, A., Ng, A., Cao, Z., Kuballa, P., Komatsu, M., Daly, M. J., …Xavier, R. J. (2009). A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy. Journal of Immunology, 182(8), 4917-4930. https://doi.org/10.4049/jimmunol.0803050

Autophagy is a conserved cellular process required for the removal of defective organelles, protein aggregates, and intracellular pathogens. We used a network analysis strategy to identify novel human autophagy components based upon the yeast interac... Read More about A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy.

On the level: IRGM gene function is all about expression (2009)
Journal Article
Huett, A., McCarroll, S. A., Daly, M. J., & Xavier, R. J. (2009). On the level: IRGM gene function is all about expression. Autophagy, 5(1), 96-99. https://doi.org/10.4161/auto.5.1.7263

Crohn disease is a complex, multigenic, chronic inflammatory bowel disease of uncertain etiology. Recent advances in genetics, including high-throughput single-nucleotide polymorphism typing platforms and deep sequencing technologies have begun to sh... Read More about On the level: IRGM gene function is all about expression.

Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant (2008)
Journal Article
Kuballa, P., Huett, A., Rioux, J. D., Daly, M. J., & Xavier, R. J. (2008). Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant. PLoS ONE, 3(10), Article e3391. https://doi.org/10.1371/journal.pone.0003391

The genetic risk factors predisposing individuals to the development of inflammatory bowel disease are beginning to be deciphered by genome-wide association studies. Surprisingly, these new data point towards a critical role of autophagy in the patho... Read More about Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant.

Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease (2008)
Journal Article
McCarroll, S. A., Huett, A., Kuballa, P., Chilewski, S. D., Landry, A., Goyette, P., …Xavier, R. J. (2008). Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nature Genetics, 40(9), 1107-1112. https://doi.org/10.1038/ng.215

Following recent success in genome-wide association studies, a critical focus of human genetics is to understand how genetic variation at implicated loci influences cellular and disease processes. Crohn's disease (CD) is associated with SNPs around I... Read More about Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease.

Neither Hide Nor Hair: The Difficulty of Identifying Useful Disease Biomarkers (2008)
Journal Article
Huett, A., & Xavier, R. J. (2008). Neither Hide Nor Hair: The Difficulty of Identifying Useful Disease Biomarkers. Gastroenterology, 134(7), 2164-2168. https://doi.org/10.1053/j.gastro.2008.04.013

Robert Koch was the first to propose a series of definitive tests to determine the agents of infectious disease. Koch's postulates, first published in 1890, were subsequently updated for the molecular era in 1988 by Stanley Falkow1 and continue to fo... Read More about Neither Hide Nor Hair: The Difficulty of Identifying Useful Disease Biomarkers.

Autophagy as an important process in gut homeostasis and Crohn's disease pathogenesis (2008)
Journal Article
Xavier, R. J., Huett, A., & Rioux, J. D. (2008). Autophagy as an important process in gut homeostasis and Crohn's disease pathogenesis. Gut, 57(6), 717-720. https://doi.org/10.1136/gut.2007.134254

Crohns disease (CD) is a complex polygenic trait whereby multiple genetic and non-genetic risk factors contribute to disease susceptibility. Association testing is a statistical approach commonly used for identifying genetic risk factors for complex/... Read More about Autophagy as an important process in gut homeostasis and Crohn's disease pathogenesis.