- Overview
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Infectious diseases are 3 of the top 10 leading causes of death globally. In low-income countries, communicable diseases cause more than half of all deaths, especially among vulnerable newborns. In high-income countries such as Canada, infections account for 2-7% of deaths. Bacterial infections are often treatable using antibiotics, but chronic misuse of antibiotics has created a critical global health threat by increasing the presence of antimicrobial resistant organisms, thus further compounding the problem. Given that communicable diseases cause significant personal, societal and economic burdens worldwide, the United Nations highlighted the importance to “accelerate the pace of progress made in fighting … communicable diseases and epidemics, including by addressing growing antimicrobial resistance” in its Sustainable Development Goals.
Our group is interested in applying systems biology approaches to untangle the dynamic interactions between antimicrobial resistant pathogens and the host by:
1. Understanding host immune responses during infection, focusing on the critical area of neonatal sepsis
2. Characterizing how bacterial pathogens can maintain or disseminate antimicrobial resistant genes in diverse environments
3. Identifying novel virulence or antimicrobial resistance genes in these bacterial pathogens
- Publications
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Concentration-dependent alterations in the human plasma proteome following controlled exposure to diesel exhaust
Environmental Pollution
Juma Orach and Mahadevappa Hemshekhar and Christopher Francis Rider and Victor Spicer and Amy H. Lee and Agnes Che Yan Yuen and Neeloffer Mookherjee and Chris Carlsten
DOI: 10.1016/j.envpol.2023.123087
02/2024Pathogen-associated gene discovery workflows for novel antivirulence therapeutic development
eBioMedicine
Wing Yin Venus Lau and Patrick K. Taylor and Fiona S.L. Brinkman and Amy H.Y. Lee
DOI: 10.1016/j.ebiom.2022.104429
02/2023A systems biology approach to better understand human tick-borne diseases
Trends in Parasitology
Wenna Lee and Amanda D. Barbosa and Peter J. Irwin and Andrew Currie and Tobias R. Kollmann and Miles Beaman and Amy H. Lee and Charlotte L. Oskam
DOI: 10.1016/j.pt.2022.10.006
01/2023Predicting severity in COVID-19 disease using sepsis blood gene expression signatures
Scientific Reports
Baghela, A. and An, A. and Zhang, P. and Acton, E. and Gauthier, J. and Brunet-Ratnasingham, E. and Blimkie, T. and Freue, G.C. and Kaufmann, D. and Lee, A.H.Y. and Levesque, R.C. and Hancock, R.E.W.
DOI: 10.1038/s41598-023-28259-y
2023Predicting sepsis severity at first clinical presentation: The role of endotypes and mechanistic signatures
eBioMedicine
Baghela, A. and Pena, O.M. and Lee, A.H. and Baquir, B. and Falsafi, R. and An, A. and Farmer, S.W. and Hurlburt, A. and Mondragon-Cardona, A. and Rivera, J.D. and Baker, A. and Trahtemberg, U. and Shojaei, M. and Jimenez-Canizales, C.E. and dos Santos, C.C. and Tang, B. and Bouma, H.R. and Cohen Freue, G.V. and Hancock, R.E.W.
DOI: 10.1016/j.ebiom.2021.103776
2022Surviving the host: Microbial metabolic genes required for growth of Pseudomonas aeruginosa in physiologically-relevant conditions
Frontiers in Microbiology
Belanger, C.R. and Dostert, M. and Blimkie, T.M. and Lee, A.H.-Y. and Dhillon, B.K. and Wu, B.C. and Akhoundsadegh, N. and Rahanjam, N. and Castillo-Arnemann, J. and Falsafi, R. and Pletzer, D. and Haney, C.H. and Hancock, R.E.W.
DOI: 10.3389/fmicb.2022.1055512
2022BosR: A novel biofilm-specific regulator in Pseudomonas aeruginosa
Frontiers in Microbiology
Dostert, M. and Belanger, C.R. and Pedraz, L. and Alford, M.A. and Blimkie, T.M. and Falsafi, R.F. and Bains, M. and Dhillon, B.K. and Haney, C.H. and Lee, A.H. and Hancock, R.E.W.
DOI: 10.3389/fmicb.2022.1021021
2022A transcriptomic analysis of the effects of macrophage polarization and endotoxin tolerance on the response to Salmonella
PLoS ONE
Sedivy-Haley, K. and Blimkie, T. and Falsafi, R. and Lee, A.H.-Y. and Hancock, R.E.W.
DOI: 10.1371/journal.pone.0276010
2022Salt and surfactant coated filters with antiviral properties and low pressure drop for prospective SARS-CoV2 applications
Scientific Reports
Ebadi, M. and McCague, C. and Vallee, O. and Taylor, P.K. and Lee, A.H.Y. and Bahrami, M.
DOI: 10.1038/s41598-022-15203-9
2022Gut microbes shape microglia and cognitive function during malnutrition
GLIA
Bauer, K.C. and York, E.M. and Cirstea, M.S. and Radisavljevic, N. and Petersen, C. and Huus, K.E. and Brown, E.M. and Bozorgmehr, T. and Berd{\'u}n, R. and Bernier, L.-P. and Lee, A.H.Y. and Woodward, S.E. and Krekhno, Z. and Han, J. and Hancock, R.E.W. and Ayala, V. and MacVicar, B.A. and Finlay, B.B.
DOI: 10.1002/glia.24139
2022Genomic insights into the diversity, virulence and resistance of Klebsiella pneumoniae extensively drug resistant clinical isolates
Microbial Genomics
Amy H. Y Lee and William F. Porto and Célio de Faria Jr and Simoni C. Dias and Sérgio A. Alencar and Derek J. Pickard and Robert E. W. Hancock and Octavio L. Franco
DOI: 10.1099/mgen.0.000613
08/2021Human-induced pluripotent stem cell-derived macrophages for studying infection biology and immunology
Current Progress in iPSC-derived Cell Types
Baquir, B. and An, A.Y. and Lee, A.H.Y. and Hancock, R.E.W.
DOI: 10.1016/B978-0-12-823884-4.00002-X
2021Machine Learning-Based Single Cell and Integrative Analysis Reveals That Baseline mDC Predisposition Correlates With Hepatitis B Vaccine Antibody Response
Frontiers in Immunology
Aevermann, B.D. and Shannon, C.P. and Novotny, M. and Ben-Othman, R. and Cai, B. and Zhang, Y. and Ye, J.C. and Kobor, M.S. and Gladish, N. and Lee, A.H.-Y. and Blimkie, T.M. and Hancock, R.E. and Llibre, A. and Duffy, D. and Koff, W.C. and Sadarangani, M. and Tebbutt, S.J. and Kollmann, T.R. and Scheuermann, R.H.
DOI: 10.3389/fimmu.2021.690470
2021Genomic insights into the diversity, virulence and resistance of klebsiella pneumoniae extensively drug resistant clinical isolates
Microbial Genomics
Lee, A.H.Y. and Porto, W.F. and de Faria, C. and Dias, S.C. and Alencar, S.A. and Pickard, D.J. and Hancock, R.E.W. and Franco, O.L.
DOI: 10.1099/MGEN.0.000613
2021Machine learning-based single cell and integrative analysis reveals that baseline mDC predisposition predicts protective Hepatitis B vaccine response
medRxiv
Aevermann, B. and Shannon, C.P. and Novotny, M. and Ben-Othman, R. and Cai, B. and Zhang, Y. and Ye, J.C. and Kobor, M.S. and Gladish, N. and Lee, A. and Blimke, T.M. and Hancock, R.E. and Llibre, A. and Duffy, D. and Koff, W.C. and Sadarangani, M. and Tebbutt, S.J. and Kollmann, T.R. and Scheuermann, R.H.
DOI: 10.1101/2021.02.22.21251864
2021Peptide 1018 inhibits swarming and influences Anr-regulated gene expression downstream of the stringent stress response in Pseudomonas aeruginosa
PLoS ONE
Wilkinson, L.V. and Alford, M.A. and Coleman, S.R. and Wu, B.C. and Lee, A.H.Y. and Blimkie, T.M. and Bains, M. and Falsafi, R. and Pletzer, D. and Hancock, R.E.W.
DOI: 10.1371/journal.pone.0250977
2021Ivacaftor or lumacaftor/ivacaftor treatment does not alter the core CF airway epithelial gene response to rhinovirus
Journal of Cystic Fibrosis
De Jong, E. and Garratt, L.W. and Looi, K. and Lee, A.H.Y. and Ling, K.-M. and Smith, M.L. and Falsafi, R. and Sutanto, E.N. and Hillas, J. and Iosifidis, T. and Martinovich, K.M. and Shaw, N.C. and Montgomery, S.T. and Kicic-Starcevich, E. and Lannigan, F.J. and Vijayasekaran, S. and Hancock, R.E.W. and Stick, S.M. and Kicic, A. and AREST, C.F.
DOI: 10.1016/j.jcf.2020.07.004
2021RNase III and RNase E Influence Posttranscriptional Regulatory Networks Involved in Virulence Factor Production, Metabolism, and Regulatory RNA Processing in Bordetella pertussis
mSphere
Ifill, G. and Blimkie, T. and Lee, A.H.-Y. and Mackie, G.A. and Chen, Q. and Stibitz, S. and Hancock, R.E.W. and Fernandez, R.C.
DOI: 10.1128/mSphere.00650-21
2021Different Disease Endotypes in Phenotypically Similar Vasculitides Affecting Small-to-Medium Sized Blood Vessels
Frontiers in Immunology
Gill, E.E. and Smith, M.L. and Gibson, K.M. and Morishita, K.A. and Lee, A.H.Y. and Falsafi, R. and Graham, J. and Foell, D. and Benseler, S.M. and Ross, C.J. and Luqmani, R.A. and Cabral, D.A. and Hancock, R.E.W. and Brown, K.L.
DOI: 10.3389/fimmu.2021.638571
2021Identification of novel targets of azithromycin activity against Pseudomonas aeruginosa grown in physiologically relevant media
Proceedings of the National Academy of Sciences
Corrie R. Belanger and Amy Huei-Yi Lee and Daniel Pletzer and Bhavjinder Kaur Dhillon and Reza Falsafi and Robert E. W. Hancock
DOI: 10.1073/pnas.2007626117
12/2020Whole blood genome-wide transcriptome profiling and metagenomics next-generation sequencing in young infants with suspected sepsis in a low-and middle-income country: A study protocol
Gates Open Research
Constantin R. Popescu and Bentry Tembo and Rhoda Chifisi and Miranda M.M. Cavanagh and Amy Huei-Yi Lee and Blessings Chiluzi and Emily J. Ciccone and Gerald Tegha and Esther Alonso-Prieto and Jennifer Claydon and Dustin Dunsmuir and Mike Irvine and Guy Dumont and J. Mark Ansermino and Matthew O. Wiens and Jonathan J. Juliano and Niranjan Kissoon and Tisungane Mvalo and Norman Lufesi and Msandeni Chiume-Kayuni and Pascal M. Lavoie
DOI: 10.12688/gatesopenres.13172.2
11/2020MetaBridge: An Integrative Multi-Omics Tool for Metabolite-Enzyme Mapping.
Current protocols in bioinformatics
DOI: 10.1002/cpbi.98
PubMed: 32199034
06/2020Aberrant cell migration contributes to defective airway epithelial repair in childhood wheeze
JCI Insight
Thomas Iosifidis and Erika N. Sutanto and Alysia G. Buckley and Laura Coleman and Erin E. Gill and Amy H. Lee and Kak-Ming Ling and Jessica Hillas and Kevin Looi and Luke W. Garratt and Kelly M. Martinovich and Nicole C. Shaw and Samuel T. Montgomery and Elizabeth Kicic-Starcevich and Yuliya V. Karpievitch and Peter Le Souëf and Ingrid A. Laing and Shyan Vijayasekaran and Francis J. Lannigan and Paul J. Rigby and Robert E.W. Hancock and Darryl A. Knight and Stephen M. Stick and Anthony Kicic.
DOI: 10.1172/jci.insight.133125
04/2020Whole blood transcriptional responses of very preterm infants during late-onset sepsis
PLoS ONE
Ng, S. and Strunk, T. and Lee, A.H. and Gill, E.E. and Falsafi, R. and Woodman, T. and Hibbert, J. and Hancock, R.E.W. and Currie, A.
DOI: 10.1371/journal.pone.0233841
2020BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis
Science translational medicine
Brook, Byron and Harbeson, Danny J and Shannon, Casey P and Cai, Bing and He, Daniel and Ben-Othman, Rym and Francis, Freddy and Huang, Joe and Varankovich, Natallia and Liu, Aaron and Bao, Winnie and Bjerregaard-Andersen, Morten and Schaltz-Buchholzer, Frederik and Sanca, Lilica and Golding, Christian N and Larsen, Kristina Lindberg and Levy, Ofer and Kampmann, Beate and {EPIC Consortium} and Tan, Rusung and Charles, Adrian and Wynn, James L and Shann, Frank and Aaby, Peter and Benn, Christine S and Tebbutt, Scott J and Kollmann, Tobias R and Amenyogbe, Nelly
DOI: 10.1126/scitranslmed.aax4517
2020Characterization of immune responses and the lung transcriptome in a murine model of IL-33 challenge
Biochimica et biophysica acta. Molecular basis of disease
Piyadasa, Hadeesha and Lloyd, Dylan and Lee, Amy H Y and Altieri, Anthony and Hemshekhar, Mahadevappa and Osawa, Natasha and Basu, Sujata and Blimkie, Travis and Falsafi, Reza and Halayko, Andrew J and Hancock, Robert E W and Mookherjee, Neeloffer
DOI: 10.1016/j.bbadis.2020.165950
2020Rhinovirus Infection Drives Complex Host Airway Molecular Responses in Children With Cystic Fibrosis
Frontiers in immunology
Ling, Kak-Ming and Garratt, Luke W and Gill, Erin E and Lee, Amy H Y and Agudelo-Romero, Patricia and Sutanto, Erika N and Iosifidis, Thomas and Rosenow, Tim and Turvey, Stuart E and Lassmann, Timo and Hancock, Robert E W and Kicic, Anthony and Stick, Stephen M
DOI: 10.3389/fimmu.2020.01327
2020Utilizing Organoid and Air-Liquid Interface Models as a Screening Method in the Development of New Host Defense Peptides
Frontiers in cellular and infection microbiology
Choi, Ka-Yee Grace and Wu, Bing Catherine and Lee, Amy Huei-Yi and Baquir, Beverlie and Hancock, Robert E W
DOI: 10.3389/fcimb.2020.00228
2020Regional Dichotomy in Enteric Mucosal Immune Responses to a Persistent <i>Mycobacterium avium</i> ssp. <i>paratuberculosis</i> Infection
Frontiers in immunology
Facciuolo, Antonio and Lee, Amy H and Gonzalez Cano, Patricia and Townsend, Hugh G G and Falsafi, Reza and Gerdts, Volker and Potter, Andrew and Napper, Scott and Hancock, REW and Mutharia, Lucy M and Griebel, Philip J
DOI: 10.3389/fimmu.2020.01020
2020The Stringent Stress Response Controls Proteases and Global Regulators under Optimal Growth Conditions in Pseudomonas aeruginosa
mSystems
Pletzer, Daniel and Blimkie, Travis M and Wolfmeier, Heidi and Li, Yicong and Baghela, Arjun and Lee, Amy H Y and Falsafi, Reza and Hancock, Robert E W
DOI: 10.1128/mSystems.00495-20
2020Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults
Frontiers in immunology
Ben-Othman, Rym and Cai, Bing and Liu, Aaron C and Varankovich, Natallia and He, Daniel and Blimkie, Travis M and Lee, Amy H and Gill, Erin E and Novotny, Mark and Aevermann, Brian and Drissler, Sibyl and Shannon, Casey P and McCann, Sarah and Marty, Kim and Bjornson, Gordean and Edgar, Rachel D and Lin, David Tse Shen and Gladish, Nicole and Maclsaac, Julia and Amenyogbe, Nelly and Chan, Queenie and Llibre, Alba and Collin, Joyce and Landais, Elise and Le, Khoa and Reiss, Samantha M and Koff, Wayne C and Havenar-Daughton, Colin and Heran, Manraj and Sangha, Bippan and Walt, David and Krajden, Mel and Crotty, Shane and Sok, Devin and Briney, Bryan and Burton, Dennis R and Duffy, Darragh and Foster, Leonard J and Mohn, William W and Kobor, Michael S and Tebbutt, Scott J and Brinkman, Ryan R and Scheuermann, Richard H and Hancock, Robert E W and Kollmann, Tobias R and Sadarangani, Manish
DOI: 10.3389/fimmu.2020.580373
2020Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life
Frontiers in immunology
Bennike, Tue Bjerg and Fatou, Benoit and Angelidou, Asimenia and Diray-Arce, Joann and Falsafi, Reza and Ford, Rebecca and Gill, Erin E and van Haren, Simon D and Idoko, Olubukola T and Lee, Amy H and Ben-Othman, Rym and Pomat, William S and Shannon, Casey P and Smolen, Kinga K and Tebbutt, Scott J and Ozonoff, Al and Richmond, Peter C and van den Biggelaar, Anita H J and Hancock, Robert E W and Kampmann, Beate and Kollmann, Tobias R and Levy, Ofer and Steen, Hanno
DOI: 10.3389/fimmu.2020.578505
2020Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort
Frontiers in immunology
Shannon, Casey P and Blimkie, Travis M and Ben-Othman, Rym and Gladish, Nicole and Amenyogbe, Nelly and Drissler, Sibyl and Edgar, Rachel D and Chan, Queenie and Krajden, Mel and Foster, Leonard J and Kobor, Michael S and Mohn, William W and Brinkman, Ryan R and Le Cao, Kim-Anh and Scheuermann, Richard H and Tebbutt, Scott J and Hancock, Robert E W and Koff, Wayne C and Kollmann, Tobias R and Sadarangani, Manish and Lee, Amy Huei-Yi
DOI: 10.3389/fimmu.2020.578801
2020A Bovine Enteric <i>Mycobacterium</i> Infection Model to Analyze Parenteral Vaccine-Induced Mucosal Immunity and Accelerate Vaccine Discovery
Frontiers in immunology
Facciuolo, Antonio and Lee, Amy H and Trimble, Michael J and Rawlyk, Neil and Townsend, Hugh G G and Bains, Manjeet and Arsic, Natasa and Mutharia, Lucy M and Potter, Andrew and Gerdts, Volker and Napper, Scott and Hancock, Robert E W and Griebel, Philip J
DOI: 10.3389/fimmu.2020.586659
2020The stringent stress response controls proteases and global regulators under optimal growth conditions in Pseudomonas aeruginosa
bioRxiv
Pletzer, D. and Blimkie, T.M. and Wolfmeier, H. and Li, Y. and Baghela, A. and Lee, A.H.Y. and Falsafi, R. and Hancock, R.E.W.
DOI: 10.1101/2020.05.23.112573
2020Aberrant cell migration contributes to defective airway epithelial repair in childhood wheeze
JCI Insight
Iosifidis, T. and Sutanto, E.N. and Buckley, A.G. and Coleman, L. and Gill, E.E. and Lee, A.H. and Ling, K.-M. and Hillas, J. and Looi, K. and Garratt, L.W. and Martinovich, K.M. and Shaw, N.C. and Montgomery, S.T. and Kicic-Starcevich, E. and Karpievitch, Y.V. and Le Sou{\"e}f, P. and Laing, I.A. and Vijayasekaran, S. and Lannigan, F.J. and Rigby, P.J. and Hancock, R.E.W. and Knight, D.A. and Stick, S.M. and Kicic, A.
DOI: 10.1172/JCI.INSIGHT.133125
2020The importance of reporting house dust mite endotoxin abundance: Impact on the lung transcriptome
American Journal of Physiology - Lung Cellular and Molecular Physiology
Pascoe, C.D. and Jha, A. and Basu, S. and Mahood, T. and Lee, A. and Hinshaw, S. and Falsafi, R. and Hancock, R.E.W. and Mookherjee, N. and Halayko, A.J.
DOI: 10.1152/ajplung.00103.2020
2020Systems Biology Approaches to Understanding the Human Immune System
Frontiers in Immunology
Dhillon, B.K. and Smith, M. and Baghela, A. and Lee, A.H.Y. and Hancock, R.E.W.
DOI: 10.3389/fimmu.2020.01683
2020BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis
Science Translational Medicine
Brook, B. and Harbeson, D.J. and Shannon, C.P. and Cai, B. and He, D. and Ben-Othman, R. and Francis, F. and Huang, J. and Varankovich, N. and Liu, A. and Bao, W. and Bjerregaard-Andersen, M. and Schaltz-Buchholzer, F. and Sanca, L. and Golding, C.N. and Larsen, K.L. and Levy, O. and Kampmann, B. and Tan, R. and Charles, A. and Wynn, J.L. and Shann, F. and Aaby, P. and Benn, C.S. and Tebbutt, S.J. and Kollmann, T.R. and Amenyogbe, N. and Lee, A.H. and Bennike, T.B. and Diray-Arce, J. and Idoko, O. and Pomat, W.S. and van Haren, S. and Cox, M. and Darboe, A. and Falsafi, R. and Hinshaw, S.H. and Ndure, J. and Njie-Jobe, J. and Pettengill, M.A. and Marchant, A. and Richmond, P.C. and Ford, R. and Saleu, G. and Masiria, G. and Matlam, J.P. and Kirarock, W. and Roberts, E. and Malek, M. and Sanchez-Schmitz, G. and Singh, A. and Angelidou, A. and Smolen, K.K. and Brinkman, R.R. and Ozonoff, A. and Hancock, R.E.W. and van den Biggelaar, A.H.J. and Steen, H. and Vo, D. and Kraft, K. and McEnaney, K. and Vignolo, S.
DOI: 10.1126/SCITRANSLMED.AAX4517
2020A Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Salmonella Infection.
mBio
DOI: 10.1128/mBio.02169-19
PubMed: 31594818
10/2019Perturbations of the ZED1 pseudokinase activate plant immunity
PLOS Pathogens
D. Patrick Bastedo and Madiha Khan and Alexandre Martel and Derek Seto and Inga Kireeva and Jianfeng Zhang and Wardah Masud and David Millar and Jee Yeon Lee and Amy Huei-Yi Lee and Yunchen Gong and André Santos-Severino and David S. Guttman and Darrell Desveaux
DOI: 10.1371/journal.ppat.1007900
07/2019Dynamic molecular changes during the first week of human life follow a robust developmental trajectory
Nature Communications
Amy H. Lee and Casey P. Shannon and Nelly Amenyogbe and Tue B. Bennike and Joann Diray-Arce and Olubukola T. Idoko and Erin E. Gill and Rym Ben-Othman and William S. Pomat and Simon D. van Haren and Kim-Anh Lê Cao and Momoudou Cox and Alansana Darboe and Reza Falsafi and Davide Ferrari and Daniel J. Harbeson and Daniel He and Cai Bing and Samuel J. Hinshaw and Jorjoh Ndure and Jainaba Njie-Jobe and Matthew A. Pettengill and Peter C. Richmond and Rebecca Ford and Gerard Saleu and Geraldine Masiria and John Paul Matlam and Wendy Kirarock and Elishia Roberts and Mehrnoush Malek and Guzmán Sanchez-Schmitz and Amrit Singh and Asimenia Angelidou and Kinga K. Smolen and Diana Vo and Ken Kraft and Kerry McEnaney and Sofia Vignolo and Arnaud Marchant and Ryan R. Brinkman and Al Ozonoff and Robert E. W. Hancock and Anita H. J. van den Biggelaar and Hanno Steen and Scott J. Tebbutt and Beate Kampmann and Ofer Levy and Tobias R. Kollmann
DOI: 10.1038/s41467-019-08794-x
03/2019Identifying Pseudomonas syringae Type III Secreted Effector Function via a Yeast Genomic Screen.
G3 (Bethesda, Md.)
DOI: 10.1534/g3.118.200877
PubMed: 30573466
02/2019Characterization of Host Responses during Pseudomonas aeruginosa Acute Infection in the Lungs and Blood and after Treatment with the Synthetic Immunomodulatory Peptide IDR-1002
Infection and Immunity
Kelli Wuerth and Amy H. Y. Lee and Reza Falsafi and Erin E. Gill and Robert E. W. Hancock
DOI: 10.1128/IAI.00661-18
01/2019A Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Salmonella Infection
mBio
Yeung, Amy T Y and Choi, Yoon Ha and Lee, Amy H Y and Hale, Christine and Ponstingl, Hannes and Pickard, Derek and Goulding, David and Thomas, Mark and Gill, Erin and Kim, Jong Kyoung and Bradley, Allan and Hancock, Robert E W and Dougan, Gordon
DOI: 10.1128/mbio.02169-19
2019Characterization of Host Responses during Pseudomonas aeruginosa Acute Infection in the Lungs and Blood and after Treatment with the Synthetic Immunomodulatory Peptide IDR-1002
Infection and immunity
Wuerth, Kelli and Lee, Amy H Y and Falsafi, Reza and Gill, Erin E and Hancock, Robert E W
DOI: 10.1128/iai.00661-18
2019Perturbations of the ZED1 Pseudokinase Activate Plant Immunity
bioRxiv
Bastedo, D.P. and Khan, M. and Martel, A. and Seto, D. and Kireeva, I. and Zhang, J. and Masud, W. and Millar, D. and Lee, J.Y. and Lee, A.H.-Y. and Gong, Y. and Santos-Severino, A. and Guttman, D.S. and Desveaux, D.
DOI: 10.1101/531665
2019Yeast Genomic Screens Identify Kinesins as Potential Targets of the Pseudomonas syringae Type III Effector, HopZ1a
Lee AH and Bastedo DP and Lo T and Middleton MA and Youn J and Kireeva I and Lee JY and Sharifpoor S and Baryshnikova A and Zhang J and Wang PW and Peisajovich SG and Costanzo M and Guttman DS
DOI: 10.1101/365692
07/2018Retinoic acid elicits a coordinated expression of gut homing markers on T lymphocytes of Zambian men receiving oral Vivotif, but not Rotarix, Dukoral or OPVERO vaccines.
Vaccine
Mwanza-Lisulo M and Chomba MS and Chama M and Besa EC and Funjika E and Zyambo K and Banda R and Imikendu M and Sianongo S and Hancock REW and Lee A and Chilengi R and Stagg AJ and Kelly PM
DOI: 10.1016/j.vaccine.2018.04.083
PubMed: 29801999
05/2018MetaBridge: Enabling Network-Based Integrative Analysis via Direct Protein Interactors of Metabolites.
Bioinformatics (Oxford, England)
Hinshaw SJ and Lee AHY and Gill EE and Hancock REW
DOI: 10.1093/bioinformatics/bty331
PubMed: 29688253
04/2018Mechanisms of the Innate Defense Regulator Peptide-1002 Anti-Inflammatory Activity in a Sterile Inflammation Mouse Model.
Journal of immunology (Baltimore, Md. : 1950)
DOI: 10.4049/jimmunol.1700985
PubMed: 28993516
10/2017Comparative functional genomic screens of three yeast deletion collections reveal unexpected effects of genotype in response to diverse stress
Open Biology
Erica Acton and Amy Huei-Yi Lee and Pei Jun Zhao and Stephane Flibotte and Mauricio Neira and Sunita Sinha and Jennifer Chiang and Patrick Flaherty and Corey Nislow and Guri Giaever
DOI: 10.1098/rsob.160330
06/2017Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs
Genome Research
Amy Huei-Yi Lee and Stephane Flibotte and Sunita Sinha and Adrianna Paiero and Rachel L. Ehrlich and Sergey Balashov and Garth D. Ehrlich and James E.A. Zlosnik and Joshua Chang Mell and Corey Nislow
DOI: 10.1101/gr.213363.116
04/2017Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis.
Nature communications
DOI: 10.1038/ncomms15013
PubMed: 28440293
04/2017hackseq: Catalyzing collaboration between biological and computational scientists via hackathon.
F1000Research
hackseq Organizing Committee 2016
DOI: 10.12688/f1000research.10964.2
PubMed: 28417000
02/2017Functional profiling using the Saccharomyces genome deletion project collections
Cold Spring Harbor Protocols
Nislow, C. and Wong, L.H. and Lee, A.H.-Y. and Giaever, G.
DOI: 10.1101/pdb.prot088039
2016Functional Genomics Using the Saccharomyces cerevisiae Yeast Deletion Collections.
Nislow C and Wong LH and Lee AH and Giaever G
DOI: 10.1101/pdb.top080945
PubMed: 27587784
2016The Arabidopsis ZED1 pseudokinase is required for ZAR1-mediated immunity induced by the Pseudomonas syringae type III effector HopZ1a.
Lewis JD and Lee AH and Hassan JA and Wan J and Hurley B and Jhingree JR and Wang PW and Lo T and Youn JY and Guttman DS and Desveaux D
DOI: 10.1073/pnas.1315520110
PubMed: 24170858
11/2013Phytopathogen type III effectors as probes of biological systems.
Lee AH and Middleton MA and Guttman DS and Desveaux D
DOI: 10.1111/1751-7915.12042
PubMed: 23433088
05/2013Effector wisdom.
Lee AH and Petre B and Joly DL
DOI: 10.1111/nph.12058
PubMed: 23253332
01/2013A bacterial acetyltransferase destroys plant microtubule networks and blocks secretion.
Lee AH and Hurley B and Felsensteiner C and Yea C and Ckurshumova W and Bartetzko V and Wang PW and Quach V and Lewis JD and Liu YC and Börnke F and Angers S and Wilde A and Guttman DS and Desveaux D
DOI: 10.1371/journal.ppat.1002523
PubMed: 22319451
02/2012The YopJ superfamily in plant-associated bacteria.
Lewis JD and Lee A and Ma W and Zhou H and Guttman DS and Desveaux D
DOI: 10.1111/j.1364-3703.2011.00719.x
PubMed: 21726386
12/2011ClpX inhibits FtsZ assembly in a manner that does not require its ATP hydrolysis-dependent chaperone activity.
Haeusser DP and Lee AH and Weart RB and Levin PA
DOI: 10.1128/jb.01606-07
PubMed: 19136590
03/2009ClpX Inhibits FtsZ Assembly in a manner that does not require its ATP hydrolysis-dependent chaperone activity
Journal of Bacteriology
Haeusser, D.P. and Lee, A.H. and Weart, R.B. and Levin, P.A.
DOI: 10.1128/JB.01606-07
2009A metabolic sensor governing cell size in bacteria.
Weart RB and Lee AH and Chien AC and Haeusser DP and Hill NS and Levin PA
DOI: 10.1016/j.cell.2007.05.043
PubMed: 17662947
07/2007Urea sensitization caused by separation of Helicobacter pylori RNA polymerase beta and beta' subunits.
Dailidiene D and Tan S and Ogura K and Zhang M and Lee AH and Severinov K and Berg DE
DOI: 10.1111/j.1523-5378.2007.00479.x
PubMed: 17309746
04/2007Genes controlling circadian rhythm are widely distributed in cyanobacteria
FEMS Microbiology Letters
Lorne, J. and Scheffer, J. and Lee, A. and Painter, M. and Miao, V.P.W.
DOI: 10.1016/S0378-1097(00)00237-8
2000Cultural and molecular characterization of photobionts of Peltigera membranacea
Lichenologist
Miao, V.P.W. and Rabenau, A. and Lee, A.
DOI: 10.1006/lich.1997.0114
1997 - Research
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Neonatal Immune Development
Infection is the most common cause of death in newborns, causing at least 2.6 million infant deaths per year. Even though the majority of newborn deaths occur in resource-poor countries, neonatal morbidity and mortality is also a significant problem in resource-rich countries. For instance, in Canada, 75% of infant deaths under 1 year occur during this critical newborn stage. Our group is working to understand why newborns are so prone to infections and the pathogens at play, so that we can develop effective interventions and preventions against diseases. Our previous work demonstrates that newborn immunity, rather than being simply immature as previously thought, actually follow an exquisite, consistent and detailed developmental trajectory that most likely reflects adaptation to the demands of early life. We are currently working on using multi-omics data (transcriptomics, epigenomics, proteomics, metabolomics and microbiome) to extend and build an integrated molecular profile of a neonatal immune system during the first week of life.Neonatal Sepsis
Each second, five newborn babies die from suspected life-threatening infections somewhere in the world. Newborns and young babies are more vulnerable to severe infections than all other age groups. However, there is no fast and easy way to tell which microbes are involved, resulting in babies being both over- and under-treated with antibiotics that may or may not help them, contributing to antibiotic resistance and wasting limited resources. In a recently funded CIHR study, we will use whole-blood transcriptomics and advanced bioinformatic analyses including machine learning and clustering to determine specific transcriptomic signatures that identify babies who are infected by bacteria and require urgent antibiotics. Our ultimate goal is to develop a rapid, easy-to-use tool that can be used around the world to guide the diagnosis and treatment of babies with systemic infections such as sepsis.Pathogen Genomics and Hypothetical Proteins
Since the completion of the first bacterial genome in 1995, we have seen massive technological advances and cost reduction in genome sequencing over the last 25 years. This has resulted in a large number of available bacterial genomes (263,273 bacterial genomes available on NCBI as of 2020/09/19). However, our ability to sequence a bacterial genome is much faster than we can functionally characterize the genome. For instance, even in perhaps the best-studied model organism, Escherichia coli K-12 MG1655, ~35% of its genome has poor functional annotations. These poorly annotated genes, typically named as ‘hypothetical proteins’, are propagated across genome databases as standard bioinformatic pipelines cannot predict their functions. Given that many of these hypothetical proteins play a critical role in host-pathogen interactions, we have developed a prioritization strategy to identify candidate genes for functional characterization. Specifically, we propose to (1) perform bioinformatic data analyses to identify conserved hypothetical proteins that are associated with resistance or virulence phenotypes, (2) validate these phenotypes experimentally in the lab using deletion mutants, followed by (3) protein expression, purification and biochemical characterization of interesting candidates. Current pathogens of interest include: Pseudomonas aeruginosa and Klebsiella pneumoniae.GrantsCIHR Project Grant: Molecular epidemiology of neonatal sepsis in low- and middle- income countries
NSERC Discovery Grant: Dissecting the virulence and antibiotic resistance potential of Klebsiella pneumoniae in disparate environments
CFI-JELF: Centre for the systems biology of host-pathogen interactions
NHMRC-Ideas: Innate defense regulator peptide for protecting the preterm infant from postnatal sepsis
Honours & AwardsBanting Research Foundation – Discovery Award 2022
Mozilla Foundation – Network50
New research tools can shed light on an understudied organ essential to our lives
The placenta is essential to a healthy start in life. Despite its importance, little is known about it, including why it might not develop properly, which can lead to long-term health issues. Dr. Alexander Beristain’s lab is investigating two state-of-the-art stem cell-based tools that model a human placenta to find answers that can positively impact children’s health.
