Overview

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

Predicting 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
2022

Gut 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
2022

Human-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
2021

Machine 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
2021

Genomic 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
2021

Machine 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
2021

Peptide 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
2021

Ivacaftor 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
2021

RNase 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
2021

Different 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
2021

Identification 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
12/2020

Whole 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
11/2020

MetaBridge: An Integrative Multi-Omics Tool for Metabolite-Enzyme Mapping.
Current protocols in bioinformatics
DOI: 10.1002/cpbi.98
PubMed: 32199034
06/2020

Whole 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
2020

BCG 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
2020

Characterization 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
2020

Rhinovirus 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
2020

Regional 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
2020

The 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
2020

Systems 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
2020

Utilizing 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
2020

Preparing 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
2020

Multi-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
2020

A 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
2020

The 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
2020

Aberrant 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
2020

The 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
2020

Systems 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
2020

BCG 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
2020

A Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Salmonella Infection.
mBio
DOI: 10.1128/mBio.02169-19
PubMed: 31594818
10/2019

Perturbations of the ZED1 pseudokinase activate plant immunity
PLOS Pathogens
DOI: 10.1371/journal.ppat.1007900
07/2019

Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.
Nature communications
DOI: 10.1038/s41467-019-08794-x
PubMed: 30862783
03/2019

Identifying Pseudomonas syringae Type III Secreted Effector Function via a Yeast Genomic Screen.
G3 (Bethesda, Md.)
DOI: 10.1534/g3.118.200877
PubMed: 30573466
02/2019

A 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
2019

Characterization 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
2019

Perturbations 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
2019

Characterization 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, K. and Lee, A.H.Y. and Falsafi, R. and Gill, E.E. and Hancocka, R.E.W.
DOI: 10.1128/IAI.00661-18
2019

Yeast 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
07/2018

Retinoic 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
05/2018

MetaBridge: 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
04/2018

Mechanisms 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
10/2017

Comparative functional genomic screens of three yeast deletion collections reveal unexpected effects of genotype in response to diverse stress.
Open biology
DOI: 10.1098/rsob.160330
PubMed: 28592509
06/2017

Phenotypic diversity and genotypic flexibility of Burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs.
Genome research
DOI: 10.1101/gr.213363.116
PubMed: 28325850
04/2017

Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis.
Nature communications
DOI: 10.1038/ncomms15013
PubMed: 28440293
04/2017

hackseq: Catalyzing collaboration between biological and computational scientists via hackathon.
F1000Research
hackseq Organizing Committee 2016
DOI: 10.12688/f1000research.10964.2
PubMed: 28417000
02/2017

Functional 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
2016

Functional 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
2016

The 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
11/2013

Phytopathogen 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
05/2013

Effector wisdom.
Lee AH and Petre B and Joly DL
DOI: 10.1111/nph.12058
PubMed: 23253332
01/2013

A 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
02/2012

The 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
12/2011

ClpX 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
03/2009

ClpX 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
2009

A 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
07/2007

Urea 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
04/2007

Research

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.

Grants

CIHR 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 & Awards

Banting Research Foundation – Discovery Award 2022

Mozilla Foundation – Network50