Microbiology and Immunology Research Profile

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Research in the Department of Microbiology and Immunology revolves around two major fields of scientific endeavor, these fields involve studies on bacteria, virus, parasites, cancer and immune cells with an emphasis on molecular biology, biochemistry, and pathogenesis.

 

i) The molecular and cellular biology of microorganisms:
       
ii) The molecular and cellular biology of the immune system.

 

 


Eric Arts
   

Stephen Barr
Barr

 

E3 ligases are proteins that can alter the function of other proteins by tagging them with small proteins. We study two newly identified E3 ligases called TRIM22 and HERC5. TRIM22 and HERC5 are produced in high abundance during the interferon response and are capable of potently inhibiting various steps of the HIV life cycle. Our research will provide a deeper understanding of the human innate immune response towards HIV, which will in turn lead to novel approaches for antiviral therapeutics and personalized medicine for HIV-infected individuals. A second focus of the Barr laboratory is on better understanding one of the most fundamental cellular processes in biology, the development of sperm. Our research will provide insight about male infertility and the molecular mechanisms underlying proper development of sperm.

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  • HIV
  • host-pathogen interactions
  • molecular virology
  • sperm development
  • gene therapy

The major research interest of Dr. Barra's laboratory is the role of autoantibodies in Rheumatoid Arthritis (RA) and its associated complications, in particular vascular disease. We aim to investigate the immune mechanisms contributing to the increased rate of cardiovascular disease in patients with RA. The research is translational involving mouse models of RA and atherosclerosis, biomaker studies as well as epidemiologic studies with participation in various cohort studies. We are currently accepting graduate students.

 

We conduct research on the role of microbes in various human conditions. Our primary focus is the microbiome which influences urological conditions. The microbiome at distal sites is now the most intriguing, as it is thought to have an influence on systemic health well beyond the primary mucosal sites they occupy.

 


Our laboratory is interested in rheumatic autoimmune diseases. Specifically, our current research focuses on the pathogenesis of Rheumatoid Arthritis (RA). We are studying the role of MHC class II molecules as well as auto-antigens (e.g.citrullinated proteins) in the development of this disease. Our research is performed using human RA clinical specimens and humanized (MHC class II) tg mice as animal model for RA.


We aim at identifying the role played by surface carbohydrates in the virulence of two genetically related gastro-intestinal human pathogens that cause very different and specific pathologies: Campylobacter jejuni and Helicobacter pylori. One hallmark of these two bacteria is to produce glycosylated proteins. We have made great progress in the elucidation of the N- and/or O-linked protein glycosylation pathways in these bacteria, and in the determination of their role in pathogenesis. We are now investigating the role of glycosylation on the function of select glycoproteins. Other significant research topics in the laboratory also include investigating the biosynthesis and role of C. jejuni capsular components, and investigating the use of lactobacilli as probiotics to treat/prevent H. pylori infections


Dr. Dekaban's research is focused on two areas: (1) Vaccine research is focused on developing novel vaccine vectors that carry immunomodulatory genes or utilize dendritic cell-based vaccines that result in prime-boost vaccine regimens that yield strong cell-mediated immune responses. This research is aimed at developing improved vaccines for HIV/AIDS and cancer. (2) Develop novel acute anti-inflammatory treatments for spinal cord injury based on understanding the mechanisms at the cellular and molecular level that control inflammation in the injured spinal cord.


Transcription factor proteins positively or negatively regulate gene expression in the nucleus of cells. Our laboratory studies transcription factors that regulate gene expression in the immune system. There are currently two areas of investigation in our laboratory. First, we are investigating how E26-transformation specific (Ets) family proteins regulate genes involved in B cell receptor (BCR) expression and signal transduction. Misinterpreted BCR signaling can lead to a failure of central tolerance and cause autoimmune disease. Second, we are investigating how the Ets protein PU.1 regulates gene expression in myeloid cells. Reduced PU.1 levels can cause Acute myeloid leukemia (AML). We have generated mouse models for studying the consequences of reduced PU.1 levels in vivo and are working to identify key target genes responsible for causing disease.


In addition to the virally encoded enzymes required for replication and assembly, HIV-1 expresses a collection of accessory proteins that lack intrinsic enzymatic activity but which are essential for disease pathogenesis by dysregulating host cell enzymatic activities to counterattack the host antiviral response and promote virus replication. In particular, the HIV-1 accessory protein Nef is required for the efficient onset of AIDS following HIV-1 infection. Nef modifies the host cellular environment in many ways, including alteration of T cell activation, modulation of apoptotic and autophagic pathways, as well as disrupts the intracellular trafficking of MHC-I and other cell surface molecules of helper T cells and macrophages. Our laboratory is interested in the various interactions between Nef and host cellular partners and how these interactions modulate membrane trafficking pathways to evade the immune system

  • HIV-1
  • Nef
  • membrane trafficking
  • immune evasion
  • protein structure
  • protein-protein interactions

Lakshman Gunaratnam

The laboratory of Dr. Gunaratnam is studying the potential role of kidney injury molecule-1, a protein that is expressed by the kidney tubular epithelial cells soon after injury, in regulating the innate immune response and in preventing rejection. By uncovering the detailed mechanisms that enable kidney epithelial cells to control early inflammation following transplant surgery, we hope to identify specific therapeutic strategies to increase the lifespan of transplanted kidneys.

  • transplantation
  • autoimmunity
  • CHI

 


Mansour Haeryfar
Haeryfar

(1) Cytotoxic T lymphocyte (CTL) development in response to viral pathogens and tumor antigens; (2) Immunodominance hierarchies of CD8+ T cells; (3) Direct priming and cross-priming in CD8+ T cell responses; (4) Immunobiology of dendritic cells and other antigen-presenting cells in immunity and tolerance 5) Modulation of innate and adaptive immune responses by regulatory/suppressor lymphocytes such as naturally occurring CD4+CD25+ regulatory T (nTreg ) cells, natural killer T (NKT) cells, etc. (6) Non-classical pathways of T cell activation and costimulation.

 


As an established major source of life threatening hospital infections, the Staphylococcus aureus superbug is also causing serious infections in the community. The primary focus of my laboratory is on the study of S. aureus proteins that are essential for the acquisition of iron, a critical nutrient. Bacterial proteins involved in the acquisition of host iron sources are considered virulence factors, and studying how these proteins operate will allow us to design rationale approaches to inhibit their function and thus attenuate S. aureus infections.


heit

Phagocytes (macrophage and dendritic cells) play a central role in our bodies immune defences.  The Heit lab is interested in the mechanisms by which these cells take up pathogens (phagocytosis) and dead/dying cells (efferocytosis), and how these very different targets are processed by phagocytes.  We are also interested in how these processes impact the development of pathological conditions such as athlersclerosis, autoimmunity and cancer.



  • phagocytosis
  • efferocytosis
  • immunity
  • athlersclerosis
  • autoimmunity

Tony Jevnikar
Jevnikar

"Dr. Jevnikar’s laboratory is focused on epithelial and endothelial cell injury and the regulation of cellular death by as a means to promote transplant allograft survival. While there are a number of pathways that mediate cell death, regulated forms of death have the capacity to be regulated by fusion proteins, RNA silencing and small molecules, and are thus of clinical interest. Recently, the Jevnikar lab was the first to describe the role of regulated necrosis (necroptosis) within donor organs in decreasing inflammation and promoting survival post transplant. As well members of this laboratory and collaborators have been studying novel cytokines such as IL37 to attenuate or eliminate ischemia repercussion injury that invariably occurs post transplant in donor organs. Novel and costly reagents may be created in clinically feasible quantities using novel expression systems we have developed with genetically altered plants – another unique aspect of this laboratory. Collectively these areas of interest bridge the interface between innate and adaptive immunity, and the dynamic relation that exists between donor organ responses and recipient immunity. The lab is interested in transplantation related studies that have high translational potential which is a strength of this translational research group.

  • transplantation
  • autoimmunity
  • CHI

We are working on the molecular biology of several RNA viruses. Our ultimate goal is to control viral diseases. We are taking two approaches: the first approach is the development of efficacious vaccines against various human viral diseases including AIDS, hepatitis and hemorrhagic fever , and the second approach is the development of viral-specific antiviral therapeutic agents by using state-of-the-art technologies of genetic engineering and biotechnology. For the development of antiviral therapeutic agents, we have been investigating the molecular mechanism of homologous viral interference mediated by defective interfering particles using the vesicular stomatitis virus system and the viral reverse genetics.

  • antiviral agents
  • vaccines
  • hepatitis
  • HIV

Steven Kerfoot

Dr. Steven Kerfoot

T cells and B cells are tasked with targeting and regulating immune responses. When this goes wrong, autoimmune disease can result. Multiple Sclerosis is an autoimmune disease that targets the central nervous system. We study the mechanisms by which B and T cells drive chronic inflammation of the brain and spinal cord. These cells move and interact with each other within lymphoid tissue, where immune responses originate, as well as within the inflamed tissue. We visualize these interactions to understand their consequences and how they contribute to disease.

  • Multiple Sclerosis
  • B cells
  • T follicular helper cells
  • Multiphoton Microscopy

Macrophages residing in almost all tissues are specialized phagocytes positioned in the first line of host defense and a rich source of cytokines regulating immune responses. Different microbes manipulate macrophage to live in harmony with their host or target macrophages to colonize and proliferate. Our laboratory investigates the molecular and signalling mechanisms by which macrophages interact and response to different microbes, including Bacillus anthracis, commensals and probiotics. Our researches will provide new tools and therapeutic strategies for treating inflammatory and infectious diseases.

 

  • anthrax lethal toxin
  • in vitro-gene trapping in somatic cells
  • innate immune signaling
  • probiotics
  • CHI

Metal ions are everywhere in our environment. Some are purely toxic, others are essential for life -- and some are both. We are exploring the roles of metallothioneins, and metal ion and amino acid transporter proteins, that affect the toxicity and physiological activity of metals. Metallothioneins can mediate the activity of zinc-requiring transcription factors (NF- k B and the glucocorticoid receptor) and that function is being explored in immune and other cells (funded by the CIHR). In addition, we are developing antisense drugs to target mRNAs (thymidylate synthase and bcl-2) that mediate anticancer drug resistance (funded by the CIHR); and to measure hypoxic response in primary human tumours (in collaboration with clinical researchers in the London Regional Cancer Program).

 

  • metal homeostasis

Research in our laboratory is directed towards an understanding of the structure and function of bacterial surface components. Our current research is focussed on the prokaryotic obligate predators Bdellovibrio‑and‑like organisms (BALOs).  These bacteria have a developmental life cycle which includes a free‑living attack phase and a periplasmic growth phase.  We are interested in the mechanism of attachment and invasion of predators to the Gram‑negative prey cells, with the goal of determining the components of predator and prey surfaces that dictate attachment and penetration. We also have a long-standing interest in paracrystalline protein surface layers (S-layers) and flagella of both Bacteria and Archaea.

  • predatory prokaryotes
  • prokaryotic development
  • bacterial ultrastructure

The general interest of my lab centers on the transcriptional and translational control mechanisms that regulate gene expression in prokaryotes. Recently we have begun to examine regulating expression of virulence genes in Bacillus cereus. B. cereus is a human and animal pathogen that is most commonly associated with food poisoning, but it can also cause serious local and systemic infections. Moreover it is closely related to Bacillus anthracis, the causative agent of anthrax.

  • gene expression
  • RNA polymerase
  • bacterial virulence

 

 

Our major research focus includes a detailed structural and functional characterization of a group of potent "superantigen" toxins produced by the notorious human pathogens Streptococcus pyogenes and Staphylococcus aureus . Our goals include the development of novel inhibitors for these toxins and harnessing their properties for immunotherapeutic agents.We are also interested in host-pathogen and interspecies bacterial communication systems. This work includes communication between pathogens and commensal or probiotic organisms, and we are utilizing proteomic and in vivo expression technology systems to achieve these goals.

 



Staphylococcus aureus can establish asymptomatic nasal carriage in approximately 15-25% of the human population, but is also a successful pathogen in several different guises, including (i), hospital associated multiply antibiotic resistant S. aureus (HA-MRSA); (ii), community associated and hyper-virulent methicillin resistant CA-MRSA; and (iii), community associated hyper-virulent methicillin-susceptible CA-MSSA. My research is aimed at understanding how secreted virulence factors, including serine- cysteine- and metalloproteases promote a rapid transition between the colonization and invasion phases of infection, and modify the host inflammatory response. From a population biology perspective, we are also identifying strains of S. aureus that specialize in chronic persistent infection, as compared to severe acute infections. This will allow us to better understand how S. aureus can control or evade the host inflammatory response, and possibly to understand how it may adapt and evolve in response to our efforts to control it with antibiotics.


My research is focused on using small DNA viruses as tools to explore and discover fundamental mechanisms regulating eukaryotic cell growth and gene expression. We study the early viral proteins of the small DNA tumor viruses, particularly human adenovirus E1A and papillomavirus E7, which can convert normal cells into cancer. Our goal is to exploit these viral oncogenes to identify and characterize cellular regulatory pathways that, when altered, contribute to cancer formation and its spread.

  • metastasis
  • tumor viruses

Our lab is interested in understanding how indigenous and exogenously applied (probiotics) bacteria, especially lactobacilli confer health benefits primarily in the female gut, breast and urogenital tract. Our projects include: high throughput sequencing, transcriptomics, metabolomics, bacterial culture and in vitro testing, and human trials. We have projects in Africa, Netherlands, New Zealand and other countries. All our students publish papers, attend conferences and work collectively to try and improve the well-being of others.


Autoimmune diseases affect 5-7% of the population. The focus of our laboratory is to develop specific immunotherapeutic approaches for autoimmune type 1 diabetes (T1D). For this purpose we investigate the regulation of autoimmunity by understanding the molecular, cellular and genetic basis of the T cell-mediated immune responses in diabetes.


The nature of transplantation leads to tissue injury as organs are damaged by the loss of blood supply and ischemia associated with the procurement procedure. The potential benefit of donor tissue and storage modification to protect organs has not been intensively investigated as mainstream approaches to improving transplant survival remains focused on pharmacological inhibition of immune cell activation. As the discrepancy between the availability of donor organs the increasing rate of patients who require renal transplants continues to diverge, the search for methods of prolonging renal graft survival becomes paramount. My laboratory is interested in establishing novel strategies of minimizing post-transplant graft rejection and in promoting improved early and late renal allograft survival using both in vitro and in vivo models for donor tissue and cell modification, as this represents a complementary approach to T cell mediated tolerance in promoting both short and long-term graft survival.


Our lab is both a Research & Development lab and a Service lab that is focused on evaluating cellular immune responses in various clinical settings including autoimmune diseases, inflammatory disorders/conditions, plus drug efficacy and mechanisms. This includes using and developing innovative, multiplex bead-based assays to quantify multiple protein immune regulators (up to 40) simultaneously in small sample volumes (< 50 uL) of most biological fluids. Our goal is to identify new target biomarkers with diagnostic and/or therapeutic significance in clinical settings. We have several collaborative research projects with local Clinicians, Scientists, and private companies and gladly welcome new collaborations!

 

Miguel Valvano
Valvano

We work on two projects: (i) Mechanism of assembly of O antigen lipopolysaccharide (LPS), and (ii) Pathogenesis of the Burkholderia cepacia complex. LPS is a complex glycolipid on the surface of Gram-negative bacteria. We study the structure-function of membrane proteins needed for O antigen synthesis to design inhibitors that will interfere with this process, which may be useful as novel antimicrobials. The Burkholderia cepacia complex (Bcc) is a group of related species that are a major health risk for patients with the genetic disease cystic fibrosis. We discovered that Bcc bacteria survive in free-living amoebae and macrophages. We work on the elucidation of bacterial virulence factors involved in intracellular persistence.

  • lipopolysaccharide
  • membrane proteins
  • pathogenesis
  • intracellular bacterial survival in macrophages
  • antimicrobial peptides
  • CHI

Ze-Chun Yuan

We are employing multidisciplinary approaches including molecular genetics, functional genomics, bioinformatics, metagenomics and chromosome engineering to elucidate how environmental signals, plant- or microbe-derived chemicals/signals modulate bacterial pathogenesis, biofilm formation, cell-to-cell communication (quorum sensing), and how plant-associated bacteria and plant hosts perceive and transduce these signals (biotic, abiotic stress responses), in particular, the mutual perception and interaction between plants and plant-associated bacteria (beneficial or detrimental). We are also studying bacteria that participate in nutrient cycling, bioremediation, biofuel conversion, biological control, promoting plant growth, health and productivity, tolerance to biotic, abiotic stresses, or producing antimicrobial agents. Our researches offer many opportunities for cross-disciplinary training for undergraduate/graduate students and postdoctoral fellows.

  • bacterial genetics
  • signal transduction
  • metagenomics
  • molecular plant-bacteria interactionss
  • biotic and abiotic stress responses
 

 

 

 

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