Baca Chan

Baca Chan
University of Western Australia | UWA · Lung Institute of Western Australia

PhD

About

26
Publications
2,565
Reads
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422
Citations
Introduction
My research focus is in host-virus interactions. I am interested in understanding the host immune system via dissection of the mechanisms by which viruses antagonise host immune responses. I am experienced in viral pathogenesis, biochemistry and cell and molecular biology techniques. Currently I am developing a transmissible vaccine aimed at preventing spillover of zoonotic infections from wildlife to human populations.
Additional affiliations
November 2018 - present
University of Western Australia
Position
  • Research Associate
Description
  • Mechanisms of antigen decay in cytomegalovirus vaccine vectors
December 2014 - January 2016
Technische Universität Braunschweig
Position
  • Lecturer
Description
  • IB26 Virology module of the Infection Biology focus of the Master’s Program ‘Biology’ Lecture topics: DNA viruses; Antivirals and Vaccines
April 2013 - July 2016
Helmholtz Centre for Infection Research
Position
  • PostDoc Position
Description
  • Modulation of type I interferon responses by cytomegalovirus
Education
February 2008 - November 2012
University of Western Australia
Field of study
  • Microbiology

Publications

Publications (26)
Article
Full-text available
It is becoming increasingly clear that many diseases are the result of infection from multiple genetically distinct strains of a pathogen. Such multi-strain infections have the capacity to alter both disease and pathogen dynamics. Infection with multiple strains of human cytomegalovirus (HCMV) is common and has been linked to enhanced disease. Sugg...
Article
Significance In addition to the well-characterized main nuclear latency-associated nuclear antigen (LANA) protein of Kaposi sarcoma herpesvirus (KSHV), cytoplasmic LANA isoforms are known to exist, but their function has thus far been unknown. Here we show that N-terminally truncated cytoplasmic isoforms of LANA play a role in antagonizing the inna...
Article
Full-text available
The type I interferon (IFN) response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV) that shuts down signaling following pattern recognition receptor (PRR) sensing. Screening of an MCMV open reading frame (ORF) l...
Article
Full-text available
The two human gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), can cause aggressive forms of cancer. These herpesviruses are strictly host specific, and therefore the homolog murine gammaherpesvirus 68 (MHV68) is a widely used model to obtain in vivo insights into the interaction between these two gam...
Article
Full-text available
Cytomegaloviruses (CMVs) are master manipulators of the host immune response. Here, we reveal that the murine CMV (MCMV) protein m152 specifically targets the type I interferon (IFN) response by binding to stimulator of interferon genes (STING), thereby delaying its trafficking to the Golgi compartment from where STING initiates type I IFN signalin...
Article
Full-text available
Diverse applications rely on engineering microbes to carry and express foreign transgenes. This engineered baggage rarely benefits the microbe and is thus prone to rapid evolutionary loss when the microbe is propagated. For applications where a transgene must be maintained for extended periods of growth, slowing the rate of transgene evolution is c...
Article
Full-text available
As the largest herpesviruses, the 230 kb genomes of cytomegaloviruses (CMVs) have increased our understanding of host immunity and viral escape mechanisms, although many of the annotated genes remain as yet uncharacterised. Here we identify the m15 locus of murine CMV (MCMV) as a viral modulator of natural killer (NK) cell immunity. We show that, r...
Article
Full-text available
Murine cytomegalovirus (MCMV) is widely used as a model of human CMV (HCMV) infection. However, this model relies on strains of MCMV that have been serially passaged in the laboratory for over four decades. These laboratory strains have been cloned as bacterial artificial chromosomes (BACs), which permits rapid and precise manipulation. Low-passage...
Article
Full-text available
The rapid activation of pattern recognition receptor (PRR)-mediated type I interferon (IFN) signaling is crucial for the host response to infection. In turn, human cytomegalovirus (HCMV) must evade this potent response to establish life-long infection. Here, we reveal that the HCMV tegument protein UL35 antagonizes the activation of type I IFN tran...
Article
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the leptin and insulin signalling pathways. This phosphate is of great interest as PTP1B knockout mice are protected against the development of obesity and diabetes. Here, we provide evidence for a novel function of PTP1B, which is independent of its phosphatase activity, but requir...
Article
Full-text available
The host immune system is engaged in a constant battle with microorganisms, with the immediate detection of pathogenic invasion and subsequent signalling acting as crucial deterrents against the establishment of a successful infection. For this purpose, cells are equipped with a variety of sensors called pattern recognition receptors (PRR), which r...
Article
Full-text available
Early detection of viral invasion by pattern recognition receptors (PRR) is crucial for the induction of a rapid and efficient immune response. Cytosolic DNA sensors are the most recently described class of PRR, and induce transcription of type I interferons (IFN) and proinflammatory cytokines via the key adaptor protein stimulator of interferon ge...
Data
Activation of NF-κB and IRF responsive luciferase reporter constructs upon expression of constitutively active IRF3. 293T cells were co-transfected with expression plasmids for either the constitutively active form of IRF3 designated IRF3-5D (stimulated) or GFP (unstimulated) together with the pRL-TK luciferase plasmid, pcDNA and the IFNβ, p55-CIB,...
Data
M35 curtails type I IFN transcription downstream of multiple PRR. Sensing of MCMV infection by multiple PRR, including cGAS, RIG-I-like receptors (RLR), and Toll-like receptors (TLR), activates signaling cascades leading to the production of antiviral type I IFN. Upon MCMV infection, tegument M35 is rapidly transported to the nucleus in order to sp...
Data
STING plays a crucial role for detection of MCMV in primary BMDM. Primary BMDM generated from wildtype (WT) and STING knockout mice were infected with MCMV-GFP at MOI 0.5 or 2 or left uninfected and IFNα/β levels at 16 hours p.i. were analyzed by ELISA. Data is shown as mean ± SD of three independent experiments. (TIF)
Data
M35 does not affect IRF3 and p65 phosphorylation upon RLR stimulation. (A) Quantification of phospho-IRF3 levels relative to total IRF3 levels was performed on Fig 4A using ImageJ. (B) Quantification of phospho-p65 levels relative to total tubulin levels was performed on three independent experiments using ImageJ. One representative immunoblot is s...
Data
M35-deficient MCMV induces elevated IFNα secretion in dendritic cells compared to WT MCMV. pDC and cDC were infected with MCMV-M35stop-REV (REV) or MCMV-M35stop (M35stop) at an MOI of 0.01 (pDC), 0.1 (cDC), or left uninfected (mock). Supernatants were harvested 16 hours p.i. for quantification of IFNα levels by ELISA. Data is shown as mean ± SD and...

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