Professor Paul Hertzog

MIIN Co-convenor

Centre for Functional Genomics and Human Disease
Monash Institute of Medical Research
+61395947260
paul.hertzog@med.monash.edu.au

Research Activities:

Overall interest is in the molecular regulation of signal transduction in innate immunity. In particular our group is interested in Toll-Like Receptor signaling, the elicited transcriptional responses including IRF, STAT, ETS and NFκ B pathways and the ensuing cytokine responses.  The particular cytokines of interest are the type I interferons (IFNs). We investigate the mechanisms of signaling beginning at reengagement of the receptors, IFNAR1 and IFNAR2.  Receptor function is studies using genetically modified mouse models, protein-protein interactions, structural biology, imaging and signal transduction studies. Another aspect of signaling is negative regulation, particularly that mediated by the SOCS family of cytokines. We are investigating their regulation of IFN (α, β and γ) as well as TLR signaling. One outcome of the nature of our research is a growing capability in cell based screens for activators and inhibitors of innate immunity signaling.
We are investigating the global nature of TLR and cytokine signaling using microarrays to analyse gene transcriptional profiling incorporated with bioinformatics to predict regulatory networks and identify novel transcriptional regulation candidates.
We have a longstanding expertise in the generation of genetically modified mice and their pathophysiological characterisation.  Disease models include viral and bacterial infections and models of tumourigenesis.

Techniques/Expertise:

Molecular signaling (protein-protein interactions, IP-Westerns, kinases, etc...; particularly related to cytokines and TLRs)
Generation and characterisation of genetically modified mice
Animal models of infectious disease, inflammation and cancer
Microarray profiling (human and mouse)
Gene regulatory mechanisms (EMSA, protein-protein interactions, nuclear translocation, ChIP, reporters, promoter mapping)
Flow cytometry
Immunoassays (antibody-based; cell mediated, immpunophenotyping, monoclonal generation)

Collaborations:

Within Monash:

Professor Jamie Rossjohn's laboratory - structure-function of IFN-receptor interaction
ARC Centre of Excellence in Structural and Functional Microbial Genomics - TLR signaling

State:

D Hilton (Walter and Eliza Hall Institute) and Zenyth Therapeutics - negative regulation of IFNs and TLRs by SOCS proteins
K Shortman (Walter and Eliza Hall Institute) - Interferon and TLR activation of dendritic cells
G Anderson (University of Melbourne) -  lung inflammatory and infectious disease
J Hamilton (University of Melbourne) - inflammatory joint disease

National:

D Hume (Institute of Molecular Bioscience, University of Queensland) – macrophage signaling and regulatory networks
I Campbell (University of New South Wales) – Cytokines in infectious disease of the CNS
N Hunt (University of New South Wales) - brain inflammation

International:

L O’Neill (Trinity College, Dublin) - TLR signaling
R D Schreiber ( Washington University, St Louis) - type I IFNs in tumour development
P Pitha-Rowe (Johns Hopkins, Baltimore) - antiviral actions of IFNs and IRFs.
E Fish (University of Toronto) - regulation of type I IFNs
N Reich (State University of New York) - IFN signaling
P Utz (Stanford) - IFNs in autoimmunity
X-T Cao (Shanghai/Hang-jou) - negative regulation of signaling in innate immunity
T Decker (Vienna) -  IFNARs in infectious disease

Animal Disease Models:

Variety of viral and bacterial infection models in mice
Induced and transplantable models

Genetically Modified Animals:

Assorted genetically modified mouse models associated with TLR signaling, cytokines

Existing Websites:

http://www.monashinstitute.org/functional-genomics.html

Lab Group Personnel:

Centre for Functional Genomics and Human Disease group leaders:

Dr Melanie Pritchard
Dr Bernadette Scott
Dr Brendan Jenkins
Dr Ashley Mansell
Dr Trevor Wilson

Host Defence (Hertzog) Group:

Dr Helen Cumming
Dr Nicky de Weerd
Dr Shamith Samarajiwa
Ms Jodee Gould
Mr Dale Cary
Susie Noppert (PhD student)
Connie Wong (PhD student)
Rebecca Piganis (honours student)
Ka-Yee Fong (honours student)
Mushka Raoofi (UROP student)