Professor Paul Hertzog

VIIN Co-convenor

Centre for Innate Immunity and Infectious 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 pattern recognition receptor signaling, the elicited transcriptional responses including IRF, STAT, ETS and NFκB 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.  We have discovered a new family member involved in mucosal immunity. 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/cytokine/interferon signaling using microarrays to analyse gene transcriptional profiling incorporated with bioinformatics to predict regulatory networks and identify novel transcriptional regulation candidates. One outcome is the INTERFEROME database for annotating response pathways.

We have a longstanding expertise in the generation of genetically modified mise and their pathophysiological characterisation.  Disease models include viral and bacterial infections and models of tumourigenesis. A current international program, MONMAN, in collaboration with Norcomm/Canada is to generate reporter mice for inflammation research.

Techniques/Expertise:

Molecular signaling (protein-protein interactions, IP-Westerns, kinases)
Generation and characterisation of genetically modified mice
Animal models of infectious disease, inflammation and cancer
Bioinformatics and Microarray profiling (human and mouse)
Gene regulatory mechanisms ( EMSA, 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:

L. Hartland (Melbourne) -IFNs in infections
D. Hilton lab (WEHI- negative regulation by SOCS proteins.
K. Shortman lab (WEHI) Interferon and TLR activation of Dendritic cells.
G. Anderson lab (U. Melbourne) -  lung inflammatory and infections .
B. Parker (Peter MacCallum) - Innate immune pathways in metastasis

National:

A. Cunningham (NSW) - HSV and HIV infections
C.James - Influenza infections and IFNs

International:

L.O'Neill (Trinity College, Dublin) - TLR signaling
E. Latz (Bonn, Germany) - PRR signaling
G. Hicks (Manitoba) - GMM models of disease
R.D. Schreiber ( Washington U, St Louis) - type I IFNs
P. Pitha-Rowe (John's Hopkins, Baltimore) - antiviral f IFNs and IRFs.
E. Fish (U.Toronto) - regulation of type I IFNs
N. Reich (SUNY) - IFN signaling
P.Utz (Stanford) - IFNs in autoimmunity
X-T Cao (Shanghai/Hang-jou) - negative regulation in innate immunity
Hong Tang (CAS, Beijing) - infection and 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, cytokine signaling (IFNs IFNARs, STATs, SOCS, etc)  and ETS transcription factors (ETS1, ETS2, ELF3, ELF5, GABPa). Include conventional and conditionally targeted lines.

Existing Websites:

http://www.monashinstitute.org/centres//ciiid/ciiid-home.html

Lab Group Personnel:

Centre for Innate Immunity and Infectious Disease group leaders:

Dr Brendan Jenkins
Dr Ashley Mansell
Dr Richard Ferrero
Dr Phillip Bardin

Signal Regulation in Immunity Group:

Dr Niamh Mangan
Dr Nicky de Weerd
Dr Irina Rusinova
Dr Alec Drew
Ms Jodee Gould
Leyla Kakar-Tabrizi
Dale Cary
Rebecca Piganis
Ka-Yee Fung
Sebastian Sifter
Sam Forster