Epigenomic Medicine

- Logo - McCord

Dr Tom Karagiannis
Head, Epigenomic Medicine
ARC Future Fellow
tom.karagiannis@bakeridi.edu.au
Phone: +61 3 8532 1309

Laboratory Phone: +61 3 8532 2157
Lounge Phone: +61 3 8532 1692 

Student enquiries: Katherine Ververis
katherine.ververis@bakeridi.edu.au
Phone: +61 3 8532 1319

Epigenomic Medicine is supported by
McCord Research

Research Overview

- Epigenomics Lab - lab photo - Epigenomics Lab - girls

The discipline of epigenomics represents the merged science of epigenetics and genomics. The ultimate aim of this field is to map and unravel the biological and biomedical significance of epigenetic phenomena. The term epigenetics was introduced by the British scientist Conrad Waddington in the 1940s to incorporate all of the factors controlling gene expression and cell differentiation. It was derived from the virtually redundant Aristotelian word of epigenesis, which was used by the Hellenic philosopher to describe his theory of gradual and progressive developmental changes.

Today, epigenetics is typically defined as inherited phenotypic changes that are not due to changes in gene sequence. However, an expanded approach may be to refer to epigenetics as an integrative view of the cellular and molecular mechanisms governing DNA metabolic processes including transcription, replication and repair.

- Epigenomics Lab Image 1

The 11 metal-dependent histone deacetylase enzymes are classified into three classes on the basis of their homology to yeast proteins. Histone deacetylase inhibitors are emerging as important anti-cancer therapeutics and are being investigated for a wide range of other medical applications.

The aim of the EpiMed (Epigenomic Medicine) laboratory is to investigate epigenetic modifications and responses in models of human disease, particularly chronic progressive conditions such as cardiovascular disease, diabetes and cancer. A further aim is to develop pharmacologic and dietary interventions, targeting genetic and epigenetic marks of disease. More specifically, research in the laboratory is focussed on three distinct but complementary directions:

  1. Epigenetic markers of DNA damage in ageing and disease
  2. Genetic and epigenetic modulation using dietary polyphenols and chromatin modifying compounds and
  3. Nanoparticle-targeted therapeutics and imaging agents.

Research Projects

Epigenetic markers of DNA damage in ageing and disease

gammaH2AX as a molecular marker of DNA double-strand breaks

Phoshophorylation of the Ser-139 residue on the histone variant H2AX, forming gammaH2AX, represents a highly sensitive marker of DNA double-strand breaks. Following induction of double-breaks nuclear gammaH2AX foci form which are easily visualized and quantitated by immunofluorescence.

We explore gammaH2AX in disease process and we utilize this marker to investigate cellular responses to DNA damaging agents.

Genetic and epigenetic events in diabetic wound healing

The normal wound healing response is a complex process involving numerous cell types. It is typically associated with three main phases, 1) acute inflammation, 2) proliferation and 3) remodelling. Impaired wound healing in diabetes is usually the result of angiopathy or neuropathy. Aberrant inflammatory responses, angiogenesis, reepithelialisation and keratinocyte and fibroblast migration have been associated with impaired diabetic wound healing.

We investigate genetic and epigenetic variations using cell-based models of diabetes and next generation sequencing technologies.

Genetic and epigenetic modulation using dietary polyphenols and chromatin modifying compounds

Biological evaluation of olive polyphenols in models of disease

The medicinal properties of the leaves and fruit of Olea europaea (olive tree) have been known since antiquity. Evidence indicates that the Cretans have been cultivating olive trees and using olive oil for over 3000 years. Modern research is indicating that the polyphenols, such as hydroxytyrosol, are the most likely candidates accounting for the cardioprotective and cancer preventative effects of extra virgin olive oil.

We are investigating the biological effects and molecular mechanisms of action in cellular models of human disease using a wide-range of biochemical assays as well next generation sequencing technologies.

- Epigenomics Lab Image 2 (Hydroxytyrosol pathway)

Modern research is highlighting the potential medicinal
properties of the leaves and fruit of the olive tree.

Nanoparticle-targeted therapeutics and imaging agents

Receptor-specific imaging using nanoparticles

We are developing receptor targeting nanoparticles incorporating a DNA binding ligand for diagnostic imaging applications. Given the finite number of receptors on target cells, the rationale is to improve the resolution of imaging with the use of a DNA binding ligand.

- Epigenomics Lab Image 3 (Targeted imaging)

Summary of the receptor-mediated DNA-targeted
approach for high resolution imaging.

Lab Head Profile

Dr Tom Karagiannis is an ARC Future Fellow. At the Baker IDI Heart and Diabetes Institute, he heads the Epigenomic Medicine Laboratory. He has an honorary affiliation with the Department of Pathology at the University of Melbourne. His research is focussed on two broad and complimentary research directions: 1) development of nanoparticle-based vehicles for DNA-targeted therapeutics and imaging agents and 2) evaluation of the genetic and epigenetic effects of dietary polyphenols and chromatin modifying compounds with a particular focus on histone deacetylase inhibitors.

Publication Highlights

Karagiannis TC, Lobachevsky PN, Leung BK, White JM, Martin RF. Receptor-mediated DNA-targeted photoimmunotherapy. Cancer Res 2006;66(21):10548-52.

Karagiannis TC, El-Osta A. Will broad-spectrum histone deacetylase inhibitors be superseded by more specific compounds? Leukemia 2007;21(1):61-5.

Karagiannis TC, Kn H, El-Osta A. Disparity of histone deacetylase inhibition on repair of radiation-induced DNA damage on euchromatin and constitutive heterochromatin compartments. Oncogene 2007; 26(27):3963-71.

Briggs B, Ververis K, Rodd AL, Foong LJL, Da Silva FM, Karagiannis TC. Photosensitization by iodinated DNA minor groove binding ligands: evaluation of DNA double-strand break induction and repair. Photochem Photobiol B 2011;103(2):145-52.

Kwa FA, Balcerczyk A, Licciardi P, El-Osta A, Karagiannis TC. Chromatin modifying agents - the cutting edge of anticancer therapy. Drug Discov Today 2011;16(13-14):543-7.

Ververis K, Rodd AL, Tang MM, El-Osta A, Karagiannis TC. Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes. Cell Mol Life Sci 2011;68(24):4101-14.

Royce SR, Dang W, Ververis K, De Sampayo N, El-Osta A, Tang MLK, Karagiannis TC. Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease. Epigenetics 2011;6(12):1463-70.

Licciardi PV, Kwa FAA, Ververis K, Di Costanzo N, Balcerczyk A, Tang ML, El-Osta A, Karagiannis TC. Influence of natural and synthetic histone deacetylase inhibitors on chromatin. Antioxid Redox Signal 2012;17(2):340-54.

Karagiannis TC, Maulik N. Factors influencing epigenetic mechanisms and related diseases. Antioxid Redox Signal 2012;17(2):192-4.

Royce SG, Karagiannis TC. Histone deacetylases and their role in asthma. J Asthma 2012;49(2):121-8.

Staff

Scientific Staff
Dr Simon Royce
Nadia Mazarakis
Sameera Bollu

Students
Katherine Ververis
Stephanie Tortorella
Li-Jeen Mah
Erith Nash
Jane Jisun Sung

 

Download a 2 page lab profile here 

Download a publications list here