David Martino
Head, Clinical Epigenetics
BSc PhD
david.martino@thekids.org.au
David is an NHMRC biomedical research fellow and Team Leader of Clinical Epigenetics at Telethon Kids Institute. His research explores the links between the molecular determinants of epigenetic control and childhood health and disease. He is engaged in understanding how periconceptual exposures translate into phenotypes with enduring effects on long-term health. He has published extensively on genetic and epigenetic mechanisms of immune development and allergic disease.
Projects
Compound Repurposing Into Novel Therapeutics In COVID-19 At risk Lungs (CRITICAL Study)
Vulnerable from the first breath - epithelial dysfunction and respiratory outcomes in children
Understanding how viral infection in early life impacts on lung function in adulthood
Water Quality and the Microbiome Study (TUMS): The effects of chlorinated drinking water on the assembly of the infant gut microbiome
Fetal alcohol exposure, nutritional status and epigenetic disruption – exploring the links
The epigenetic origin of alcohol-induced disorders: a cross-species study
Do exposures before conception influence the risk of asthma in the offspring?
ARIEL study
July 2020
Published research
DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life
Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life.
Early moderate prenatal alcohol exposure and maternal diet impact offspring DNA methylation across species
Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure resembling common patterns of alcohol consumption in pregnancy in humans.
Breastfeeding and Neonatal Age Influence Neutrophil-Driven Ontogeny of Blood Cell Populations in the First Week of Human Life
The first few days of life are characterized by rapid external and internal changes that require substantial immune system adaptations. Despite growing evidence of the impact of this period on lifelong immune health, this period remains largely uncharted.
Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways
nfants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunizations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation.
Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy
Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus, but whether stretches of differentially methylated regions can also be identified in adolescent GDM offspring is unknown.
Metagenomic Characterisation of the Gut Microbiome and Effect of Complementary Feeding on Bifidobacterium spp. in Australian Infants
Complementary feeding induces dramatic ecological shifts in the infant gut microbiota toward more diverse compositions and functional metabolic capacities, with potential implications for immune and metabolic health. The aim of this study was to examine whether the age at which solid foods are introduced differentially affects the microbiota in predominantly breastfed infants compared with predominantly formula-fed infants.
Fathers’ preconception smoking and offspring DNA methylation
Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are, however, limited. We aim to identify epigenetic marks in offspring associated with father's preconception smoking.
Epigenomic variability is associated with age-specific naïve CD4 T cell response to activation in infants and adolescents
Childhood is a critical period of immune development. During this time, naïve CD4 T cells undergo programmed cell differentiation, mediated by epigenetic changes, in response to external stimuli leading to a baseline homeostatic state that may determine lifelong disease risk. However, the ontogeny of epigenetic signatures associated with CD4 T cell activation during key developmental periods are yet to be described.
Immuno-epigenomic analysis identifies attenuated interferon responses in naïve CD4 T cells of adolescents with peanut and multi-food allergy
IgE-mediated food allergies have been linked to suboptimal naïve CD4 T (nCD4T) cell activation in infancy, underlined by epigenetic and transcriptomic variation. Similar attenuated nCD4T cell activation in adolescents with food allergy have also been reported, but these are yet to be linked to specific epigenetic or transcriptional changes.
Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells
Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate.
Parental preconception BMI trajectories from childhood to adolescence and asthma in the future offspring
Recent evidence suggests that parental exposures before conception can increase the risk of asthma in offspring. We investigated the association between parents' preconception body mass index (BMI) trajectories from childhood to adolescence and subsequent risk of asthma in their offspring.
Association of prenatal alcohol exposure with offspring DNA methylation in mammals: a systematic review of the evidence
Prenatal alcohol exposure is associated with a range of adverse offspring neurodevelopmental outcomes. Several studies suggest that PAE modifies DNA methylation in offspring cells and tissues, providing evidence for a potential mechanistic link to Fetal Alcohol Spectrum Disorder.
Risk Factors for Gut Dysbiosis in Early Life
Dysbiosis refers to a reduction in microbial diversity, combined with a loss of beneficial taxa, and an increase in pathogenic microorganisms. Dysbiosis of the intestinal microbiota can have a substantial effect on the nervous and immune systems, contributing to the onset of several inflammatory diseases.
Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation
T-cell activation induces context-specific gene expression programs that promote energy generation and biosynthesis, progression through the cell cycle and ultimately cell differentiation. The aim of this study was to apply the omni ATAC-seq method to characterize the landscape of chromatin changes induced by T-cell activation in mature naïve CD4+ T-cells.
Children of Asian ethnicity in Australia have higher risk of food allergy and early-onset eczema than those in Singapore
In Western countries, Asian children have higher food allergy risk than Caucasian children. The early-life environmental exposures for this discrepancy are unclear. We aimed to compare prevalence of food allergy and associated risk factors between Asian children in Singapore and Australia.
Genetic determinants of paediatric food allergy: A systematic review
We systematically reviewed the literature on the genetic basis of food allergy, identifying areas for further investigation
Children with East Asian-Born Parents Have an Increased Risk of Allergy but May Not Have More Asthma in Early Childhood
Children of East Asian ancestry born in Australia have a higher burden of most allergic diseases in the first 6 years of life, whereas asthma may follow a different pattern
Early life innate immune signatures of persistent food allergy
Early life innate immune dysfunction may represent a key immunological driver and predictor of persistent food allergy in childhood
Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy
Our data indicate epigenetic dysregulation in the early stages of signal transduction through the T cell receptor complex, and likely reflects pathways modified by gene-environment interactions in food allergy
Candidate gene testing in clinical cohort studies with multiplexed genotyping and mass spectrometry
We describe a cost-effective tag single nucleotide polymorphism approach using a multiplexed genotyping assay with mass spectrometry
Education and Qualifications
David studied science at the University of Western Australia where he completed a BSc.(Hons) majoring in Anatomy and Human Biology. He undertook PhD studies on a scholarship in genome-wide expression profiling in paediatric food allergy. He became interested in why these genes were differentially expressed which led him into the world of epigenetics. He moved to Melbourne to study epigenetics under A/Prof Richard Saffery, and subsequently led a program of epigenetic studies of paediatric food allergy with Prof. Katie Allen.
Awards/Honours
2017 - NHMRC Career Development Fellowship
2013 - NHMCR Early Career Research Fellowship
2007 - Australian Postgraduate Scholarship
Active Collaborations
Centre for Food and Allergy Research
Genomics Advisory Group – Immune Tolerance Network (NIAID)