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Dr Novakovic is a Senior Research Officer with over 10 years’ experience in Molecular Biology and Epigenetics and 5 years’ experience in innate immunity. He leads a ‘Trained Immunity epigenetics’ team within the Epigenetics Group of Professor Richard Saffery.
Dr Novakovic is a trained molecular biologist with a research interest in epigenetics of human immune cell function and disease. He is particularly interested in applying complementary epigenetic techniques to profile different aspects of chromatin structure and to integrate these data to explain biology.
Dr Novakovic is proficient in analysing DNA methylation data. This includes measuring DNA methylation on a global scale using high performance liquid chromatography (HPLC), on a genome-wide scale using array-based methodologies and on a locus-specific level using bisulfite-based approaches. During his Postdoc (2014 to 2018) in the functional genomics lab of Professor Henk Stunnenberg (Radboud University, Nijmegen), Dr Novakovic applied different epigenomic techniques to study innate immunity. He has generated over 900 sequencing libraries for genome-wide assessment of RNA expression (RNA-seq), histone modifications (ChIP-seq), open chromatin (ATAC-seq) and whole-genome bisulfite sequencing (WGBS). Dr Novakovic has made important contributions to the field of innate immunity, including the first characterization of the epigenetic basis for altered gene expression in endotoxin tolerance in humans (Novakovic et al. Cell 2016).
Dr Novakovic has published over 40 manuscripts, including in top journals Cell, Cell Metabolism, Cell Host Microbe, PNAS and Genome Research. He is currently CIA on an NHMRC New Investigator Grant (2019-2021) and CIC on an NHMRC Project Grant (2019-2021).
2018 – NHMRC New Investigator Project Grant
2013 – NHMRC (Australia) Early Career Fellowship (CJ Martin Overseas Fellowship)
2010 – M.A. Bartlett Research Scholarship Fund Special Travel Grants-in-Aid
2010 – University of Melbourne Abroad Travelling Scholarship – MATS
2010 – MCRI Postgraduate Student Association travel award
2010 – Australian Twin Registry Research Travel Grant
2009 – IFPA Y.W. Loke New Investigator Travel Award
2008 – NHMRC (Australia) Dora Lush Biomedial Postgraduate Scholarship
Epigenetic reprogramming of monocytes by the BCG vaccine
The Bacillus Calmette–Guérin (BCG) vaccine confers protection against severe Mycobacterium tuberculosis infection, and is the most widely used vaccine internationally. In addition to the effect on TB, BCG has been associated with protection against a range of non-TB infections and an overall decrease in mortality in children in low income countries. These non-specific effects are partially explained by Trained Innate Immunity (TRIM), a phenomenon where innate immune cells, such as monocytes, can be reprogrammed by exposure to microbe-associated molecular patterns, which is associated with enhanced pro-inflammatory responses and higher clearance of future infections. Dr Novakovic is CIA on a New Investigator Grant (2019-2021) to study the epigenetic processes involved in monocyte reprogramming by the BCG vaccine using samples from the MIS-BAIR clinical trial (led by Professor Nigel Curtis).
Epigenetics of Trained Immunity in food allergy
The aim of this research theme is to identify epigenetic and other molecular disruption associated with common childhood diseases including food allergy. The phenomenon of TRIM is reminiscent of the hyper inflammatory monocyte phenotype recently described in food allergic children. Dr Novakovic is CIC on an NHMRC Project Grant led by Professor Richard Saffery (2019-2021) to perform epigenomic analysis on monocytes and T cells from Food allergic children.
Epigenetics of pregnancy and fetal programming
In pregnancy, the developing fetus is highly vulnerable to maternal immune regulation, and the placenta produces a range of signals with potential to modulate maternal immunity. Maternal and fetal immune cells, both at the fetal-maternal interface (placenta) and in the circulation, have altered phenotypes during pregnancy compared to the non-pregnant state. These involve changes in surface receptor expression, response to microbe stimuli and presence of pregnancy-specific cell subtypes. Despite this, little is known about the degree to which epigenetic variation plays a role in modulating immune cell phenotypes in pregnancy in both immune and non-immune compartments (such as placenta endothelial cells). This projects examines the epigenetics of inflammatory memory in different cells during pregnancy and in pregnancy-associated disease, and how this may contribute to developmental programming.
Domínguez-Andrés J, Novakovic B*, Li Y, Scicluna BP, Gresnigt MS, Arts RJW, Zwaag J, ter Horst R, Joosten LAB, Wijmenga C, van der Poll T, Kox M, Pickkers P, Kumar V, Stunnenberg HG, Netea MG (2018) Itaconate pathway is a central regulatory node between innate immune tolerance and trained immunity. Cell Metabolism, pii: S1550-4131(18)30568-0.
Arts RJW, Moorlag SJCFM, Novakovic B*, Li Y, Wang SY, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG. (2018) BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell Host Microbe, 23(1):89-100.e5.
Bekkering S*, Arts RJW*, Novakovic B*, Kourtzelis I, Popa C, ter Horst R, van Tuijl J1 Simon A, van de Veerdonk FL, Chavakis T, Stunnenberg H, Joosten LAB, Van der Meer JWM, Riksen NP, Netea MG (2018) The mevalonate pathway drives metabolic and epigenetic reprogramming during induction of trained immunity. Cell, 172(1-2):135-146.e9.
Novakovic B *and Stunnenberg HG (2017) I Remember You: Epigenetic Priming in Epithelial Stem Cells. Immunity, 47(6):1019-1021.
Novakovic B*, Wang C, Logie C (2017) We can still be friends: IFN-y breaks up macrophage enhancers. Immunity, 47(2):209-211. Impact Factor: 23.0
Novakovic B*, Evain-Brion D, Murthi P, Fournier T, Saffery R (2017) Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia and response to hypoxia. FASEB Journal, 31(6):2380-2392.
Novakovic B*, Habibi E, Wang SY, Arts RJW, Davar R, Megchelenbrink W, Kim BW, Kuznetsova T, Kox M, Zwaag J, Matarese F, van Heeringen S,Janssen-Megens EM, Sharifi N, Wang C, Schoonenberg V, Flicek P, Clarke L, Pickkers P, Heath S, Gut I, Netea MG, Martens JH, Logie C, Stunnenberg HG (2016) β-glucan reverses the epigenetic state of LPS induced immunological tolerance. Cell, 167(5):1354-1368.e14.
Arts RJW, Novakovic B*, ter Horst R, Carvalho A, Bekkering S, Lachmandas E, Rodrigues F, Silvestre R, Cheng SC, Wang S, Habibi E, Gonçalves LG, Mesquita I, Cunha C, van de Veerdonk F, Williams DL, van der Meer JWM, O'Neill LA, Dinarello CA, Riksen NP, van Crevel R, Clish C, Notebaart RA, Joosten LAB, Stunnenberg HG, Xavier RJ, Netea MG (2016) Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity. Cell Metabolism, 24(6):807-819.