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Maria Chatziapostolou

Senior Independent Research Fellow

School of Science & Technology

Staff Group(s)
Bioscience

Role

Senior Independent Research Fellow in Epigenetics of Diseases.

Dr. Hatziapostolou's research focusses on  the molecular characterization of cancer initiation, growth, chemoresistance and metastasis. Cancers of interest are those of the gastrointestinal tract with an emphasis on pancreatic and liver cancer.

Dr. Hatziapostolou explores novel areas of basic research and specifically works on projects that span from tumour-stroma interactions, to the implications of epigenetic machinery and non-coding RNAs in oncogenesis and chemoresistance. She uses high-throughput approaches, sophisticated molecular techniques, and functional in vitro and in vivo approaches focussing on basic research outcomes that can be translated in potential clinical applications.

Career overview

Since her doctoral studies, Dr. Hatziapostolou has worked on the identification of mechanisms that regulate tumour growth and metastasis. Dr. Hatziapostolou completed her PhD in Cell Biology at the University of Patras in Greece. She then moved to the USA and joined the Molecular Oncology Research Institute at Tufts Medical Center (Boston, MA, USA), as a postdoctoral fellow, where she studied signalling pathways implicated in oncogenic transformation and gained expertise in the field of miRNAs and epigenetics. She continued her research on mechanisms of carcinogenesis at the Dana Farber Cancer Institute and Harvard Medical School (Boston, MA, USA), as a postdoctoral fellow. She explored the role of inflammation in oncogenic transformation and metastasis and acquired expertise of microRNA therapeutics. After her postdoctoral trainings, she was appointed Assistant Professor at the UCLA School of Medicine (Los Angeles, CA, USA), where she has gained expertise in long non-coding RNAs, high-throughput and systems biology approaches. Following UCLA, she moved to the United Kingdom and was appointed a Lecturer of Epigenetics, at the Centre for Biomedical Sciences, University of Southampton. In Southampton she worked on the complex molecular interactions that characterize pancreatic carcinogenesis. Recently, she has moved to her current position here at Nottingham Trent University.

Research areas

Research in Hatziapostolou laboratory focuses on the molecular interplay between the genome and the epigenome during oncogenic transformation, cancer growth and metastasis.

Epigenetic Networks in Pancreatic Cancer

The dismal prognosis of pancreatic cancer due to the delayed diagnosis, the rapid metastatic manifestations and the strong resistance to current therapeutics, signifies the importance of identifying novel approaches in the treatment of pancreatic cancer. The wide availability of tools and systems for high throughput screenings and analysis, may represent a unique opportunity in fighting the battle against pancreatic cancer. The goal of our study is to characterize the molecular interactome of human pancreatic cancer and identify novel druggable pancreatic cancer regulators.

Long Non-Coding RNAs (lncRNAs) in Liver Cancer

Long non-coding RNAs (lncRNAs) have gained massive attention in recent years as novel mediators of gene expression with implications in hepatic pathophysiology. LncRNAs have been shown to play a major role in hepatocellular carcinoma (HCC). However, their implication in HCC chemoresistance has not been investigated. For this type of cancer, with increasing incidence and high mortality rates, it is crucial to identify new therapeutic targets and biomarkers to predict response to therapy. LncRNAs may represent a promising new resource.

HNF4A in Liver Cancer Aggressiveness

Hepatocyte nuclear factor 4A (HNF4A), is a liver-enriched transcription factor that controls hepatic epithelium formation, hepatocyte differentiation and liver functional activity. We have shown (Hatziapostolou et al., Cell, 2011) that HNF4A is a key regulator of hepatocellular carcinoma (HCC) development in murine liver cancer models and human tissues. The goal of this project is to elucidate the role of HNF4A-regulated gene networks in liver cancer chemoresistance and metastasis, and identify new therapeutic schemes that could potentially target both the dissemination of cancer cells and drug resistance.

Targeting the lncRNA interactomes in cancer

The dysregulation of lncRNAs has increasingly been linked to many human diseases, including many types of cancer. Most lncRNAs work with DNA-binding proteins, such as chromatin modifying complexes, and epigenetically regulate the expression of multiple genes. The goal of this project is the development of sequence specific oligonucleotides which block the interaction of lncRNAs with epigenetic modifiers and consequently supress the functions triggered from these complexes.

Opportunities to carry out postgraduate research towards an MPhil / PhD exist and further information may be obtained from the NTU Doctoral School.

External activity

Editorial Board Memberships

Reviewer

Conference Presentations-Invited Speaker

  • “HNF4A   as a tumor suppressor gene”. Invited Lecture at the 16th International  Congress of Endocrinology held jointly with The Endocrine Society's 96th  Annual Meeting & Expo, ICE/ENDO 2014. Chicago, IL, USA, June 24, 2014.
  • “HNF4A-miRNA   networks in hepatocellular oncogenesis”. Invited Lecture at the 8th annual miRNA in Human Disease and Development, Cambridge, MA, USA, March 12-13 2012.
  • “HNF4A-miRNA networks regulate hepatocellular oncogenesis”. Invited Lecture at the New England RNA Data Club Meeting, Harvard Medical School, Boston, MA, USA, February 22 2012.

Sponsors and collaborators

Current research is supported by Pancreatic Cancer Research UK, Research Innovation Award

Dr. Hatziapostolou collaborates with top researchers in the field of cancer from a number of universities across the UK, Europe and USA.

Publications

A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma. Palumbo T, Poultsides GA, Kouraklis G, Liakakos T, Drakaki A, Peros G, Hatziapostolou M*, Iliopoulos D*, BMC Cancer, 2016, 16 (1), 353, (*co-correspondence)

Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer. Vorvis C, Hatziapostolou M, Mahurkar-Joshi S, Koutsioumpa M, Williams J, Donahue TR, Poultsides GA, Eibl G, Iliopoulos D. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2016, 310 (11), 1124-37

XBP1 promotes triple negative breast cancer by controlling the HIF1A pathway. Chen X, Iliopoulos D#, Zhang Q#, Tang Q#, Greenblatt MB, Hatziapostolou M, Lim E, Tam WL, Ni M, Chen Y, Mai J, Shen H, Hu DZ, Adoro S, Hu B, Song M, Tan C, Landis MD, Ferrari M, Shin SJ, Brown M, Chang JC, Liu XS, Glimcher LH, Nature, 2014, 508 (7494), 103-7, (#equal contribution)

Phosphoproteomics screen reveals Akt isoform-specific signals linking RNA processing to lung cancer. Sanidas I#, Polytarchou C#, Hatziapostolou M, Ezell SA, Kottakis F, Hu L, Guo A, Xie J, Comb M, Iliopoulos D, Tsichlis PN, Molecular Cell, 2014, 53 (4), 577-90 (#equal contribution)

Identification of liver cancer progenitors whose malignant progression depends on IL-6 signaling. He G, Dhar D, Nakagawa H, Font-Burgada J, Ogata H, Jiang Y, Shalapour S, Seki E, Yost SE, Jepsen K, Frazer KA, Harismendy O, Hatziapostolou M, Iliopoulos D, Suetsugu A, Hoffman RM, Tateishi R, Koike K, Karin M, Cell, 2013, 155 (2), 384-96

Salutary effects of adiponectin on colon cancer: in vivo and in vitro studies in mice. Moon HS, Liu X, Nagel JM, Chamberland JP, Hatziapostolou M, Wu Y, Sienkiewicz E, Diakopoulos KN, Brinkoetter MT, Iliopoulos D,  Robson SC, Mantzoros CS, Gut, 2013, 62 (4), 561-70

An HNF4A-microRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Hatziapostolou M, Polytarchou C, Aggelidou E, Drakaki A, Poultsides GA, Jaeger SA, Ogata H, Karin M, Struhl K, Hadzopoulou-Cladaras M, Iliopoulos D, Cell, 2011, 147 (6), 1233-47

Tumor progression locus 2 regulates signal-induced calcium release from the endoplasmic reticulum and cell migration. Hatziapostolou M, Koukos G, Polytarchou C, Serebrennikova O, Kuliopulos A, Tsichlis PN, Science Signaling, 4 (187)

See all of Maria Hatziapostolou's publications...