Dr Malgorzata Wiench

Dr Malgorzata Wiench

School of Dentistry
Lecturer in Cancer Biology

Contact details

Address
The School of Dentistry
5 Mill Pool Way
Edgbaston
Birmingham
B5 7EG
United Kingdom

Malgorzata Wiench is a Lecturer in Cancer Biology. Uniquely based between the School of Dentistry in the Institute of Clinical Sciences and the Institute of Cancer and Genomic Medicine she aims to understand the mechanisms by which chromatin organization and DNA methylation regulate gene expression in health and disease and to develop the basis for patient-tailored epigenetic cancer therapies. The investigations focus on the role of nuclear receptors, DNA methylation and hydroxymethylation in the functioning of distal regulatory elements. Malgorzata has recently received grants from the Marie Curie Action (FP7) and The Royal Society. Her research is also funded by the CR UK Centre.

Qualifications

  • PhD in Medical Biology 2001
  • MSc in Biochemistry 1997

Biography

Malgorzata qualified with MSc in Biochemistry from The Silesian University, Poland. Her career started in the Center of Oncology in Gliwice in the group of Prof. Barbara Jarzab and focused on developing molecular techniques for diagnostic applications in oncology, specifically in genetic predisposition to medullary thyroid carcinoma.  This research was awarded a prize by the Polish Academy of Science and the developed algorithm for genetic testing was implemented in the health care system’s recommendations. After completing her Ph.D. Thesis, she applied gene expression profiling for identifying new prognostic markers in papillary and follicular thyroid carcinomas. 

In 2004 she received the International Endocrine Scholars Program Reward (Endocrine Society) and joined Dr Gordon Hager’s laboratory at the National Cancer Institute, NIH in Bethesda. Whilst at the NIH she studied dynamic events of chromatin structure and its interactions with transcription factors and co-regulators when triggered by hormone stimulation. Her main focus was on tissue-specific gene regulation by nuclear receptors through DNA methylation and chromatin accessibility (DNaseI hypersensitivity).

Malgorzata joined the University of Birmingham in March 2012 with an aim to combine her experiences in a clinical environment and fundamental research in order to develop tools for epigenetic targeting of the cancer genome through the study of chromatin alterations. Her primary focus is on head and neck tumours. 

Teaching

Postgraduate supervision

Dr Wiench is interested in supervising doctoral research students in the following areas:

  • Chromatin organization and DNA methylation in HPV-positive and HPV-negative head and neck cancers;
  • The role of DNA hydroxymethylation in the functioning  of distal regulatory elements;
  • DNA demethylation therapies in head and neck cancers;
  • Epigenetic silencing of nuclear receptor RARB in the onset of head and neck cancer.

If you are interested in studying any of these subject areas please contact Malgorzata, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44(0)212 414 5005.

Research

Research themes:

Gene regulation, cancer epigenetics, DNA methylation and hydroxymethylation, chromatin organization, epigenetic therapies

Research activity:

The principle focus of our research is to understand how DNA methylation and chromatin organization affect tissue-specific and cancer-related gene regulation and transcription factors binding to distal regulatory elements (DREs). Our projects involve the coupling of approaches that probe ‘open’ or accessible chromatin with high-throughput sequencing methods; this allows for the unbiased, genome-wide identification of all regulatory elements (Digital DNaseI-Seq, FAIRE). Combined with DNA methylation studies they provide a good overview of activity of enhancers, promoters, insulators, etc.

The interplay between DNA methylation and chromatin accessibility is an important part of both normal cell differentiation and tumour biology. Despite extensive research on CpG islands methylation in cancer not much is known about how common and important the changes are at DREs. Similarly, we do not know how DNA methylation could be targeted to these elements and how they behave in response to epigenetic therapies with DNA methylation and HDAC inhibitors. These problems need to be addressed as enhancers are important regulators of gene expression.

Recently, we have shown that low levels of DNA methylation at distal regulatory elements reflect their active state in a highly tissue-specific manner and are in fact an integral feature of gene regulation by nuclear receptors. We also demonstrated that DNA methylation can change rapidly after stimulation with hormone – a finding that contributes to the current debate in mechanisms of dynamic DNA demethylation. Thus, we hypothesize that distal regulatory elements frequently undergo dynamic methylation changes, involving DNA hydroxymethylation and therefore could be highly responsive to epigenetic therapies.

Oral cancer is an interesting model to study such questions. There is a broad range of accessible precancerous lesions while tumours are surrounded by partially transformed field of cancerization which has potential to become malignant. The aetiology of oral cancers involves toxic agents (alcohol, tobacco) and HPV infection, the actions of which are possible to reproduce in experimental set ups thus allowing studying towards development of preventive therapies and therapeutic approaches.  

Publications

Morris SA, Baek S, Sung MH, John S, Wiench M, Johnson TA, Schiltz LR, Hager GL (2013) Overlapping chromatin-remodeling systems collaborate genome wide at dynamic chromatin transitions. Nat Struct Mol Biol, doi: 10.1038/nsmb.2718.

Bhattacharyya N, Wiench M, Dumitrescu C, Connolly BM, Bugge TH, Patel HV, Gafni RI, Cherman N, Cho M, Hager GL, Collins MT (2012) Mechanism of FGF23 processing  in fibrous dysplasia. J Bone Miner Res, 27: 1132-1141.

Wiench M, John S, Baek S, Sung M-H, Escobar T, Johnson TA, Simmons CA, Pearce KH, Biddie SC, Sabo PJ, Thurman RE, Stamatoyannopoulos JA, Hager GL (2011) DNA methylation status predicts cell type-specific enhancer activity. EMBO J, 30: 30128-3039.

Wiench M and Hager GL. Control of nuclear receptor function by local chromatin structure (2011) FEBS Journal, 278: 2211-2230.

Wiench M, Hager GL (2010) Expanding horizons for nuclear receptors. EMBO Rep, 11:569-71.

Stavreva DA, Wiench M, John S, Conway-Campbell BL, McKenna MA, Pooley JR, Johnson TA, Voss TC, Lightman SL, Hager GL (2009) Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nature Cell Biol, 11: 1093-102.

Eszlinger M, Wiench M, Jarzab B, Krohn K, Beck M, Lauter J, Gubala E, Fujarewicz K, Swierniak A, Paschke R (2006) Meta- and reanalysis of gene expression profiles of hot and cold thyroid nodules and papillary thyroid carcinoma for gene groups. J Clin Endocrinol Metab 91: 1934-42.

Qiu Y, Zhao Y, Becker M, John S, Parekh BS, Huang S, Hendarwanto A, Martinez ED, Chen Y, Lu H, Adkins NL, Wiench M, Georgel PT, Schiltz RL, Hager GL (2006) HDAC1 acetylation is linked to progressive modulation of steroid receptor induced gene transcription. Mol Cell 22(5):669-679.

Jarzab  B, Wiench M, Fujarewicz K, Simek K, Jarzab M, Oczko-Wojciechowska M, Wloch J, Czarniecka A, Chmielik E, Lange D, Pawlaczek A, Szpak S, Gubala E, Swierniak A (2005) Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications. Cancer Res 65: 1587-97.