Professor Tatjana Stankovic MD, PhD

Professor Tatjana Stankovic

Institute of Cancer and Genomic Sciences
Professor in Cancer Genetics

Contact details

Email
t.stankovic@bham.ac.uk
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Address
Department of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Professor Stankovic is a passionate advocate of translational research in the fields of DNA damage response and hematologic malignancies. For over two decades, her group has studied different ways to manipulate defective DNA damage responses in tumour cells for therapeutic benefit. A particular emphasis is given to the concept of synthetic lethality and pharmacological targeting of compensatory DNA damage mechanisms in tumour cells that are already defective in a single DNA damage response pathway. This approach allows tumour-specific killing that does not impose selection for DNA damage response defective subclones; that is the current problem with classic chemotherapy. 

The translational focus of the Professor Stankovic group led to a productive collaboration with the pharmaceutical industry and the initiation of two clinical trials, one with the PARP inhibitor Olaparib for refractory CLL, T-prolymphocytic leukaemia, and mantle cell lymphoma and the other with ATR and BTK inhibitors for relapsed CLL with ATM/p53 dysfunction.

Professor Stankovic work has been supported by several consequential programme grants from Blood Cancer UK and Cancer Research UK.

Qualifications

  • Ph.D., University of Birmingham, UK 1995
  • Specialist examination in Paediatrics - graded excellent, Belgrade 1987
  • M.Sc. Med., Faculty of Medicine, University of Belgrade 1985
  • M.D. Medical School, University of Belgrade, first class honours 1980

Biography

  • 1981-1987 House Officer, University Children’s Hospital, Belgrade 
  • 1987-1990 Paediatrician and Haematologist, Department of Haematology, University Children’s Hospital, Belgrade. 
  • 1989-1990  Lecturer in Paediatric Oncology/Haematology, University of Belgrade.
  • 1990 (Jan-Dec) British Council Scholar, Birmingham Children’s Hospital and the Department of Cancer Studies, University of Birmingham. 
  • 1991-1994 EB Jones Research Fellow, Department of Cancer Studies, University of Birmingham. 
  • 1994-1998 Research Fellow, supported by the Wellcome Trust,CRC Institute for Cancer Studies, University of Birmingham. 
  • 1998-1999 Research Fellow, supported by Cancer Research Campaign, CRC Institute for Cancer Studies, University of Birmingham 
  • 2000-Dec 2003 Research Fellow RII, supported by Leukaemia Research Fund, CR-UK Institute for Cancer Studies, University of Birmingham 
  • 2004-Sept 2007 Senior Lecturer, CR-UK Institute for Cancer Studies, University of Birmingham 
  • Oct 2007-Oct 2010 Reader in Cancer Genetics, CR-UK Institute for Cancer Studies, University of Birmingham 
  • Oct 2010-present Professor in Cancer Genetics, Institute of Cancer and Genomic Sciences, University of Birmingham

Teaching

Postgraduate supervision

Previously supervised to completion of 11 PhD projects. Currently involved in the supervision of 3 PhD projects:

  • Defining genomic, pharmacological and microenvironmental contexts in which to target a protein hydroxylase
  • Dissecting the role of the DNA damage response in leukaemogenesis in a zebrafish model of GATA2 deficiency
  • Investigating novel epigenetic modifiers of PARP inhibition

Research

Research Interests

A tight regulation of cellular responses to DNA damage prevents the generation of genomic alterations that can lead to tumour development. The integrity of these responses is particularly important in lymphoid progenitor cells that undergo developmentally regulated recombination of immune system genes. Cells with an intact DNA damage response (DDR) are capable of repairing a moderate level of DNA breaks and responding to an excess of unrepaired breaks by activating apoptosis. The latter mechanism is utilised by the majority of DNA-damaging chemotherapeutic agents. Therefore, defects in the DNA damage response can lead not only to tumour development but also to tumour chemoresistance.

Our current research is focused on the elucidation of the role of TP53, Ataxia Telangiectasia Mutated (ATM), the RNase H2 complex, and other DNA damage response genes in tumour initiation and tumour progression. We are addressing not only the cellular phenotype of DDR-defective tumour cells but also the impact of DDR defects on the tumour microenvironment and anti-tumour immune responses. Our hope is that the understanding of DNA damage response and its interaction with the microenvironment can lead to novel therapies that will significantly improve outcomes of patients with hematologic malignancies.

Current Projects

i)        Identification of a network of ATM dependent cellular responses and DNA repair defects that can be targeted for treatment in chronic leukaemia (CLL) and other haematologic malignancies

ii)      RNaseH2 inactivation in cancer cells: a pathogenic mechanism and therapeutic target

iii)    Addressing different mechanisms of tumorigenesis and novel therapeutic approaches in vitro and in vivo models of DNA damage response deficient malignancies

 Google Scholar Profile / ResearchGate Profile

Other activities

  • Member of Blood Cancer UK Research Committee panel since 2022
  • Member of European Research Initiative on CLL (ERIC) since 2018
  • Member of National Cancer Research Institute (NCRI) CLL Committee since 2018
  • Member of Childhood Leukaemia Research UK (CLR-UK) since 2015
  • Member of UK-CLL forum Executive Committee since 2010
  • Co-chair of the Committee panel, for French Institut National du Cancer (INCa) for ‘Paediatric oncology research: ‘Innovative models in paediatric oncology’ 2022
  • Co-chair of the Committee panel, for French Institut National du Cancer (INCa) for ‘Paediatric oncology research: Contribution from interdisciplinary approaches’2021
  • Member of ‘Blood’ editorial board 2020-2023
  • Member of the organizing Committee of the International Workshop on CLL, Edinburgh, September 2019

Publications

Selected Publications:

Bland P, et al. (2023), SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response, Nature Genetics, (8):1311-1323. 

Reijns MAM, et al. (2022), Signatures of TOP1 transcription-associated mutagenesis in cancer and germline, Nature, 602(7898):623-631.

Kennedy E, et al. (2021), TLR9 expression in chronic lymphocytic leukemia identifies a promigratory subpopulation and novel therapeutic target, Blood, 137(22):3064-3078.

Kwok M, et al. (2020), Integrative analysis of spontaneous CLL regression highlights genetic and microenvironmental interdependency in CLL, Blood, 135(6):411-428. 

Balmus G et al. (2019), ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks, Nat Commun, 10(1):87. 

Zimmermann M, et al. (2018) CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions, Nature, 559(7713):285-289.

Pratt G, et al. (2018), A phase I trial of the PARP inhibitor olaparib in patients with relapsed chronic lymphocytic leukaemia, T-prolymphocytic leukaemia or mantle cell lymphoma, BJH, 182(3):429-433. 

Agathanggelou A, et al. (2017). USP7 inhibition alters homologous recombination repair and targets CLL cells independent of ATM/p53 functional status, Blood, 130(2):156-166. 

Kwok M, et al. (2016), ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53- or ATM-defective chronic lymphocytic leukemia cells, Blood, 127(5):582-595.

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