Dr Abdelkader Essafi

Embryonic reprogramming (in disease) laboratory

Our development from a single cell requires phenomenal growth. Finely tuned embryonic programs coordinated by highly conserved regulatory networks keep this growth in check. In adult cells, the embryonic processes remain dormant, but external pathogens and cell-autonomous changes re-wire the cell’s molecular networks to re-activate the embryonic processes. It is exactly the hijacking of dormant embryonic phenomena that render cancer cells drug resistant, stem cell-like and metastatic. Regrettably, our understanding of how this hijack and re-wiring happens remains limited.

Using a multidisciplinary approach that incorporates sequencing, 3D culture and inducible gene editing tools as well as computational biology, we aim to answer two key questions:

1. How are embryonic programs re-awakened during disease progression?
2. How can we therapeutically reverse (i.e. treat), if not altogether stop (i.e. prevent), these abnormal re-activations?

My way into understanding how this re-wiring happens is a protein called Wilms Tumour protein (WT1). This focus is clinically relevant, as WT1 is a prime oncofoetal antigen, in fact  it topped a national cancer institute (NCI) antigen prioritization list. As a developmental regulator, WT1’s well-documented expression is restricted to few specialised cell types in the adult (e.g. podocytes, sertoli cells and pericytes) yet it is uniquely and abnormally reactivated in epithelial cancer cells and leukaemic  stem cells. Consequently, WT1-based immunotherapy clinical trials in haematopoietic and solid tumours are showing promising results. 

The dissection of the regulatory and epigenetic mechanisms that underlie WT1 reactivation in cancer will be a paradigm for understanding the dynamic malfunction of embryonic reprogramming in pathology.

Career history

• 2016- present: Senior Lecturer in Cancer Biology (CMM).
• 2013-2016:  Lecturer in Cancer Biology, school of Cellular and Molecular Medicine (CMM), Bristol (+2 years career break).
• 2012-2013: MRC Senior Investigator Scientist, MRC HGU.
• 2009-2012: Wellcome trust-Beit Memorial Research Fellow, MRC Institute of Genetics and Molecular Medicine (MRC IGMM), University of Edinburgh.
• 2007-2009: MRC Career Development Fellow, MRC Human Genetics (MRC HGU), Edinburgh.

Education

• 2002-2006: PhD Biochemistry, Imperial College London.
• 1999-2002: BSc (hons) Genetics, UCL.

Current Funding

• Wellcome Trust Seed Award in Science: 2017-2018
• University Lecturer Start up fund, University of Bristol: 2015-2016
• The University Cancer Research Fund Committee: 2015-2016

Career Break

Dr Essafi has had career break (2 years from April 2014) due to an accident that resulted in spinal cord injury and paraplegia.