Year 4 Graduate Student Prize Winner
When I was in high school, I was curious about every single STEM discipline and had absolutely nothing figured out. I could have easily pursued a degree in Physics, Chemistry or Informatics but ended up becoming a Biotechnology student at the University of Salamanca. And looking back, the combination of unexpected, last-minute spur-of-the-moment decisions joined to the right people putting their faith in me is what has taken me to the most amazing places. Supported by La Caixa Foundation, I enrolled onto the MRes in Cancer Biology at Imperial College London to finally pursue a career in biomedical research. Less than a year later, I was ready to devote myself to the molecular biology field when I got offered a NDM Prize Studentship to join Dr J Ross Chapman’s lab as his first DPhil student.
My research focuses on the intricate relationship between a DNA repair protein, 53BP1, and the tumour suppressor, aka guardian of the genome, p53. Discovered as a p53-binding protein more than two decades ago, 53BP1 quickly caught the eye of the DNA repair field. 53BP1 has since been attributed major roles in DNA double strand break repair; conversely, its contribution to p53-dependent tumour suppression has remained ill-defined. During my DPhil I dived into the 53BP1-p53 world to define the relevance of 53BP1 in modulation of p53 responses and how it is intrinsically distinct and separable of 53BP1’s well-known DNA repair role. An exquisite molecular characterisation of 53BP1 in this context led us to the discovery of another component of this axis, the deubiquitinating enzyme USP28. Together, 53BP1 and USP28 fine-tune p53-dependent transcription by modulating its DNA binding activity which results in efficient checkpoint activation and senescence responses. By the end of my second year, this work had resulted in a publication that was soon highlighted by review journals and attracted the interest of the DNA repair field. I have since presented this piece of research at national and international conferences and its relevance granted me the award of a Future of Science Fund Scholarship at the prestigious Keystone Conference in Genomic Instability and DNA repair.
In order to complete my DPhil work, I have been spending the past year unravelling the mechanistic details behind the USP28-53BP1-p53 axis and, more recently, the in vivo relevance in both physiological and pathological conditions.
Belonging to Dr J Ross Chapman’s group has shaped my scientific character, challenging my intellect on a daily basis. Being continuously surrounded by extraordinary people performing science to the highest standards has surely made me strive and best apply my capabilities to eventually succeed in this DPhil adventure. In addition, the University of Oxford, and specifically the WCHG, foster a working environment where collaborations and exchange of know-how allow the efficient progression of projects like the one I have developed, moving from an in vitro to an in vivo scenario in an incredibly short time frame.
Although this year marks the end of my DPhil studies (hopefully) it will also mark the amazing starting point of my academic career.
Keystone Symposia Future of Science Fund Scholarship recipient. Conference in Genomic Instability and DNA repair, Santa Fe, NM, USA. April 2017.
Cuella-Martin R,Oliveira C, Lockstone HE, Snellenberg S, Gromulsova N, Chapman JR. 53BP1 Integrates DNA Repair and p53-Dependent Cell Fate Decisions via Distinct Mechanisms. Mol Cell 64: 51-64 (2016).
Durocher D., Pelletier L. 53BP1 goes back to its p53 roots. Mol Cell 64: 3-4 (2016).
p53: Understanding the actions of 53BP1. Nat Rev Mol Cell Biol 17: 608 (2016).
53BP1 regulates p53 independent of its DNA repair function. Cancer Discov 6:OF15 (2016).