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Overview

Dr Patricia Muller

Associate Professor


Affiliations
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Associate Professor in the Department of Biosciences145 

Biography

I started my academic career as a PhD student working on copper homeostasis and the COMMD1 protein in the UMC Utrecht, the Netherlands. I got inspired by p53 nuclear export regulation to understand the function and regulation of COMMD1. My fascination for p53 lead me to do a postdoc in the lab of Prof Karen Vousden, CRUK: the Beatson Institute, Glasgow, UK. I managed to get this position funded through the Dutch organisation NWO (A Rubicon fellowship). We set out to understand why expression of a mutant p53 protein is different than loss of p53 expression in cancers. We discovered a new signalling pathway adopted by mutant p53 to promote invasion and metastasis via RCP (Rab11FIP1). Mutant p53 facilitated the recycling of integrins and growth factor receptors to the plasma membrane, leading to enhanced Erk1/2 and Akt signalling. In a screen to detect novel interaction partners of RCP, I found several membrane transporters. This screen formed the basis of my application for a Henry Dale Fellowship (Welcome Trust) with which I started my independent research group in 2014 in the MRC Toxicology Unit in Leicester, UK.

In 2016 I was awarded an early career award from the Biochemistry Society. I uncovered a role for RCP in regulating drug transporter membrane expression in mutant p53 cells. Additionally, while doing this work, we made an observation that mutant p53 cancer cells are more likely to engulf neighbouring cells. We could correlate this behaviour to cell-in-cell structures in cancers, which we believe are pro-tumourigenic. Due to relocation of the MRC institute, I decided to continue my fellowship in the CRUK Manchester Institute in 2017 and broadened my interest into discovering therapeutic opportunities in tumours with (mutant) p53. Based on my previous work in copper homeostasis during my PhD, I also started a research line into the toxic properties of the metal copper on p53 signalling.

In 2021, I moved to Durham to further the research into the relationship between metals and p53. Metals can unfold the p53 molecule and change its function. In cancer cells, p53 unfolding upon metal load impairs p53 tumour suppressor function and make it act like a mutant p53 protein. This happens at very low levels of metal and suggest a physiological role for metals in regulating p53 function. 

Research Interests

In our lab we are interested in answering the following questions:

  1. How does mutant p53 promote gain-of-function in invasion, metastasis and chemoresistance? What are the underlying mechanisms?
  2. Why are certain p53 mutants selected for in certain cancers? Is this related to the environment of the cancer?
  3. To what extent do mutant p53 induced cell-in-cell structures contribute to mutant p53 Gain-of-function and how are these structures formed?
  4. How do metals impact on p53 function in cancer, other diseases and physiological processes?

Research groups

  • Animal Cells and Systems

Publications

Journal Article