Nicholas McGranahan

2024 United Kingdom Award Winner — Faculty

Current Position:
Sir Henry Dale Fellow

Institution:
University College London

Discipline:
Genetics & Genomics

Recognized for: Developing computational analyses to understand how tumors have developed and how they might be treated. McGranahan’s work has laid a foundation for exploring tumor development as an evolutionary process. He has developed tools to assist researchers in understanding the genetic faults that have accumulated during a tumor’s development and in evaluating how these can be harnessed to predict the tumor’s future trajectory and how we might design more effective cancer treatments.

Areas of Research Interest and Expertise: Cancer, Evolution, Bioinformatics, Genomics

Previous Positions: 

• BSc, University of Bath
• MSc, University College London
• PhD, University College London (Advisors: Charles Swanton and Nicholas Luscombe)
• Postdoctoral Fellow, The Francis Crick Institute (Advisor: Charles Swanton)
• Senior Research Associate, University College London

Research Summary:

Cancer remains one of the leading causes of death worldwide. For every individual patient, cancer manifests differently, but it is always a scary and uncertain diagnosis. The improved success of cancer treatments relies on creative tools to understand cancer progression at a personalized level. Computational geneticist Nicholas McGranahan, PhD, has developed a unique suite of computational tools to broaden our understanding of cancer development, the spread of cancer cells around the body, and how cancer cells evade our body’s own immune system.

As cancer cells grow and transform, they accumulate genetic mutations that can promote metastasis to other parts of the body. McGranahan has developed novel computational tools to decipher a tumor’s evolutionary path, providing an increased understanding of how cancer cells accumulate and tolerate mutations in their DNA during these periods of rapid cell growth. This work identified several key barriers to tumor growth that may present new targets for more effective cancer treatments. Additionally, McGranahan has developed novel machine-learning methods to help us understand the key features that determine whether tumors are likely to spread to distant organs. 

In another application, McGranahan developed a tool to systematically identify novel interactions between growing cancer cells and the dynamic immune system, shedding light on the diverse ways in which cancer cells evade immune predation. Importantly, this work has created a framework to assess the tumor-immune landscape and categorize patients for immunotherapies.

McGranahan is a true leader in the field of cancer genomics, making all his bioinformatic tools freely available to the public and laying a foundation for clinical applications that leverage the predictive metrics described above to design treatment plans with high potential for disease-free survival.

"I was amazed and delighted that my group’s work has been recognised. We explore how we can harness evolutionary principles to understand cancers and why they are so hard to treat. Through this work, we aim to develop new treatment approaches."

Key Publications:

1. S. López, E.L. Lim, S. Horswell, K. Haase, A. Huebner, M. Dietzen, T. P. Mourikis, T.B. Watkins, A. Rowan, S.M. Dewhurst, N.J. Birkbak, G.A. Wilson, P. Van Loo, C. Swanton, N. McGranahan. Interplay between whole-genome doubling and the accumulation of deleterious alterations in cancer evolution. Nature Genetics, 2020.
2. R. Rosenthal, E.L. Cadieux, R. Salgado, M.A. Bakir, D.A. Moore, C.T. Hiley, T. Lund, M. Tanić, J.L. Reading, K. Joshi, J.Y. Henry, E. Ghorani, G.A. Wilson, N.J. Birkbak, S. Veeriah, Z. Szallasi, S. Loi, M.D. Hellmann, A. Feber, B. Chain, J. Huerrero, S.A. Quezada, J. Demeulemeester, P. Van Loo, S. Beck, N. McGranahan, C. Swanton, The TRACERx consortium. Neoantigen-directed immune escape in lung cancer evolution. Nature, 2019.
3. R. Bentham, K. Litchfield, T.B. Watkins, E.L. Lim, R. Rosenthal, C.T. Hiley, M.A. Bakir, R. Salgado, D.A. Moore, C. Swanton, N. McGranahan. Using DNA sequencing data to quantify T cell fraction and therapy response. Nature, 2021.
4. C. Martínez-Ruiz, J.R.M. Black, C. Puttick, M.S. Hill, J. Demeulemeester, E. Larose Cadieux, K. Thol, T.P. Jones, S. Veeriah, A. Toncheva, P. Prymas, A. Rowan, S. Ward, L. Cubitt, F. Athanasopoulou, O. Pich, T. Karasaki, D.A. Moore, R. Salgado, E. Colliver, C. Castignani, M. Dietzen, A. Huebner, M. Al Bakir, M. Tanić, T.B.K. Watkins, E.L. Lim, A.M. Al-Rashed, D. Lang, J. Clements, D.E. Cook, R. Rosenthal, G.A. Wilson, A.M. Frankell, S. de Carné Trécesson, P. East, N. Kanu, K. Litchfield, N.J. Birkbak, A. Hackshaw, S. Beck, , P. Van Loo, M. Jamal-Hanjani, TRACERx Consortium, C. Swanton, N. McGranahan. Genomic–transcriptomic evolution in lung cancer and metastasis. Nature, 2023.

Other Honors:

In the Media:

EurekAlert! – Novel ACT-Discover Liquid Biopsy Shows 30% Increased Sensitivity in Detecting Tumor DNA in Blood

Technology Networks Diagnostics – Novel Liquid Biopsy Detects ctDNA in 30% More Patients With Pancreatic Cancer

Website