[FULBRIGHT] - Investigating renal cancer metabolism using novel surgical models.

Cissy Yong spent three months in Texas as part of her research into renal cancer metabolism.

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Picture: Members of the DeBerardinis Lab, Professor DeBerardinis (far left).  Cissy is centre-left wearing a purple shirt.

The Fulbright Commission-The Urology Foundation Scholar Award 2018

Cissy Yong - Wellcome Trust PhD for Clinicians Student, Honorary Urology Speciality Registrar

Hospital               Cambridge University Hospitals NHS Foundation Trust

Host Institution   University of Texas Southwestern Medical Centre, Dallas, Texas

Personnel           The DeBerardinis Lab

Prof. Ralph DeBerardinis, Chief of Paediatric Genetics and Metabolism, Director of the Genetic and Metabolic Disease Program at the Children’s Research Institute

Reason for visit

The DeBerardinis lab is at the forefront of cancer metabolomics research that has vastly progressed society’s understanding of the metabolic processes and reprogramming that occur in cancer.  This lab has developed human in vivo based models to study cancer metabolism directly in patients, which has provided advanced insight into this crucial aspect of cancer biology 1–4.  Improving our knowledge of cancer metabolism, that is understanding how cancer cells selectively survive, adapt and evolve is vital in developing new tools and therapies for clinical practice. 

The incidence of renal cancer, one of the top 10 cancers in the USA and UK, is projected to increase by 26% by 2035 in the UK 5.  About a third of patients present with advanced stage disease and only 56% of all patients survive their disease for 5 or more years in England and Wales 5.  Dysregulated metabolism is an established component of renal cancer, and increasingly, this metabolic reprogramming is recognised to play a complex role in the development and progression of renal cancer 6–8.  However, there is a paucity of human in vivo studies to further direct and drive our understanding of metabolism in renal cancer 3.  The aim of my visit was to gain first-hand experience in this metabolomics lab, in particular with the human in vivo model, with the view to bring this expertise back to the UK to study renal cancer metabolism in patients as part of my PhD in Cambridge. 

Benefits from visit

The Fulbright-The Urology Foundation Scholar Award has provided me with the opportunity to visit one of the leading labs in the field of cancer metabolism.  My visit to the DeBerardinis lab has equipped me with a solid foundation in cancer metabolomics research that is invaluable for me starting my PhD back in the UK.  I have been able to develop my skillset and confidence as an academic urological trainee.  This includes conducting and analysing metabolomic experiments with a focus on clinical relevance and appreciating how integration of different models of renal cancer help answer specific hypotheses.  Furthermore, I have gained experience in learning the gold-standard techniques in conducting the human in vivo studies pioneered by this lab, which is crucial in setting up these studies back in the UK.  Finally, this visit has fostered an important collaboration between our labs here in the UK and the DeBerardinis Lab in the USA to conduct research synergistically to improve our understanding of renal cancer metabolism, with the underlying aim to advance future management of this disease process.

Residing in Dallas, Texas during this 3 month visit has been a fantastic opportunity to immerse myself into the Texan culture and lifestyle.  The southern hospitality and Tex-Mex cuisine were aspects I particularly enjoyed as well as exploring the cultural diversity of Texan cities such as Austin and San Antonio, and hiking in the vast swathes of the Big Bend National Park bordering Mexico.  Of note, it takes about 14 hours to drive from one side of Texas to the other side and as such, cities like Dallas are hugely spread out, which means transportation within Texas was tricky for a cycle enthusiast like me.  The silver lining to this was that I was able to really advance my international driving skills, and by the end of my visit I was driving like a Texan! 

Advice/ guidance for organising a visit

Do not be afraid to reach out and make contacts.  The gateway to my research experience in the USA was a simple email to the Professor of the lab I was interested in, explaining who I was and why I wanted to come to the lab.  A few emails and a teleconference later, to ensure our research aims and expectations aligned, I was invited to join his lab as a visiting researcher which provided the nidus for my application for the Fulbright-TUF scholar award 2018-19.

The UK Fulbright Commission were instrumental in organising the J1 visa and preparing us for life and work culture in the USA through their workshops and orientation programme.  For those as fortunate as I am to get a scholar award, my word of advice would be to complete any paperwork the Fulbright direct your way in a very timely fashion and attend their informative and fun events! 

Acknowledgements

To the UK Fulbright Commission and The Urology Foundation for supporting my visit to the USA and for their support and advice throughout the whole process.

To Prof. Ralph DeBerardinis, Dr. Akash Kaushik and all the members of the DeBerardinis lab who professionally have mentored and taught me and personally have welcomed me to Texas.

To Mr. Grant Stewart and Dr. Christian Frezza, my PhD Supervisors at the University of Cambridge, and to the Wellcome Trust, my PhD funders for their encouragement, advice and support throughout the whole process.

Bibliography

1.         Hensley, C. T. et al. Metabolic Heterogeneity in Human Lung Tumors. Cell 164, 681–694 (2016).

2.         Faubert, B. et al. Lactate Metabolism in Human Lung Tumors. Cell 171, 358-371.e9 (2017).

3.         Courtney, K. D. et al. Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo. Cell Metab. 28, 793-800.e2 (2018).

4.  Maher, E. A. et al. Metabolism of [U-13 C]glucose in human brain tumors in vivo. NMR Biomed 25, 1234–1244 (2012).

5.  Cancer Research UK, Kidney Cancer Statistics. http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/kidney-cancer#heading-Two. Accessed Online [5 November 2018].

6.         Kaelin, W. G. & McKnight, S. L. Influence of Metabolism on Epigenetics and Disease. Cell 153, 56–69 (2013).

7.         Shim, E.-H. et al. l-2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer. Cancer Discov 4, 1290–1298 (2014).

8.         Sciacovelli, M. et al. Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition. Nature 537, 544–547 (2016).

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