Ruchi Shukla Newcastle University Research Fellow Northern Institute

Ruchi Shukla Newcastle University Research Fellow Northern Institute for Cancer Research Newcastle University

Welcome to Newcastle University

Eat Sleep Make Friends Exercise Rest Vacation Study Reading is most important Gain technical skills Presentation skills Data mining and interpretation Be involved in activities not directly related to work

NURF, NICR, Newcastle, UK 2016 -2021 Postdoc, IGMM, Edinburgh, UK 2013 -2016 Postdoc The Roslin Institute Edinburgh, UK 2011 -2012 Postdoc, Inserm. U 0152 Lyon, France, 2010 -2011 Postdoc, IARC, Lyon France, 2007 -2010 Ph. D, Pune, India 2007

Lessons from my Ph. D (5 years) Discovery consists of looking at the same thing as everyone else and thinking something different -Albert Szent-Gyorgyi Don’t fall in love with your hypothesis 6 Research Articles 1 Review Article And 1 Patent Postdoctoral Research Training Fellowship from WHO-IARC, Lyon, France

Regulation of HBX protein by NF-κB signaling pathway 4 Research Articles Role of LINE 1 retrotransposition in liver cancer 4 Research Articles Understanding regulation of de novo DNA methylation in context to development 1 Research Article 2 Articles Are Currently Under Communication

Shukla et al. , Cell 2013 Mdr 2 -/- mouse Alcohol abuse related-HCC Intrahepatic cholangiocarcinoma (ICC) Genome Research, 2018

Retrotransposons in Health and Diseases Dy Epig sre en gu eti lat c io n ENVIRONMENT Stress Infection Metabolic state Colon Lungs X Liver * L 1 expression: high L 1 activity: high CANCER Adapted from Garcia-Perez et al, Development 2016

Newcastle University Research Fellowship

Cancer Statistics Percentages of new cases and cancer deaths worldwide in 2018 18. 1 million 9. 6 million 11. 6 % 18. 4 % 11. 6 % 9. 2 % 8. 2 % 10. 2 % 8. 2 % 7. 1 % 6. 6 % 5. 7 % 6 4. 7 % Adapted from source GLOBOCAN 2018

…Strategy er cov Del ive r Dis Develop “A world leader in translational cancer research”

Hepatocellular Carcinoma (HCC) – Clinical Problems Advanced disease PST 1 -2 30 -50% Intermediate 15 -20% Early stage 10 -30% >50% recur Resection Liver Transplantation Ablation 70% 5 year survival Majority progress TACE Transarterial Chemoembolisation 24 -30 months UNMET NEEDS Biomarkers to predict Adjuvant strategies Very Advanced disease Poor liver function 20 -40% Liver failure Majority progress Limited Therapies Kinase inhibitors ~11 months UNMET NEEDS Better Therapies Supportive Care <6 months Majority die within one year

1. Wellcome Seed Award (as sole applicant): Feb 2016: Mechanisms for regulation of retrotransposons: transcriptional silencing and reactivation. June 2016: Genetic instability and cancer – the role of RIPs (Retrotransposon Insertion Polymorphisms) in cancer predisposition. Mar 2018. Identifying novel retrotransposon insertion polymorphisms to screen patients for personalised monitoring for hepatocellular carcinoma (HCC) development. 2. Royal Society Research Grant (as sole applicant): May 2016. Development of an in-vitro model to study regulation of LINE 1 retrotransposons in somatic cells. 3. CRUK Career Establishment Award (as sole applicant): Feb 2016. Understanding the factors and mechanisms affecting genetic instability and epigenetic remodelling in the context of hepatocellular carcinoma (HCC). 4. CRUK Career Development Award (as sole applicant): Aug 2017. Role of LINE 1 retrotransposons as key drivers of hepatocellular carcinoma (HCC) initiation and progression. 5. Concern Foundation’s CONquer Can. CER Now Award (as PI, Prof H Reeves as Co. I): Sep 2017. LINE 1 retrotransposons – a novel driver of hepatocarcinogenesis. 6. BBSRC-DTP Ph. D studentship (as lead PI, Co. Is: Prof H Reeves, Prof F Oakley, Prof S Przyborski): Oct 2017. Mechanisms for regulation of retrotransposons: transcriptional silencing during development and reactivation associated with human disease. 7. Ph. D studentship from Newcastle Cancer Centre (as co-lead PI, other co-lead Dr G Strathdee, Co. I Prof H Reeves): Nov 2017. Identification of novel synthetic lethal therapeutic targets through integration of genome-wide DNA methylation and gene expression data. 8. MRC-Medical Research Foundation Viral Hepatitis Research Funding (as PI, Co. Is: Prof H Reeves and Prof D Hay): Nov 2017. Hepatitis C virus infection, endogenous retrotransposon activation and cancer risk. 9. Newcastle University Faculty Ph. D studentship 2018. (as PI, Co. Is: Dr V Korolchuk and Prof H Reeves) Non-Alcoholic Fatty Liver Disease Progression to Hepatocellular Carcinoma: A Focus on Autophagy and Retrotransposons 10. MRC-GCRF Cancer Research and Global Health Pump-Priming Call (as PI, Co. Is Prof H Reeves, Dr Ahmed Wahid and Prof MK El Awady): June 2018. Hepatitis C virus infection, endogenous retrotransposon activation and cancer risk in Egypt and UK populations’ S N I D G N F D E L I A F N U A P P I L A C O I T

Current Lab Structure HCC Synthetic Lethal Genes 1 Ph D student: Jan 2018 -Jan 2022 Collaborators: Dr Gordon Strathdee Prof Helen Reeves LINE 1 Diagnostic, Prognostic and Treatment Stratification Biomarkers 2 Ph D students: Sep 2016 -Sep 2020 Sep 2017 -Sep 2021 Collaborators: Prof Helen Reeves Prof John Lunec Dr Luke Gaughan Dr Ian Logan Other Teaching Activities UG and Masters students for their Research Project Seminars Act as Tutor for UG students Collaborator: Prof Helen Reeves HUNTER Network

Acknowledgments • NURF selection committee • Prof G J Faulkner, Australia • Newcastle University Liver Cancer Team • Prof R Meehan, Edinburgh • Students • NICR Research Support Group • NU Early Career Support Group • All other collaborators from NICR, other Newcastle research centres, other institutes across UK and other countries.