Ruchi Shukla Newcastle University Research Fellow Northern Institute for Cancer Research

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

2. Welcome to Newcastle University

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

4. NURF, NICR, Newcastle, UK 2016-2021 Postdoc, IGMM, Edinburgh, UK 2013-2016 Postdoc The Roslin Institute Edinburgh, UK 2011-2012 Postdoc, InsermU0152 Lyon, France, 2010-2011 Postdoc, IARC, Lyon France, 2007-2010 Ph.D, Pune, India 2007

5. 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

6. Regulation of HBX protein by NF-κB signaling pathway 4 Research Articles Role of LINE1 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

7. Shukla et al., Cell 2013 Mdr2-/- mouse Alcohol abuse related-HCC Intrahepatic cholangiocarcinoma (ICC) Genome Research, 2018

8. Retrotransposons in Health and Diseases ENVIRONMENT Stress Infection Metabolic state Epigenetic Dysregulation * Liver Colon Lungs X L1 expression: high L1 activity: high CANCER Adapted from Garcia-Perez et al, Development 2016

9. Newcastle University Research Fellowship

10. 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

11. …Strategy Deliver Discover Develop “A world leader in translational cancer research”

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

13. 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 LINE1 retrotransposons in somatic cells. • 3. CRUK Career Establishment Award (as sole applicant): Feb 2016. Understanding the factors and mechanisms affectinggenetic instability and epigenetic remodelling in the context of hepatocellular carcinoma (HCC). • 4. CRUK Career Development Award (as sole applicant): Aug 2017. Role of LINE1 retrotransposons as key drivers of hepatocellular carcinoma (HCC) initiation and progression. • 5. Concern Foundation’s CONquerCanCER Now Award (as PI, Prof H Reeves as CoI): Sep 2017. LINE1 retrotransposons – a novel driver of hepatocarcinogenesis. • 6. BBSRC-DTP Ph. D studentship (as lead PI, CoIs: 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, CoI 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, CoIs: 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, CoIs: 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, CoIs 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’ FAILED FUNDING APPLICATIONS

14. Current Lab Structure HCC Diagnostic, Prognostic and Treatment Stratification Biomarkers Synthetic Lethal Genes LINE1 2Ph D students: Sep 2016-Sep 2020 Sep 2017-Sep 2021 1 Ph D student: Jan 2018-Jan 2022 Collaborators: Prof Helen Reeves Prof John Lunec Dr Luke Gaughan Dr Ian Logan Collaborator: Prof Helen Reeves HUNTER Network Collaborators: Dr Gordon Strathdee Prof Helen Reeves Other Teaching Activities UG and Masters students for their Research Project Seminars Act as Tutor for UG students

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