Current Position:

          Newcastle University Research Fellow at Northern Institute for Cancer Research, Newcastle University.

Previous positions:

            Postdoctoral Fellow : MRC Human Genetics Unit, IGMM, Edinburgh University, UK.

            Postdoctoral Fellow : The Roslin Institute, Edinburgh University, UK.

            Postdoctoral Fellow :  INSERM U1052, Lyon, France.

            Postdoctoral Fellow : International Agency for Research on Cancer, Lyon, France. 

Qualifications :

           Ph D : National Center for Cell Science, Pune, India. 

           Masters in Biotechnology : Devi Ahilya University, Indore, India.

           Bachelor of Science (Hons. in Microbiology) : Delhi University, India.

Research Interest: Understanding the factors and mechanisms affecting genetic instability and epigenetic remodelling in the context of hepatocellular carcinoma (HCC) 

Summary: HCC is the sixth most common type of cancer and the second most frequent cause of cancer-related deaths worldwide. Over 70% of patients have incurable disease at presentation, due to late detection.  The combination of rising incidence and lack of treatments has contributed to marked increases in HCC mortality – which is predicted to continue increasing for the next 20 years. Hence, much clinical research is focused on developing novel more effective therapeutic options for these patients. It is widely recognized that to have a major impact on survival, early detection and better treatment strategies are urgently required. Hence my focus is the identification of novel therapeutic target(s) and diagnostic and treatment stratification biomarkers for HCC patients.

The main focus of the lab is to identify and characterise epigenetically deregulated therapeutic targets, primarily L1 autonomous retrotransposons. Also, we are exploring DNA methylation patterns in HCC samples to identify potential Synthetic Lethal genes and evaluate them as novel therapeutic targets for HCC. Activation of retrotransposons has been well documented in cancers of different origins leading to an increase in genetic instability by promoting gene deletions/duplications and genomic rearrangements. Active retrotransposons can influence gene expression patterns, generate truncated or antisense gene transcripts and alter splicing patterns [1, 2]. I have demonstrated that active retrotransposition is associated with activation of oncogenic pathways in hepatocellular carcinoma (HCC) [3,4]. However, the mechanism/factors leading to activation of retrotransposons during cancer development are unclear. Hence the research questions we are addressing are:

1. The relationship between the activation of L1s and HCC status.

2. The mechanism (s) of retrotransposons activation in the context of HCC.

3. Role of retrotransposons insertion polymorphism in cancer predisposition.

In parallel, we are aiming to identify diagnostic, prognostic and treatment stratification biomarkers by focusing on gene expression changes and DNA methylation in peripheral immune cells and circulating cell-free DNA to develop 'liquid biopsy tools'. The ultimate aim is to develop potential therapeutic strategies and biomarkers for HCC patients in order to reduce lethality associated with the disease.

Collaborators: 

Within NICR: Prof Helen Reeves, Prof John Lunec, Dr Gordon Strathdee, Dr Luke Gaughan

Other Newcastle University Research Institutes: Liver Fibrosis Unit, Institute of Cellular Medicine.

Outside Newcastle: Prof Richard Meehan, MRC Human Genetics Unit, IGMM, Edinburgh University.

                                  Dr Jose L. Garcia-Perez, MRC Human Genetics Unit, IGMM, Edinburgh University.

                                  Prof Gerald G. Schuman, Paul-Ehrlich-Institute, Germany.

                                  Dr Jamila Faivre, U1193 INSERM, University Paris-Sud, France. 

                                  Dr Geoff Faulkner, Mater Research Institute, Brisbane, Australia.

References:

1. Kazazian HH, Jr.: Mobile elements: drivers of genome evolution. Science 2004, 303(5664):1626-1632.

2. Ayarpadikannan S, Kim HS: The impact of transposable elements in genome evolution and genetic instability and their implications in various diseases. Genomics & informatics 2014, 12(3):98-104.

3. Shukla R, Upton KR, Munoz-Lopez M, Gerhardt DJ, Fisher ME, Nguyen T, Brennan PM, Baillie JK, Collino A, Ghisletti S et al: Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma. Cell 2013, 153(1):101-111.

4. Schauer SN^†, Carreira PE^†, Shukla R^†, Gerhardt DJ, Gerdes P, Sanchez-Luque FJ, Ghisletti S, Faivre J, Ewing AD, Richardson SR, and Faulkner GJ: L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis. Genome Research 2018, 28(5):639-653. (^† These authors contributed equally).

Undergraduate Teaching

• Supervision of research projects of undergraduate students in Biomedical Sciences
• Tutor for undergraduate students

Postgraduate Teaching

Supervision of the Faculty of Medical Sciences MRes and MPharm students

Ph. D Students

Bassier Zadran: Sep 2016 – Sep 2020: Role of retrotransposons in hepatocellular carcinoma origin and progression – potential biomarker and therapeutic target?

Praveen D Sudhindhar: Sep 2017 – Sep 2021:   Understanding factors involved in regulation of Long-Interspersed-Nuclear-Elements retrotransposons in the context of Hepatocellular Carcinoma.

Chalermsin Permtermsin: Jan 2018 – Jan 2022:  Analysis of DNA methylation patterns in Hepatocellular Carcinoma to identify novel therapeutic targets and biomarkers that predict response to therapy.

• Schauer SN, Carreira PE, Shukla R, Gerhardt DJ, Gerdes P, Sanchez-Luque FJ, Nicoli P, Kindlova M, Ghisletti S, Santos AD, Rapoud D, Samuel D, Faivre J, Ewing AD, Richardson SR, Faulkner GJ. L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis. Genome Research 2018, 28(5), 639-653.
• Ravà M, D'Andrea A, Doni M, Kress TR, Ostuni R, Bianchi V, Morelli MJ, Collino A, Ghisletti S, Nicoli P, Recordati C, Iascone M, Sonzogni A, D'Antiga L, Shukla R, Faulkner GJ, Natoli G, Campaner S, Amati B. Mutual epithelium-macrophage dependency in liver carcinogenesis mediated by ST18. Hepatology 2017, 65(5), 1708-1719.
• Shukla R. Retrotransposons and genetic instability in hepatocellular carcinoma. Hepatic Oncology 2017, 4(1), 5-8.
• McLaughlin K, Flyamer IM, Thomson JP, Mjoseng HK, Shukla R, Williamson I, Grimes GR, Illingworth RS, Adams IR, Pennings S, Meehan RR, Bickmore WA. DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency. Cell Reports 2019, 29(7), 1974-1985.e6.
• Klawitter S, Fuchs NV, Upton KR, Muñoz-Lopez M, Shukla R, Wang J, Garcia-Canadas M, Lopez-Ruiz C, Gerhardt DJ, Sebe A, Grabundzija I, Merkert S, Bock A, Held U, Witthuhn A, Haase A, Sarkadi B, Löwer J, Wolvetang EJ, Martin U, Ivics Z, Izsvák Z, Garcia-Perez JL, Faulkner GJ, Schumann GG. Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells. Nature Communications 2016, 7, 10286.
• Thomson JP, Fawkes A, Ottaviano R, Hunter JM, Shukla R, Mjoseng HK, Clark R, Coutts A, Murphy L, Meehan RR. DNA immunoprecipitation semiconductor sequencing (DIP-SC-seq) as a rapid method to generate genome wide epigenetic signatures. Scientific Reports 2015, 5, 9778.