Northern Institute for Cancer Research

Staff Profile

Dr Ruchi Shukla

Newcastle University Research Fellow

Background

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

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

Summary: 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]. However, the mechanism/factors leading to activation of retrotransposons during cancer development are unclear. Now my research focus is:

1. Understand the mechanism(s) of retrotransposons activation by monitoring the dynamic epigenetic landscape of hepatocytes exposed to various HCC associated carcinogenic factors (both viral and non-viral).

2. Evaluate the relationship between L1s (autonomous-retrotransposons) activation and HCC status.

3. Role of retrotransposons insertion polymorphism in cancer predisposition.

The ultimate aim  is to develop potential therapeutic strategies and early biomarkers for HCC patients in order to reduce lethality associated with the disease.


Collaborators: 

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

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.