Blizard Institute - Barts and The London

Dr Pradeepa Madapura

Pradeepa

Lecturer

Centre: Centre for Genomics and Child Health

Email: p.m.madapura@qmul.ac.uk
Telephone: 020 7882 2594

Profile

Pradeepa Madapura did his Ph.D research (Bengaluru, India) on chromatin remodelling during spermatogenesis. Pradeep moved to Edinburgh, UK for postdoctoral research with Prof. Wendy Bickmore, a world leading scientist in epigenetics and chromatin field. In 2016 Pradeep started independent research as a University lecturer of genomics at the University of Essex, and is a fellow of higher education academy (FHEA). Pradeep’s lab is relocated to Blizard Institute in September 2018.

Our lab is interested in studying the functional contribution of chromatin proteins, histone modifications and noncoding RNAs in the regulation of gene expression. We also actively collaborate with clinicians and genomics data scientists to use cutting edge methods to investigate the contribution of sequence variation in noncoding regulatory regulatory elements in genetic disorders and cancer.

Website: https://madapuralab.com/

Teaching

Topics for MSc and PhD supervision: Chromatin biology, regulation of gene expression, histone modifications.

Research

Research Interests:

Pradeep’s lab is interested in understanding how noncoding cis regulatory elements called enhancers function. Specifically, his work demonstrated novel classes of transcriptional enhancers that are identified based on the presence of lesser known histone acetylation marks - H4K16ac, H3K64ac, and H3K122ac, which lack H3K27ac, a histone mark widely used previously to define active enhancers (Genome Res 2013, Nature Genet 2016, Transcription 2017 and Nature Genet 2018). Recently, in collaboration with Prof. David FitzPatrick group in Edinburgh, Pradeep discovered de novo mutations in BRD4 protein in patients with a rare developmental disorder – Cornelia deLange Syndrome (CdLS) leads to enhancer dysfunction.

While studying the cellular function of an interesting protein called LEDGF or PSIP1, implicated in HIV integration and leukaemia, Pradeep’s work transformed the view that histone modifications have roles not only in transcription but also in RNA processing (PloS Genet 2012). Using multiple state-of-the-art methods Pradeep’s lab demonstrated the mechanism through which PSIP1 regulates homeobox (HOX) genes through interplay between polycomb and trithorax complexes and a long noncoding RNA called HOTTIP ((Nucleic Acid Res 2014, PloS Genet 2017).

 

Current project in the chromatin and gene regulation lab include:

  1. Investigate the role of histone H3 globular acetylations (H3K122ac and H3K64ac), H4 tail acetylation (H4K16ac) and transcriptional coactivators including acetyl binding protein - BRD4 in enhancer function. We have also been developing and using genome-wide methodologies to better identify enhancers in the mammalian genome and factors contributing to enhancer function.
  2. We also continue to work on the role of a chromatin protein called PSIP1, homeobox (HOX) transcription factors and long noncoding RNA HOTTIP in cancer development and therapy resistance due to altered enhancer function. 
  3. We actively collaborate with clinicians and genomics data scientists, we use cutting-edge functional genomics methods including sequencing based and CRISPR derived methods to investigate the contribution of coding and noncoding sequence variants found in genetic disorders and cancer.

Pradeep’s lab is a part of QMUL Epigentics Hub.

Research Group Members: 

  • Dr. Myles Garstang email: m.garstang@qmul.ac.uk (Postdoctoral fellow)
  • Ms. Fionnuala McKenna (visiting PhD student, experimental)
  • Mr. Jareth Wolfe (visiting PhD student, computational)

Publications

 

Olley G, Ansari M, Bengani H, Grimes GR, Rhodes J, Kriegsheim AV, Blatnik A, Stewart F J, Ross A, Bickmore WA*, Pradeepa MM*, and FitzPatrick DR*. BRD4 interacts with NIPBL and is mutated in a Cornelia de Lange-like Syndrome. Nature Genet. 2018. doi:10.1038/s41588-018-0042-y * corresponding author

Pradeepa M M*, McKenna F, Taylor GCA, Bengani H, Grimes GR, Wood A, Bhatia S, and Bickmore W A*. (2017) Psip1/p52 regulates distal Hoxa genes through activation of lncRNA Hottip PloS Genet 13, e1006677 (2017). *corresponding author Perspective article highlighting this work is published in PLoS Genet 13(6): e1006797.

Pradeepa M M*, Grimes G, Kumar Y, Taylor G, Olley G, Schneider R and Bickmore W A* (2016) Histone H3 globular domain acetylation identifies a new class of enhancers. Nature Genet. 48, 681–686 doi:10.1038/ng.3550. *corresponding author Two recommendations by F1000 Prime.

Taylor G, Eskeland R. Balkan B H, Pradeepa M M* & Bickmore W A*. (2013) H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction. Genome Res. doi: 10.1101/gr.155028.113. * corresponding author

Pradeepa, M M., Sutherland, H. G., Ule, J., Grimes, G. R., & Bickmore, W. A. (2012). Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing. PLoS Genet, 8(5), e1002717. doi:10.1371.

Updated and full list of publications: https://scholar.google.co.uk/citations?user=ddBQF80AAAAJ&hl=en