Pradeepa Madapura did his Ph.D research at JNCASR Bengaluru, India on chromatin remodelling during spermatogenesis. Pradeep moved to Edinburgh, UK for postdoctoral research with Prof. Wendy Bickmore.
Pradeep’s lab at the Blizard Institute is interested in studying the functional contribution of chromatin proteins, histone modifications and noncoding RNAs in the regulation of gene expression. His also actively collaborate with clinicians and genomics data scientists to use cutting-edge methods to investigate the contribution of sequence variation in noncoding regulatory elements in genetic disorders and cancer.
2021 – Associate professor (Senior lecturer) at the Queen Mary University of London, UK
2018 – 2021 Assistant professor (Lecturer) at the Queen Mary University of London, UK
2016 – 2018 Assistant professor (Lecturer) at the University of Essex, Colchester, UK
2009 – 2015 Postdoctoral Fellow in the laboratory of Prof Wendy Bickmore
2004 – 2009 PhD in Molecular biology and Genetics from JNCASR, Bangalore (Supervisor: MRS Rao)
2001– 2003 MSc(Agri) Biochemistry, University of Agriculture Sciences, Bangalore
1997– 2001 BSc(Agriculture), University of Agriculture Sciences, Bangalore
MBBS programme: PBL facilitator on three modules – Human Development 1, Human Development 2, and locomotor.
MEDPRO mentoring Scheme: MBBS students
Experimental pathology: Marking
Lab Supervisor for BSc, MSc and intercalated MBBS students
My research is focused on investigating the role of chromatin proteins, histone modifications in regulation of gene expression, splicing and DNA repair. We use genome-wide methodologies and single locus precision editing and gene engineering methods investigate how genome is regulated and factors contributing to function of gene regulatory elements. Highlight of my work includes identification of novel class of enhancer elements that lack acetylation of histone H3 at lysine 27 (H3K27ac), a widely used marker of active enhancers. We showed H3 globular acetylation at lysine 112 (H3K122ac) (Nature Genet 2016) and acetylation at H4 lysine 16 (H4K16ac) (Genome Res 2013) marks active enhancers. More importantly, we show that there are many enhancers in the genome that lack H3K27ac but are acetylated at H3K122 or H4K16 lysines. Our recently work demonstrated de novo mutations in a key transcriptional regulator BRD4 which is known to function at enhancers and promoters by binding to acetylated histones causes a neurodevelopmental disorder called Cornelia deLange Syndrome (CdLS) (Nature Genet 2018). Our ongoing work suggests that CdLS mutations in BRD4 leads to altered DNA damage response pathway (Nature Commun 2021).
Apart from my main focus on genome regulation, our lab is also interested in deciphering the role of chromatin proteins, homeobox (HOX) transcription factors and long noncoding RNA HOTTIP in cancer development and therapy resistance due to altered enhancer function. My lab is interested in deciphering the function of a very interesting multifunctional chromatin protein (PSIP1) implicated in HIV integration and Leukaemia. My work has demonstrated role of PSIP1 in coupling histone modification with RNA splicing (PLoS Genet 2012) and in regulation of HOX genes (Nucleic Acid Res 2014). Using cutting edge methods, we have demonstrated enhancer like function of a long noncoding RNA called HOTTIP (PLoS Genet 2017). Current and future projects include: 1) Improving our understanding of how pathogenic mutations in MOF/MSL3 impact normal development due to altered enhancer function; 2) Establish human embryonic stem cell (hPSC) to neuronal differentiation and brain organoid to study the effect of coding and noncoding mutations frequently found in neurodevelopmental disorder patients; 3) Development and use of highthroughput enhancer assays (STARRseq) to identify and further characterize enhancer elements. 4) Role of PSIP1 in cancer and drug resistance (Wellcome Open Res 2021).
Sundarraj, J., Taylor GCA., Von Kriegsheim A. and Pradeepa MM*, H3K36me3 and PSIP1/LEDGF associate with several DNA repair proteins, suggesting their role in efficient DNA repair at actively transcribing loci. 2021, Wellcome Open Res. 2, 83.
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
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). 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. 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.
Dr. Debosree Pal (PDRA)
Dr. Jayakumar Sundarraj (Marie Curie Fellow)
Dr. Manthan B Patel (PDRA)
Dr Fanny Boulet (PDRA, starting in Nov 2021)
Dr. Ahmed Saleh Ali Saleh (M.B.B.Ch) (MD/PhD student)
Ms. Minal Patel (MRC DTP PhD student, submitted)