Dr Pradeepa Madapura, PhD, MSc, BSc

Profile

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.

Current research in the lab is funded by UKRI/MRC, Barts Charity. Previous funders include: Wellcome Trust, MSCA fellowship.

2023 –          Associate professor (Reader) at the Queen Mary University of London, UK
2021 – 2023 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

Website: madapuralab.net
QMUL Epigenetics: /madapura
LinkedIn: /pradeepamm2207

Teaching

MBBS programme: PBL facilitator on three modules – Human Development 1, Human Development 2, and locomotor

MEDPRO mentoring Scheme: MBBS students

Experimental pathology: supervision and marking

Lab Supervisor for BSc, MSc and intercalated MBBS students

PhD opportunities: 
We are always looking out for motivated PhD students, please enquire if you have already secured funding or are interested in applying for a fellowship.

Deciphering the mechanism through which mutations in BRD4 cause neurodevelopmental disorder

Research

Research Interests:

Madapura lab research is focused on investigating the role of chromatin proteins, histone modifications in the regulation of gene expression, splicing and DNA repair. We use genome-wide methodologies and single locus precision editing, and gene engineering methods to investigate how the genome is regulated and the factors contributing to the function of gene regulatory elements. One of the highlights of Pradeep’s work includes the identification of the novel class of enhancer elements that lack acetylation of histone H3 at lysine 27 (H3K27ac), a widely used marker of active enhancers. H3 globular acetylation at lysine 112 (H3K122ac) (Nature Genet 2016) and acetylation at H4 lysine 16 (H4K16ac) (Genome Res 2013) mark 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 recent 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). Recent work in Pradeep’s lab has discovered a novel function of MSL complex-mediated H4K16ac in regulating the expression of transposable elements. This work is also the first to demonstrate that H4K16ac marked LINE1 elements function as enhancers to regulate genes in cis (Nature Struct. Mol. Biol 2023).

Apart from my main focus on genome regulation, our lab is also interested in deciphering the role of chromatin proteins, including a very interesting multifunctional chromatin protein (PSIP1) implicated in HIV integration and Leukaemia. My work has demonstrated the role of PSIP1 in coupling histone modification with RNA splicing (PLoS Genet 2012) and in the regulation of HOX genes (Nucleic Acid Res 2014). Using cutting-edge methods, we have demonstrated the 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) Establishing 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 high throughput enhancer assays (STARRseq) to identify and further characterise enhancer elements (Patel et al In preparation 2023). 4) Role of PSIP1 in preventing R-loop mediated genomic instability (BioRxiv 2022, under revision 2023).

Research Group

• Fanny Boulet
• Manthan Patel

Publications

Key Publications

Sundarraj J., Patel M., Aziz H., Brooke G., Tummala H., Pradeepa MM* PSIP1/LEDGF reduces R-loops at transcription sites to maintain genome integrity BioRxiv 2022 https://doi.org/10.1101/2022.12.02.518862 (under revision)

Pal, D., Patel M., Boulet F., Sundarraj J., Grant OA., Branco MR., Basu S., Santos S., Zabet, N R., Scaffidi, P., Pradeepa, MM* H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function Nature. Struct. Mol. Biol 12 July 2023 https://doi.org.10.1038/s41594-023-01016-5

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*, 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

All Publications

Supervision

Dr Manthan B Patel (PDRA)
Dr Fanny Boulet (PDRA)
Ms Ziba Shadman (PhD student)
Ms Katarina Gregorovicssova (Starting in October 2023)
Ms Adrianna Debrowska (Research Assistant)