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David Heery

Professor of Eukaryotic Gene Regulation, Faculty of Science

Contact

  • workRoom C29 Gene Regulation & RNA Biology Laboratory, Psychology Bldg
    University Park
    Nottingham
    NG7 2RD
    UK
  • work0115 9515087
  • fax0115 8468877

Biography

I am a molecular biologist and lead of the Gene Regulation & RNA Biology Laboratory. Following a PhD at NUI, Galway, Ireland working on bacterial gene regulation, I worked with Pierre Chambon & Regine Losson at the IGBMC Strasbourg, France (1990-1995) supported by fellowship awards from EMBO, ARC and Univ. Louis Pasteur. My research investigated Nuclear Receptor activation functions and set up yeast two-hybrid approaches to identify transcriptional cofactors (e.g. Heery et al, PNAS 1993; Heery et al, NAR 1994; Pierrat et al, Gene 1994; LeDouarin et al, EMBO J 1995; vom Baur et al, EMBO J 1996). I then joined Malcolm Parker's group at Imperial Cancer Research, London as a Marie Curie Fellow, where a major advance from my research was the identification of the LXXLL motifs that mediate NR/cofactor interactions (e.g. Heery et al Nature 1997; Kalkhoven et al, EMBO J; Bevan et al, Mol Cell Biol 1999). I was awarded a Wellcome Trust Senior Fellowship in Basic Biomedical Sciences to establish a group at Biochemistry, U. Leicester (1998-2006). We continued to characterise the structure function of NRs and cofactors, (e.g. Heery et al, JBC 2001; Sheppard et al, Mol Cell Biol 2001; Coulthard et al, JBC 2003; Waters et al JBC 2006; Ryan et al Cell Cycle 2006) but also the function of MOZ/KAT6A histone acetyltransferase in oncogeneic fusions in AML (Kindle et al Mol Cell Biol 1995; Collins et al, JBC 1996). We have continued these research themes at the School of Pharmacy Nottingham (e.g. Kindle et al, Leukemia 2010; Chan et al NAR 2013, Wadelin et al PLOS One 2013; Dreveny et al NAR 2014; Fulton et al, CDDis 2017; Garvin et al NAR 2019).

We enjoy a wide network of collaborators at Nottingham (Paula Moran; Nigel Mongan; Anna Piccinini, Simon Johnston; Alan McIntyre, Cameron Alexander, Pavel Gershkovich; Franco Falcone); and internationally (Jenny Persson, Umea; Lukas Kenner, Vienna).

Expertise Summary

Molecular & Cell Biology

CRISPR CAS9 Genome Editing

Protein-Protein & Protein-DNA Interactions

Nuclear Receptor Signaling; Transcription Factors & Coactivators

Histone Modifications; Chromatin Recognition, Oncogenic Fusion Proteins

Cancer- Leukemia; Prostate Cancer; Breast Cancer

Confocal Microscopy, Cell-based Assays, RNA Seq, Chromatin -IP,

Protein Expression for Structure/ Function Studies

MYST Acetyltransferases

PIP5K1A Function

Teaching Summary

I teach on a number of modules across several of the degree courses offered by the School of Pharmacy, the details of which are outlined below. The topics covered fall largely within my research… read more

Research Summary

Prof. David Heery's research team is housed within the Gene Regulation & RNA Biology Laboratory (GRRB) located in the Psychology/Pharmacy Building Science Road, Main Campus. Our research is… read more

Selected Publications

Current Group Members

Prof. David M Heery - Group Leader

Dr. Hilary M Collins -Senior Experimental Officer/ formerly CRUK PDRA

Christopher Roberts BBSRC DTP

Mitchell Masterson BBSRC DTP (with Prof PM Moran)

Jonas Schoenfeld MRes

Ryan Morris BBSRC DTP

Ruby Chrisp BBSRC DTP (with Prof PM Moran)

Barbara Rampersad Technician

ALUMNI from the DMH Lab

Dr Jonathan Whitchurch BBSRC DTP

Dr Cintia Monteiro CAPES Science without Borders

Dr. Bismoy Mazumder Vice Chancellor Scholarship

Dr. Miguel Hernandez MRes

Dr Maria Clemente MRes

Dr Amit Bhattacharrya MRes

Dr Neetu Bharti MRes

Dr. Joel Fulton - RPSGB scholar; CRUK Research Associate

Dr. Chun Chan Leukemia Research Gordon Pillar scholarship

Olaide Oyegbami PhD Student (with Prof PM Moran)

Dr Nikolaos Tertipis - MSc student

Dr. Sian Deeves - BBSRC scholarship

Dr. Magdy K Abdelghany PhD Scholarship (Egyptian Govt.)

Dr. Baigong Yue MRC Postdoctoral Fellow

Dr. Frances Wadelin Leukaemia Research- Clinical Training Fellow

Dr. Marie Messmer CRUK Postdoctoral Fellow

Dr. Karin Kindle LLR/AICR/Wellcome Trust Postdoctoral Fellow

Dr. Cristina Montiel-Duarte LLR/AICR Postdoctoral Fellow

Dr. Colm Ryan BBSRC Studentship

Dr. Chun Ming Chan LLR Gordon Piller PhD Studentship

Dr. Cecilie Bay-Richter PhD Student (with Prof P Moran)

Dr. Nijjareeya Sirisriro PhD student

Dr. Maria Viskaduraki LLR Postdoctoral Fellow

Hao Liu MSc student

Dr. Lorna Waters BBSRC PhD Student (with Dr Mark Carr)

Dr. Sachiko Matsuda Wellcome Trust RA/ PhD Student

Dr. Janet Bramham Wellcome Trust Postdoctoral Fellow

Dr. Victoria Coulthard Wellcome Prize PhD Student

Dr. Sagair Hussain MSc Student

Dr. Phil Troke MRC PhD scholarship

Dr. Hilary Sheppard Wellcome Trust Postdoctoral Fellow

Ms. Jan Harries Wellcome Trust Research Assistant

I teach on a number of modules across several of the degree courses offered by the School of Pharmacy, the details of which are outlined below. The topics covered fall largely within my research expertise, including recombinant DNA technology, gene regulation, endocrinology and cancer, thus enabling research-led teaching.

TEACHING & MODULE MANAGEMENT

Degree: M.Pharm. Pharmacy

PHAR2004 B32RED Renal & Endocrine Disease: Module Convenor

PHAR2001 B32GIL GI & Liver Disorders

PHAR4020 B34PLM Professional Leadership & Management

PHAR3005 B33RPJ Research Projects

PHAR1006 B31PRO /B31PC1 Professional Competencies

PHAR2008 B32PRO /B32PC2 Professional Competencies

PHAR3004 B33PRO /B33PC3 Professional Competencies

PHAR4022 B34PRO /B34PC4 Professional Competencies

Degree : BSc International Pharmacy

PHAR2027 B32RAE Renal & Endocrine Disease: Module Convenor

PHAR2025 B32GLD GI & Liver Disorders

Degree: M.Pharm Sci

PHAR1019 B31EAM Endocrine & Metabolism

PG Training Module:

'Introduction to Gene Regulation'

Current Research

Prof. David Heery's research team is housed within the Gene Regulation & RNA Biology Laboratory (GRRB) located in the Psychology/Pharmacy Building Science Road, Main Campus. Our research is focussed on molecular mechanisms in gene regulation, chromatin modification and cell signalling pathways, in the context of cancer and other human diseases. Our lab infrastructure has facilities for bacterial, yeast and mammalian cell culture, biochemistry, molecular and cell biology and confocal microscopy. My team has expertise in protein, DNA and RNA analysis, molecular cloning, bacterial expression, RT-qPCR, enzyme and reporter assays, chromatin IP, transcription profiling, histone modifications, protein-protein and protein-nucleic acid interactions including yeast two-hybrid, GST pulldown, co-immunoprecipitations, EMSA and FRET.

CURRENT PROJECTS:

STRUCTURE / FUNCTION OF NUCLEAR RECEPTOR COMPLEXES

I have a long-standing interest in transcription factors, and in particular the Nuclear Receptor family of ligand regulated TFs. We have investigated protein-DNA and protein-protein interactions of NRs, identifying novel heterodimer complexes and discovering short conserved motifs such as the LXXLL in NR coactivators (Heery et al., PNAS 1992; Heery et al NAR 1994; Heery et al., Nature 1997; Heery et al JBC 2001; Kalkhoven et al., 1998 EMBO J; Bevan et al., Mol Cell Biol 1999; Coulthard et al JBC 2003; Matsuda et al., JBC 2004;Waters et al., JBC 2006; Chan et al NAR 2013; Fulton et al, Cell Death Disease 2017). Recent efforts have focussed on androgen receptor function in collaboration with Prof Lukas Kenner at the Ludwig Boltzmann Institute for Cancer Research, Vienna (Aksoy et al., 2019 submitted).

HISTONE ACETYLTRANSFERASES IN CANCER AND DEVELOPMENTAL DISORDERS

Another major interest is how 'Epigenetic regulators' engage with histones and chromatin to regulate gene expression. Having studied NR coactivators such as RIP140, SRC1, CBP, p300 and BCL11A, we are currently focussed on investigating the structure and function of the MYST acetyltransferase proteins MOZ and MORF that are encoded by the KAT6A and KAT6B genes. These are important for the development of blood, brain and other tissues and function as chromatin regulators, and we have previously studied their role as oncogenic fusion proteins in leukemia (Kindle et al., 2005 MCB; Collins et al., 2006 JBC; Kindle et al., 2010 Leukaemia 2010).

Our Breakthrough paper published in Nucleic Acids Research showed that the Double PHD finger domain recognises specific modifications of lysines and arginines in the Histone H3 tail. Moreover, crystal structures of the DPF in complex with acetylated H3 peptides revealed for the first time that chromatin regulators can induce helical structure in Histone N-terminal tails (Dreveny, Deeves et al, NAR 2014). We are currently using CRISPR CAS9 genome editing and RNA Seq to identify MOZ gene targets and characterise MOZ functional domains important for gene transcription and leukemogenesis, or to recapitulate mutations associated with KAT6A global developmental delay syndrome.

UNDERSTANDING GENE FUNCTION THROUGH GENOME EDITING

We have a number of ongoing collaborations involving CRISPR CAS9 editing of selected genes in cancer cell lines including with Dr Alan McIntyre (BET proteins in Breast Cancer- funded by Breast Cancer Now); Prof Nigel Mongan (KDM6A- funded by Prostate Cancer UK; and METTL3 function in prostate cancer); Dr. Anna Piccinini (TNC gene in macrophages); Prof Paula Moran (circadian regulation by CLOCK proteins). We are also using genome editing and RNA Seq to study the role of PIP2 signalling in prostate cancer with a view to understanding how it intersects with Androgen Receptor function. This is part of a wider collaborative effort to identify novel targets in prostate cancer in collaboration with Prof. J Persson Umea, Sweden and others (Miftakhova et al., Cancer Research 2016; Sarwar et al., Oncotarget 2016).

OTHER PROJECTS:

Other recent studies include the characterisation of human cell nucleus infiltration by proteins secreted from schistosome eggs with Franco Falcone (Kaur et al., Infection & Immunity, 2014; Pennington et al., Infection & Immunity, 2017) , functional analysis of AR mutations in DSD patients with Prof Ieuan Hughes, Cambridge (Lek et al., EBioMedicine 2019 and circadian histone acetylation and dopamine receptorswith Prof Paula Moran (O'Callaghan et al. J. Psychopharm 2014; Oyegbami et al., Current Alzheimers Research 2017). A new collaboration with Dr Simon Johnston (NRF fellow) and colleagues will investigate FOXA1 mutations in invasive lobular breast cancer using RIME analysis of human tumours (funded by AMS).

EXTERNAL FUNDING:

Our research activities have been funded by grants, fellowships and studentships awarded by the Wellcome Trust Cancer Research UK, MRC, Leukaemia Lymphoma Research, AICR, BBSRC, RPSGB, Breast Cancer Now and Prostate Cancer UK.

School of Pharmacy

University of Nottingham
University Park
Nottingham, NG7 2RD

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