Professor Jo Morris PhD BSc

Professor Jo Morris

Institute of Cancer and Genomic Sciences
Professor of Molecular Genetics

Contact details

Address
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Professor Jo Morris is interested in the way our cells maintain and repair our genome, keeping our DNA intact.

A particular interest is the functions of the breast and ovarian cancer predisposition protein BRCA1 and the way it works in controlling DNA resection and DNA replication. She also works on the small modifier proteins, ubiquitin and SUMO and is interested in how these change the way that proteins behave in order to aid DNA repair and DNA replication.

Jo has published research papers in scientific journals as well as reviews and book chapters in the fields of breast cancer genetics, the cellular response to DNA damage and small modifier biology of ubiquitin and SUMO. She has research grants from the Breast Cancer Now and Cancer Research UK.

Qualifications

  • PhD in Molecular Genetics (1999)
  • BSc (Hons) 1995

Biography

CAREER TO DATE

2013-                  Reader in Cancer Genetics, University of Birmingham.

2010-2013           Senior Lecturer, University of Birmingham.

2007-2010           Breast Cancer Campaign Fellow, King’s College London.

2003-2006           Medical Research Council Fellow, King’s College London.

2000-2002           Post doc, King’s College London.

WIDENING PARTICIPATION

Beyond allowing lab’ members to contribute to Big-bang and STEM activities (eg. Ruth Densham representing UoB at the house of parliament event), and giving the occasional talk in schools I have not initiated or led a major contribution to widening participation.

Lab tour (2013) CRUK 

CITIZENSHIP

External engagement

I was nominated to the “Innovators in Breast Cancer (UK)” group in 2011. This is an invitation only mix of surgeons, oncologists, and scientists. I have served on the scientific advisory board for the Breast Cancer Campaign (2009-2010) and will again in 2015 -2018.

I was deputy Lead on one of the nine working groups for the Breast Cancer Campaign Gap Analysis-2012 to direct funding strategy for the Charity over the next six years (working group: ‘Genetics, Epigenetics and Epidemiology’). I have been an external PhD examiner in the area of DNA damage response and cancer at Queens University Belfast, the University of Cambridge Imperial College London (UK) and University of Sydney (Australia). 

Contribution to University Management

Committees and working groups

I have served on the School of Cancer Sciences Strategy committee and the College Research Strategy committee to communicate and connect school and college .I was deputy REF led for School of Cancer Sciences (ECRs and outputs).

 

Panels

Long-listing, short-listing and interview panels for the Birmingham Fellows (2012).

Interview panel for lecturer (Biosciences), and several post-doc appointments outside my lab (Stewart, Peterman).

 

Now on the Scientific Advisory Board for the Breast cancer Campaign (2015-2018).

Contribution to the development of others

I have given formal ‘career development’ presentations at College events; the Research Gala (post-grad’ researchers event) entitled “Get a life: be a lab rat!” (2012) and PERCAT (Post-doc’ and early career development and training) workshop entitled “Career Planning” (2012).

I have coached post-doc Alex Garvin, and Academic clinical fellow, Ravindhi Nathavitharana, in the process of writing a small research grants for a small development grant (£5K) and CRUK bursary (£25K),  respectively. Both have been successful. Similarly following coaching post-doc Ruth Densham has just submitted her idea to the Innovative Biomedicine Award Fund.  I have mentored Aga Gambus in her submission of BCC pilot grant and Birmingham Fellowship and overseen MRC interview practices and been mentor to Claire Davies in her Birmingham Fellowship application (2011). 

Teaching

  • Module Lead for Genomics on the Cancer Sciences MRes course
  • BMedSci
  • DNA damage pathways in human disease (UG)
  • Advanced Molecular  Experimental Genetics
  • Invasion and Metastasis Small group teaching (found Medical Pract Cancer)
  • Introduction to Experimental Skills (UG)

Postgraduate supervision

Dr Morris currently supervises doctoral researchers in the following areas:

Ubiquitin pathways in the mammalian DNA damage response
BRCA1 missense gene changes and the link to breast and ovarian cancer

Research

RESEARCH ACTIVITY

Statement of current research interests

 

Key contributions to date:

My research interest is at the intersection of cancer predisposition, DNA repair and post-translational modifications. In 2004 I showed that ubiquitin conjugation was prevalent at sites of DNA double-strand breaks and dependent in part on the Breast and ovarian cancer predisposition protein, BRCA1 (HMG 2004). This is a highly cited paper (108 times) and the first to demonstrate ubiquitin conjugation in relation to this type of DNA damage. Recently we have shown that a key regulator of the amount of localized ubiquitin at sites of damage and the amplitude of the cellular response to the break is the proteasomal de-ubqiutinating enzyme, POH1 (EMBO J 2012).

In 2006 I showed that the interactions of BRCA1 with components that allow it to catalyze the ligation of ubiquitin are likely to be important in cancer predisposition (HMG 2006). This conclusion remains controversial with mouse experiments demonstrating evidence both for and against the idea. My own mouse model (published 2011, Cancer Cell) demonstrates that the region required for ligase activity is also required for tumour suppression and shows separation of tumour suppression function from treatment response. In 2009 my investigations of post-translation modifications in the DNA damage response led to an understanding that the small modifier, SUMO, regulates the wider DNA damage response and specifically regulates BRCA1 ubiquitin ligase activity (Nature 2009).  In 2013 we showed that a eky regulator of chromatin state is the SUMO deconjugating enzyme, SENP7 and that its activity is required to allow the relaxation of DNA required for homologous recombination and DNA repair (EMBO R). These contributions show a strong narrative in my research trajectory that I aim to build on.

 

 

Current Grants.

Role

Date

Description

Funder

Value

PI

Jan 2015- Dec2019

Ubiquitin   processing in Cancer

Cancer   Research UK

£1,400,000

PI

July- 2014 –June-2015

Investigation   of a Novel Biomarker of treatment response in basal breast cancer.

Breast Cancer   Campaign

£20,000

PI

1/2/2014-31/1/2016

New Models of   breast cancer genetics.

Breast Cancer Campaign.

£121,000

PI

01/09/2013- 31/08/2017

Post-translational   modifications as drivers of breast cancer

CRUK Centre studentship

£150,000

 

Expired Grants

Supervisor

 

01/03/2013-

31/06/2013

Genomic   Analysis of BRCA1 Variant Tumours (Bursary to Ravindhi   Nathavitharana, Academic Research Fellow)

CRUK Training & Career Development Board (Research   Bursary)

£25,000

PI

01/12/2011-31/11/2014

BRCA1 N-terminus in   cancer development

CRUK (project)

£265,500

PI

1/1/2014- 31/8/2014

Generation of   Senp7 deficient mice.

Wellcome   Trust (ISSF)

£25,000

PI

1/10/2011 -31/9/2014

The BRCA1-Proteasome link

Breast Cancer Campaign

(Studentship)

£106,756

PI

1/09/2013- 31/08/2014

New   assay for BRCA1 missense variant testing

Breast Cancer Campaign   Pilot Grant.

£19,999

PI

01/12/2010-31/11/2013

Cytoskeletal regulation   of BRCA1

Breast Cancer Campaign   (project)

£193,318

PI

1/8/2012- 31/3/2013

The generation of human   BRCA1 mutant cell lines

Breast Cancer Campaign

(Pilot)

£20,00

PI

03-09/2012,

The generation of human   BRCA1 mutant cell lines

Welcome Trust ISSF

£24,000

PI

1/9/2011- 31/11/2011

Novel regulation of 53BP1

Breast Cancer Campaign

(Pilot)

£19,989

PI

1/9/2008-31/8/2011

SUMOylation of BRCA1

CRUK (project)

£216,000

PI

01/2007-12/2011

BRCA1   in breast cancer

Breast   Cancer Campaign (Fellowship)

£454,500

 

 

Collaborative

 

Role

Submission

Decision

Period

Description

Funder

Value

 Collaborator with Aga Gambus (MRC Fellow and potential Birmingham Fellow).

06/09/2012

5/12/2012

12 months

'New approach to identifying proteins regulated by   BRCA1/BARD1 ubiquitin ligase'.

Breast Cancer Campaign (Pilot)

£19,516

RESEARCH MEASURE

Web of Science, H-index :13

Total times cited (Without self-citations):  573. 

Winner of Breast Cancer Campaign “Team of the Year 2009” (Awarded to PI J Morris and research technician A Alamshah).

Breast Cancer Campaign Genetics Expert, see:

http://www.breastcancercampaign.org/our-science/genetics

Other activities

Member of Breast Cancer Now Scientific Advisory Board (2015-2018)

Publications

Recent publications

Article

Ronson, GE, Starowicz, K, Anthony, EJ, Piberger, AL, Clarke, LC, Garvin, AJ, Beggs, AD, Whalley, CM, Edmonds, MJ, Beesley, JFJ & Morris, JR 2023, 'Mechanisms of synthetic lethality between BRCA1/2 and 53BP1 deficiencies and DNA polymerase theta targeting', Nature Communications, vol. 14, no. 1, 7834. https://doi.org/10.1038/s41467-023-43677-2

Rana, M, Perotti, A, Bisset, LM, Smith, JD, Lamden, E, Khan, Z, Ismail, MK, Ellis, K, Armstrong, KA, Hodder, SL, Bertoli, C, Meneguello, L, de Bruin, RAM, Morris, JR, Romero-Canelon, I, Tucker, JHR & Hodges, NJ 2022, 'A ferrocene-containing nucleoside analogue targets DNA replication in pancreatic cancer cells', Metallomics, vol. 14, no. 7, mfac041. https://doi.org/10.1093/mtomcs/mfac041

Faulkner, E, Pike, J, Densham, R, Garlick, E, Thomas, S, Neely, R & Morris, J 2022, 'Imaging nanoscale nuclear structures with expansion microscopy', Journal of Cell Science, vol. 135, no. 14, jcs259009. https://doi.org/10.1242/jcs.259009

Garvin, AJ, Lanz, AJ & Morris, JR 2022, 'SUMO monoclonal antibodies vary in sensitivity, specificity, and ability to detect types of SUMO conjugate', Scientific Reports, vol. 12, no. 1, 21343. https://doi.org/10.1038/s41598-022-25665-6

Piberger, L, Bowry, A, Kelly, R, Walker, A, Gonzalez-Acosta, D, Bailey, L, Doherty, A, Mendez, J, Morris, J, Bryant, HE & Petermann, E 2020, 'PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts', Nature Communications, vol. 11, no. 1, 5863. https://doi.org/10.1038/s41467-020-19570-7

Daza-martin, M, Densham, RM & Morris, JR 2019, 'BRCA1-BARD1: the importance of being in shape', Molecular and Cellular Oncology, vol. 6, no. 6, e1656500. https://doi.org/10.1080/23723556.2019.1656500

Garvin, AJ, Khalaf, AHA, Rettino, A, Xicluna, J, Butler, L, Morris, JR, Heery, DM & Clarke, NM 2019, 'GSK3-SCFFBXW7 mediated phosphorylation and ubiquitination of IRF1 are required for its transcription-dependent turnover', Nucleic Acids Research, vol. 47, no. 9, pp. 4476-4494. https://doi.org/10.1093/nar/gkz163

Daza-Martin, M, Starowicz, K, Jamshad, M, Tye, S, Ronson, GE, MacKay, HL, Chauhan, AS, Walker, AK, Stone, HR, Beesley, JFJ, Coles, JL, Garvin, AJ, Stewart, GS, McCorvie, TJ, Zhang, X, Densham, RM & Morris, JR 2019, 'Isomerization of BRCA1-BARD1 promotes replication fork protection', Nature, vol. 571, no. 7766, pp. 521-527. https://doi.org/10.1038/s41586-019-1363-4

Garvin, AJ, Walker, AK, Densham, RM, Chauhan, AS, Stone, HR, Mackay, HL, Jamshad, M, Starowicz, K, Daza-Martin, M, Ronson, GE, Lanz, AJ, Beesley, JF & Morris, JR 2019, 'The deSUMOylase SENP2 coordinates homologous recombination and nonhomologous end joining by independent mechanisms', Genes & Development, vol. 33, no. 5-6, pp. 333-347. https://doi.org/10.1101/gad.321125.118

Spiliotopoulos, A, Blokpoel Ferreras, L, Densham, RM, Caulton, SG, Maddison, BC, Morris, JR, Dixon, JE, Gough, KC & Dreveny, I 2018, 'Discovery of peptide ligands targeting a specific ubiquitin-like domain-binding site in the deubiquitinase USP11', Journal of Biological Chemistry. https://doi.org/10.1074/jbc.RA118.004469

Uckelmann, M, Densham, RM, Baas, R, Winterwerp, HHK, Fish, A, Sixma, TK & Morris, JR 2018, 'USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A', Nature Communications, vol. 9, no. 1, 229. https://doi.org/10.1038/s41467-017-02653-3

Comment/debate

Morris, JR 2021, 'Is it a wrap? Nucleosome interactions of the BRCA1-binding partner, BARD1, steal the scene', Nature Structural and Molecular Biology, vol. 28, no. 9, pp. 708-710. https://doi.org/10.1038/s41594-021-00658-7

Preprint

Faulkner, EL, Pike, JA, Densham, RM, Garlick, E, Thomas, SG, Neely, RK & Morris, JR 2021 'Imaging nanoscale nuclear structures with expansion microscopy' bioRxiv. https://doi.org/10.1101/2021.05.04.442164

Review article

Tye, S, Ronson, G & Morris, J 2021, 'A fork in the road: Where homologous recombination and stalled replication fork protection part ways', Seminars in Cell and Developmental Biology, vol. 113, pp. 14-26. https://doi.org/10.1016/j.semcdb.2020.07.004

Densham, RM & Morris, JR 2019, 'Moving Mountains-The BRCA1 Promotion of DNA Resection', Frontiers in Molecular Bioscience, vol. 6, 79. https://doi.org/10.3389/fmolb.2019.00079

View all publications in research portal