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Dr Kathryn Taylor

Dr Kathryn Taylor

Principal Research Fellow

School of Pharmacy and Pharmaceutical Sciences

Email:
taylorkm@cardiff.ac.uk
Telephone:
+44 (0)29 2087 5292
Fax:
+44 (0)29 2087 5152
Location:
2.47, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB

Qualifications

  • BSc (Honours) in Physiology and Biochemistry, Reading University, 1974
  • PhD from Kings' College Hospital, London University in kidney preservation 1982

Relevant websites

  • Breast Cancer (Molecular Pharmacology) Group
  • Zinc-UK - an Association for scientists actively engaged in researching zinc in biology in the UK and Europe.
  • International Society for Zinc Biology - https://iszb.org/ - The main international society bringing together scientists from a diversity of fields with a common interest in the structural, biochemical, genetic and physiological aspects of zinc biology

Funding bodies that have supported my research

Career profile

Kathryn Taylor began her post-doctoral career in the field of kidney preservation for transplantation at the department of surgery in Kings' College Hospital, Denmark Hill, London.

After a 9 year maternal career break she returned to investigate the role of complement component C9 in arthritis at the department of Medical Biochemistry, Heath Hospital, Cardiff.

Kathryn joined the Tenovus Centre for Cancer Research in 1997 where she has been investigating the role of the LIV-1 family of zinc transporters in breast cancer.

Professional memberships

  • An invited member of the editorial advisory panel of the Biochemistry Journal since 2004
  • A member of the Biochemical Society since 2002
  • An inaugural member of the International Society for Zinc Biology since 2007
  • Board member of the International Society for Zinc Biology 2013-2017
  • President of the International Society for Zinc Biology 2017-2019

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  • PHT801 MSC Cancer Cell Biology and Therapeutics
  • PHT802 MSC Cancer Cell Biology and Therapeutics
  • PHT803 MSC Cancer Cell Biology and Therapeutics
  • PHT804 MSC Cancer Cell Biology and Therapeutics
  • PHT805 MSC Cancer Cell Biology and Therapeutics
  • PHT806 MSC Cancer Cell Biology and Therapeutics
  • Module leader for PHT804
  • Supervision of MPharm undergraduate research projects
  • Supervision of postgraduate PhD students
  • Supervision of undergraduate PTY students
  • Supervision of MSc research student projects

Member of the School's Pharmacology & Physiology Research Discipline.

Research interests

  • The mechanism of action of zinc transporters
  • The regulation of intracellular zinc homeostasis
  • The role of zinc transporters in cell migration
  • The role of zinc and zinc transporters in breast cancer progression

I am most interested in investigating the mechanism of action of cellular zinc transporters, especially the ZIP family (also known as SLC39A). The intention is to substantiate a model for integrated zinc signalling in cells, confirming the key role of zinc transporters, especially ZIP7, and relating the findings to the fundamental biological effects of cellular zinc. These zinc signalling events are thought to be primarily controlled by specific zinc transporters or channels and my recent novel finding that their zinc transport ability can be controlled by phosphorylation, a mechanism previously unprecedented for zinc transporters, will be examined for a direct structural and/or functional relationship with cellular signalling pathways. These events lead to diverse cellular effects on normal processes such as growth, development and migration or, when aberrantly regulated, diseases such as cancer, diabetes and neurodegeneration ensuring that this project has widespread application for normal and disease states.

The primary focus of my research is to understand how zinc transporters work in cells to control intracellular zinc homeostasis. I am especially interested in the 9 human members of the LIV-1 family of zinc transporters and their role in the progression of breast cancer. These studies include the effects of zinc on multiple signalling pathways as well as growth and invasion, all elements known to lead to cancer progression. This can be acheieved by using phospho-kinase arrays in conjunction with site-directed mutagenesis of zinc transporters.

Zinc handling in cells

Two families of zinc transporters enable zinc to traverse biological membranes: The ZnT family of zinc efflux transporters (termed SLC30A) and the ZIP family of zinc influx transporters (termed SLC39A). The ZIP family of zinc transporters generate labile cytosolic zinc and as such have been demonstrated to have wide ranging biological roles both in normal and disease states. Zinc transporter ZIP7, uniquely among ZIP transporters, is located on the ER membrane and we have recently proposed a controlling role for ZIP7 in zinc release from intracellular stores resulting in activation of multiple tyrosine kinases through zinc-mediated inactivation of protein phosphatases. We propose that, uniquely, ZIP7 is a hub in the new pathway of zinc-mediated growth factor signalling.

The mechanism of action of the LIV-1 family of zinc transporters

Using computer software to compare protein sequences, I was able to demonstrate that LIV-1 belongs to a new family of zinc influx transporters which totals nine human family members. Computer searches of secondary structure predicted that these molecules contain 8 transmembrane domains, a long extracellular N-terminus, a short extracellular C-terminus, a consensus sequence for the ZIP family of zinc transporters  and a consensus sequence for the catalytic zinc-binding site of metalloproteases, (HEXXH, where H = histidine, E = glutamic acid and X = any amino acid). This latter motif was unusual in that it also contained two novel residues (HEXPHE), proline (P) and glutamic acid (E), previously unprecedented in these positions in any other metalloprotease motifs. Searching the non-redundant NCBI database using BLAST and the unique HEXPHEXGD motif of LIV-1, we have identified over 39 sequences from 12 species, including human, mouse, C.elegans, Drosophila, yeast and bacteria, that contain this unique and highly conserved motif. This family has now been termed SLC39A. The members of the LIV-1 subfamily are similar to ZIP superfamily transporters in secondary structure and ability to transport metal ions across the plasma membrane or intracellular membranes. The localisation of some family members to lamellipodiae mirrors cellular location of the membrane-type matrix metalloproteases. These differences to other zinc transporters may be consistent with an alternative role for them in cells, particularly in diseases such as cancer.

The role of zinc transporters in health and disease

The 9 human members of the LIV-1 family of zinc transporters are increasingly being implicated in a variety of disease states, notably neurodegeneration, asthma, prostate cancer and breast cancer. Investigation of how the cellular localisation and tissue specificity of these zinc transporters can alter zinc homeostasis is paramount to understanding the exact role of these transporters in these different disease states.

The role of zinc transporters in cell migration

ZIP6 (or LIV-1 as it used to be known) is an oestrogen-regulated gene that has been implicated in metastatic breast cancer. Its detection has been associated with oestrogen receptor positive breast cancer and with the metastatic spread of these cancers to the regional lymph nodes. We have demonstrated a role for both ZIP6 and ZIP10 in promoting cell migration and have now extended this to understand the role that they play in initiating mitosis.

The role of zinc and zinc transporters in breast cancer

We have observed an increased level of intracellular zinc in our 'in house' model of tamoxifen resistant breast cancer. This has initiated an investigation of a potential role for zinc in the activation of signalling pathways observed in these cells as well as in the increase in aggressive behaviour observed in these cells. Through this invetsigation we have demonstrated an importnat role for zinc transporter ZIP7 in driving the growth and activation of tamoxifen-resistant breast cancers. Our discovery that ZIP7 requires phopshorylation before it can release zinc from stores has allowe dus to generate a unique phopsho-ZIP7 antibody that only recognises ZIP7 when it is actively releasing zinc from stores. This antibody has much potential for clinical use as its activity is aligned to increased cell growth and proliferation.

Collaborators

Cardiff University

  • Dr. Julia Gee, School of Pharmacy and Pharmaceutical Sciences, Cardiff University
  • Dr Stephen Hiscox, School of Pharmacy and Pharmaceutical Sciences, Cardiff University
  • Dr. Peter Kille, School of Biosciences, Cardiff University,

UK

  • Prof Christer Hogstrand, Kings College, London
  • Prof Wolfgang Maret, Kings College, London
  • Prof. Iain Ellis, Molecular Medical Sciences, City Hospital, Nottingham: collaboration on clinical breast cancer series
  • Prof John Robertson, City Hospital, Nottingham: collaboration on clinical breast cancer series

International

  • Prof. Glen Andrews, Dept of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas, USA
  • Prof Leigh Ackland, Deakin University, Australia
  • Prof Michal Hershfinkel, Israel
  • Prof Lothar Rink, Aachen, Germany
  • Prof Gerold Schmitt-Ulms, Toronto, Canada

Technologies used

  • Engineering constructs for expression of recombinant proteins in mammalian cells using TOPO-TA cloning and PCR.
  • Knockdown of protein expression using siRNA
  • Generation of mutants using site-directed mutagenesis to enable investigation of key residues in functional activity of different molecules
  • Use of tags for monitoring expression of recombinant proteins in cells
  • Fluorescent and confocal microscopy of multiple probes in live and fixed cells
  • Proximity Ligation Assay
  • Real-time monitoring of Zn2+ concentrations in cells using different zinc specific indicators such as Newport Green, Fluozin-3 and Zinquin.
  • Design and generation of novel antibodies to zinc transporter proteins
  • SDS-PAGE, Western Blotting, FACS analysis, immunocytochemistry.

Current supervision

Ahmed Alzahrani

Research student

Sara Almadani

Research student

Olivia Ogle

Olivia Ogle

Research student

Past projects

Supervised Normawati Zahari completed 2007, ‘Functional evaluation of members of the LIV-1 family of proteins and their role in breast cancer’ 

Supervised Rhiannon Hendley completed January 2012; Identification of Lyn kinase as a therapeutic target for tamoxifen resistant breast cancer’

Co-supervised Benjamin Ertefai from April 2012 ‘the role of zinc signalling in anti-hormone resistant breast cancer’ joint supervision 50/50 with Dr. Julia Gee, qualified 2016.

Supervised Thirayost Nimmanon completed September 2016, ‘Study of cellular mechanisms of zinc transporters’. 

Supervised Silvia Ziliotto completed April 2019, ‘Understanding how targeting zinc signalling prevents the development of aggressive cancer.’ 

Supervised Olivia Ogle from October 2016-present, ‘Targeting zinc signalling to prevent cell division in cancer.’

Supervised Sara Almadani from October 2017-present, ‘Examining the role of ZIP7 in zinc signalling mechanisms and its relevance to cancer.’

Supervised Ahmed Alzahrani from July 2019-present, 'Biochemical Investigation of zinc transporters to discover functional mechnaisms in cells'