Catherine L.R. Merry, PH.D.
Research authored by Dr. Merry
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
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Embryonic Stem Cells can be used to investigate the role of Heparan Sulphate in
Development and Disease
Abstract 2005 MHE Conference
Claire E. Johnson, Rebecca Baldwin, Annie Wat, Graham Rushton, Catherine L.R. Merry
and John T. Gallagher
The University of Manchester,
School of Materials,
Lecturer in Biomedical Materials
For several years now, work using model organisms has demonstrated that heparan sulphate (HS)
in association with specific core proteins is a downstream effecter of several regulatory molecules
that modulate changes in the morphology, mobility and proliferation of developing cells. The genetic
analysis of inherited diseases such as HME has revealed the importance of HS in cell growth
regulation and tissue-specific patterning during human development.
In addition to our on-going study of the role of HS at the molecular level, we have established the
novel approach of using murine and human embryonic stem (ES) cells to provide in vitro model
systems for the study of the developmental biology of HS. ES cells undergo symmetrical
self-renewal in culture whilst retaining the ability to differentiate into all foetal and adult lineages.
There are three alternative fates for ES cells; they can remain pluripotent, they can differentiate or
they can undergo apoptosis. The signalling molecules that control this decision process are
complex, and consist of a subtle interplay of secreted factors, cell-autonomous factors and
cell-adhesion molecules. Many of these signalling proteins are familiar to the proteoglycan (PG) field,
being HS-dependent growth factors, morphogens or matrix-resident PGs secreted by the ES cells,
or by the fibroblasts used as a feeder layer. ES cells therefore present an experimentally tractable in
vitro system in which the role of HS in multiple interacting signalling processes can be assessed.
The major benefit of the system is that we can monitor cells as they transform from a pluripotent
phenotype to differentiated lineages. This enables us to study the relationship between
developmentally-regulated expression of HS-biosynthetic enzymes (such as EXT-1) and the
structural and functional attributes of HS. This has become a hotly debated issue in the field as
evidence has emerged concerning the deleterious effects of mutations in these enzymes on
embryogenesis and the functions of HS in the adult.
We are currently using an ext1 knock-out mouse ES cell line (from Prof. Esko, UCSD) to detail the
role of cell-surface HS in the earliest stages of differentiation and lineage commitment. This work
will enable us to better understand the function of HS in co-ordinating the multiple interacting
pathways influencing cell development and differentiation in the normal and disease state.
Professional biography
Cathy Merry graduated in Biochemistry from The University of Manchester in 1995. As part of this
course, she spent a year working for Amgen Inc. in California. She obtained her Ph.D. from the
University of Manchester (1999), transferring to the Paterson Institute where she worked with
Professor John Gallagher in Medical Oncology.
Following on from her Ph.D. studies, during which she developed and patented a novel method for
sequencing heparan sulphate (HS), she stayed within Medical Oncology to establish facilities for the
culture and study of embryonic stem (ES) cells. Over the next six years, Cathy was able to exploit
the use of various developmental models with which to study the biological effects of alteration of
HS structure. As part of these studies, ES cells became a central focus, and three studentships, a
Post Doc and a senior technician within the Medical Oncology group were dedicated to this research
area. The group published the first detailed analysis of ES cell HS in early 2006.
In March 2006 Cathy joined the Biomaterials group in the School of Materials. Working within the
Manchester Stem Cell Network, her main interests are in the role of cell surface and extracellular
matrix molecules in influencing cell fate. Glycobiology remains a central theme, with
glycosaminoglycans of particular interest. Future projects will focus on the use of various
biomaterials to provide scaffolds to promote the culture of ES cells, either to scale-up their growth
in the pluripotent state or to direct differentiation to specific cell types.
Development and Disease
Abstract 2005 MHE Conference
Claire E. Johnson, Rebecca Baldwin, Annie Wat, Graham Rushton, Catherine L.R. Merry
and John T. Gallagher
The University of Manchester,
School of Materials,
Lecturer in Biomedical Materials
For several years now, work using model organisms has demonstrated that heparan sulphate (HS)
in association with specific core proteins is a downstream effecter of several regulatory molecules
that modulate changes in the morphology, mobility and proliferation of developing cells. The genetic
analysis of inherited diseases such as HME has revealed the importance of HS in cell growth
regulation and tissue-specific patterning during human development.
In addition to our on-going study of the role of HS at the molecular level, we have established the
novel approach of using murine and human embryonic stem (ES) cells to provide in vitro model
systems for the study of the developmental biology of HS. ES cells undergo symmetrical
self-renewal in culture whilst retaining the ability to differentiate into all foetal and adult lineages.
There are three alternative fates for ES cells; they can remain pluripotent, they can differentiate or
they can undergo apoptosis. The signalling molecules that control this decision process are
complex, and consist of a subtle interplay of secreted factors, cell-autonomous factors and
cell-adhesion molecules. Many of these signalling proteins are familiar to the proteoglycan (PG) field,
being HS-dependent growth factors, morphogens or matrix-resident PGs secreted by the ES cells,
or by the fibroblasts used as a feeder layer. ES cells therefore present an experimentally tractable in
vitro system in which the role of HS in multiple interacting signalling processes can be assessed.
The major benefit of the system is that we can monitor cells as they transform from a pluripotent
phenotype to differentiated lineages. This enables us to study the relationship between
developmentally-regulated expression of HS-biosynthetic enzymes (such as EXT-1) and the
structural and functional attributes of HS. This has become a hotly debated issue in the field as
evidence has emerged concerning the deleterious effects of mutations in these enzymes on
embryogenesis and the functions of HS in the adult.
We are currently using an ext1 knock-out mouse ES cell line (from Prof. Esko, UCSD) to detail the
role of cell-surface HS in the earliest stages of differentiation and lineage commitment. This work
will enable us to better understand the function of HS in co-ordinating the multiple interacting
pathways influencing cell development and differentiation in the normal and disease state.
Professional biography
Cathy Merry graduated in Biochemistry from The University of Manchester in 1995. As part of this
course, she spent a year working for Amgen Inc. in California. She obtained her Ph.D. from the
University of Manchester (1999), transferring to the Paterson Institute where she worked with
Professor John Gallagher in Medical Oncology.
Following on from her Ph.D. studies, during which she developed and patented a novel method for
sequencing heparan sulphate (HS), she stayed within Medical Oncology to establish facilities for the
culture and study of embryonic stem (ES) cells. Over the next six years, Cathy was able to exploit
the use of various developmental models with which to study the biological effects of alteration of
HS structure. As part of these studies, ES cells became a central focus, and three studentships, a
Post Doc and a senior technician within the Medical Oncology group were dedicated to this research
area. The group published the first detailed analysis of ES cell HS in early 2006.
In March 2006 Cathy joined the Biomaterials group in the School of Materials. Working within the
Manchester Stem Cell Network, her main interests are in the role of cell surface and extracellular
matrix molecules in influencing cell fate. Glycobiology remains a central theme, with
glycosaminoglycans of particular interest. Future projects will focus on the use of various
biomaterials to provide scaffolds to promote the culture of ES cells, either to scale-up their growth
in the pluripotent state or to direct differentiation to specific cell types.
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| Dr. Merry's research |
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By the Health On the Net Foundation. Click here to verify.# HON Conduct 282463 and is linked on the NIH
National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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