Caroline Milner

Caroline Milner, BA, MA, DPhil

Dr

  • D.3417, Michael Smith Building, Oxford Road

    M13 9PT Manchester

    United Kingdom

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Personal profile

Biography

Caroline joined the Faculty of Life Sciences as a Research Fellow in 2006 and took up a Lectureship in October 2009.  She was previously based at the University of Oxford, where she studied Chemistry (BA, Wadham College, 1988) and obtained a DPhil in Biochemistry (Wolfson College, 1991).  Caroline was a Research Fellow at the MRC Immunochemistry Unit in Oxford (funded by the MRC, ARC and Nuffield Foundation) from 1991 until her move to Manchester in 2006. Her current work is funded by grants from the MRC and ARUK.

Research interests

My research falls into two key areas:

 

1. Mammalian reproduction - I am particularly interested in understanding the mechanisms that underlie ovulation, which is central to female fertility. Prior to the release of an oocyte from the ovary, a jelly-like extracellular matrix (the cumulus matrix) forms and expands around the oocyte and its associated cumulus cells. The major component of this matrix is the polysaccharide hylauronan (HA), but a number of proteins are also required for matrix organisation/stability. For example, TSG-6, which is expressed by cumulus cells, is essential for ovulation in mice. TSG-6 can bind to HA and also catalyses the covalent modification of HA with heavy chains (HC) from the serum protein inter-alpha-inhibitor, to form HC-HA. We have shown that this latter function is essential for cumulus matrix expansion in mice. Ongoing work includes the use of immunofluorescent microscopy to determine the distributions of TSG-6, HCs and HA in mouse ovaries throughout the time course of ovulation. Alongside this, structural and functional studies are allowing us to further define the molecular mechaisms/interactions that mediate HA cross-linking within the cumulus matrix. We are also using clinical samples (in collaboration with colleagues at the Oxford Fertility Unit) to establish the importance in human ovulation of the mechanisms identified in mice (e.g. HC-HA formation); this might lead to improved treatments for female infertility.

2. Musculoskeletal disease - chronic, degenerative conditions such as arthritis and osteoporosis affect a large proportion of the elderly population. Our own work and that of others has implicated TSG-6 as an endogenous protector of tissues from the damaging effects of inflammation. For example, it is a potent inhibitor of neutrophil extravasation and can down regulate the protease network, both of which contribute to its chondroprotective effects in arthritis. Most recently, we have shown that TSG-6 inhibits bone erosion, where it is expressed by osteoclasts in response to inflammatory cytokines and acts as an autocrine inhibitor of their resorptive activity. These properties make TSG-6 an important therapeutic target and we are working to understand the mechanisms underlying its protective activities, with the long-term aim of developing new treatments for conditions such as osteoporosis.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Research Beacons, Institutes and Platforms

  • Manchester Regenerative Medicine Network
  • Lydia Becker Institute
  • Christabel Pankhurst Institute

Keywords

  • TSG-6
  • Inflammation
  • osteoarthritis
  • Musculoskeletal Disorders

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