If you made any changes in Pure these will be visible here soon.

Personal profile

Overview

The Piper Hanley lab:

Fibrosis Research: Karen leads a research group investigating the cellular and molecular mechanisms underlying fibrotic disease. Fibrosis (or scarring) is a common step in the majority of chronic diseases that can affect any organ. Diagnosis is poor and there are currently no anti-fibrotic therapies. My lab combines in vitro, in vivo and human modelling to drive novel discoveries for diagnostic and therapeutic strategies.

Development & Regeneration: Karen maintains a collaborative interest in understanding human development. Understanding how organs develop normally gives insight into why processes go wrong in disease and how we might fix this through tissue regeneration for example.

Biography

Karen Piper Hanley has had an unusual and varied introduction into medical research. Her early career began in 1990 as a junior researcher in Biochemistry and Genetics at the University of Newcastle, under the guidance of Professor Steve Yeaman. Following graduation in 1995 with a BSc Hons in Biomedical Science from the University of Northumbria, she worked as a research assistant in the Molecular Genetics Unit at the University of Newcastle with Drs Martyn Farrer and Ann Curtis investigating genetic associations in cardiovascular disease. In 1999, Karen became interested in human development and, as the only researcher on a single year pump funding project with Professor David Wilson in the Molecular Genetics Unit, she generated all of the data that went on to secure a £500K project grant from the Juvenile Diabetes Foundation (JDRF) with Professors Neil Hanley, David Wilson and Steve Ball. This grant enabled Karen to study for a PhD in Human Pancreas Development which she completed in 2003 at the University of Southampton following a relocation of the Hanley and Wilson groups in 2000. In 2006 she was awarded a Career-track postdoctoral fellowship from the University of Southampton. In 2008, she moved to become Lecturer in Molecular Medicine at the University of Manchester and is currently Professor of Molecular Medicine in the Division of Diabetes, Endocrinology and Gastroenterology. Karen is the fibrosis lead in the Wellcome Trust Centre for Cell-Matrix Research (wellcome-matrix.org) and Director of Core Research Technologies (2019-2022).

Teaching

PhD students present and past

Karen is passionate about postgraduate education for both scientist and clinicical fellows and is the senior postgraduate tutor for the Division of Diabetes, Endocrinology & Gastroenetrology. Since arriving in Manchester in 2008, all  students have submitted and been awarded their PhD within 4 years. In recognition that a career in science is competative, all of Karen's PhD students have presented at key meetings relevant to their research (Keystone conference series) and authored high quality manuscripts. 

Current PhD students:

  • Kim Su (MRC clinical training fellow)
  • Laurence Pearmain (MRC clinical training fellow)
  • Jenny Scott (clinical training fellow)

Co-Supervision: In collaboration with Professor Neil Hanley she also co-supervise PhD students investigating human development and liver biology / stem cells.

Past students include:

  • Neil Roberts (Gerald Kerkut Trust) - KRUK fellow, University of Manchester.
  • Emma Harvey (BBSRC) - scientist, Oxford.
  • Dr Varinder Athwal (MRC clinical training fellow) - Dean's Prize Fellow.
  • Dr Katherine Martin (MRC clinical training fellow) - clinical lecturer within the group.
  • Jessica Llewellyn (MRC) - postdoc UPenn
  • Aoibheann Mullan (MRC) - postdoc University of Manchester
  • Dr Ammar Raza (KRUK clinical training fellow)

Academic Clinical Fellows (ACFs)

Both of Karen's previous ACFs investigating fibrotic mechanism won MRC clinical training fellowships (Kim and Laurence).

Current ACF - Dr Daniel Dohery (Transplant Surgeon).

Undergraduate and Postgraduate teaching

Tutor for Personal & Professional Development (TPPD) - MBChB Programme Yrs 1&2: Karen spent 4 years as TPPD tutor providing leadership and management to a group of undergraduate student throughout their first 2 years of study. 

Additional teaching roles: Karen provides tutorials and research project supervision for the MRes and BSc students in the Faculty.

I am passionate about training the next generation of academics in medical science and provide an excellent environment and level of training to all research students in my lab. The majority of my undergraduate intercalated medical students have obtained a 1st Class BSc degrees and postgraduate Masters students achieved Merit or Distinctions for their project dissertations. Of note and in addition:

Rachel Khaw, intercalated MRes medical student: Awarded MAHSC project grant (£2K) for her work, presented data at the BASL Hepatology workshop 2017.

Dan Henderson, 4th year medical student: Awarded two internally funded lab placements in my lab (2012 and 2013).

Philip Ireland, intercalated BSc student: Author on PlosOne manuscript 2014. Oral and prize winning presentation at the Salford Medical Student Oscars, Manchester (2011). Awarded Genetics Society Summer Studentship 2011.

Alexander Nicolaides, intercalated BSc student: Author on PlosOne manuscript 2014.

Potential students with an interest in pursuing an academic career investigating mechanisms of organ fibrosis should contact Karen directly.

Memberships of committees and professional bodies

  • Member of the British Association for the Study of Liver (BASL)
  • Member of the European Association for the Study of Liver (EASL)

Qualifications

Research interests

 

Overview: Fibrosis (or scarring) is a common step in the majority of chronic diseases that can affect any organ. Diagnosis is poor and there are currently no anti-fibrotic therapies. My lab is interested in uncovering the cellular and molecular basis of fibrosis to drive novel discoveries for diagnostic and therapeutic strategies. My lab has a major interested in how components of the pathological scar are produced and how this signals to surrounding cells to perpetuate the fibrotic response. The majority of our work to date has focussed on liver fibrosis (funded by MRC). However, we have active research projects in kidney (supported by KRUK & Kidneys for Life) and lung (funded by MRC) fibrosis.

 

Liver Fibrosis: Liver fibrosis is a major, increasing cause of death characterised by excessive extracellular matrix (ECM) production which causes scarring and disrupts tissue function. Several cell types contribute to fibrosis in the liver, but a major role is played by hepatic stellate cells as the primary source of myofibroblasts and ECM production. Under healthy conditions HSCs are ‘quiescent’ and non-proliferative. However, following injury and inflammation, HSCs become ‘activated’ into contractile, proliferative, migratory myofibroblasts, marked by the actin cytoskeleton protein, α-smooth muscle actin (αSMA). Activated HSCs deposit fibrotic ECM ultimately resulting in scarring, increased organ stiffness to perpetuate the process.

How are components of the scar regulated? The transcription factor Sex-determining Region Y (SRY) box 9 (SOX9) plays a key role in development of multiple organs. Mechanistic understanding of development has revealed roles for SOX9 regulating, amongst other aspects, cartilage extracellular matrix (ECM) production and cell proliferation (Mech. Dev, 2004; Trends in Mol. Med. 2011; Diabetes, 2013; Stem Cell Rep, 2017).

More recently, it transpires that SOX9 becomes expressed and induces destructive ECM components during liver fibrosis. We have shown SOX9 becomes ectopically expressed by liver myofibroblasts and regulates multiple aspects of ECM components in vitro and in vivo. Whereas in human liver fibrosis SOX9 prevalence in patient biopsy samples directly correlates with severity and predicts worsening fibrosis; representing a novel prognostic marker in liver disease (JBC, 2008; Hepatology, 2012, PlosOne, 2014; Nat. Comms, 2016; EMBO mol. Med, 2017).

How does increasing scar and stiffness signal to surrounding cells? Extracellular stiffness is a critical factor for HSC activation. The in vitro model for activating HSCs on tissue culture plastic exemplifies this. Using cell biology and transcriptomic approaches, my group has shown signalling via integrin beta-1 is important in the profibrotic response of HSCs. Inhibiting Integrin beta-1 in HSCs reduces the ability of HSCs to adhere to COL1-rich fibrotic ECM, with reduced actin organisation in the cytoskeleton. Downstream of Itgb1, we showed that Group 1 PAKs (PAK1, PAK2 and PAK3) were important in HSC activation and liver fibrosis. PAK1 emerged as the most important isoform. Blocking PAK function pharmacologically arrested liver fibrosis in vivo in mice in both CCl4 and BDL models and inhibited myofibroblast activation in vitro. Our data also identified the mechanosensitive transcription factor Yes Associated Protein-1 (YAP1) downstream of ITGB1 and PAK. Blocking YAP1 function with its inhibitor verteporfin lessened liver fibrosis. Interestingly, profibrotic factors SOX9, CTGF and GLI2 are all transcriptional targets of YAP1 (Nat. Comms, 2016; EMBO mol. Med, 2017).

 

Human Development, Stem Cells & Regenerative Medicine: In collaboration with Professor Neil Hanley, my lab maintains an interest in understanding pancreas and, more recently, liver development during human embryogenesis. This work includes stem cell platforms for regenerative medicine and toxicology screening (Hepatology, 2013; J.Hep, 2015; eLife, 2016; Stem Cell Rep, 2017). This is an active collaboration and which brings together our knowledge of development and fibrosis to uncover why regeneration is impaired during chronic diseases. In particular my group are investigating how aberrant expression of key development genes function in regeneration and disease in liver, kidney and lung.

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

Education/Academic qualification

Doctor of Philosophy, PhD (University of Southampton)

Award Date: 16 Dec 2003

Bachelor of Science, BSc Hons in Biomedical Science (University of Northumbria)

External positions

Editorial board member - Scientific Reports

Fingerprint

Dive into the research topics where Karen Piper Hanley is active. These topic labels come from the works of this person. Together they form a unique fingerprint.
  • 1 Similar Profiles

Network

Recent external collaboration on country/territory level. Dive into details by clicking on the dots or