Dr Mark Bass

Mark BassLecturer
Department of Biomedical Science
The University of Sheffield
Western Bank
Sheffield S10 2TN
United Kingdom

Room: B2 05 Florey building
Telephone: +44(0) 114 222 5278
Email: mark.bass@sheffield.ac.uk

Bateson CentreCMIAD

Cell Biology and Cancer

Developmental Biology


Brief career history

  • 2015-present: University of Sheffield Lecturer, Department of Biomedical Science, University of Sheffield, UK
  • 2009-2015: Wellcome Trust Research Career Development Fellow, School of Biochemistry, University of Bristol, UK
  • 2001-2009: Postdoctoral Research Associate, Faculty of Life Sciences, University of Manchester, UK
  • 1997-2001: PhD, Biochemistry, School of Biological Sciences, University of Leicester, UK
  • 1996-1997: MRes, Biochemistry University of Leicester, UK
  • 1993-1996: BSc (Hons), Biochemistry University of Leicester, UK

Research interests

Fibroblast migration during wound healing: signalling from extracellular matrix receptors to Rho-family GTPases.

Full publications


Fibroblast migration during wound healing: signalling from extracellular matrix receptors to Rho-family GTPases

Healing defects are one of the largest current health challenges, with chronic wounds frequently requiring amputation of the affected limb. In 2008, 200,000 UK patients were suffering chronic wounds, costing the health service £3.1 billion annually.  Since then, a 26-49% increase in risk factors such as age and diabetes has made the situation worse.

Upon wounding healthy skin, inflammatory cells combat infection, fibroblasts migrate into the wound bed and contract the defect, and finally re-epithelialisation closes the gap.

However, these processes become less efficient with age and risk factors such as diabetes, obesity or smoking, eventually leading to the formation of chronic wounds that include pressure ulcers, venous leg ulcers and diabetic foot ulcers. 

The two hallmarks of a chronic wound are a chronic inflammatory response as the skin tries unsuccessfully to deal with infection and failure by fibroblasts to proliferate and migrate.  The fact that scars are usually a fraction of the size of the original wound demonstrates very simply the importance of fibroblast migration and wound contraction, and improving this process is the core objective of our work.

Our laboratory investigates the activation of fibroblasts upon wounding, and the mechanisms by which migration is directed by regulation of the Rho family GTPases, especially the protrusion regulator, Rac1.  Our work ranges from the investigation of signalling networks in single cells, through the analysis of in vivo wound healing models, to the development of therapies for treatment of patients.

The work can be divided into three main areas:

1) Regulation of membrane protrusion by Rho-family GTPases

Cell migration requires cycles of protrusion at the leading edge and contraction within the cell body, driven by the activation of Rac1 and RhoA respectively.  The appearance of fibronectin in wounded tissue triggers cycles of Rac1 and RhoA activity in fibroblasts by engagement of the fibronectin sensor, syndecan-4.

We are examining how syndecan-4 regulates and coordinates Rac1 and RhoA signals by combining traditional biochemistry (A) with live cell imaging and FRET-based analysis (B). Perturbation of components of the syndecan-4 signalling chain by RNAi is revealing that syndecan-4 synchronises the activation/inhibition of Rac1 and RhoA signals and more importantly localises protrusion.  By examining the migration of cells through complex fibrillar matrices, which are structurally similar to skin (C), we find that sydecan-4-directed GTPase regulation is necessary for persistent migration along matrix fibers. 

Figure 1

A) Activation of Rac1 upon engagement of syndecan-4 by fibronectin, detected by pull-down assay.
B) Active Rac1 (green) is polarised to the front of a migrating cell, detected by FRET.
C) Fibroblasts stained for focal adhesion markers (red) embed into a 3D fibrous matrix (green).

2) Cooperation between extracellular matrix receptors regulates focal adhesion dynamics

Membrane protrusion must be coordinated with formation and dissolution of focal adhesions for migration to occur. We are investigating the regulation of integrin trafficking by syndecan-4 using atomic force microscopy to measure adhesive strength (D+E) and TIRF to follow removal of β1-integrin from the adhesion plane upon engagement of syndecan-4 (F). We are also using mass spectrometry to identify key trafficking regulators, and through this approach uncovering key roles for sorting nexins in integrin trafficking (G).

Figure 2

D) Single cells captured on the cantilever of an atomic force microscope can be brought into contact with an extracellular matrix before withdrawal of the cell to measure strength of adhesion.
E) Comparison of contacts by atomic force microscopy (D) reveals that cells contacting integrin ligands alone (red curve) have higher strength than those contacting a combined integrin and syndecan-4 ligand (black curve).
F) Imaging of GFP-β1-integrin in the adhesion plane by TIRF reveals that syndecan-4 engagement triggers internalisation of integrin.
G) β1-integrin is sorted by sorting nexin 17 (SNX17), demonstration of colocalisation by confocal microscopy.

3) Regulation of Rac1 by matrix receptors regulates cell migration in vivo and allows the development of healing therapies

The translation of our findings to in vivo healing models, and subsequently patient therapies is a crucial aspect of our work. The consequences of disrupting Rac1 signalling are that migration becomes less efficient, leading to delays in developmental and healing processes, and can be demonstrated in both fish (H) and mammalian (I) models.

We are investigating techniques to reverse healing defects by activating Rac1. Our most notable advances have come from the use of low-intensity pulsed ultrasound to stimulate fibroblast migration (Video protocol). (J) We find that skin wounds heal more slowly in diabetics (green curve) than healthy individuals (orange curve).

However, normal healing can be restored by daily treatments with ultrasound (pink line). The effect of ultrasound can be seen at the cellular level in biopsies as the number of brown fibroblasts recruited to an ultrasound-treated diabetic wound far exceeds that recruited to an untreated wound (K).

Figure 3

H) Knockdown of the Rac1 trafficking molecule, coronin 1C causes misalignment of pharyngeal arches in the developing zebrafish, due to compromised neural crest migration.
I) Knockout of syndecan-4 reduces healing rates.
J) The healing defects of diabetic individuals (green) can be restored to the rates of healthy control individuals (orange) by the application of ultrasound (pink).
K) Ultrasound treatment stimulates the recruitment of fibroblasts (brown) to the wounds of diabetic individuals.

By combining this range of approaches to address the mechanism of fibroblast migration during wound healing, we move closer to developing some promising therapies, and bringing them into mainstream clinical use.


Undergraduate and postgraduate taught modules


  • BMS109 Cell & Molecular
  • Level 3 Practical and Dissertation Modules (Coordinator)

Masters (MSc):

  • BMS6082 Practical Cell Biology (Coordinator)

Selected publications

Journal articles