Dr Daniel W Lambert B.Sc. (Hons) Ph.D.
Non-clinical Lecturer in Biochemistry and Cell Biology
Member of the Integrated Biosciences Group
Tel: 0114 271 7959
Fax: 0114 271 7894
Email: D.W.Lambert@sheffield.ac.uk
Teaching
Undergraduate:
DEN103 - The Human Body
DEN104 - The Oral Cavity in Health & Disease
DEN203 - Growth, Development, Ageing & Nutrition
Postgraduate
ORP608 - Research Problems and Approaches
Administrative roles
Postgraduate Research Tutor for School of Clinical Dentistry
Theme Leader - DEN104
Module Coordinator - ORP608
Sub-course Leader - DEN203
Research Interests
Molecular mechanisms underlying head and neck cancer progression
Head and neck cancer (HNSCC) ranks among the top ten most common cancers worldwide and is increasingly prevalent, particularly in younger age groups. The survival rate for this devastating disease is poor, largely due to late diagnosis and a lack of effective therapeutic agents. We are pursuing a number of research avenues which aim to identify diagnostic markers and prognostic indicators and to elucidate novel therapeutic targets to halt disease progression:
The role of microRNA in HNSCC
MicroRNA are small, non-coding, RNA which regulate the expression of target genes by binding to complementary sequences in their transcripts. Changes in the levels of a number of microRNA have been detected in a variety of cancers, including HNSCC. We are currently carrying out a number of projects studying the involvement of microRNA in the motility of HNSCC, with particular interest centring on their roles in modulating cell:extracellular matrix interactions and signalling pathway activity. In addition we are assessing the possibility of using specific microRNA as prognostic indicators in HNSCC progression. These studies complement work investigating microRNA involvement in prostate cancer and cardiovascular disease being carried out in collaboration with Prof Anthony J Turner at the University of Leeds.
The influence of microenvironment on tumour progression
It is becoming increasingly apparent that cancer cell behaviour is dictated, at least to some extent, by the surrounding microenvironment. HNSCC cells are surrounded in vivo by a stromal milieu, composed of fibroblasts, endothelial cell and immune cells. We are currently studying the mechanisms by which the cancer-associated stroma influences HNSCC progression.
Host-microbe interactions in periodontal disease
Chronic periodontitis, an inflammatory disease leading to tooth loss, affects over 300 million people worldwide and is a significant healthcare burden particularly in the older population. Although not a classical infectious disease, the role of bacteria in causing periodontitis is unequivocal with several bacterial species such as Porphyromonas gingivalis and Tannerella forsythia being implicated as causative agents. The virulence of periodontal pathogens is attributed not only to bacterial factors that directly damage tissue but also to their ability to dysregulate the host immune response. We are currently investigating the ability of periodontal pathogens to modulate the immune response by altering the expression of specific microRNA, which in turn influence the expression of components of the innate immune response
Funding
Work in the laboratory is supported by Yorkshire Cancer Research, Wellcome Trust, The Dunhill Medical Trust, The Royal Society and The British Society for Oral and Maxillofacial Pathology
Members of the Laboratory
Dr Prachi Stafford - Post-doctoral Research Associate
Emma Hinsley - PhD student
Genevieve Melling - PhD student
Tasnuva Kabir - PhD student
Lav Darda - PhD student (with Dr K Hunter)
Recent publications
Hinsley, E. E., Kumar, S., Hunter, K. D., Whawell, S. A., & Lambert, D. W. (2012). Endothelin-1 stimulates oral fibroblasts to promote oral cancer invasion.. Life Sci. doi:10.1016/j.lfs.2012.04.001
Clarke, N. E., Fisher, M. J., Porter, K. E., Lambert, D. W., & Turner, A. J. (2012). Angiotensin converting enzyme (ACE) and ACE2 bind integrins and ACE2 regulates integrin signalling.. PLoS One, 7(4), e34747. doi:10.1371/journal.pone.0034747
Hinsley EE, Hunt S, Hunter KD, Whawell SA and Lambert DW (2011) Endothelin-1 stimulates motility of head and neck squamous carcinoma cells by promoting stromal-epithelial interactions. Int J Cancer 130:40-47
Hunt S, Jones AV, Hinsley EE, Whawell SA and Lambert DW (2011) MicroRNA-124 suppresses oral squamous cell carcinoma motility by targeting ITGB1. FEBS Lett. 585:187-92 [link to text]
Lambert DW, Clarke NE and Turner AJ (2010) Not just angiotensinases: new roles for the angiotensin converting enzymes. Cell Mol Life Sci. 67: 89-98 [link to text]
Guy JL, Lambert DW, Turner AJ, Porter KE (2008) Functional angiotensin converting enzyme-2 (ACE2) is expressed in human cardiac myofibroblasts. Experimental Physiology 93: 631-638 [link to text]
Lambert DW, Clarke N, Hooper NM, Turner AJ. (2008) Calmodulin interacts with angiotensin-converting enzyme-2 (ACE2) and inhibits shedding of its ectodomain. FEBS Letters 582: 385-390. [link to text]
Lambert DW, Hooper NM, Turner AJ (2008) Angiotensin-converting enzyme 2 and new insights into the renin-angiotensin system. Biochemical Pharmacology 75: 781-786. [link to text]
Lambert DW, Yarski M, Warner FJ, Thornhill P, Parkin ET, Smith AI, Hooper NM, and Turner AJ (2005) Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2). Journal of Biological Chemistry 280: 30113-301139. [link to text]
Lambert DW, Guy JL, Warner FJ, Hooper NM, Turner AJ (2005) Membrane-associated zinc peptidase families: comparing ACE and ACE2. Biochimica et Biophysica Acta 1751: 2-8. [link to text]
Warner FJ, Lew RA, Smith AI, Lambert DW, Hooper NM and Turner AJ (2005) Angiotensin-converting enzyme 2 (ACE2), but not ACE, is preferentially localized to the apical surface of polarized kidney cells. Journal of Biological Chemistry 280: 39353-39362. [link to text]
External Collaborations
Professor Anthony J Turner, University of Leeds, UK
Dr Yin Y Mo, Southern Illinois University, USA
Dr Ed Parkin, Lancaster University, UK
Professor Shigeki Higashiyama, Ehime University, Japan
Dr Ian Wood , University of Leeds, UK
