Division of Cardiovascular and Diabetes Medicine,
Medical Research Institute
MACHS2 Level 4 Mailroom,
Ninewells Hospital and Medical School,
University of Dundee,
Dundee, DD1 9SY
+(44) 01382 496542
I graduated with a BSc Hons in Zoology (Environmental Physiology) from Aberdeen University in 1988 and subsequently won a Commonwealth Scholarship to study for a PhD investigating the control of metabolic suppression in models of animal dormancy under Prof. Peter Hochachka at the University of British Columbia, Vancouver, Canada. In 1995 I took up a postdoctoral position at the NIH-NCRR BioCurrents Research Center at the Marine Biological Laboratory, Woods Hole, USA, investigating non-invasive methods for measuring cellular oxygen and ion fluxes using a self-referencing electrode technique. In 1997 I moved to Dundee to take up a Lectureship investigating pulmonary ion transport and oxygen sensing mechanisms in fetal lung development and these research themes have since evolved to encompass studies examining how airway and vascular growth is co-ordinated in the fetal lung and also how these processes become altered in diseases that fundamentally alter the architecture of the lung.
Co-ordination of airway and vascular growth in the fetal lung
Proper lung function requires a branched network of airway and vascular tubes which dissipate resistance to blood and gas movement to the site of gas exchange in the alveolus. The development of this network is governed by cues which control the duration of tubular out-growth and which induce, orientate and down-size each subsequent branch generation. My research has established that one key regulator of this process, Sprouty2, co-ordinates vascular and airway growth by controlling the activity of Hypoxia Inducible Factors (HIFs) in response to the primary cue for airway outgrowth, Fibroblast Growth Factor-10 (FGF-10). This has led us to investigate novel functions of Sprouty2 as an epigenetic regulator of key vascular signalling genes (e.g. Vascular Endothelial Growth Factor (VEGF)) and has wide relevance for the understanding of vascular patterning in development and in diseases such as diabetes and cancer.
Mechanism of pulmonary cyst formation in Birt-Hogg-Dubé Syndrome (BHD).
Birt-Hogg-Dubé syndrome is an autosomal dominant disorder that is linked to frame-shift or missense mutations in the Folliculin gene (Flcn) and/or its interacting partners, FNIP1 and FNIP2. This causes a range of systemic disorders that typically include fibrofolliculomas on the face and chest, renal carcinoma, pulmonary cysts and pneumothorax. In collaboration with groups around the UK and Europe we are exploring the process of lung cyst formation and identifying therapies which could be adapted to an inhaler format to arrest or reverse this process. Key pathways under investigation include VEGF/VEGF-receptor signalling between pulmonary epithelium and vasculature and also the role of matrix metalloproteinases (MMPs) as mediators of growth factor cleavage and basement membrane remodelling.
(Last 8 years; Selected from 45 Peer Reviewed Publications):
1. Watt GB, Ismail NA, Garcia Caballero A, Land SC, Wilson SM. (2012). Epithelial Na(+) channel activity in human airway epithelial cells: the role of Serum and glucocorticoid-inducible kinase 1. Br J Pharmacol. In Press.
2. Land, S.C. (2012). The Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists. Int J. Physiol, Pathophysiol. Pharmacol. In Press.
3. Land, S.C. Vascular Growth in the Fetal Lung. In: Vasculogenesis and Angiogenesis: From Embryonic Development to Regenerative Medicine. Ed D. T. and A Simionescu, Chapter 3, pp49-70, In Tech, ISBN 978-953-307-882-3, 2011.
4. Dunlop EA, Dodd KM, Land SC, Davies PA, Martins N, Stuart H, McKee S, Kingswood C, Saggar A, Corderio I, Medeira AM, Kingston H, Sampson JR, Davies DM, Tee AR. (2011). Determining the pathogenicity of patient-derived TSC2 mutations by functional characterization and clinical evidence. Eur J Hum Genet. 19(7):789-95.
5. Preston RS, Philp A, Claessens T, Gijezen L, Dydensborg AB, Dunlop EA, Harper KT, Brinkhuizen T, Menko FH, Davies DM, Land SC, Pause A, Baar K, van Steensel MA, Tee AR. (2011). Absence of the Birt-Hogg-Dubé gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility. Oncogene. 30(10):1159-73.
6. Scott CL, Walker DJ, Cwiklinski E, Tait C, Tee AR, Land SC. (2010). Control of HIF-1a and vascular signaling in fetal lung involves cross talk between mTORC1 and the FGF-10/FGFR2b/Spry2 airway branching periodicity clock. Am J Physiol Lung Cell Mol Physiol. 299(4):L455-71.
7. Hunter MJ, Treharne KJ, Winter AK, Cassidy DM, Land S, Mehta A. (2010). Expression of wild-type CFTR suppresses NF-kappaB-driven inflammatory signalling. PLoS One. 2010; 5(7):e11598.
8. Land SC, Tee AR. (2007). Hypoxia-inducible factor 1a is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif. J Biol Chem. 2007;282(28):20534-43.
9. Rae C, Cherry JI, Land FM, Land SC. (2006) Endotoxin-induced nitric oxide production rescues airway growth and maturation in atrophic fetal rat lung explants. Biochem Biophys Res Commun. 349(1):416-25.
10. Land SC, Rae C. (2005). iNOS initiates and sustains metabolic arrest in hypoxic lung adenocarcinoma cells: mechanism of cell survival in solid tumor core. Am J Physiol Cell Physiol. 289(4):C918-33.
11. Land SC, Wilson SM. (2005). Redox regulation of lung development and perinatal lung epithelial function. Antioxid Redox Signal. 7(1-2):92-107. Invited Review
12. Land SC. (2004) Hochachka's "Hypoxia Defense Strategies" and the development of the pathway for oxygen. Comp Biochem Physiol B Biochem Mol Biol. 139(3):415-33. Invited Review.
13. Land SC, Darakhshan F. (2004) Thymulin evokes IL-6-C/EBP regenerative repair and TNF-a silencing during endotoxin exposure in fetal lung explants. Am J Physiol Lung Cell Mol Physiol. 286(3):L473-87.
14. Ramminger SJ, Richard K, Inglis SK, Land SC, Olver RE, Wilson SM. (2004). A regulated apical Na(+) conductance in dexamethasone-treated H441 airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 287(2):L411-9.
15. Land SC. (2003). Oxygen-sensing pathways and the development of mammalian gas exchange. Redox Rep. 8(6):325-40. Invited Review
16. Richard K, Ramminger SJ, Inglis SK, Olver RE, Land SC, Wilson SM. (2003). O2 can raise fetal pneumocyte Na+ conductance without affecting ENaC mRNA abundance. Biochem Biophys Res Commun. 305(3):671-6.
- Lung Development and Function (Honours Life Sciences)
- Regulation of Oxygen Utilisation (Honours Life Sciences)
- Respiratory Physiology and Lung Mechanics (3rd Year Physiology)
- Angiogenesis (Masters in Cancer Biology)
- Undergraduate Advisor of Studies