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Customer profile: Iain Greenwood

Customer profile: Iain Greenwood
By Sam Roome 11 months ago 1311 Views No comments

Name: Professor Iain Greenwood
Qualifications: BSc (hons) Applied biology (physiology/pharmacology), PhD, Fellow of BPS
Job title: Professor of vascular pharmacology
Place of work: Molecular and clinical sciences research institute, St George’s, University of London (SGUL)

Your 5 most recent publications
Povstyan et al (2017) Synergistic interplay of Gβγ and phosphatidylinositol 4,5-bisphosphate dictates Kv7.4 channel activity. Pflugers Arch. 2017 Feb;469(2):213-223. PubMed PMID: 27981364 Stott et al (2016) Kv7 Channel Activation Underpins EPAC-Dependent Relaxations of Rat Arteries. Arterioscler Thromb Vasc Biol. 2016 Dec;36(12):2404-2411. PubMed PMID: 27789473. Carr et al (2016) MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension. Cardiovasc Res. 2016 Jul 7. pii: cvw177. PubMed PMID: 27389411 Jepps et al (2016) Molecular and functional characterization of Kv 7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats. Br J Pharmacol. 2016 May;173(9):1478-90. PubMed PMID: 26802314 Stott et al (2015) G-protein βγ subunits are positive regulators of Kv7.4 and native vascular Kv7 channel activity. Proc Natl Acad Sci U S A.. 2015 May 19;112(20):6497-502. PubMed PMID: 25941381.

Can you tell us about your background?
I did my BSc at the University of Hertfordshire, my PhD at the University of Manchester and I came to SGUL as a post doc. In 1998 I was given a Welcome Trust career development fellowship for four years and during this time I also worked at the University of Nevada for a year. At the end of my fellowship I became senior lecturer at St George’s, University of London. I then progressed through Reader and then to Professor in 2013. I also have an adjunct position in the University of Copenhagen.

Can you summarise your research now?
We are interested in how smooth muscle cell activity is controlled in both vascular and non-vascular (uterus, bowel, bladder etc.) tissue. We’re particularly interested in how ion channels impact on smooth muscle activity and how those ion channels can be regulated by receptors, intracellular signaling and molecular reagents such as microRNAs. In summary – we study how ion channels regulate smooth muscle and how those ion channels are controlled by different cellular and intracellular mediators.

Why is this research important?
Smooth muscle cells regulate a whole host of involuntary activities (from blood pressure, blood flow, airways, breathing, bowel movements, bladder control, reproduction). If these go wrong it can be inconvenient e.g. sexual dysfunction/ diarrhoea/ incontinence etc. and if seriously compromised, this can be life threatening e.g. pre-term labour, premature birth, erectile dysfunction, bowel stasis, hypertension or compromised kidney function.

What techniques do you use?
We try to do everything from the whole tissue down to the sub cellular and molecular. Focusing on arteries; we do whole artery myography and single cell electrophysiology, on native cells and over expression systems. We also do quantitative PCR, quantitative western blot, immunohistochemistry (IHC), proximity ligation assays and co-immunoprecipitation. We look at mediators of different responses using various reagents such as miRNAs, chemicals and molecular interference which helps to support our pharmacological endeavours.

What Hello Bio products do you use your research? And why are you using those particular products?
We’ve used various ion channel modulators such as:
ICA 069673 (selective KV7.2/KV7.3 activator)
ML 213 (selective KV7.2 activator)
NS1643 (Kv11.1 activator)
Paroxetine (a SSRI and a proteasomal degradation inhibitor) and
Y-27632 (for investigation of how an ion channel blocker acts in the presence/absence of Rho kinase inhibition)

We’re also planning on using your GRK2/3 inhibitor Cmpd101. We know that GPCRs carry out their signalling through the Gα subunit, while the Gβγ subunits have a different function. Two years ago, we identified that Kv7 channels are stimulated by Gβγ subunits (PubMed ID 25941381) and following this discovery, we received a grant to continue our work and we’re now investigating the vascular implications of this. Cmpd101 will help us with this.

When looking at protein trafficking we often look at the proteasome, endosome and lysosome and in our research, we also use the proteasome inhibitor MG-132.
We’re also interested in looking at protein interactions in a slightly different way using fluorescence so we potentially may be interested in your fluorescent beta adrenoceptor ligands

What has using these products helped you to achieve?
There are five Kv7 channel family members (Kv7.1-7.5) and mutations of some of these isoforms have been implicated in a variety of heredity conditions (arrhythmias, epilepsies, deafness).

In 2001 we asked the question, if Kv7 channels are so important in brain and heart – what about smooth muscle? In collaboration with Prof Soren Olsen who helped develop various Kv7 inhibitors and activators, I had a toolbox of tools which helped me crack open this question.

What are your ambitions for your future career?
I’m currently very busy teaching and I’m also creating a new pharmacology degree. At the same time, I’m also running a research group so I’m forever writing project grants. I’m keen to keep on the great people in my group. So really, my ambition is to keep my research group going so that I can keep on doing research whilst teaching.

Thanks so much for sharing this with us Iain - it's fascinating stuff. It sounds like you and your team are incredibly busy, with some further exciting research planned.

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