We are seeking support towards a new project at the University College London/ University
College London Hospital (UCL/UCLH) called Lungs for Living (L4L). We are looking to fund the
creation of Lungs for Living, a new translational research centre, comprising of four state of the
art laboratories, where our researchers will have the common goal of biological discovery and
improving patient care. Lungs for Living will become a world class centre and the UK’s leading
authority on lung cancer research.
Lung cancer: leading cause of cancer death but lacking research investment
Lung cancer is the commonest cause of cancer death worldwide in both men and women,
causing more deaths than the next four commonest cancers combined (i.e. breast, colorectal,
prostate and pancreas cancers; Jemal et al, 2009). Patients with early stage disease can
undergo curative surgery, but unfortunately the majority of patients (85%) present with
incurable advanced disease.
Spending on lung cancer research is low in the UK (see figure). This has been recognized by
major institutional funding bodies, which are making efforts to improve lung cancer project
funding.
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Lung cancer accounts for 22 per cent of all cancer deaths in Britain, but attracts only 3.9 per
cent of research funding. The National Cancer Research Institute (NCRI) has recently called
for greater translational research into lung cancer and stated that its priority area of
biological research is to understand how normal lung cells first become dysplastic and
subsequently progress to cancer. This is the area we already have a strong track record in and
wish to dramatically expand in an attempt to improve lung cancer outcomes for patients.
UCLH: Strategic Place for a World Class Lung Cancer Research Facility in the UK
Creating a world class centre for lung cancer research at UCLH builds on our existing
reputation of being at the forefront of discovery and clinical excellence, and opens the
opportunity for UCLH to win more research project grants, and deliver new discoveries in
lung cancer diagnosis and treatment, that will make a real and lasting difference to the
cancer landscape, and the potential outlook for lung cancer patients.
Our internationally recognised researchers are currently based across the vast UCL/UCLH
campus, making collaboration difficult. Moving these researchers into a specific lung
cancer/epithelial regeneration research facility will enable collection of tissue and sharing of
clinical samples, joint use of facilities, fertilisation of ideas and joint large programme grant
applications.
Despite the difficulties operating across campus, UCLH has a rich history in pioneering
treatments in lung cancer, running studies and national lung cancer trials. UCLH was
instrumental in pioneering Photodynamic Therapy (PDT), a procedure which involves injecting
patients with a light sensitive dye that is preferentially attracted to cancerous tumours which
are then destroyed by shining laser light of a specific wavelength on it. PDT is a non-invasive
treatment making it ideal for patients who are unsuitable for surgery; patients also heal
quickly with limited damage to surrounding tissue. Studies show that PDT has a 70% success
rate for treating early lung cancer.
In addition to being at the forefront of discoveries like PDT, UCLH is home to some of the
world’s leading researchers in lung epithelial biology and cancer research. Our staff are mostly
early-career and have rapidly expanding groups and include Dr Sam Janes, Dr Neal Navani and
Dr Adam Giangreco. (Please see Appendix 2 for more information about leading experts in lung
cancer based at UCLH). They work closely with other investigators who rely on samples
collected by the team including Professor Charles Swanton and Prof Stephan Beck at CRUK and
UCL and Prof Peter Campbell at the Welcome Trust Sanger Institute.
The Lungs for Living Research Centre
In order to create the Lungs for Living research centre we are seeking support to help us fund
the refurbishment of four laboratories to create a translational research centre; core staff that
will run the day to day research and manage the laboratories; new equipment; and a new
professorial appointment to work along side the research groups that will be based at the
Centre.
The Research Centre will be based on the UCL/UCLH campus and 365 square meters of space
has already been identified and allocated for the Centre.
The available space will be refurbished to include 4 new laboratories, three multi-user offices
(for 6-12 people in each office), 5 offices for Principle Investigators, a Store and a Common
Room. The four laboratories will include a general laboratory, cell culture laboratory (a sterile
environment where cells can grow and be manipulated in “hoods”; clean enclosed spaces that
prevent the cells from being infected), a microscopy lab (a dark and quiet environment which
houses microscopes, usually situated away from footfall to prevent the microscopes from
vibrating), and a specialist laboratory which will provide the appropriate environment for a
histopathology unit, where tissue samples are blocked, cut and stained.
In addition to the refurbishment of the laboratories and the office space, we will be furnishing
the laboratories with vital equipment such as incubators, microscopes (with white light,
fluorescence and cameras), centrifuges and state of the art imaging systems.
We will also be seeking support to cover staff costs for 5 new employees who will be central to
the running of the research on a day to day basis, in the first three years. In addition we will
appoint a new professorial position. This person will be world leading and will be appointed by
Professor David Lomas (Dean) and Professor Chris Boshoff (Director of Cancer) to work along
side Dr Janes and Dr GIangreco complimenting their work with expertise in drug design.
Once the Centre is equipped, refurbished and staffed, the teams will be set to deliver cutting
edge clinical, translational and basic science research into the pathogenesis and treatment of
lung cancer. In particular, the Centre aims to delineate the key events in early lung cancer
pathogenesis, which will make it possible to identify novel lung cancer targets and facilitate
the development of new therapeutic interventions. The immediate objectives of Lungs for
Living fit within the overarching drive in experimental medicine at UCL/UCLH and include:
1. Establishment of a comprehensive lung tissue biobank and early lung cancer lesion cell
culture system for use in lung research across UCL and beyond
2. Understand the pathogenic sequence of events leading to lung cancer formation in an
attempt to define treatment strategies to halt its development
2.1 Determine the key cells and signalling molecules involved in human airway
homeostasis and the abnormalities leading to lung cancer
2.2 Define the early transcriptional modifications driving progression between
normal airways and pre-invasive lung cancer
2.3 Define early genomic events in lung cancer pathogenesis
2.4 Determine the functional relevance of stem cells in normal human airways and
pre-invasive lung cancers
3. Develop novel targets into novel therapeutics (new or reuse of old drugs/molecules)
4. Delineate a method for human airway epithelial regeneration
5. Deliver ‘state of the art’ clinical translational studies alongside clinical trials
Any contributions towards our funding total would be greatly appreciated, no matter how
large or small. We are able to fund individual parts of the refurbishment/equipment if you
would like your money to fund something specific and naming opportunities are also possible.
Appendix 2: Overview of existing Lung Cancer Research Groups and Clinical Trials taking
place at UCLH
2.1
The Janes Group
Dr Sam Janes was recruited to UCL as an MRC Clinician Scientist in 2005 and in 2010 he
became a Wellcome Senior Fellow in Clinical Science. His work examines two aspects of stem
cell biology in relation to lung cancer. First the use of exogenous (bone marrow-derived) stem
cells as vectors to deliver anti-cancer therapies. This work has led to the design of a phase I
safety study in humans. Second, he examines the key signalling pathways involved in
endogenous airway stem cell maintenance and how dysregulation leads to the early stages of
cancer development. He has particular focus on the Wnt and EGFR pathways. His important
work has been recognised by a number of international awards for his research team and the
personal award of European Thoracic Oncology Investigator of the Year in 2010.
Dr Janes’ lab work dovetails closely with his clinical interests in pre-invasive disease. UCLH has
the largest cohort in the UK of patients with pre-invasive disease lesions and runs the CTAAC
funded Lung SEARCH trial (Professor Spiro and Dr George), screening patients with COPD for
early lung cancers. The unique tissue from these patients feeds the translational work carried
out and has led to exciting collaborations with other institutions including the Sanger Institute.
Dr Janes now has an expanding group of 15 researchers including post doctoral researchers,
technicians, clinical fellows and PhD students.
2.2
The Giangreco Group
Dr Giangreco has moved from skin biology to lung biology and has recently secured his own EU
New Investigator Fellowship examining a novel tumour suppressor gene in the lung. Dr
Giangreco has published the seminal work on murine airway regeneration with Barry Stripp
and is now focussed on human airway regeneration.
His group is expanding and he has huge potential given the correct space and surroundings. His
group currently consists of 4 people.
2.3
Dr Neal Navani
The Lung Cancer Programme continues to invest heavily in patients as demonstrated by recent
appointment of Dr Neal Navani as a thoracic consultant to run clinical trials in improving lung
cancer patient pathways and experience. Dr Navani has submitted several clinical studies and
has an honorary Senior Scientist position at the MRC clinical trials unit. The Lungs for Living
Research Centre would allow office space for Dr Navani to encourage new trials to have
translational elements that would run through the Janes/Giangreco/ groups.
Selected Articles by Janes/Giangreco and Navani
- Lu L, Teixeira VH, Yuan ZQ, Graham TA, Endesfelder D, Kolluri K, Al-Juffali N, Nicholson
A, Falzon M, Kschischo M, Swanton C, Wright NA, Carroll B, Watt FM, George PJ, Jensen
KB, Giangreco A, Janes SM. LRIG1 regulates cadherin-dependent contact inhibition
directing epithelial homeostasis and preinvasive squamous cell carcinoma development
Accepted Journal of Pathology
- Mitchell N, Kalber TL, Cooper MS, Sunassee K, Chalker SL, Shaw KP, Ordidge KL, Badar A,
Janes SM, Blower PJ, Lythgoe MF, Hailes HC, Tabor AB. Incorporation of paramagnetic,
fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging.
Biomaterials.
2012
Nov
3.
doi:pii:
S0142-9612(12)01093-9.
10.1016/j.
biomaterials.2012.09.070. [Epub ahead of print]
- Elliott MJ, De Coppi P, Speggiorin S, Roebuck D, Butler CR, Samuel E, Crowley C, McLaren C,
Fierens A, Vondrys D, Cochrane L, Jephson C, Janes S, Beaumont NJ, Cogan T, Bader A, Seifalian
AM, Hsuan JJ, Lowdell MW, Birchall MA. Stem-cell-based, tissue engineered tracheal
replacement in a child: a 2-year follow-up study Lancet. 2012 Sep 15;380(9846):994-1000.
- Navani N, Lawrence DR, Kolvekar S, Hayward M, McAsey D, Kocjan G, Falzon M,
Capitanio A, Shaw P, Morris S, Omar RZ, Janes SM. EBUS-TBNA Prevents Mediastinocopies in
the Diagnosis of Isolated Mediastinal Lymphadenopathy: A Prospective Trial. Am J Respir Crit
Care Med. 2012 May 31.
- Navani N, Brown JM, Nankivell M, Woolhouse I, Harrison RN, Jeebun V, Munavvar
M, Ng BJ, Rassl DM, Falzon M, Kocjan G, Rintoul RC, Nicholson AG, Janes SM.
Suitability of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration
Specimens for Subtyping and Genotyping of Non-Small Cell Lung Cancer: A
Multicenter Study of 774 Patients. Am J Respir Crit Care Med. 2012 Jun 15;185(12):1316-22.
- Shastry M, Miles KA, Win T, Janes SM, Endozo R, Meagher M, Ell PJ, Groves AM.
Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrastenhanced computed tomography to phenotype non-small cell lung carcinoma. Mol Imaging.
2012 Sep-Oct;11(5):353-60.
- Ordidge KL, Duffy BA, Wells JA, Kalber TL, Janes SM, Lythgoe MF. Imaging the paediatric
lung: what does nanotechnology have to offer? Paediatr Respir Rev.2012 Jun;13(2):84-8. Epub
2011 Aug 4.
- Smith LJ, Lawrence DR, Kayani I, Capitanio A, Falzon M, Janes SM, Navani N. Pulmonary mass
in a 19-year-old male. Inflammatory myofibroblastic tumour. Thorax. 2012 May;67(5):468-70.
Epub 2011 Nov 21.
- Giangreco A, Lu L, Vickers C, Teixeira VH, Groot KR, Ilieva EV, George J, Nicholson AG, Sage
EK, Watt FM, Janes SM. β- catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial-to-mesenchymal
transition. J Pathol. 2012 Mar;226(4):575-87.
- Navani N, Nankivell M, Woolhouse I, Harrison RN, Munavvar M, Oltmanns U, Falzon M,
Kocjan G, Rintoul RC, Janes SM. Endobronchial ultrasound-guided transbronchial needle
aspiration for the diagnosis of intrathoracic lymphadenopathy in patients with extrathoracic
malignancy: a multicenter study. J ThoracOncol. 2011 Sep;6(9):1505-9.
- Hunziker L, Benitah SA, Braun KM, Jensen K, McNulty K, Butler C, Potton E, Nye E, Boyd R,
Laurent G, Glogauer M, Wright NA, Watt FM, Janes SM. Rac1 deletion causes thymic atrophy.
PLoS One. 2011 Apr 29;6(4):e19292.
- Giangreco A, Lu L, Mazzatti DJ, Spencer-Dene B, Nye E, Teixeira VH, Janes SM. Myd88
deficiency influences murine tracheal epithelial metaplasia and submucosal gland abundance.
J Pathol. 2011 Jun;224(2):190-202.
- Loebinger MR, Sage EK, Davies D, Janes SM. TRAIL-expressing mesenchymal stem cells kill the
putative cancer stem cell population. Br J Cancer. 2010 Nov 23;103(11):1692-7.
- Aguilar S, Scotton C, McNulty K, Nye E, Stamp G, Laurent G, Bonnet D and Janes SM
Bone Marrow Stem Cells Expressing Keratinocyte Growth Factor via an Inducible Lentivirus
Protects against Bleomycin-induced Pulmonary Fibrosis.PLoS One. 2009 Nov 24;4(11):e8013.
- Loebinger MR, Kyrtatos PG, Turmaine M, Price AN, Pankhurst Q, Lythgoe M and Janes SM.
Magnetic resonance imaging of mesenchymal stem cells homing to pulmonary metastases
using biocompatible magnetic nanoparticles. Cancer Res. 2009 Dec 1;69(23):8862-7.
- Loebinger MR, Eddaoudi A, Davies D, Janes SM. Mesenchymal stem cell delivery of TRAIL can
eliminate metastatic cancer. Cancer Res. 2009 May 15;69(10):4134-42.
- Janes SM, Ofstad TA, Campbell DH, Eddaoudi A, Warnes G, Davies D, Watt FM. PI3-kinasedependent activation of apoptotic machinery occurs on commitment of epidermal
keratinocytes to terminal differentiation. Cell Res. 2009 Mar;19(3):328-39.
- Loebinger MR, Giangreco A, Groot KR, Prichard L, Allen K, Simpson C, Bazley L, Navani N,
Tibrewal S, Davies D, Janes SM. Squamous cell cancers contain a side population of stem-like
cells that are made chemosensitive by ABC transporter blockade. Br J Cancer. 2008 Jan
29;98(2):380-7.
- Aguilar S, Nye E, Chan J, Loebinger M, Spencer-Dene B, Fisk N, Stamp G, Bonnet D, Janes SM.
Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the
lung. Stem Cells. 2007 Jun;25(6):1586-94.
- Janes SM, Ofstad TA, Campbell DH, Watt FM, Prowse DM. Transient activation of FOXN1 in
keratinocytes induces a transcriptional programme that promotes terminal differentiation:
contrasting roles of FOXN1 and Akt. J Cell Sci. 2004 Aug 15;117(Pt 18):4157-68.
- Janes SM, Watt FM. Switch from alphavbeta5 to alphavbeta6 integrin expression protects
squamous cell carcinomas from anoikis. J Cell Biol. 2004 Aug 2;166(3):419-31. Mediastinal
staging of NSCLC with endoscopic and endobronchial ultrasound.Nat Rev ClinOncol. 2009
May;6(5):278-86.
- Janes SM, Watt FM. New roles for integrins in squamous-cell carcinoma. Nat Rev Cancer.
2006 Mar;6(3):175-83.
- Griffiths MJ, Bonnet D, Janes SM. Stem cells of the alveolar epithelium.Lancet. 2005 Jul 1622;366(9481):249-60.
- Giangreco A, Hoste E, Takai Y, Rosewell I, Watt FM. Epidermal Cadm1 expression promotes
autoimmune alopecia via enhanced T cell adhesion and cytotoxicity. J Immunol. 2012 Feb
1;188(3):1514-22. (cover article)
- Giangreco A, Jensen KB, Takai Y, Miyoshi J, Watt FM. Necl2 regulates epidermal adhesion
and wound repair. Development 2009 Oct;136(20):3505-14.
- Giangreco A, Arwert EN, Rosewell IR, Snyder J, Watt FM, Stripp BR. Stem cells are
dispensable for lung homeostasis but restore airways after injury.ProcNatlAcadSci U S A. 2009
Jun 9;106(23):9286-91. (corresponding author; cover article)
- Giangreco A, Goldie SJ, Failla V, Saintigny G, and Watt FM. Human skin aging is associated
with reduced expression of the stem cell markers beta1 integrin and MCSP. Journal of
Investigative Dermatology 2009, Sep 24.
-Driskell RR, Giangreco A, Jensen KB, Mulder K and Watt FM. Sox2 positive dermal papilla cells
specify hair follicle type in mammalian epidermis. Development 2009 Aug;136(16):2815-23
(cover article)
-Zemke AC, Teisanu RM, Giangreco A, Drake JA, Brockway BL, Reynolds SD, Stripp BR. {beta}Catenin is not Necessary for Maintenance or Repair of the Bronchiolar Epithelium.Am J Respir
Cell Mol Biol. 2009 Feb 12.
- Giangreco A, Qin M, Pintar JM, Watt FM. Epidermal stem cells are retained in vivo
throughout skin aging. Aging Cell. 2008 Mar;7(2):250-9. (corresponding author)
- Reynolds SD, Zemke AC, Giangreco A, Brockway BL, Teisanu RM, Drake JA, Mariani TJ, Yp D,
Taketo MM, Stripp BR. Conditional Stabilization of beta-Catenin Expands the Pool of Lung
Stem Cells. Stem Cells. 2008 May;26(5):1337-46.
-Loebinger MR*, Giangreco A*, Groot KR, Prichard L, Allen K, Simpson C, Bazley L, Navani N,
Tibrewal S, Davies D, Janes SM. Squamous cell cancers contain a side population of stem-like
cells that are made chemo sensitive by ABC-transporter blockade. Br J Cancer. 2008 Jan
29;98(2):380-7. (* - equal contribution).
- Giangreco A, Groot KR, Janes SM. Lung cancer and lung stem cells: strange bedfellows? Am.
J. Respir. Crit. Care Med. 2007 Mar 15;175(6):547-53. Epub 2006 Dec 7
- Giangreco A, Shen H, Reynolds SD, Stripp BR. Molecular Phenotype of Airway Side
Population Cells.Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L624-30.
- Giangreco A, Reynolds SD, Stripp BR. Terminal bronchioles harbor a unique airway stem cell
population that localizes to the bronchoalveolar duct junction. Am J Pathol.2002 Jul; 161(1)
173-182.
- Giangreco A, Sowden MP, Mikityansky I, Smith HC. Ethanol stimulates apolipoprotein B
mRNA editing in the absence of de novo RNA or protein synthesis. BiochemBiophys Res
Commun.2001 Dec; 289(5):1162-1167.
-Pombrio JM, Giangreco A, Li L, Wempe MF, Anders MW, Sweet DH, Pritchard JB, Ballatori N.
Mercapturic acids (N-acetylcysteine S-conjugates) as endogenous substrates for the renal
organic anion transporter-1.MolPharmacol. 2001 Nov; 60 (5):1091-1099.
- Hong KU, Reynolds SD, Giangreco A, Hurley CM, Stripp BR. Clara cell secretory proteinexpressing cells of the airway neuroepithelial body microenvironment include a label-retaining
subset and are critical for epithelial renewal after progenitor cell depletion. Am J Respir Cell
MolBiol.2001 Jun; 24 (6): 671-681.
- Reynolds SD, Hong KU, Giangreco A, Mango GW, Guron C, Morimoto Y, Stripp BR.
Conditional Clara cell ablation reveals a self-renewing progenitor function of pulmonary
neuroendocrine cells. Am J Physiol Lung Cell MolPhysiol.2000 Jun; 278(6): L1256-1263.