UCL Cancer Institute Seminar Series 

Dr Nuria Lopez-Bigas

ICREA Research Professor at University Pompeu Fabra, Barcelona, Spain
Therapeutic lanscape of cancer drivers

Date and Location:

Thursday 1st October, 12.00pm
UCL Cancer Institute
Courtyard Café
Paul O'Gorman Building
72 Huntley Street, WC1E 6DD

Dr Nuria Lopez-Bigas

Dr Lopez-Bigas is a biologist with expertise in Medical Genetics and Computational Biology. Nuria joined the University Pompeu Fabra in April 2006 and was appointed ICREA Research Professor in October 2011. Her research is focused on the study of cancer from a genomics perspective. Her lab has contributed to the identification of cancer driver genes by developing computational methodologies to detect signals of positive selection in the pattern of somatic mutations observed in tumors. They have applied these methods to the analysis of thousands of tumor genomes from multiple cancer types creating a Cancer Drivers database available at IntOGen.org. Dra Lopez-Bigas is also interested in finding therapeutic opportunities to target cancer drivers and in refining the process to precisely assign the most effective targeted therapy to each patient based on the genomic events driving the tumor. Towards this direction her lab has developed an In silico cancer drug prescription protocol that applied to thousands of tumor genomes across 28 different cancer types to obtain a landscape of usability of targeted therapies.

Carlota Rubio-Perez et all.In silico prescription of anticancer drugs to cohorts of 28 tumor types reveals unexploited targeting opportunities. Cancer Cell. 2015
Gallardo F et all. Cytoplasmic accumulation of NCoR in malignant melanoma: consequences of altered gene repression and prognostic significance. Oncotarget. 2015
Leiserson MD et all. Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes. Nat Genet. 2015

Hosted by Javier Herrero

Professor Mirka Uhlirova

University of Cologne, Institute of Genetics and CECAD
'Transcriptional (Dys)regulation of Epithelial Homeostasis'

Date and Location:

Thursday 24th September, 12.30pm
UCL Cancer Institute
Courtyard Café
Paul O'Gorman Building
72 Huntley Street, WC1E 6DD

Mirka Uhlirova

Epithelia are fundamental building blocks of tissues in metazoans. Their coordinated establishment and maintenance are orchestrated by specific, evolutionarily conserved signaling programs. Loss of epithelial function and homeostasis underlies numerous human diseases including cancer. My lab has a long-standing interest in deciphering the role of stress signaling in epithelial morphogenesis and its contribution to diseases by exploiting the relatively simple, yet relevant model of Drosophila melanogaster. We concentrate on understanding the interplay between stress signaling modules and transcription factor networks that integrate developmental as well as stress signals and translate them into meaningful, context-specific responses by regulating target gene expression. Our recent work demonstrates that a transcription factor network comprising proteins of three distinct families is integral to tumorigenesis provoked by oncogenic Ras signaling and loss of the apicobasal polarity gene scribble in the Drosophila epithelial tumor model. We provide causal genetic evidence that the three transcription factors, all acting downstream of Jun-N-terminal kinase (JNK), cooperate in vivo and exert both unique and common functions to establish and maintain the key tumor capabilities.
Further, we identify a novel role for activating transcription factor 3 (atf3) as a polarity response gene that drives morphological and differentiation defects following the breakdown of epithelial integrity. Given the conserved nature of these factors, it is likely that they also operate in human epithelia. Thus, our work highlights the potential of the Drosophila model to study genetic mechanisms underlying epithelial homeostasis and its disruption with clear relevance to pathology of human cancer.

Hosted by Ivana Bjedov

The seminar will be followed by a sandwich buffet lunch

Dr Wendy Woodward

University of Texas, MD Anderson Cancer Center, USA
'Inflammatory breast cancer: unique biologic and local therapy considerations'

Date and Location:

Monday 21st September, 12.00noon
Cancer Trials Centre
5th Floor Seminar Room
90 Tottenham Court Road

Dr Wendy Woodward

In 2006 The University of Texas MD Anderson Cancer opened a dedicated Inflammatory Breast Cancer (IBC) clinic and research program. Nearing 10 years seeing over 100 patients a year with this rare and aggressive form of breast cancer several novel concepts and treatment considerations have emerged. Clinically, bilateral nodal involvement is common and curable. Pre-chemotherapy medical photography and cross-sectional imaging is imperative in guiding post-mastectomy radiation field design. Surgery may be considered even in stage IV patients given the high propensity for local-regional failure and progression. Molecular analysis of IBC tumors reveals significant overlap with aggressive non-IBC tumors. In the “normal” breast tissue of IBC patients however, normal stem cells and macrophage infiltrates are markedly elevated compared to the “normal” breast of non-IBC patients. Modelling stromal cell engagement in a mouse model recapitulates the IBC phenotype in the mouse. Statins target the pro-tumor normal cell interactions that promote IBC and improve both DFS and local control after radiotherapy for IBC patients.

Host: Prof. Jonathan Ledermann, Cancer Institute Clinical Director

Refreshments will be available after the seminar.

Dr Ilaria Malanchi

The Francis Crick Institute
'The Social Nature of Cancer Cells'

Ilaria Malanchi

Date and Location:

Thursday 2nd July, 12.00noon
UCL Cancer Institute
Courtyard Café
Paul O'Gorman Building
72 Huntley Street, WC1E 6DD

Dr Malanchi laboratory approaches cancer as all body disease, studying the complex interactions cancer cells establish with the surrounding tissue cells in the search of opportunity to improved patient treatments. Cancer rises when a cell of a certain tissue loses its specialized function, stop contributing to organ activity and importantly start breaking the rules limiting its growth within the tissue. This cancer-initiating cell restarts the embryonic program of “construction”, activates extensively proliferation and builds new interactions with the surrounding healthy cells of the tissue plaguing their behaviour.

The powerful growth program of cancer cells is crucially sustained by this crosstalk with host-derived cells, which make the tumour constantly evolving and spreading to the entire body. The lab uses various mouse model for spontaneous and genetically induced tumourigenesis, as well genetic or chemical approaches to block signals from the host organism. Our final aim is to find therapeutic approaches to interfere with the tumour-host crosstalk, a first step toward novel, more effective anti-cancer therapies.

Cancer Research UK - Ilaria Malanchi
Francis Crick profile 

Hosted by Sergio Quezada

This seminar has been sponsored in part by Taconic Bioscience and the Biomedical Research Centre.

Professor Liming Sun

Institute of Biochemistry and Cell Biology, SIBS, CAS, China
'Necrosis: A Kinase Initiated Death Pathway'

Professor Liming Sun

Date and Location:

Tuesday 26th May 10.00am
Courtyard Café
Paul O'Gorman Building

Programmed necrosis, also known as necroptosis, is morphologically marked by the swelling of cellular organelles, rapid loss of cell membrane integrity and release of cellular contents. Necrosis functions during pathogen infection, drug-induced cell injuries and trauma-induced tissue damages. The necrotic death of injured cells help to isolate and remove the pathogens and induce immune response to viral infection. On the other hand, dysfunction of apoptosis underlies tumor genesis, proliferation and resistance to chemotherapy. 

As the alternative cell death, necrosis induced by various therapeutic stimuli will provide us a new direction in the treatment of cancer. Programmed necrosis is a kinase initiated death pathway. In the case of TNFR1 activation, the most studied model of necrosis to date, the necrotic cell death depends on the kinase activity of RIP1 and RIP3. Mixed lineage kinase domain-like protein (MLKL) is a critical substrate of RIP3 in necrosis pathway. The formation of necrosome by the interaction of RIP1, RIP3, MLKL and other molecules would mediate the signaling downstream of death cytokines (such as TNF), finally causing cell death and inflammation. We have deliberately focused on mechanisms that convey from RIP kinases to MLKL. It has been known that downstream necrosis signals works through MLKL. Accordingly, phosphorylated MLKL would be expected to transduce death signals. Both in vivo and in vitro biochemical analyses characterized the oligomerization nature of MLKL. Biochemical fractionation revealed that phospho-MLKL translocate to plasma membrane after necrosis was induced.

 Hosted by Henning Walczak

Multidisciplinary Seminar 

This seminar will be focused on Chemistry

Chemistry equipment

Professor Alethea Tabor

UCL Dept. of Chemistry
'Self-assembling Nanoparticles for Targeted Multimodal Imaging'

Dr James Baker

UCL Dept. of Chemistry
'Homogeneous Antibody Conjugates by Disulfide Bridging'

Dr Eric Arstad

UCL Dept. of Chemistry
'Radiochemistry at UCL'

Date and Location:

Thursday 21st May 12.00pm
Courtyard Café
Paul O'Gorman Building

The UCL Cancer Institute Multidisciplinary Seminar Series will highlight research from disciplines across UCL. The seminars will be held monthly, with the aim to present new and exciting work to Cancer Institute researchers and to forge collaborations across different disciplines in UCL.

A light lunch will be provided afterwards.

Professor John Silke

The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia

'How to improve a good anti-cancer drug - Tales of the unexpected'

Professor John Silke

Date and Location:

Thursday 14th May 5.00pm
Courtyard Café
Paul O'Gorman Building

Population-based data on the survival of all cancer patients in a country or region are a valuable metric of the overall effectiveness of its health system. Until now, internationally comparable data of Birinapant is a Smac-mimetic (SM) being evaluated in phase 2 trials for the treatment of cancer. SMs antagonize Inhibitor of Apoptosis (IAP) proteins and simultaneously induce TNF secretion to render cancers sensitive to TNF induced killing.

To find clinically relevant ways to enhance birinapant efficacy, we screened established kinase inhibitor drugs for their ability to increase TNF production by SM treated cells. The p38/MK2 pathway is known to be required for production of TNF which is over expressed in many inflammatory diseases. This fact led to a concerted effort by many pharmaceutical companies to develop p38 inhibitors as anti-inflammatory drugs. Remarkably however we show that p38 inhibitors work via an on-target mechanism to increase TNF induced by SM. Although p38 inhibitors are relatively well tolerated by patients, they have not performed well as anti-inflammatory drugs in trials. Gratifyingly, the combination of birinapant and p38 inhibitors was well-tolerated in vivo by mice and proved a highly effective combination treatment for 3 models of primary AML. Our preclinical study therefore provides a rationale for repurposing p38 or MK2 inhibitors to treat AML, a disease where there has not been a new effective therapy for the past 20 years.

The Seminar will be followed by a drink reception

Hosted by Henning Walczak

Professor Michel Coleman

London School of Hygiene and Tropical Medicine

'Cancer survival world-wide: some insights from the CONCORD-2 study'


Date and Location:

Thursday 30th May 5.00pm
Courtyard Café
Paul O'Gorman Building

Population-based data on the survival of all cancer patients in a country or region are a valuable metric of the overall effectiveness of its health system. Until now, internationally comparable data of this type have been scarce. The CONCORD programme is designed to provide long-term surveillance of cancer survival world-wide, to inform national and global policy on cancer control. We analysed individual tumour records for 25.7 million adults (15-99 years) diagnosed during 1995-2009 with a cancer of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary or prostate, or leukaemia, and 75,000 children with leukaemia. Data were provided by 279 population-based cancer registries in 67 countries. For 40 countries, including the UK, the data provided 100% national coverage. More than 6,500 life tables were constructed to enable correction for background mortality. We estimated net survival up to 5 years, correcting for background mortality by single year of age, sex, calendar year (and race) in each country or region. 

All-ages survival estimates were standardised with International Cancer Survival Standard weights. World-wide cancer survival trends since 1995 are extremely diverse. Five-year survival has increased for colon, rectal and breast cancers in many countries. Survival remains low for liver and lung cancer in all world regions. Striking increases in prostate cancer survival have occurred in many countries, but the range is wide. The global range in cervical and ovarian cancer survival is also wide, with little recent progress. In Eastern Asia, stomach cancer survival is very high, whereas survival is remarkably low for adult and childhood leukaemia. Global disparities in cancer survival are extremely wide. The economic costs are huge. Robust comparison of world-wide trends and inequalities in cancer survival should prompt investment to improve national health systems and to provide equitable access to optimal health care.

Hosted by Bart Vanhaesebroeck

The Seminar will be followed by a drinks reception

Seminar flyer

Informatics Seminar

Dr Andrea Sottoriva

Institute of Cancer Research

'Natural evolution and star-like phylogenies in next-generation sequencing data'


Wednesday 22nd April, 12.00noon
Bill Lyons Informatics Centre Paul O'Gorman Building - 6th Floor
UCL Cancer Institute

If you wish to meet with Dr Sottoriva, please contact javier.herrero@ucl.ac.uk 

All welcome

Multidisciplinary Seminar 

This seminar will be focused on Physics

Nano molecules

Dr David Bowler

UCL Dept. of Physics and Astronomy
'Accurate quantum mechanical calculations of entire biological molecules'

Dr Bart W Hoogenboom

London Centre for Nanotechnology
'Better than super resolution: What we can learn by visualising biomolecules at the nanoscale'

Thursday 16th April, 12.00noon
UCL Cancer Institute
Courtyard Café
Paul O'Gorman Building, WC1E 6BT

The UCL Cancer Institute Multidisciplinary Seminar Series will highlight research from disciplines across UCL. The aim is to present new and exciting work to Cancer Institute researchers and to forge collaborations across different disciplines in UCL.

All welcome. A light lunch will be served afterwards. 

NHS National Institute of Health Research logo

NIHR University College London Hospitals
Biomedical Research Centre

Professor Adrian Hayday

Professor Adrian Hayday

Kay Glendinning Prof of Immunobiology
King's College London

'Learning the language of tissue T-cell communications and exploiting it in cancer'

12noon, Thursday 19th March 2015
UCL Cancer Institute 
Paul O’Gorman Building 
Courtyard Café

In 2001, we showed that mice were much more susceptible to myriad types of cutaneous carcinogenesis if they specifically lacked gd T cells, a white blood cell whose unanticipated discovery we initiated in 1985.  Our implication of gd T cells in immunosurveillance was at a time of great scepticism concerning tumour immunology, consistent with which we found much more variable contributions of ab T cells to host protection. Since then, the impressive clinical efficacy of immune checkpoint blockades has appropriately raised optimism concerning the existence and application of tumour immunology. However, this optimism easily glosses over many treatment failures, some extreme adverse events, and a seeming lack of general applicability. This situation cannot be satisfactorily redressed until we understand tumour immunology, and in particular the molecular language that regulates T cells within the tissues in which solid tumours form.  

To this end, we have identified novel, organ-specific B7-like molecules by which epithelial cells determine and regulate their local T cell compartments.  Our studies have identified unanticipated parallels between the regulation of mouse and human T cells in healthy tissue and in tumours, and thereby point to novel clinical targets.  In parallel, we have developed large scale means to monitor human immune responsiveness and to identify novel regulators of tissue-associated immune compartments.

Hosted by Sergio Quezada

The Seminar will be followed by a sandwich buffet lunch

Dr Andreas Linkermann

Nephrology Laboratory, University-Hospital Schleswig-Holstein - Campus Kiel

'The quest for a cure: how to prevent regulated necrosis'

5.00pm, Monday 9th March 2015
Courtyard Café, Paul O’Gorman Building 
All welcome

Andreas Linkermann

Until recently, necrosis has mainly been investigated clinically by pathologists. Regarding morphological changes, several macroscopically distinct forms of necrosis in whole organs have been described. It is entirely unclear which molecular pathway of regulated necrosis underlie the specific morphological changes associated with necrosis and whether or not they are regulated on a genetic level. The identification of necroptosis, defined by the molecular interplay between RIPK3 and MLKL and its negative regulation by caspase-8 and FADD will be discussed. Non-apoptotic, non-necroptotic pathways of regulated cell death, like cyclophilin D-mediated regulated necrosis and ferroptosis, have led to the intriguing possibility to specifically target necrosis in various pathologies. 

The seminar will be followed by a drinks reception

Professor Phil Jones

MRC Cancer Unit, University of Cambridge

'How stem cell fate changes during squamous carcinogenesis'

12.00pm, Thursday 26th February 2015
Courtyard Café, Paul O’Gorman Building All welcome

Dr Phil Jones

Deep sequencing has started to shed light on the evolution of haematological cancers, but little is known about the early stages in the development of solid tumours.   We have developed a lineage tracing based approach to quantify cell behaviour in normal tissues and tumours, using mouse oesophageal epithelium as a model.  

In homeostasis, wild type progenitors generate equal proportions of progenitor and differentiating cells, dividing to generate two progenitor daughters, two differentiating daughters or one of each.  Transgenic inhibition of Notch signalling in scattered progenitor cells, modelling the effect of inactivating mutations common in squamous cancer, creates dominant clones.  The mutant cells lose the two differentiating cell division outcome, resulting in exponential growth and functional immortality. This cellular mechanism explains the phenomenon of ‘field change’.  

Lineage tracing in tumours in a new model of squamous carcinogenesis reveals that the rate of cell division is not increased in lesions compared with the surrounding epithelium, rather the rate at which differentiated cells are lost is substantially reduced.  These findings have significant implications for cancer treatment and prevention.

The Seminar will be followed by a sandwich buffet lunch

Multidisciplinary Seminar

Thursday 19th February 5:00pm 
Courtyard Cafe, Paul O'Gorman Building

Prof Alexey Zaikin

Chair in Applied Mathematics and Computational Biomedicine
'Noise and intelligence in intracellular gene-regulatory networks'

Dr Oleg Blyuss

Institute for Women's Health 
'Analysis of ovarian cancer proteomic biomarkers”

The UCL Cancer Institute Multidisciplinary Seminar Series highlights research from disciplines across UCL. This seminar in the series will be focused on Mathematics.

All welcome.

Professor Giorgio Stassi

Surgical and Oncological Sciences, University of Palermo
'Cancer Stem Cells: from Bench to Bedside'

Wednesday 18th February 2015
Courtyard Cafe, Paul O'Gorman Building

Host: Professor Henning Walczak (h.walczak@ucl.ac.uk).  


Even though it is clear that larger and more invasive colorectoral cancers (CRCs) represent a more efficient source of metastatic cells, the cell population able to migrate from the primary site and generate distant metastasis is still unknown. Prof. Stassi’s research team have recently demonstrated that CRC contains a small and variable number of cells that express CD44v6 and which are uniquely able to generate metastatic tumors in orthotopic xenograft models. Importantly, the team observed that BMP7 impairs the tumorigenic and metastatic potential of colon cancer stem cells. CSCs have peculiar features that potentially make them ideal models in the study of drug resistance and sensitivity. The research team have provided evidence that CSC isolation and in vitro sensitivity assay, are feasible and clinically suitable to identify a potentially effective treatment for chemo-refractory lung and colorectal cancer.

All are welcome.  An informal reception will be held after the seminar.

UCL Cancer Institute Special Seminar
5.00pm, 29th January 2015
Courtyard Café, Paul O’Gorman Building
All welcome.

Prof Alison Lloyd

MRC Laboratory for Molecular Cell Biology, UCL, London

'Links between the multicellular tissue repair response and tumourigenesis'

Alison Lloyd

The research in Prof Lloyd’s laboratory focuses on two fundamental cell biological processes: Cell Growth and Tissue Regeneration and the role of these processes in cancer. The Lab uses the mammalian peripheral nervous system (PNS) as model system. The combination of primary in vitro culture systems and in vivo mouse models is used to study the molecular and cellular mechanisms underlying the homeostatic regulation of these processes and how they become deregulated in cancer.  

While Prof Lloyd work has broad implications for cancer biology, it also has direct relevance for the tumour predisposition syndrome, Neurofibromatosis Type 1 (NF1). In her talk, she will focus on the  complex multicellular response required for tissue repair in the adult and the relevance of these processes to tumourigenesis.

Alison Lloyd Research Group

The Seminar will be followed by a drinks reception.