Xin Lu, Ludwig Institute for Cancer Research, Oxford, UK
Xin
Lu
Tumor biology
Bio

I am a cancer cell biologist focused on tumor suppression with strong interests in cell polarity, transcriptional target selection and cell fate determination. I strive to advance the development of the next generation of therapeutics to selectively kill cancer cells.

After earning my Masters Degree in China, I received a competitive research training fellowship from the World Health Organization’s International Agency for Research on Cancer. I then moved to the UK to complete my PhD and postdoctoral training, and established my own research group at the Ludwig Institute for Cancer Research. After successive promotions I became the Director of the Ludwig Institute for Cancer Research in London in 2004. In 2007, I moved the research activities to Oxford where we are based today. Ludwig Oxford’s focus is the identification and investigation of the molecular regulators of cancer progression and cellular heterogeneity, with the aim of translating our discoveries to benefit patients.

My research is focused on understanding tumor suppression. We were among the first researchers to show that the tumor suppressor protein p53 responds to both oncogene activation and DNA damaging signals. Subsequently, we investigated cross-talk between the p53 and Rb tumor suppressor pathways, demonstrating how alterations in the Rb pathway could sensitize tumor cells to p53-induced apoptosis. We also were one of the first groups to show how to selectively activate p53 to kill cancer cells through our identification and characterization of the evolutionarily conserved ASPP family of proteins. Our current studies are focused on investigating the potential of the ASPPs as biomarkers and targets for the development of novel anti-cancer therapies.

I have recruited and mentored many talented young investigators, and several former PhD students and postdoctoral Fellows have received appointments as hospital physicians and have received prestigious research fellowships from EMBO. Some now hold independent faculty positions in renowned institutions, including the NIH (USA), CNIO (Madrid), Barts and The London, and the University of Montpellier (France). I am also a Receiving Editor for Oncogene and a member of several prestigious scientific advisory, grant and prize-awarding boards.

Education
PhD in Cell and Molecular Biology, Imperial Cancer Research Fund and University College London, London, UK, 1991

MSc in Cell and Molecular Biology, Cancer Institute, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China, 1985

BSc in Biochemistry, Sichuan University, China, 1982


Achievements

Elected Member of the Academy of Medical Sciences (FMedSci), 2013

Supernumerary Fellowship, Magdalen College, Oxford, 2013

Elected Member of the European Molecular Biology Organization, 2011

Elected Fellow of the Society of Biologists, UK, 2011

Elected Fellow of the Royal College of Pathologists (FRCPath), UK, 2007

Ninth James Gibson Visiting Professor, University of Hong Kong, 2007

Young Cell Biologist of 1989, British Society for Cell Biology, UK. 1989

Research Training Fellowship Award, World Health Organization International Agency for Research on Cancer, Lyon, France, 1986-1987

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Xin Lu lab

We study tumor suppression by identifying molecular switches of cell fate, with the aim of selectively eliminating cancer cells.

 

Xin Lu, Ludwig Institute for Cancer Research, Oxford, UK
Xin
Lu
Tumor biology
Bio

I am a cancer cell biologist focused on tumor suppression with strong interests in cell polarity, transcriptional target selection and cell fate determination. I strive to advance the development of the next generation of therapeutics to selectively kill cancer cells.

After earning my Masters Degree in China, I received a competitive research training fellowship from the World Health Organization’s International Agency for Research on Cancer. I then moved to the UK to complete my PhD and postdoctoral training, and established my own research group at the Ludwig Institute for Cancer Research. After successive promotions I became the Director of the Ludwig Institute for Cancer Research in London in 2004. In 2007, I moved the research activities to Oxford where we are based today. Ludwig Oxford’s focus is the identification and investigation of the molecular regulators of cancer progression and cellular heterogeneity, with the aim of translating our discoveries to benefit patients.

My research is focused on understanding tumor suppression. We were among the first researchers to show that the tumor suppressor protein p53 responds to both oncogene activation and DNA damaging signals. Subsequently, we investigated cross-talk between the p53 and Rb tumor suppressor pathways, demonstrating how alterations in the Rb pathway could sensitize tumor cells to p53-induced apoptosis. We also were one of the first groups to show how to selectively activate p53 to kill cancer cells through our identification and characterization of the evolutionarily conserved ASPP family of proteins. Our current studies are focused on investigating the potential of the ASPPs as biomarkers and targets for the development of novel anti-cancer therapies.

I have recruited and mentored many talented young investigators, and several former PhD students and postdoctoral Fellows have received appointments as hospital physicians and have received prestigious research fellowships from EMBO. Some now hold independent faculty positions in renowned institutions, including the NIH (USA), CNIO (Madrid), Barts and The London, and the University of Montpellier (France). I am also a Receiving Editor for Oncogene and a member of several prestigious scientific advisory, grant and prize-awarding boards.

Education
PhD in Cell and Molecular Biology, Imperial Cancer Research Fund and University College London, London, UK, 1991

MSc in Cell and Molecular Biology, Cancer Institute, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China, 1985

BSc in Biochemistry, Sichuan University, China, 1982


Achievements

Elected Member of the Academy of Medical Sciences (FMedSci), 2013

Supernumerary Fellowship, Magdalen College, Oxford, 2013

Elected Member of the European Molecular Biology Organization, 2011

Elected Fellow of the Society of Biologists, UK, 2011

Elected Fellow of the Royal College of Pathologists (FRCPath), UK, 2007

Ninth James Gibson Visiting Professor, University of Hong Kong, 2007

Young Cell Biologist of 1989, British Society for Cell Biology, UK. 1989

Research Training Fellowship Award, World Health Organization International Agency for Research on Cancer, Lyon, France, 1986-1987

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TEAM

Richard
Bryant
Bio

I am an academic higher surgical trainee in Urology in Oxford, combining surgical training with academic and research time as a clinical lecturer in Urology. My main research interests are the mechanisms underpinning the progression of prostate cancer to an advanced phenotype. I previously investigated the role of the Polycomb Group protein EZH2 in prostate cancer progression. More recently, I have been investigating the role of the ASPP family of proteins in prostate cancer.

Education
ISB and JCIE, FRCSUrol (Edinburgh), 2012

PhD, University of Sheffield, 2008

MRC Clinical Research Training Fellowship (Joint with RCSEd), 2004

Royal College of Surgeons (Edinburgh), MRCS (Edinburgh), 2002

MBChB (Hons), University of Sheffield, 1998

BMedSci (Hons), University of Sheffield, 1995

Awards
Cancer Research UK Intermediate Surgical Oncology Fellowship, 2013

Gordon Bryden Medal, Trent Urology Group, 2005, 2007

Merck Sharp and Dohme prize (2nd MB neuroscience), University of Sheffield, 1994

Shuo
Chen
Bio

Postdoctoral Fellow.

Zinaida
Dedeic
Bio

I am reading for a DPhil in Clinical Medicine. The focus of my research is to provide insights into cancer metastasis that will help identify potential pharmaceutical targets for treatment. The key idea is to identify strategies for restricting metastasis, thereby avoiding the most dangerous aspect of cancer. As models that will help me identify such strategies, I am studying embryonic eyelid development and wound healing, which have several processes in common with metastasis, including cell migration, proliferation and programmed cell death. Delineating the molecular pathways important for eyelid closure and wound healing could therefore provide insights into metastasis.

Education
MSc in Developmental Biology, University of Chicago, Illinois, USA

BA in Human Ecology, College of the Atlantic, Bar Harbor, Maine, USA

Yean (Jennifer)
Lim
Bio

I am studying for a DPhil in Clinical Medicine. My project focuses on investigating the roles of the ASPP/p53 and Notch signaling pathways in the pathogenesis of Epstein Barr Virus (EBV)-related carcinoma.

Education
BSc in Biomedical Sciences, University of Manchester, 2012

Awards
NDM Prize Studentship, 2012

Paul
Miller
Bio

Angiogenesis is critical in cancer growth and metastasis. Vascular endothelial growth factor (VEGF) is required for angiogenesis and can be targeted in the treatment of cancer. The focus of my fellowship is to investigate the role of ASPP/p53 and Dll4/Notch crosstalk in patient response to anti-VEGFR-based therapy. Professor Xin Lu and Dr. Sarah De Val are my scientific supervisors. Clinical supervision is provided by Professor Adrian Harris.

Education
NIHR Academic Clinical Fellowship in Medicine, University of Oxford, 2013

MB BChir, University of Cambridge, 2008

BSc in Cell Biology, University of Durham, 2003

Awards
Gordon Holmes Clinical Neurosciences Prize, Royal Society of Medicine, 2010

Gopinath
Sutendra
Bio

I am investigating the role of iASPP and p53 in the cardiovascular system. Specifically, I am interested in the role of these proteins in right ventricular failure and vascular remodeling. We hope to identify new potential therapeutic targets against diseases where right ventricular failure and vascular remodeling is prominent, such as pulmonary arterial hypertension.

Education
PhD, University of Alberta, Edmonton, Canada, 2012

MSc, University of Calgary, Alberta, Canada, 2005

BSc, University of Saskatchewan, Saskatoon, Canada, 2002

Awards
Max Harry Weil Resuscitation Science Finalist (American Heart Association), 2012

Golden Key National Honor Society, 2012

Frank Witkowski Publication Award, 2010

Med Star Publication Award, 2010

Cournard and Comroe Young Investigator Finalist (American Heart Association), 2010

Sharon Wilkens Graduate Teaching Award, 2005

Yihua
Wang
Bio

My research focuses on investigating the role of ASPP2 in autophagy, apoptosis, cell polarity, EMT and hypoxia. The project could shed light on the underlying molecular mechanisms that cause cancers to arise and metastasize, and might lead to the discovery of new anti-cancer therapies.

Education
PhD in Cell Biology, Peking Union Medical College, Cancer Institute & Cancer Hospital, 2006

MB BS, Medicine, Tongji Medical University, 2001

Awards
Peking Union Medical College, Cancer Institute & Cancer Hospital, Excellent Research Paper, 2007

Peking Union Medical College, Cancer Institute & Cancer Hospital, Excellent Research Paper, 2006

AACR-ITO EN, Ltd. Scholar-in-Training Award, AACR 96th Annual Meeting, 2005

Peking Union Medical College, Cancer Institute & Cancer Hospital, Excellent Postgraduate Student, 2005

Ludovico
Buti
Bio

Postdoctoral Fellow.

Kathryn
Chung
Bio

I am studying for a DPhil in Clinical Medicine. The aim of my research is to investigate the biological role of iASPP in skin homeostasis. Skin homeostasis involves spatiotemporally controlled keratinocyte proliferation and differentiation, as well as coordinated cell migration in the case of wounding. Imbalances in such physiological processes lead to the development of epidermal disorders and tumors.

Education
MSc in Cancer, University College London, 2009

BA in Genetics, University of Cambridge, 2006

Awards
NDM Prize Studentship, 2010

International Genetically Engineered Machine Competition Studentship, 2007

College Scholarship and Book Prize, 2007

Sofia
Koch
Bio

I am studying the role of ASPP2, a known tumor suppressor and tight junctional protein, in intestinal cell polarity and homeostasis. Using transgenic in vivo models, I am establishing DSS-induced colitis models and am able to generate intestinal primary cells.

Education
DPhil in Clinical Medicine, University of Oxford, 2013

BSc (Major in Biochemistry), University of Porto, Portugal, 2009

Min
Lu
Bio

My research focuses on the roles of the ASPPs related to tumor occurrence and metastasis, with the aim of developing novel therapies based on the ASPP pathway. I am investigating the mechanisms behind the abnormal behavior of iASPP and other Ankyrin Repeat Domain-containing proteins (such as p16ink4a) in tumors.

Education
PhD in Biochemistry, Zhejiang University, 2003-07

PhD BIDMC, Harvard Medical School, 2007-08

Awards
Research Assistant Scholarship, Harvard Medical School, 2007

JuRen Scholarship, Zhejiang University, 2006

David
Severson
Bio

PhD student

Casmir
Turnquist
Bio

As part of the National Institutes of Health-University of Oxford Biomedical Scholars Program, my PhD/DPhil project is a collaboration between Professor Xin Lu, (Ludwig Oxford) and Dr. Curtis Harris (NCI/NIH). I am exploring the role of ASPP2 in cerebral inflammation and toll-like receptor signaling.

Education
MSc in Neuroscience, University of Oxford, 2011

BA, University of Wisconsin-Madison, 2010

Awards
National Institutes of Health-University of Oxford Biomedical Scholar, 2011-15

Trewartha Senior Honors Thesis Award, 2010

Wisconsin Wirth Scholarship, 2009

Phi Beta Kappa, 2009

Jaroslav (Jerry)
Zak
Bio

My PhD/DPhil project is a collaboration between the University of Oxford and The Scripps Research Institute. We use a combination of chemical biology, bioinformatics and in vivo methods to identify pathways regulated by ASPP2, and probe cancer genomics data sets to assess its dysregulation in human cancer. ASPP2 is essential for mammalian development and regulates many of the pathways key to cancer progression, including the p53 and Ras pathways. My research seeks to identify ASPP2’s endogenous roles in the healthy organism, expand the portfolio of its known functions and evaluate whether and how they affect tumor initiation and progression.

Education
MSci Natural Sciences, University of Cambridge, 2011

BA Natural Sciences, University of Cambridge, 2011

Awards
Lincoln College Senior Scholarship, 2013-14

Skaggs-Oxford Scholarship, 2011-16

Cambridge European Trust Scholarship, 2007-11

International Chemistry Olympiad, Bronze Medal, 2007

RESEARCH AREAS

Selectively killing cancer cells is one of the major challenges in cancer therapy. My group’s focus is understanding how to selectively activate the tumor suppressor p53 to kill cancer cells, which has led to our identification of the evolutionarily conserved ASPP family of proteins. The three ASPP members (ASPP1, ASPP2 and iASPP) act as molecular switches of cell fate by regulating the target selectivity of p53 and its siblings (p63 and p73). By controlling transcriptional target selectivity and cell polarity, the ASPPs determine whether a cell undergoes cell proliferation, differentiation, autophagy or apoptosis. Deregulation of this pathway is seen in developmental disorders and many cancers. Thus the ASPP family of proteins are emerging as new biomarkers and excellent targets for the development of novel anti-cancer therapies.

The move of the UK Branch of the Ludwig Institute from University College London to the University of Oxford in 2007 gave us the opportunity to explore new research directions. Cell polarity in tumor suppression has become an exciting new area of research. We recently observed that the ASPPs play fundamental roles in regulating cell polarity and epithelial stratification. Cell polarity is required for organ development and homeostasis, while a loss of cell polarity is a hallmark of cancer. Our finding that the tumor suppressor ASPP2 is a novel regulator of cell polarity has established a new link between cell polarity and tumor suppression. A lack of apoptosis, deregulation of autophagy and an increase in cell proliferation are similarly hallmarks of cancer malignancy, and we have recently observed that ASPP2 is a novel regulator of autophagy, which dictates the cell’s response to the activity of the Ras oncogene. 

Most recently, we have observed that the ASPPs are highly expressed in epithelial cells, are regulated by cell proliferation and differentiation signals both in vitro and in vivo, and function at different cellular sites. Mechanistically, ASPP2's N-terminus can bind Par3 and Ras at the cell membrane, whereas its C-terminus binds nuclear p53. Similarly, phosphorylation of iASPP by cyclin B/cdk1 at its N-terminus promotes its entry into the nucleus and enhances p53’s ability to bind to its C-terminus. The dynamic nature of the localizations of the ASPPs within the cell, together with their unique structural motifs, makes them ideally placed to survey and integrate signals between the cell membrane and nucleus, i.e., controlling transcription and determining cell fate.

A key question in cancer research is why more than 80% of human tumors are epithelial in origin. As p53 is inactivated in most human epithelial tumors, the identification of the ASPP family of proteins as key regulators of cell polarity and adhesion at the cell membrane, and transcriptional co-factors of p53 in the nucleus, provides us with a unique opportunity to investigate whether cell polarity is a checkpoint of tumor suppression. We are addressing this issue using molecular and cellular biology approaches alongside the use of transgenic animal and human ex vivo model systems. We are studying how cell polarity integrates p53, WNT and Notch signaling pathways to regulate epithelial plasticity and cell fate determination.

PUBLICATIONS

Lu M, Breyssens H, Salter V, Zhong S, Hu Y, Baer C, Ratnayaka I, Sullivan A, Brown NR, Endicott J, Knapp S, Kessler B, Middleton MR, Siebold C, Jones Y, Sviderskaya EV, Cebon J, John T, Caballero O, Goding CR, Lu X (2013). Restoring p53 function in human melanoma cells by inhibiting mdm2 and cyclin B1/cdk1 phosphorylated nuclear iASPP. Cancer Cell Volume 23, Issue 5, 618-633, 25 April 2013.

Wang Y, Wang XD, Lapi E, Sullivan A, Jia W, He YW, Ratnayaka I, Zhong S, Goldin RD, Goemans CG, Tolkovsky AM, and Lu X (2012). Autophagic activity dictates the cellular response to oncogenic RAS. Proc Natl Acad Sci USA. Aug 14;109(33):13325-30. Epub 2012 Jul 30.

Notari M, Hu Y, Koch S, Lu M, Ratnayaka I, Zhong S, Baer C, Pagotto A, Salter V, Candi E, Melino G and Lu X (2011). iASPP prevents premature cellular senescence and is required for normal epithelial stratification. Proc Natl Acad Sci USA. Oct 4;108(40):16645-50. Epub 2011 Sep 19.

Slee EA, Benassi B, Goldin R, Zhong S, Ratnayaka I, Blandino G, Lu X (2010). Phosphorylation of Ser312 contributes to tumour suppression by p53 in vivo. Proc. Natl. Acad. Sci. USA 107: 19479-84.

Sottocornola R, Royer C, Vives V, Tordella L, Zhong S, Wang Y, Ratnayaka I, Shipman M, Cheung A, Ferretti P, Molnár Z, Lu X (2010). ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Dev. Cell 19: 126-37.