Professor Gerhardt Attard
Prof Attard is a John Black Charitable Foundation Endowed Chair in Urological Cancer Research at University College London.
He holds an advanced Cancer Research UK Clinician Scientist award and is Team Leader of the Treatment Resistance Group at the UCL Cancer Institute.
He graduated with a degree in Medicine from the University of Malta in June 1999 and obtained a PhD in Medicine from the University of London (ICR) in 2010.
His main research interest is dissecting treatment resistance, currently with a focus on plasma DNA analysis, in order to inform on the development of novel therapeutics and biomarkers for castration resistant prostate cancer (CRPC).
He is an experienced clinical trialist in CRPC and a co-author of more than 130 peer-reviewed manuscripts, including several important papers on advanced prostate cancer.
Prof Attard’s many awards over the years include the ASCO Foundation Annual Merit Award in 2007, Prostate Cancer Foundation Young Investigator Award in 2008, the AACR-GlaxoSmithKline Outstanding Clinical Scholar Award in 2009, the Medical Research Society/Academy of Medical Sciences Sue McCarthy Prize in 2010 and the McElwain award in 2010.
He received the Cancer Research UK Future Leader Award in 2017.
Prof Attard sits on a number of advisory boards and is the GU associate editor of Annals of Oncology.
Mrs Anna Wingate is the Laboratory Manager and she has been a member of the team since 2010. She is responsible for managing the day-to-day running of the laboratory as well as helping with various ongoing projects, in particular overseeing commercial ones. She keeps the lab up to date with the latest technologies and equipment.
In addition to her role as a laboratory manager, she oversees patient sample collection, storage and processing from numerous clinical trials. As part of this role, she trains and supervises junior staff, as well as manages the financial aspects of the translational aspect of the trials.
She completed her MSc in Medical Molecular Biology at Westminster University and an MSc in Microbiology at University of Gdansk. Her previous experience includes product development and project management in a biotech company.
Dr Anjui Wu started his PhD in 2015 and his main research interest is to quantify DNA methylation events from low input plasma DNA, and identify clonal and subclonal changes. During his PhD, he received several awards including a CRUK Young Investigator travel grant, Wellcome trust summer school bursaries, Taiwanese Young Elite Research grant, and the cfDNA conference award.
Prior to starting his PhD, he obtained his Medical Degree from the National Taiwan University in 2013.
Aside from his research, he is interested in tennis, hiking, arts and history.
Dr Anuradha Jayaram is a clinical research fellow. She graduated with an honours degree from Trinity College Dublin in 2006, and after completing her medical oncology training in Ireland, she was awarded a Health Research Board grant to purse a clinical fellowship in prostate cancer at the Institute of Cancer Research and Royal Marsden NHS Foundation Trust with Gerhardt Attard.
In 2016, she was awarded a Medical Research Council UK PhD fellowship. Her research focus is primarily on liquid biopsies mainly circulating plasma DNA to define the evolutionary complexities that underlie drug resistance and molecularly characterize prostate cancer.
Her long-term research goal is to incorporate plasma DNA analysis into standard of care management of prostate cancer, allowing real-time molecular characterization and response monitoring using a minimally invasive blood test, enabling patient stratification.
She is also interested in running translational based trials that will help predict treatment responses in prostate cancer patients. She was recently awarded with Professor Attard funding from Prostate Cancer UK to run a clinical trial using plasma DNA called PARADIGM. She is a co-author on several publications including in Science Translation Medicine and Annals of Oncology.
Dr Daniel Wetterskog is a Senior Research Fellow in charge of project supervision and implementation and development of methods for interrogation of clinical samples with a focus on cell free DNA found in plasma.
Daniel completed his PhD in 2008, working on transcriptional dysregulation in cancer at the University of Gothenburg, Sweden. After a post-doctoral position at the Institute of Cancer Research, London focusing on identification of resistance mechanisms to HER2-targeting agents and a second post-doctoral position at UCL Cancer Institute focusing on radiosensitization of cancers he re-joined the Institute of Cancer Research in 2014 and subsequently returned to UCL to continue his work on understanding and overcoming treatment resistances in cancer.
Dr Karolina Nowakowska is a Research Fellow and was awarded her PhD in 2018 from The Institute of Cancer Research, London, which involved studying steroid receptors, as well as single cell transcriptomics in the context of castration resistant prostate cancer.
At UCL, she is continuing her work trying to identify rare populations of cells within prostate cancer samples, that may be a starting point for the development of castration resistant prostate cancer. The long-term goal of her research is to identify a gene signature that will help stratify patients for the best treatment option.
Before pursuing her PhD, Karolina completed her BSc in Genetics and Biochemistry at Aberystwyth University in 2010, and MSc in Cancer Biology at Kingston University in 2011.
Dr A M Mahedi Hasan is a Research Fellow/Computational Biologist who joined the team in November 2018. He is working on interpreting genomic and transcriptomic data from plasma samples and tumours from clinically-relevant prostate cancer cohorts with carefully annotated clinical follow-up data collected in prospective randomised clinical trials.
He completed his PhD in Cellular and Molecular Biology in 2015 from the University of Edinburgh. Later he joined the Institute of Cell Biology at the University of Edinburgh as a Post-doctoral Research Associate/Bioinformatician and worked there for three years (2015-2018). He also earned his Associate Fellowship from the Higher Education Academy while at the University of Edinburgh.
Maria Ruiz Vico
Dr Maria Ruiz Vico is a Medical Oncologist who joined the team in January 2019, after having been awarded a SEOM (Spanish Society of Medical Oncology) grant for translational research training in Sept 2018.
She completed her Medical Degree in 2012 at the University of Granada, Spain, and her Medical Oncology training in 2018 at the University Hospital (HRU) in Malaga, Spain. During this period, she developed a particular interest in prostate cancer research. Due to that interest, she completed an internship period in the Prostate Cancer Clinical Research Unit at the Spanish National Cancer Research (CNIO), with David Olmos, MD, PhD and Elena Castro MD, PhD, collaborating on ongoing studies within the PROCURE projects.
She continued her apprenticeship at the Genitourinary CNIO-IBIMA Unit, in Malaga, led by David Olmos, MD, PhD and Emilio Alba, MD, PhD participating in translational research projects and clinical trials developed in the Unit, mainly focused on prostate cancer.
In 2016, she entered the PhD Program in Biomedicine and Translational Research at The University of Malaga, Spain, with a project based on plasma DNA analysis in advanced prostate cancer. She also has a Master’s Degree in Medical Oncology from SEOM.
Her main interest is treatment personalisation and resistance in prostate cancer patients and her goal is to start a postdoctoral degree in the group as soon as she finishes her PhD.
Dr. Stefano Pirrò is a Research Fellow in Bioinformatics who joined the group in July 2019. He completed his Master’s Degree in Bioinformatics in 2012, at the University of Rome “Tor Vergata”. During his master’s internship, he collaborated with Proxagen Ltd - Sofia, Bulgaria - to develop software for the prediction of continuous and discontinuous B-cell epitopes.
In 2012, he founded “MirNat”, a start-up company focused on nutraceutical products, enriched with plant microRNAs. His research activity is focused on the prediction of miRNA targets and their cross-kingdom regulation mechanism.
In January 2017, he obtained a PhD degree in Cellular and Molecular Biology at the University of Rome Tor Vergata. He developed a computational method for the characterization of homogenous cell populations from mass cytometry (CyTOF) data. Moreover, he studied the stratification of cancer patients, using community discovery approaches. In February 2017, he joined the Barts Cancer Institute, London, as a Postdoctoral Research Assistant. He worked on the spatial analysis of breast cancer and matched histologically normal tissues resected adjacent (<2 cm) and surrounding (5-10 cm) primary breast cancer. He also led the development and maintenance of the Pancreas Expression Database (http://www.analytics.pancreasexpression.org).
He is currently working on the analysis and interpretation of DNA methylation data of prostate cancer cells. The aim is to better elucidate the molecular mechanism underlying resistance to treatment.
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Dr Emily Grist is a CRUK funded clinical research fellow undertaking a PhD. Emily’s PhD is focused on personalising treatment for prostate cancer patients and identifying novel tests to better stratify patients to effective treatments. Currently, Emily’s translational research involves genomic analyses of tumour material from patients recruited to the STAMPEDE trial and she is working closely with the Medical Research Council Clinical Trials Unit.
Emily completed her medical degree in 2009 at the University of Southampton. She was an NIHR funded academic research fellow at Southampton University Hospital NHS Foundation Trust. In 2012, Emily was a clinical research fellow working within the Prostate Cancer Targeted Therapy Group, Institute of Cancer Research, where she worked within a team to describe tumour clone dynamics in lethal prostate cancer from circulating tumour DNA.
In 2013 Emily was awarded a further NIHR academic research fellowship and commenced training in medical oncology at the Royal Marsden NHS Foundation Trust. She has been a sub-investigator within a number of national and international trials across a variety of tumour types. Emily has a keen interest in patient and public engagement, speaking at both the Pint of Science Festival and a British Science Association event.
Dr Larissa Mendes is a clinician from Brazil with training in Anatomic Pathology. She is a Clinical Research Fellow/ PhD student working with the STRATOSPHERE Consortium, a pan-UK organisation aiming to accelerate the introduction of rational biomarker treatment pairings for precision treatment of men with advanced prostate cancer initiating androgen-deprivation therapy. The diagnosis of neoplastic diseases has been a major part of her routine as a Pathologist. There is not, in her opinion, a more important and consequential aspect of a pathologist's job than to provide the best and most thorough diagnosis to effectively guide patient care.
In this new millennium, the diagnostic task will most certainly include data beyond traditional histological features and compromised surgical margins. Physicians, and an increasingly well-informed patient population, will want to know how the molecular underpinnings of tumours can impact choice of and responses to treatments. To her, joining this team is a unique opportunity to be at the forefront of this paradigm shift and to help advance precision medicine in the field of prostate cancer.
Dr Marina Parry is a Senior Research Fellow in the team and her aim is to understand why certain prostate cancer patients respond to particular treatments, while others do not. She joined the Attard lab in September 2017 to work with the STRATOSPHERE Consortium on samples from the STAMPEDE clinical trial.
Prior to that, she was a postdoc for three years (2014-2017) at the CRUK Manchester Institute where she was investigating intratumoural heterogeneity using fresh samples from prostate cancer patients. Between 2012 and 2014, she was a postdoc at the Cancer Sciences Institute at the University of Southampton where she was uncovering the genetic changes in Splenic Marginal Zone Lymphoma, a rare type of blood cancer. She obtained her PhD from the University of Sheffield in 2011, focusing on inherited susceptibility to breast and prostate cancer.
In addition to her research role, Marina is an ardent science communicator and regularly engages with the public at various events in museums, research institutes and even virtually! Passionate about improving the culture of scientific research and the place of science in society, she attends workshops, debates and training courses to this end. She was a member of the early career researchers group at CRUK MI and is a member of the Postdoc Association at UCL CI and was Co-Chair of the UCL Cancer Domain Early Careers Network Committee, as well as being on the CI's Athena SWAN committee. She can be found on Twitter @marina_parry.
Dr Paolo Cremaschi is a Senior Research Fellow and is in charge of the bioinformatic analysis of next generation sequencing and microarray data produced by the team's research activities.
Paolo completed his Master's degree in Molecular Biology in 1996. Then he moved to the informatics field working as an IT consultant for 15 years, creating applications for industry and marketing. In 2012, he started a PhD in Bioinformatics to pursue his academic interests and that allowed him to use all the experience gained in both research and consultancy.
He completed his PhD in 2015 in the Computational Biology unit of the Institute of Molecular Genetics - Italian National Research Council - in Pavia, working on the meta-analysis of expression data. He joined the Institute of Cancer Research in 2016 as a Bioinformatics Officer, working on the analysis of single-cell transcriptomic and DNA methylation data of prostate cancer cells with the aim of improving the understanding of molecular mechanism responsible for treatment resistance.
Dr Mazlina Ismail is a computational Research Fellow who joined the group in October 2018, and is interested in understanding treatment resistance in prostate cancer using multi-dimensional sequence data.
She obtained her PhD from University College London where she focused on the analysis of high-throughput sequencing of T cell receptor (TCR) repertoire in healthy and in two different disease settings; primary immunodeficiency, and early stage non-small-cell lung cancer. She continues to pursue her interest in using computational methods to solve biological problems, and looking at different ways of visualising data as a means of effective science communication.
She is currently working on transcriptomics data in order to understand the mechanisms of treatment resistance in men with prostate cancer.
Miss Sharan Lall joined the Team in February 2019 as a highly experienced technician. She brings with her an extensive knowledge and expertise in histological techniques.
Holding a Bsc in Biological Science, Miss Lall has focused her career interest on cancer studies since 2010. Throughout this time, she has acquired invaluable skills whilst working with both diagnostic and research teams.
Previous responsibilities include facilitating a clinical trial by overseeing patient consent, sample collection, processing and storage whilst also being exposed to a wide range of histology and molecular techniques and technologies.
Her role currently involves processing samples as part of the STAMPEDE clinical trial and supporting other projects going on in the lab.
Miss Lall aims to continue honing and developing her skill set, create long lasting professional relationships as well as being thoroughly up to date in latest advances in our field.
Dr Blanca Trujillo is a clinical research fellow. She joined the team in September 2018 after being awarded a 2-year translational research fellowship from the Alfonso Martínez Escudero Foundation to work on prostate cancer.
Blanca completed her medical degree in 2012 at the University Autónoma of Madrid and her training as a Medical Oncologist in 2018 at Virgen de la Salud Hospital of Toledo.
From the beginning of her training, she had a great interest in genitourinary tumors. This is why she obtained an exchange program at Memorial Sloan Kettering Cancer Centre in NYC, USA, focused on bladder and prostate cancer. In the last year of her training, she also joined the Genitourinary Phase I Clinical Trial Unit at 12 de Octubre Hospital.
Since Blanca joined the team, she has shown an increasing interest in the development of liquid biopsy in prostate cancer and the mechanisms of resistance that underlie progression. She is currently working on different projects on this topic.
She has just been awarded a CRUK funded clinical research fellow to start her PhD in October 2019. She will join the PRIME team: an international collaborative project whose aim is to develop a clinically implementable test which will maximize the utility of liquid biopsy by integrating genomic and transcriptomic changes and methylome status.
Led by Professor Gert Attard and comprised of three Senior Research Fellows and six Research Fellows, of which five are computational biologists, six Clinical Fellows, one PhD student, five Research Assistants and a lab manager, the Treatment Resistance Group has its home at the UCL Cancer Institute, London.
Miss Suparna Thakali joined the group in July 2019 as a Research Assistant. A major component of her role involves supporting the ReIMAGINE Prostate Cancer Risk Study through collection and processing of clinical trial samples in accordance to GCLP standards and regulations.
She obtained her BSc Hons in Biochemistry in 2016 from the University of Kent, where she took part in molecular biology research projects such as IGEM 2015 Kent. She has worked extensively within a diagnostic laboratory setting in a Microbiology Department where she has acquired valuable transferable skills. Subsequently, she worked briefly at King’s College London TwinsUK laboratory, assisting their nutritional clinical studies and maintaining the Biobank.
She hopes to widen her insight and knowledge of the field of cancer research through supporting all the ongoing projects in the lab.
Dr Stefanie Friedrich is a Research Fellow and computational biologist. She is working on identifying patterns and establishing benchmarks related to cancer treatment resistance. She collaborates with the STRATOSPHERE Consortium, a pan-UK consortium studying the link between molecular sub-types and clinical outcomes in order to improve cancer treatment effectiveness.
Stefanie was awarded her PhD in 2020 from Stockholm University/Science for Life Laboratory, Stockholm, Sweden, focusing on the development of computer algorithms and methods for analyzing tumour heterogeneity.
Her research interest is on computational methods and strategies to decipher -omics data in the context of cancer development. She is passionate about interdisciplinary studies and sciences.
Dr Gianmarco Leone is a Clinical Research Fellow. He joined the team in September 2020 as part of the international collaboration for the PRIME project, funded through the Accelerator Award granted by CRUK.
Gianmarco completed his medical degree in 2015 at the University of Catania. He will complete his 5th and last year of specialization training in Medical Oncology at the University of Turin.
He especially focused his attention on genitourinary tumours, spending most of his training managing patients in the uro-oncology clinic at San Luigi Gonzaga Hospital (Turin). During this period, he contributed as a sub-investigator to the ARAMIS and TITAN trials. Since he joined the team he has been involved in different projects for the development of liquid biopsies in prostate cancer.
He is keen to learn more about lab protocols and experiment design.
Miss Kamila Sychowska joined the team as a Research Assistant in July 2019. She is a part of the ReIMAGINE trial and her responsibilities primarily revolve around sample collection and processing.
Kamila completed her BSc and MSc in Chemistry at the University of Gdansk in 2015. She continued to work at the University researching design and manual synthesis of combinatorial libraries of peptides. The major focus of her research was on enzymatic studies for serine proteases to regulate their activity. This led to the publication of two papers, one of which she was second author on, and published in a leading combinatorial chemistry journal.
Outside of academia, Kamila was part of a laboratory team in a private Clinical Research Organisation where she was responsible for the processing and analysis of biological samples for numerous trials.
Miss Sychowska is truly passionate about laboratory work and hopes to pursue her research career much further in the future.
Leila Zakka joined the group in August 2019 as a Research Assistant for STRATOSPHERE; later in the year, her duties were extended, and she has become our part-time Trial Practitioner for the PARADIGM study.
Leila completed her MSc in Environmental Science at the University of Szeged, Hungary, then she obtained a PhD in Airborne Manganese Toxicity, at the same university. She has gathered several years of experience in medical research, by working on Prion disease at MRC, on Triple Negative Breast Cancer at King’s College and on Brain Cancer at Imperial College.
She is keen to learn more about clinical trial coordination and is looking forward to gain more experience in that while in the team.
Mrs. Goncalves joined the Team in February 2020 as a technician. Her role currently involves supporting the ReIMAGINE Prostate Cancer Risk Study through collection and processing of clinical trial samples in accordance to GCLP standards and regulations.
She obtained her BSc Hons in Biological Sciences in 2008 in Brazil and previously worked within a diagnostic laboratory setting in a Pre-analytical Department for one year, and in a Cellular Pathology Department for another three years where she has acquired valuable skills.
She hopes to continue developing her skill set, widen her knowledge to further pursue her career on the field of cancer research.
Osvaldas Vainauskas joined the Attard team in September 2020 as a PhD student in Bioinformatics, after being awarded a 4-year CRUK funded studentship to work on prostate cancer translational research.
Osvaldas completed his Biology degree in 2017 at the University of Alicante. He went into the industry for a year, where he worked as a junior Bioinformatician, developing pipelines for congenital disease screening with an emphasis on autism.
This transition sparked his interest in Bioinformatics, which lead him to obtain a Masters’ degree in this field in 2019 at the University of Murcia. During this time, he had the chance to work on prostate cancer research as part of his Masters’ thesis, where he studied the clinical implications of whole-blood genetic profiles in metastatic castration-resistant prostate cancer.
As part of his PhD, Osvaldas will be developing pipelines for multi-omic approaches to study advanced prostate cancer using liquid biopsies. More precisely, he will be using the fragment length data from cfDNA extracted from plasma to evaluate prostate cancer response to treatment. To do so, he will be integrating his findings in fragment length with other forms of genomic and epigenomic data, creating an overall picture of the cancer response.
By working within the Attard lab, he hopes to expand his knowledge and leave a mark in the field of Cancer Research and Bioinformatics.
Dr Vincenza Conteduca was a Clinical Research Fellow in the group from July 2014 to December 2017.
She graduated with a degree in Medicine in 2006 and completed her medical oncology training in 2011 in Italy. Subsequently, she got her Ph.D. in Clinical and Experimental Oncology and, in 2013, She became a Medical Oncology Consultant who specializes in the treatment of advanced urological tumors at Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) in Meldola, Italy.
In 2014, she won an ESMO translational fellowship and was awarded the best ESMO fellowship thanks to her research project which was aimed at identifying novel biological profiles of sensitivity and/or resistance to abiraterone and enzalutamide by analysing plasma DNA.
She has been extensively involved in several translational research projects aiming to implement patient-oriented medicine, also in collaboration with some of the most influential research institutes in Europe and United States. She currently splits her time as a Medical Oncologist in Italy and as a Research Fellow at Weill Cornell University, New York City, USA.
Mariana Buongermino Pereira
Dr Mariana Buongermino Pereira is a biostatistician/bioinformatician and is passionate about interdisciplinary sciences and the use of mathematical, statistical and computational tools to provide a better understanding of medical sciences. She is responsible for processing and analysing DNA sequence data. In particular, she has implemented a work-flow to estimate tumour content from DNA found in the plasma, and is also working on the validation of a panel study to the detection of break-points and SNVs with low frequency.
Before joining the group, she completed her PhD in mathematical statistics/ bioinformatics at Chalmers University of Technology, Sweden. During this time, she studied statistical modelling of DNA sequence data. More specifically, she applied hidden Markov models to the prediction of mobile elements in bacterial genomes, and studied normalisation methods of shotgun metagenomic data.
Mariana took up a position at Genomics England in April 2019.
Mr Alex Landless is a Research Assistant and joined the team in summer 2017 after having completed a BSc in Cellular and Molecular Medicine at the University of Bristol.
His roles include assessing the effect of point mutations on the efficacy of treatment for prostate cancer, processing and logging blood samples sent to the lab as part of the STAMPEDE clinical trial as well as generally supporting the various projects being undertaken by the lab.
In the future he hopes to continue to learn and develop skills in areas such as immunophenotyping and also to develop a larger project for his own research. Alex has also worked in structural biology at EMBL Heidelberg in Germany in 2016/17 and undertook a project with the NHS Blood and Transplant service in 2017.
Alex started an MSc (Physician Associate Studies) in January 2020 at Queen Mary University, London.
Dr Francesco Pierantoni is a clinical research fellow working at Istituto Oncologico Veneto (Padova, Italy). He is part of the Italian PRIME group, and joined the UK team between June and November 2019 on the PRIME clinical fellows exchange program. PRIME is an international project with the aim of developing a clinically implementable test integrating genomic, transcriptomic and methylome status, in patients affected by prostate cancer.
He completed his medical degree in 2014 at the University of Padova (Italy), and he is currently training as a Medical Oncologist at the same institution. His main interests are genitourinary cancers, with a particular focus on advanced prostate tumours. He participated as sub-investigator in many phase II and III clinical trials, sponsored both by Industry or charities. He is also involved in translational studies for the development of circulating biomarkers in oncological diseases.
Francesco aims to develop his skills both in the clinical and translational research settings, while collaborating on projects aimed at the implementation of liquid biopsies in genitourinary tumours.
Miss Mohini Kalyan is a highly experienced Research Assistant who has contributed significantly to several publications including those published in Cell and the Journal of Clinical Investigation. She joined the UCL Cancer Institute in August 2019.
Mohini obtained a First Class BA Honours degree in Biological Natural Sciences from the University of Cambridge specialising in the fields of Immunology and Virology. After being awarded a prestigious Faculty of Medicine Master’s scholarship, she completed her MSc in Immunology at Imperial College London, graduated at the top of her class and received the Dean’s prize for her thesis.
She continued to work at the University in the Department of Infectious Diseases and Vaccinology. The focus of her projects were to conduct clinical trials to better understand the immune responses directed towards respiratory viruses and thus facilitate the development of effective vaccines. Mohini has gained extensive experience in conducting ELISA assays to determine vaccine efficiency and has worked on various projects in collaboration with Janssen Pharmaceuticals and the US Department of Defence.
Her role in the team currently involves working on the PARADIGM clinical trial. This trial aims to identify molecular signatures in circulating plasma tumour DNA (ptDNA) that associate with progression free survival and overall survival in patients treated with abiraterone or docetaxel. Miss Kalyan aims to use her immunology skill set to aid in the translational aspect of the study to identify changes in peripheral blood mononuclear cells (PBMCs) and levels of plasma cytokines after treatment.
Mohini started a position at Imperial College London working on a Covid-19 vaccine in September 2020.
Dr Charles Parker is a Clinical Research Training Fellow who joined the Attard group in October 2020 on a 1 year Pathological Society/Jean Shanks Foundation predoctoral research bursary.
Charles completed his medical degree in 2013 at Gonville & Caius College, University of Cambridge with an intercalated BA (Hons) in Clinical Pathology and a distinction in the Final MB pathology examination. He initially completed the Academic Foundation programme in Cambridge, followed by Core Surgical Training in London, before starting Histopathology training in Edinburgh where he received a Distinction in the Postgraduate Certificate in Molecular Pathology and Genomic Medicine from the University of Edinburgh.
Charles is interested in how digital analysis of histological features can be harnessed to improve the prognostic information yield from patient biopsies, and how morphological assessment can be integrated with genomic data and other molecular techniques.