{"id":28697,"date":"2023-03-10T13:18:01","date_gmt":"2023-03-10T13:18:01","guid":{"rendered":"https:\/\/news.cancerresearchuk.org\/?p=25408"},"modified":"2024-11-03T15:12:50","modified_gmt":"2024-11-03T15:12:50","slug":"a-career-forged-in-team-science","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/a-career-forged-in-team-science\/","title":{"rendered":"A career forged in team science"},"content":{"rendered":"
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From clonal evolution to metastasis and cachexia, Mariam Jamal-Hanjani has taken on some serious challenges during her research journey. We spoke to her and asked her to reflect on a career embedded in large-scale, collaborative and ambitious projects<\/em>\u2026<\/p>\n<\/div>\n

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The work cancer researchers undertake has incredible ambition. Perhaps understandable then, that it\u2019s so often described in celestial terms. Visionary projects become moonshots<\/em>, new research strategies reach for the stars<\/em> and biopharma spinouts explode from the launch pad.<\/em><\/p>\n

For one emerging leader of the cancer research community this has real resonance.<\/p>\n

\u201cWhen I was a kid, I always wanted to be an astronaut,\u201d says Mariam Jamal-Hanjani. \u201cI remember being obsessed with stars and, you know, I\u2019m quite tiny so at the very least I figured my center of gravity wouldn\u2019t be an issue!\u201d<\/p>\n

\u201cAnd then I suddenly needed spectacles \u2013 so that was the end of that.\u201d<\/p>\n

NASA\u2019s loss most certainly became oncology\u2019s gain.<\/p>\n

Mariam is now group leader for the CRUK Lung Cancer Centre of Excellence Cancer Metastasis lab at the UCL Cancer Institute \u2013 as well as an honorary consultant in translational lung oncology for the Department of Medical Oncology at UCL Hospital. From an early academic career in physics, to a nascent clinical career she then gravitated back to research. Finding herself in the right place at just the right time, in 2012 she joined Professor Charles Swanton\u2019s lab on a CRUK funded clinical fellowship to undertake a PhD.<\/p>\n

Shortly after she had joined his lab, Charlie \u2013 who was to go on to be appointed CRUK chief clinician \u2013 published a paper in The New England Journal of Medicine<\/a> showing how genomic heterogeneity within a tumour can essentially power tumour adaptation and therapeutic failure through Darwinian selection.<\/p>\n

\u201cIt became clear that actually, to study this properly, we needed more than a single biopsy,\u201d Mariam says. \u201cWe needed multiple biopsies to understand the evolutionary history.\u201d It was this thinking which led on to become TRACERx<\/a>. At over \u00a310million, it was the biggest single investment in lung cancer research CRUK had ever made, and the start of a strategic focus on the disease.<\/p>\n

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\u201cMy immediate thought was that this was highly controversial and something patients would not be in favour of \u2013 I was very wrong.\u201d<\/em><\/p>\n<\/blockquote>\n

Hot on the heels of this auspicious start, a late-night discussion with Charlie sowed a seed which was to bloom into another world first. \u201cIt really was a random thought that Charlie had one winter night,\u201d explains Mariam. \u201cHe said \u2018you know, we should set up autopsy studies.\u2019 My immediate thought was that this was highly controversial and something patients would not be in favour of \u2013 I was very wrong.\u201d<\/p>\n

Several years \u2013 and much sweat and tears \u2013 later, Mariam became the lead for the PEACE (Posthumous Evaluation of Advanced Cancer Environment) study<\/a>. It involves people living with incurable cancer donating their bodies for research after they die, so that Mariam and her team, as well many other cancer researchers, can better understand how cancer develops and spreads, why treatments stop working, and how the body reacts in the final stages of cancer.<\/p>\n

Her career, then, has been forged within very ambitious projects \u2013 but, for Mariam, to get here wasn\u2019t necessarily a straightforward journey.<\/p>\n

A numbers game<\/h2>\n

It was a love of numbers which first sparked a young Mariam\u2019s imagination.<\/p>\n

\u201cMaths was a real strong point in the family,\u201d she says. \u201cBoth my parents are mathematicians and I have two brothers who are also mathematicians. But I studied theoretical physics, because I was a bit obsessed with Einstein when I was a child.\u201d<\/p>\n

At post-graduate level she reached a turning point. \u201cI got an offer to stay on and do a PhD in physics at UCL. But to be honest, back in the 1990s I found that environment quite isolating \u2013 it was quite male dominated, and I missed that human contact,\u201d she says. \u201cI just didn\u2019t think that it was something I could do for the rest of my life.\u201d<\/p>\n

On a whim, she had a conversation with the medical school at UCL, applied and got in to study medicine as a graduate student. After a stint in renal medicine, a colleague pointed her in the direction of oncology. And, as a junior doctor, it was a challenge she certainly found compelling. \u201cIt\u2019s pathology at its most advanced,\u201d she says. \u201cThe minute you\u2019ve got metastatic disease, and there\u2019s organ failure, it could be all the medicine disciplines rolled into one, whether it\u2019s bleeding in the brain, whether it\u2019s heart failure \u2013 it was really hardcore clinical medicine.\u201d<\/p>\n

It was this tough clinical work, combined with her own personal experience of cancer, which got Mariam thinking about improvements in cancer care. Back in the 1970s one of her brothers was diagnosed with leukaemia, and whilst the resultant chemo- and radiotherapy did prove to be successful, it put real strain on the family. \u201cMy parents struggled a lot, but he was one of the very few that was cured during that period of time,\u201d she says. \u201cTreatments have of course changed and improved now, but when I was surrounded by it as a clinician, you still question what else could be done.\u201d<\/p>\n

And so, the call of research became loud and clear for Mariam. After being connected to Charlie via one of her clinical consultants, she was awarded a CRUK clinical fellowship to do a PhD.<\/p>\n

The dawn of TRACERx<\/h2>\n

Many a research career is rooted in at least a little serendipity. And Mariam was perfectly placed to make the most of hers. Shortly after she joined Charlie\u2019s lab, he published a paper<\/a> which really became a cornerstone of tumour heterogeneity. It was instrumental in forming the lab\u2019s ideas on how to tackle some of the therapeutic barriers which could emerge as a tumour develops.<\/p>\n

And from one of those ideas TRACERx<\/a> was born. \u201cIt was clear that we needed multiple biopsies, to understand the evolutionary history of a patient\u2019s tumour,\u201d explains Mariam. \u201cBut at this point, it was just a thought in Charlie\u2019s head, it wasn\u2019t even called TRACERx. He wanted to do something ambitious and large scale that tried to understand how tumours evolve in lung cancer, because that\u2019s an unmet need. And it\u2019s hard not to be driven and motivated by that kind of enthusiasm.\u201d<\/p>\n

CRUK bought into the idea and a collaborative project between the Francis Crick Institute, UCL and the University of Manchester was born.<\/p>\n

\u201cIn the very early days, when we first started with the pilot study, we were studying multi-region tumour samples from lung cancers, and we were getting a lot of data. We didn\u2019t have fancy genetic sequencing pipelines, or a massive team of bioinformaticians,\u201d says Mariam. \u201cWe would sit and look at every single mutation on the computer using genomic sequencing, looking at the genome browsers trying to make sure if it\u2019s real or not, and we would manually make the evolutionary trees for each tumour.\u201d<\/p>\n

But the project grew, and the nine-year programme would go on to study the evolution of lung cancer in unprecedented detail, from diagnosis through to disease relapse, with the aim of learning how to treat people based on the individual characteristics of their cancer. The findings continue to give vital insight into the disease, and what\u2019s more, the data set collected has taken on a gravity of its own having attracted researchers from across multiple disciplines \u2013 and Mariam is at the heart of it all.<\/p>\n

\u201cI learned from Charlie. It was his vision, and he brought all these different investigators across the country with him. It was truly team science before the term even existed, and there were aspects he was happy for me to lead on because I felt passionate about them. Together, we felt that the patient was always at the heart of our research\u201d she says.<\/p>\n

One ambitious, collaborative and logistically ground-breaking study is often all you might get to work in a career as a researcher. And you\u2019d be lucky at that. But Mariam soon found herself at the cusp of another.<\/p>\n

Legacy of the patients<\/h2>\n

Close to a decade ago, Mariam began exploring the idea of setting up an autopsy study to examine how patients\u2019 cancer evolves and spreads. From the get-go, she says, it was always going to be a challenge.<\/p>\n

\u201cThere were several small cohort autopsy studies already set up in the US, often involving \u2018warm autopsies\u2019, whereby samples are collected within six to eight hours after death. This isn\u2019t something we can achieve given that we work within the constraints of the NHS and its infrastructure.\u201d<\/p>\n

And then was the non-trivial problem of communicating this to potential donors. Would patients even want to have that discussion? \u201cActually, it was mostly the doctors treating these patients that were worried about having these discussions given the stigma of death,\u201d she says. \u201cBut then the patient advocates we worked with closely were very encouraging and open minded about the idea of autopsies to support cancer research.\u201d<\/p>\n

So, after a few years of getting into the detail of the logistics, the ethics and the patient advocacy, in 2016 Charlie and Mariam established the PEACE research autopsy<\/a> programme for which she is also the chief investigator. As a clinician, of course, she wasn\u2019t a complete stranger to the mortuary. \u201cYou become familiar with it when you\u2019re a medical student and a doctor because sometimes you have to view a body in order to complete the death certificate paperwork,\u201d she says. \u201cBut this was a whole different thing. This involved performing an autopsy for research purposes and collecting tissue samples from different parts of the body where the cancer had spread.\u201d<\/p>\n

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\u201cPEACE is something I have never stopped wanting to make a success\u2026 it\u2019s the legacy of our patients.\u201d <\/em><\/p>\n<\/blockquote>\n

The project has now performed over 230 autopsies and has recruited over 390 patients. It gives Mariam and the team \u2013 and many other researchers in the PEACE Consortium \u2013 unique access to tissue that simply couldn\u2019t be studied while patients are alive. Like TRACERx, it\u2019s giving real insights, but the most striking thing for Mariam is the staggering altruism on display from her donors.<\/p>\n

\u201cThis has been a really tough study to set up logistically, and the fact that patients are willing to donate their bodies knowing they gain nothing from it directly is truly humbling,\u201d she says. \u201cInstead, they hope that future generations of patients with cancer and researchers will benefit and because of that, PEACE is something I have never stopped wanting to make a success\u2026 it\u2019s the legacy of our patients.\u201d<\/p>\n

\u201cThere\u2019s so much you can learn given the opportunity to study these precious samples, and we\u2019ve already begun to study the patterns in which cancer cells migrate from one site of the body to the next,\u201d she adds.<\/p>\n

New and continuing challenges<\/h2>\n

Despite being firmly rooted in the lab for the inception of two innovative team-science programmes, the pull of the clinic hadn\u2019t entirely left Mariam.<\/p>\n

\u201cAfter my PhD, I was ready to go back to clinical training. That\u2019s, after all, why I had gone to medical school,\u201d she says. \u201cAnd then I realised I couldn\u2019t leave studies like TRACERx and PEACE and that I wanted to continue to be part of the research we had always hoped would make a difference for patients.\u201d<\/p>\n

Then, a few years ago, she capitulated to the lure of research. \u201cI just thought there\u2019s so much I want to do. I need a lab of my own and the ability to continue working with colleagues and collaborators, and to bring other early career researchers into the fold,\u201d she says.<\/p>\n

Now a group leader at the UCL Cancer Institute, the future looks bright as ever for Mariam. And, having blossomed as a researcher in the crucible of two highly collaborative projects, it\u2019s perhaps natural that many of her current endeavours fit firmly into a thoroughly modern vision of team science.<\/p>\n

As a member of the Cancer Grand Challenge CANCAN team<\/a>, she is part of an international effort to understand the biology behind cancer cachexia. It\u2019s an involvement that has stemmed from the spectacularly well curated TRACERx longitudinal data set.<\/p>\n

\u201cBy analysing scans performed longitudinally in patients during follow up using semi-automated pipelines to examine body composition, we\u2019re beginning to develop more efficient ways of looking at muscle and fat in the body,\u201d she explains. \u201cAnd we can use this to identify patients who develop the cachexia-like phenotype of muscle and or fat wasting during the course of their disease.\u201d<\/p>\n

Despite major clinical applications, there is still relatively little known about the condition. And that must change, says Mariam. \u201cI\u2019ve seen it many times in the patients I care for \u2013 the muscle and fat loss are a very real thing, and we have no idea how to manage it. We know it means they die sooner. We know it means they don\u2019t tolerate treatment, and we\u2019re helpless.\u201d<\/p>\n

There has been research \u2013 almost 30 years of mouse and in vitro<\/em> work in fact, but real breakthroughs in understanding are yet to emerge. The frontier of this understanding of a complex set of interactions between tumours and patients, through metabolism and the immune, endocrine and central nervous systems is now of real interest to Mariam.<\/p>\n

And as for Cancer Grand Challenges, she is also a member of the eDyNAmiC team<\/a>. In this, she is interested in understanding the role of extrachromosomal DNA (ecDNA) in cancer evolution, its interaction with the tumour microenvironment and how it leads to drug resistance. Both TRACERx and PEACE play a crucial role in the study of ecDNA from early to late-stage disease. In particular has the potential to shed light on how ecDNA drives cancer progression.<\/p>\n

Then there is the next iteration of TRACERx. Patient recruitment is coming to a close soon, and despite the continuing value of the data generated, it\u2019s time to look to the future. The TRACERx EVO programme<\/a> has been awarded \u00a314.9 million in funding by Cancer Research UK and the UCL Biomedical Research Centre to drive another step change in the way we understand and treat lung cancer.<\/p>\n

And it\u2019s this, the treatment of the disease, which has always been key for Mariam. \u201cWe had to look forward and think, how can we further advance what we had learnt from TRACERx and what are the questions we can address in light of new technologies?\u201d She says. \u201cWe knew that we always wished we could do more with the entire genome, rather than just the exome, but, really, the key factor is asking \u2018how do you translate this to patient benefit?\u2019 One of the things that EVO will allow us to do is investigate whether some of our previous findings in TRACERx can be validated in an entirely different patient cohort, and that\u2019s vital for patient impact.\u201d<\/p>\n

But that\u2019s the future. For now, TRACERx has generated data from blood and tumour samples from over 800 patients with non-small cell lung cancer. The PEACE team have performed over 230 autopsies. Both studies continue to forward our knowledge of cancer in unique ways, but there is also incredible power in the overlap says Mariam.<\/p>\n

\u201cWe have a cohort of patients who were recruited into both the TRACERx and PEACE studies,\u201d she says. \u201cWhen you combine a study, like TRACERx, which studies cancer from diagnosis through to relapse, with a study like PEACE, you have the ability to study the full spectrum of the disease.\u201d<\/p>\n

Tracing and genomically mapping individual tumours over the course of their development and metastasis, in situ<\/em>, to explore how Darwinian evolution can render therapy impotent\u2026 this is, most certainly, ambitious stuff. Moonshots, reaching for the stars<\/em>; perhaps those lofty idioms really do apply after all.<\/p>\n

Author<\/em>
Phil Prime<\/em><\/p>\n

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From clonal evolution to metastasis and cachexia, Mariam Jamal-Hanjani has taken on some serious challenges during her research journey. We spoke to her and asked her to reflect on a career embedded in large-scale, collaborative and ambitious projects\u2026 The work cancer researchers undertake has incredible ambition. Perhaps understandable then, that it\u2019s so often described in […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-28697","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/28697","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=28697"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/28697\/revisions"}],"predecessor-version":[{"id":44719,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/28697\/revisions\/44719"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=28697"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=28697"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=28697"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}