Improve treatment responses by manipulating the composition and status of the microbiota
Manipulating the microbiome
It’s becoming increasingly clear that bowel cancer – the third most common cancer worldwide – is intricately linked to microbes in the gut. By exploring how these microbes drive cancer and influence a person’s response to treatment, the OPTIMISTICC team could transform outcomes for people around the world.
A delicate balance
The human body is home to trillions of different microorganisms, including bacteria, fungi and viruses. Together, they form the microbiome – a community of microbes differing from organ to organ and person to person.
For the most part, the relationship between the microbiome and the body is mutually beneficial, especially in the gut. In return for a protected, nutrient-rich environment, bacteria assist with digestion and provide protection from pathogenic microorganisms. To live in harmony with this vast microbial metropolis, the immune system works constantly to ensure good bacteria are tolerated, and harmful species are eliminated.
It’s a delicate balance, perturbations to which are associated with the development of several diseases, including bowel cancer. It’s also becoming increasingly clear that the microbiome affects how people with cancer respond to their treatment. Understanding the complex relationship stacks up to a monumental global challenge.
Enter OPTIMISTICC: an international team with a diverse range of complementary expertise. Their goal is to pinpoint how the microbiome impacts the initiation and development of bowel cancer, translating their findings into strategies that could transform outcomes for people with the disease.
Professor Matthew Meyerson, Joint Principal Investigator, OPTIMISTICC
Professor of Genetics and Medicine and Director of the Center for Cancer Genomics
The role of the cancer microbiota remains one of the big mysteries in cancer biology. We are excited that our proposal will be supported by Cancer Grand Challenges as it will enable our team to transform understanding of how the colon cancer microbiome influences cancer growth, diagnosis and response to treatment.
The whole research pipeline: from data to the clinic
A crucial first step is to develop a vast, integrated dataset, exploring the link between a person’s risk of cancer, their gut bacteria and their lifestyle. Size matters for studies like this and the team is analysing samples and information from 17,000 people from around the world, with or at risk of bowel cancer. This dataset will provide, for the first time, a clear picture of how the microbiome convenes with other factors to determine a person’s risk of bowel cancer, potentially identifying new ways to prevent the disease.
In the lab, the team will map how the microbiome interacts with cancer cells to drive the development of the disease. Which cells are targeted by which species of bacteria? Do bacteria exert their effects inside the cells or on their surface? They’ll also interrogate how the microbiome interacts with the immune system to understand why immunotherapies have, so far, been ineffective for most people with bowel cancer.
Closer to the clinic, the team will analyse blood, tumour and stool samples from bowel cancer patients all over the world, layering this information with detailed clinical and lifestyle data. The result will be a one-of-a-kind resource for the global research community to explore how the microbiome impacts – and is itself impacted by – treatment.
Predators: a new addition to our arsenal?
OPTIMISTICC will also investigate a curious class of microbes, collectively known as predatory bacteria. While they pose no risk to human health, they seek out and target other bacteria – their preference of which can be manipulated – and could represent an intriguing way to wipe out certain cancer-causing species.
Wendy is the Irene Heinz Given Professor of Immunology and Infectious Diseases at Harvard, and a medical oncologist at Dana-Farber Cancer Institute. She co-founded and co-directs the Harvard Chan Microbiome in Public Health Center and her lab’s research focuses on the interplay between the gastrointestinal immune system and the gut microbiota in health, inflammatory bowel disease and colorectal cancer. Wendy has identified both specific species, pathways, and metabolites produced by the microbiota that influence health and disease states.
Harvard TH Chan School of Public Health
Matthew is Professor of Genetics and Medicine at the Dana-Farber Cancer Institute and Harvard Medical School, an Institute Member of the Broad Institute, and Co-Director of the Dana-Farber Center for Cancer Genomics. Among other honors, he has been awarded the Paul Marks Prize in Cancer Research from Memorial Sloan-Kettering Cancer Center and the Team Science Award from the American Association for Cancer Research.
Matthew’s research focus includes genomic analysis of human lung cancers, genome-inspired cancer drug discovery, and the cancer microbiome. One major discovery was somatic mutations in the epidermal growth factor gene, EGFR, that predict response to EGFR kinase inhibitors, a discovery that has propelled research in personalized medicine. The Meyerson laboratory developed the computational subtraction approach for discovery of novel disease-causing microbes and discovered the association of Fusobacterium with colorectal cancer.
Dana-Farber Cancer Institute, Harvard Medical School
Emma obtained her BSc (Hons) in Biochemistry from the University of London, and her PhD in Molecular Microbiology through a partnership with the Centre for Applied Microbiological Research, now Public Health England. Emma started her faculty career at the University of Calgary in 2005 studying the normal microbes of the human gut. In particular, she was among the few that focused on trying to culture these ‘unculturable’ microbes in order to better understand their biology. To do this, she developed a model gut system to emulate the conditions of the human gut and allow communities of microbes to grow together, as they do naturally.
Emma moved her lab to the University of Guelph in late 2007 and has established a specialist anaerobic fermentation laboratory there. This has been further boosted by the award of a Tier 1 Canada Research Chair in Human Gut Microbiome Function and Host Interactions . In 2013, Emma co-founded NuBiyota, a research spin-off company that aims to create therapeutic ecosystems as biologic drugs, on a commercial scale.
University of Guelph
Hans obtained his MD and PhD from Utrecht University, Holland. He has been a Professor in Molecular Genetics at Utrecht University since 1991. He runs his lab in the Hubrecht Institute. Throughout his career, he has worked on the role of Wnt signalling in stem cells and cancer.
His discoveries include TCF as Wnt effector, the role of Wnt in adult stem cell biology and of Wnt pathway mutations in colon cancer, Lgr5 as a marker of adult stem cells, and –finally- a method to grow ever-expanding mini-organs (‘organoids’) from Lgr5 stem cells derived from a range of healthy or diseased human tissues. This has led to over 700 publications and >120,000 citations. He is member of the Royal Netherlands Academy of Arts and Sciences, National Academy of Sciences of the USA, Academie des Sciences (Paris) and Royal Society London. Recipient of multiple awards, including the Swiss Louis Jeantet Prize, the Heineken Prize, and the Breakthrough Prize in Life Sciences.
Marios is a physician-scientist at the Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School. He received his Honors Bachelor of Science degree in Molecular Biology and Molecular Genetics from the University of Toronto and his M.D./Ph.D. in Molecular Genetics and Genomics at Washington University School of Medicine in Saint Louis. He was a medical resident at Brigham and Women’s Hospital in Boston, a postdoctoral researcher at the Broad Institute of MIT and Harvard and hematology-oncology fellow at the Dana-Farber Cancer Institute.
Marios has an active clinic caring for patients with gastrointestinal cancers and his laboratory studies the genomics, immunogenomics, molecular epidemiology and tumor microenvironment of colorectal cancer using patient-derived biospecimens and pre-clinical models. His research aims to identify and characterize novel oncogenic drivers, elucidate the molecular, microbial and metabolic determinants of cancer immune infiltration and resistance, and lead to early-phase clinical trials for patients with colorectal cancer.
Dana-Farber Cancer Institute, Harvard Medical School
Rob studied at the University of British Columbia, and received his PhD in Pharmacology from the University of Alberta. After a brief postdoctoral fellowship at the State University of New York, he joined Celera Genomics as the Scientific Operations Manager for initial sequencing of the human genome.
Since 2003, Rob has been a scientist at Canada's Michael Smith Genome Sciences Centre at the British Columbia Cancer Agency (BCCA), where he is also Co-director of the BCCA Immunotherapy Program. He is recognized for his leadership role in decoding some of the first model organism and pathogen genomes and, more recently, for developing next-generation sequencing methods for interrogating the genetics of the adaptive immune system. He has served as a scientific advisor to the NIH Human Microbiome Project and discoveries by his research group have linked new infectious agents to cancer risk. His current basic and clinical research directions are focused on synthetic immunology and immune interventions in cancer, and also health care implementation research.
BC Cancer Agency
Curtis is a Professor of Computational Biology and Bioinformatics in the Departments of Biostatistics and Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health, where he co-directs the Harvard Chan Microbiome in Public Health Center. He is an Associate Member at the Broad Institute's Microbiome Program.
His lab focuses on computational methods for functional analysis of microbial communities and molecular epidemiology of the human microbiome. This includes systems biology reconstructions integrating metagenomic, metatranscriptomic, and other microbial community 'omics, the microbiome in diseases such as colorectal cancer, and its potential as a diagnostic tool and point of therapeutic intervention.
Harvard TH Chan School of Public Health
Kimmie is Associate Professor of Medicine at Harvard Medical School, Founding Director of the Young-Onset Colorectal Cancer Center at Dana-Farber Cancer Institute, and Director of Translational Research in the Center for Gastrointestinal Oncology at Dana-Farber Cancer Institute.
Her research focuses on elucidating the underlying biology of young-onset colorectal cancer, as well as identifying dietary, plasma, and molecular predictors of improved survival in all patients with colorectal cancer, with a special interest in the vitamin D pathway and the microbiome. She is the recipient of numerous NIH, foundation, and industry grants, and serves as a member of the Gastrointestinal Steering Committee of the National Cancer Institute.
Dana-Farber Cancer Institute, Harvard Medical School
Shuji is the founding Chief of the Molecular Pathological Epidemiology (MPE) Program, Brigham and Women’s Hospital; Professor of Pathology at Harvard Medical School; Professor of Epidemiology at Harvard T.H. Chan School of Public Health; Associate Member of the Broad Institute of MIT and Harvard and a Member of the DFHCC Cancer Immunology Program.
Shuji established the International MPE Meeting Series in 2013 and has been serving as its Chair/Co-Chair. He spearheads the integrative science of MPE, to study the interactive roles of environment (i.e. the exposome), microbiome, immunity, and tumour in carcinogenesis. He conducts multifaceted MPE studies using large-scale prospective cohort studies, having discovered the link between fiber-poor / inflammatory diet and higher incidence of colorectal cancer enriched with Fusobacterium nucleatum as well as evidence for suppressive effect of F. nucleatum on T-cell-mediated antitumor immunity. For his unique transdisciplinary scientific contribution, Dr. Ogino has received many awards and honours.
Dana-Farber Cancer Institute, Harvard Medical School
Molecular Pathological Epidemiology
Fiona is Director of the Kennedy Institute of Rheumatology, University of Oxford. She gained a PhD from the University of Oxford before moving to the DNAX Research Institute in Palo Alto. She returned to the University of Oxford in 1996 where she was the Sidney Truelove Professor of Gastroenterology from 2009-2014.
iona’s research is focused on interactions between the intestinal microbiome and the immune system and how this dialogue breaks down in inflammatory bowel disease and cancer. Her work has identified an essential role for regulatory T cells in maintaining intestinal homeostasis. She has also shown that both adaptive and innate immune mechanisms contribute to intestinal inflammation and identified the cytokine IL-23 as a therapeutic target in inflammatory bowel disease. She received the Louis Jeantet Prize for Medicine (2012), is a Fellow of the Royal Society, international member of the US National Academy of Sciences and a Governor of the Wellcome Trust.
University of Oxford
Phil is Head of Pathology and Data Analytics at the University of Leeds, UK and a gastrointestinal pathologist by training with a long standing interest in bowel cancer (BC). He contributed to improving BC surgery and its pathological assessment in the UK and around the world. He has been on the trial management groups of major national and international phase 3 trials on surgery (Clasicc, Rolar), chemotherapy (Quasar, Focus 1-4,Foxtrot) and radiotherapy (CR07, Aristotle) as well as many phase 2 trials. He also chairs the NHS pathology committee since 2006, contributing to EU guidance.
His current research interests are identifying the early steps in the formation of BCs, the role of the microbiome in causation, screening and treatment of BC, the use of molecular pathology in the treatment of BC and improving treatment pathway’s and clinical outcomes through the use of big data and feed back to multidisciplinary teams to improve performance.
University of Leeds
Cynthia is Professor of Medicine, Oncology and Molecular Microbiology and Immunology at the Johns Hopkins University School of Medicine and the Bloomberg School of Public Health, the Microbiome Program Leader of the Bloomberg-Kimmel Institute of Cancer Immunotherapy, the Director of the Germfree Murine Core and Co-Director of the Microbiome Forum at Johns Hopkins.
Through translational and bench research stemming from her training as an infectious diseases specialist, she investigates how enteric bacteria (particularly enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium spp, pks+ Escherichia coli) and the microbiome promote colon carcinogenesis and modulate cancer immunotherapy responses. Using human tissues and mouse models combined with microbiology, bioinformatics and immunologic methods, the Sears laboratory has identified the IL-17 and myeloid mechanisms of ETBF colon carcinogenesis and the high prevalence and carcinogenicity of mucus-invasive biofilms in colon cancer.
Johns Hopkins University School of Medicine
Josep is Head of the Medical Oncology Department at Vall d’Hebron University Hospital, Professor of Medicine at the Universitat de Vic and Director of the Vall d’Hebron Institute of Oncology. He is also currently a member of the Cancer Mission Assembly linked to the European Commission - Cancer Mission Board of the next EU research and innovation programme, Horizon Europe.
He has designed a number of investigator-initiated clinical trials aimed to answer relevant questions in CRC research. He has participated and contributed to the design of a number of clinical trials, many of them developed in the context of national and international cooperative groups and some sponsored directly by pharmaceutical companies. The research work of his group (The Gastrointestinal and Endocrine Tumours Group) is focused towards the development of molecular targeted therapies and the identification of molecular biomarkers of response/ resistance, and it is formed by both clinical and translational researchers, working in various thematic areas (sophisticated preclinical models, liquid biopsies, microbiome).
Vall d’Hebron Institute of Oncology
In 2003, Laura was 43 years old, in her second year of her pediatric residency, when she was diagnosed with Stage IV Colon Cancer. She had two recurrences and in May 2006 she became cancer free after many medical interventions.
Since 2005, Laura has been a Patient Advocate Medical Consultant with several national and international organizations. Laura serves as the Medical Affairs Senior Consultant at the Colorectal Cancer Alliance and serves as the patient advocate on several guideline panels and committees at the American Society of Clinical Oncology (ASCO). She has been an advocate on the NCI Rectal-Anal Task Force for over 6 years. Laura reviews basic cancer research grants for Cancer Prevention Research Institute of Texas (CPRIT).
Laura’s medical background, battle with cancer, humor and honesty uniquely position her message of hope and her passion for sharing the message of survival with other survivors and their family members.
Anita Mitchell Isler was diagnosed with IV colorectal cancer at 41 years old. After learning more about her disease and family history she was determined to try to save others from this mostly preventable disease.
Her advocacy started at her children’s school, when she started a Dress in Blue Day to build awareness about the disease and guidelines. This is now held across the country on the first Friday in March.
She is a tireless advocate for colorectal cancer patients. She is the founder of Washington Colon Cancer Stars, a 501c3 which focuses on education for prevention and patient support. She has received various national awards for her work including Prevent Cancer Laurel of Advocacy Award, Colorectal Cancer Alliance (CCA) Visionary Award, National Colorectal Cancer Round Table (NCCRT) Blue Star award and local Rotary Self above service awards
She has volunteered for CCA as a buddy for 14 years and is a FCRC research advocate.
You are likely to find her wearing the Polly Polyp costume giving tours through the colon or sitting beside a newly diagnosed colorectal cancer patient. In her spare time, she is helping to raise 3 stepchildren in Woodinville Washington and enjoys spending time with her three grown children.
Candace is an accomplished Foundation Executive Director with significant experience in community outreach and patient education. Superior record of successful community service and engagement. Candace is a 14-year colon cancer survivor who works to help other cancer survivors make sense of the disease as well as publicly share her story of a challenging battle with a positive attitude and faith that inspires others to never give up. Her greatest fight was against the tragic turn of events that her life took after her cancer diagnosis, which overwhelmed her, robbed her of hope, tested her faith, and threatened her with defeat. Her story will make you sad, angry, cry and cheer because it's an incredible example of perseverance and strength.
Barry sits on the Board of Directors of several corporations, not-for-profit organizations and foundations including Colorectal Cancer Canada, Donald Berman Foundation, Exactis Innovation, Tikva Children’s Foundation and Anzie Accessories & Design Inc. He is a member the Board of Directors (Observer) of Quebec Clinical Research in Oncology (Q-CROC) and a member of the Board of Directors of the Canadian Personalized Healthcare Innovation Network (CPHIN). He is also a patient advisor to Alberta’s O2 Oncology Outcomes Real World Evidence Project. Barry is the president and a Director of the Coalition Priorité Cancer au Québec. He is a founding member of the Canadian Partnership Against Cancer’s National Colorectal Cancer Screening Network (NCCSN). He also currently chairs the IQVIA Advisory Council for the Advancement of Health in Quebec.
Marielle was diagnosed with young onset Stage III colon cancer in June 2017. After completing numerous rounds of chemotherapy is now cancer free. She holds a BA Spanish and an MHA in Healthcare Administration and has worked in the healthcare field for 13 years. At the time of her diagnosis and treatment, she was shocked as to how little information was available regarding colorectal cancer in young adults. After losing her job while undergoing chemotherapy, she made it her mission to bring awareness to this disease that almost claimed her life. She began her career as a Certified Bilingual Patient and Family Support Navigator at the Colorectal Cancer Alliance in June 2018. While at the Alliance, Marielle has helped collaborate with the Latino Outreach Program and oversees both the Buddy Program and Blue Hope Financial Assistance Program.
He received a degree in Psychology and Pedagogy by Complutense University of Madrid and a doctorate in Education by the University of Barcelona. He worked in a public Social Service Institute as a psychologist from1976 to 1999. Since 2000, he has been working as an Advisor for long life learning education in the Ministry of Education of the regional Govern of Aragon. Simultaneously, he has been teaching Psychology and Education for teachers and professors at the University of Zaragoza, and many other Universities in Spain. In the last 15 years, he has become a specialist in Emotional Intelligence in Spain giving many courses to teachers, public employees, company employees, doctors, nurses, and patients. He has published two books about this subject, titled: ‘Emotional thought: a method for developing self-esteem and leadership’ and ‘Teachers’ wellbeing and emotional thought’. He was diagnosed with colon cancer in 2003. In 2006 he became Vice President of Europacolon Spain which he continues to do. In this role, he has participated in many conferences and meetings and is studying about psycho oncology as well as coordinating a book for colon cancer patients that will be published by Europacolon Spain.
Lee was diagnosed with Stage IV colon cancer in March 2004, and since undergoing several rounds of chemotherapy and a liver resection in July 2006 has been cancer free. Lee has a BA in Psychology and an MBA in Finance and had a successful executive career in government, banking, consulting, and not-for-profit organizations.
To help others to survive and thrive after a cancer diagnosis, Lee became active with Fight Colorectal Cancer as a research advocate and became a member of the Georgetown Oncology Institutional Review Board (IRB). Also, he is a patient advocate member of the SWOG Survivorship Committee and the PCORI Clinical Trials Advisory Panel (CTAP), is on the Boards of the Cancer Action Coalition of Virginia (CACV), the Ruesch Center (Georgetown University) and the Cancer Policy and Advocacy Team (CPAT) of the National Coalition for Cancer Survivorship, has been a peer research proposal reviewer for ASCO, PCORI and the DOD, and is a member of ASCO, the Colorectal Cancer Roundtable and the Alliance for Regenerative Medicine (ARM). Lee has collaborated on several projects sponsored by The Friends of Cancer Research, including defining tolerability, reporting adverse events, and tightening exclusion criteria, and has been a speaker at Ruesch Center, AAADV, CPAT and NCCN conferences.
John is a bowel cancer survivor. In 2000, he was diagnosed with a Dukes stage 2 bowel cancer in transverse colon following an emergency presentation with a rectal haemorrhage. Since his operation he has acted as a ‘friend’ to others who are going through similar experiences with bowel cancer. A role that he gets immense satisfaction from. He is currently a Patient Advocate for Bowel Cancer Intelligence UK and Yorkshire Cancer Research and has represented the BCI UK at the GB Colorectal Surgeons Conference, the Public Health England Conference and also the UK Government’s cross party ‘Battle against Cancer’ Conference. He also sits on the NHS Colorectal Expert Group which is charged with producing ‘The Clinical Advice for the Commissioning of the whole Bowel Cancer Pathway’.