Our Research Aims
Our research program has two broad scientific aims, each addressed through the work of three integrated work packages:
Aim 1: Map the colorectal cancer microbiome
Work Package 1: The microbiome in cancer risk.
Work Package 2: Epidemiological correlates of the colorectal cancer microbiome.
Work Package 3: Mapping the cellular distribution of the colorectal cancer microbiome.
Aim 2: Understand the clinical impact of modulating the colon cancer microbiome
Work Package 4: Model systems to study the colorectal cancer microbiome.
Work Package 5: The interplay between the microbiota and colorectal cancer treatments.
Work Package 6: Novel treatments involving microbiome modulation.
We also have a public-facing objective: to share and disseminate our data, methodologies and concepts with the scientific, medical and patient communities.
This integrated structure of our program is illustrated in the figure on the right.
Hypothesis: Specific members of the colonic microbiota are associated with increased risk of colorectal cancer in susceptible individuals.
Rationale: Previous data from our team and others have shown that the colorectal cancer-associated microbiota are present in pre-cancerous lesions (Kostic, et al., McCoy, et al., Sears and Garrett., Boleij, et al., Arthur, et al., Dejea, et al.). Recently, we have shown that histologically normal epithelium and early adenomas from the colons of patients with hereditary susceptibility to colorectal cancer, are associated with biofilms of enterotoxigenic Bacteroides fragilis and polyketide synthase-positive Escherichia coli (Dejea, et al.).
Overall plan: We have assembled unique population cohorts to investigate the relationship between the microbiome and cancer risk. We will focus on two cohorts: >500 people at high risk for familial colorectal cancer, and an international cohort of >17,000 people with no prior known risk, who have undergone screening for colorectal cancer. Our high-risk cohort includes individuals with germline risk mutations for familial adenomatous polyposis (FAP) and with hereditary non-polyposis colon cancer (HNPCC). Our “normal” risk cohort of 17,000 people includes an international population but its centerpiece is 10,000 people who participated in the National Health Service Bowel Cancer Screening Program of the United Kingdom, with follow-up colonoscopy of positive tests to indicate cancer, polyp, or histologically normal colon. Our goal is to perform DNA sequencing and further analysis of the microbiome from stool or pre-neoplastic tissue from these two cohorts and to compare microbiome profiles between patients who do and do not develop cancer. This will allow the assessment of the value of the microbiome in routine screening programs and hereditary cancers.
Work Package Leaders
Philip Quirke, BM, PhD, FRCPath, FRCSEd (ad hominem), FFPath (Hon), RCPI, FMedSci
Phone:University of Leeds
Department:Investigator Team,Investigators,Philip Quirke,WP1
Yorkshire Cancer Research Centenary Professor of Pathology
Honorary Consultant Histopathologist, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Cynthia Sears, MD
Phone:Johns Hopkins University School of Medicine and Bloomberg School of Public Health
Email:Medicine; Infectious Diseases; Immunology
Department:Cynthia Sears,Investigator Team,Investigators,WP1
Professor of Medicine, Oncology, and Molecular Microbiology & Immunology
Department:John Barnes,Patient Advocate,WP1
I am a bowel cancer survivor. In 2000, I was diagnosed with a Dukes stage 2 bowel cancer in transverse colon following an emergency presentation with a rectal haemorrhage.
I was born in the Cambridgeshire Fens in the East of England, I went to school in the Midlands, and am a Business graduate from Coventry University. I now live near Harrogate in rural North Yorkshire, UK. I had a career in industry and owned my own lighting design and distribution company for 20 years which I sold in 2015.
Since my operation I have acted as a ‘friend’ to others who are going through similar experiences with bowel cancer. A role that I get immense satisfaction from.
I am currently a Patient Advocate for Bowel Cancer Intelligence UK and Yorkshire Cancer Research and I have 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. I also sit on the NHS Colorectal Expert Group which is charged with producing ‘The Clinical Advice for the Commissioning of the whole Bowel Cancer Pathway’.
I now willingly give my time to try and help with the improvement of the outcome of all bowel cancer patients; I feel that I am one of the lucky ones. My personal aim is to help take the luck element out of the diagnosis and treatment of this disease.
I am married with 2 adult daughters and two grandchildren. I love travelling and seeing the world, golf, cycling, art, antiques, photography, and family history research and can trace his family back to the winning side at the Battle of Hastings in 1066!
Hypothesis: Lifestyle risks, geographical variation and cancer phenotypes are each associated with the presence and distinct features of the colorectal cancer microbiome.
Rationale: Research from our group has identified patient characteristics, including diet, cancer characteristics, and location within the colon and rectum, that are associated with the presence and abundance of the colorectal cancer-associated microbiota.
Overall plan: Where Work Package 1 focuses on cohorts of individuals at risk for colorectal cancer, Work Package 2 focuses on cohorts of patients who have developed colorectal cancer. We will study colorectal cancer specimens from large longitudinal cohorts including the Nurses’ Health Study and the Health Professionals’ Follow-Up Study. In these cohorts, we will examine the relationships of demographic, genetic, environmental, dietary, nutritional, and lifestyle features with the tumor tissue microbiome. We will also examine the relationship between the tumor tissue microbiome and the location of primary tumors within the colon. To assess the impact of geographic origin of colorectal cancers on the microbiome, we will collaborate with the Mutographs study of the CRUK Grand Challenge, led by Sir Mike Stratton, to compare the microbiome as detected in whole genome sequences of 1300 colorectal carcinomas from around the world with the geographic origins and lifestyle features of patients as well as the mutational signatures of their cancers.
Work Package Leaders
Curtis Huttenhower, PhD
Phone:Harvard TH Chan School of Public Health Boston, Massachusetts
Department:Curtis Huttenhower,Investigator Team,Investigators,WP2
Professor of Computational Biology and Bioinformatics
Departments of Biostatistics and Immunology and Infectious Diseases
Associate Member, Broad Institute of MIT and Harvard
Co-director, Harvard Chan Microbiome in Public Health Center
Shuji Ogino, MD, PhD, MS
Phone:Brigham and Women’s Hospital, Harvard T.H. Chan School of Public Health/ Harvard Medical School Broad Institute of MIT and Harvard
Email:Molecular pathological epidemiology
Department:Investigator Team,Investigators,Shuji Ogino,WP2
Professor of Pathology, Brigham & Women’s Hospital, Harvard Medical School
Professor (Epidemiology), Harvard T.H. Chan School of Public Health
Chief Program in Molecular Pathological Epidemiology, Brigham and Women's
Associate Member, Broad Institute of MIT and Harvard
Lee Jones, MBA
Department:Lee Jones,Patient Advocate,WP2
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.
Hypothesis: Bacteria from the colorectal cancer microbiome are directly associated with colorectal cancer cells.
Rationale: Preliminary evidence by in situ hybridization and by single cell sequencing suggests that Fusobacterium are physically associated with individual colorectal cancer cells.
Overall plan: A clue to the microbiome’s importance in colorectal cancer is that microbes can be found within cancer tissues, based on extensive in situ hybridization studies and most recently from single cell RNA sequencing data. Further understanding the specific location and associations of the cancer-associated microbiome with cancer cells and immune and other tumor micro-environmental cells is key to elucidating the activity of the microbiome. We will do this through multiple visualization approaches including single cell sequencing and multi-spectral imaging.
Work Package Leaders
Matthew Meyerson, MD, PhD
Phone:Dana-Farber Cancer Institute, Harvard Medical School, Broad Institute of MIT & Harvard, Boston, Massachusetts and Cambridge, Massachusetts
Department:Investigator Team,Matthew Meyerson,Principal Investigator,WP3
Professor of Genetics and Medicine, Harvard Medical School
Director, Center for Cancer Genomics, Dana-Farber Cancer Institute
Institute Member, Cancer Program, Broad Institute of MIT & Harvard
Marios Giannakis, MD, PhD
Phone:Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard, Harvard Medical School Boston, Massachusetts
Department:Investigator Team,Investigators,Marios Giannakis,WP3
Assistant Professor in Medicine
Marielle Santos McLeod, CPN
Department:Marielle Santos McLeod,Patient Advocate,WP3
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.
Hypothesis: Microbial components of the colorectal cancer microbiome promote the growth of colorectal cancers in model systems and influence their immune response.
Rationale: Our team has particular expertise in colorectal cancer model systems, including the development of intestinal organoid model systems, that should provide the opportunity to assess the role of the colorectal cancer microbiome. In addition, we have preliminary data which suggest that the addition of microbiome components, whether Bacteroides or Fusobacterium species, increases the risk of colorectal cancer in genetically engineered mouse model systems and that antibiotic treatment of colorectal cancer models decreases the growth of these cancers.
Overall plan: Our team will analyze the impact of microbiome modulation in colorectal cancer model systems, including: three-dimensional organoid cultures, mouse models, and patient-derived xenografts. We will test the impact of the addition of bacterial members of the microbiome (or their diminution with antibiotics) as well as bacterial metabolites, on the growth and properties of these experimental models. In addition, we will perform experiments where we add back components of the immune system and test the response of the colorectal cancer models to microbiome modulation.
Work Package Leaders
Wendy Garrett, MD, PhD
Phone:Harvard TH Chan School of Public Health/Harvard Medical School Boston, Massachusetts
Email:Immunology; Infectious diseases
Department:Investigator Team,Principal Investigator,Wendy Garrett,WP4
Professor of Immunology and Infectious Diseases
Hans Clevers, MD, PhD
Phone:Hubrecht Institute, University Medical Center Utrecht, Princess Maxima Centre for Pediatric Oncology Utrecht, the Netherlands
Email:Cancer research; Stem cell research
Department:Hans Clevers,Investigator Team,Investigators,WP4
Professor of Molecular Genetics, University Medical Center Utrecht
Principal Investigator at the Hubrecht Institute (KNAW) and the Princess Máxima Center for Pediatric Oncology.
Prof Fiona Powrie, FRS
Phone:University of Oxford
Department:Fiona Powrie,Investigator Team,Investigators,WP4
Director Kennedy Institute of Rheumatology, Translational
Gastroenterology Unit, Experimental Medicine Division Professor of
Microbiology & Immunology
Hypothesis: The colorectal cancer microbiome influences the response to both immunotherapy and chemotherapy.
Rationale: We have shown that specific members of the microbiota are most heavily enriched in cancers of the right colon, the same cancer type that most often harbors microsatellite instability and is responsive to immune checkpoint inhibitor therapy. In addition, we have shown that Fusobacterium abundance is correlated with the expression of many immune regulatory genes, including CD274, that encodes PD-L1.
Overall plan: We will develop a novel prospective cohort, the MICROCOSM cohort, to longitudinally analyze over 2500 patients on chemotherapy or immunotherapy for their colon cancer microbiome and for their response to either fluoropyrimidine-based chemotherapy or immune checkpoint inhibition.
Work Package Leaders
Kimmie Ng, MD, MPH
Phone:Dana-Farber Cancer Institute
Department:Investigator Team,Investigators,Kimmie Ng,WP5
Associate Professor of Medicine, Harvard Medical School
Director, Young-Onset Colorectal Cancer Center
Co-Director, Colon and Rectal Cancer Center
Director of Translational Research
Center for Gastrointestinal Oncology, Dana-Farber Cancer Institute
Josep Tabernero, MD, PhD
Phone:Vall d’Hebron Institute of Oncology
Department:Investigator Team,Investigators,Josep Tabernero,WP5
Director of Vall d’Hebron Institute of Oncology
Head of the Medical Oncology Department of Vall d’Hebron University Hospital
Director of Clinical Research at Vall d’Hebron Institute of Oncology
Co-Director of Research Unit for Molecular Therapy of Cancer-“la Caixa” at Vall d’Hebron Institute of Oncology
Head of the Gastrointestinal and Endocrine Tumors Group at Vall d’Hebron Institute of Oncology
Director of Innovation, Care and Research, Catalonian Oncology Network. Barcelona, Spain.
Professor, Medicine Department, Universitat de Vic, Universitat Central de Catalunya. Vic, Barcelona, Spain.
Candace Henley, CPN
Department:Candace Henley,Patient Advocate,WP5
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.
Candace advocates for “Removing Barriers for Colorectal Cancer Screening Act (H.R.1070 — 113th Congress (2013-2014), 114th Congress (2015-2016), and reintroduced H.R.1017 - Removing Barriers to Colorectal Cancer Screening Act of 2017 115th Congress (2017-2018). A Lobbyist for Right Scan Right Time, more specifically “Access to Medical Imaging” asking Congress to enact policies to save lives by expanding patient access to existing imaging technology which is a vital part of the early detection, diagnosis, and treatment of disease.
After years of advocating, Candace identified a need for grassroots awareness and education of colorectal cancer in communities of color and medically underserved communities, she started the Blue Hat Foundation in 2015. The organization utilizes community partnerships with healthcare providers, physicians, and hospital systems to deliver the message of the importance of getting screened and created and organized a faith-based colon cancer awareness campaign, Blue Hat Bow Tie Sunday, now in its 8th year. Candace has shared her story with national audiences on The Steve Harvey show, and with Katie Couric. She has contributed to several articles regarding colorectal cancer and has several articles written about her cancer journey and her tireless advocacy.
Carlos Hue, PhD
Department:Carlos Hue,Patient Advocate,WP5
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.
Hypothesis: Targeting the colorectal cancer microbiome will improve the outcome for colorectal cancer patients.
Rationale: We have shown that antibiotic treatment decreases the growth of colorectal cancer in mouse model systems, suggesting a potential therapeutic benefit of microbiome disruption.
Overall plan: Here, we will focus on the development and testing of innovative microbiome-modulating treatment strategies in model systems and in patients. We aim to develop novel antibiotics, “predatory bacteria” and cancer vaccines targeting select oncomicrobes. We also plan to perform a clinical trial, METRIC, in collaboration with NuBiyota LLC, to evaluate the impact of microbiota replacement in improving patients’ response to therapy and ameliorating treatment-related toxicities.
Work Package Leaders
Emma Allen-Vercoe, PhD
Phone:University of Guelph Ontario, Canada
Department:Emma Allen-Vercoe,Investigator Team,Investigators,WP6
Professor and Canada Research Chair
Department of Molecular and Cellular Biology
University of Guelph
Robert Holt, PhD
Phone:BC Cancer Agency
Department:Investigator Team,Investigators,Robert Holt,WP6
Scientific Co-Director, BC Cancer, Immunotherapy Program
Distinguished Scientist, BC Cancer, Genome Sciences Centre
Professor, University of British Columbia, Department of Medical Genetics,
Professor, Simon Fraser University, Department of Molecular Biology & Biochemistry
Anita Mitchell Isler
Department:Anita Mitchell Isler,Patient Advocate,WP6
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.
Barry Stein, B.Com., B.C.L., LL.B.
Department:Barry Stein,Patient Advocate,WP6
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.
As the president and CEO of the Colorectal Cancer Canada (CCC) he actively represents the interests of cancer patients and speaks regularly to medical professionals, industry, government, and patient groups across Canada and Internationally about colorectal cancer, Patient Values and Preferences in Health Technology Assessment, Clinical Trials and Real World Evidence, Young Adults with Cancer, Personalized Medicine and Companion Diagnostics, Biosimilars, Colorectal Cancer Screening, Foods that Fight Cancer and other CCC programs and research projects.