TARGETING CLONAL HEMATOPOIESIS TO PREVENT AML
This project asks the provocative question, “Is AML preventable by intercepting the progression of its pre-malignant state, clonal hematopoiesis?” Pursuing a novel investigative strategy that brings together clinical trials and laboratory modeling, this TeamLab intends to create a new paradigm for AML management: one based on identifying individuals at greatest risk of developing the disease, and on creating strategies for early detection and prevention.
This project asks the provocative question, “Is AML preventable by intercepting the progression of its pre-malignant state, clonal hematopoiesis?” Pursuing a novel investigative strategy that brings together clinical trials and laboratory modeling, this TeamLab intends to create a new paradigm for AML management: one based on identifying individuals at greatest risk of developing the disease, and on creating strategies for early detection and prevention.
PROJECT HIGHLIGHTS
- Leveraging the relatively recent discovery of clonal hematopoiesis (CH) as a pre-malignant state for AML and working to create a major new pathway for intervening in the disease’s development.
- Developing the foundational knowledge of CH needed to create new, effective approaches for early detection and treatment.
- Establishing a biobank of patient-derived samples and of human cell models—and using the material for deep research on CH biology and pre-clinical testing of potential treatments.
- Ultimately, pursuing multi-institutional Phase I trials designed to test the feasibility of therapies that could improve blood counts and reduce clonal expansion in patients with high-risk CH.
MEET THE TEAM
The Targeting Clonal Hematopoiesis TeamLab comprises both rising stars and established thought leaders in the fields of hematology, bioinformatics, immunology, and cellular biology. Indeed, many of these researchers were involved in the original discovery of CH and the early investigations into its clinical and biological implications.
Together, they and their institutions have formed a robust clinical, basic science, and translational ecosystem with specific expertise in disease modeling, single cell technology, computational analytics, clinical identification and management of CH patients, community partnership and engagement, and clinical trials. Moreover, a planned collaboration with pharmaceutical industry partners will provide access to novel therapeutics with minimal toxicity for early intervention clinical trials.
We invite you to learn about the institutions and individual investigators driving this pioneering scientific and clinical research collaboration.
Alex K. Shalek, PhD
Amy DeZern
Benjamin Ebert, MD, PhD
Danielle Hammond, MD
Eytan M. Stein, MD
Gabriel Ghiaur, MD, PhD
Gregory A. Abel, MD, MPH
Jairo Matthews
Jeffrey Molldrem, MD
Kelly Chien, MD
Ken Chen, PhD
Koichi Takahashi, MD, PhD
Lachelle Dawn Weeks, MD, PhD
Lukasz Gondek, MD, PhD
Martin Aryee, PhD
Maximilian Stahl, MD
Omar Abdel-Wahab, MD
Roger Belizaire, MD, PhD
Simona Colla
Wenbin Xiao, MD, PhD
Zuzana Tothova, MD, PhD
Alex K. Shalek, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab(s): Conquering KRAS in Pancreatic Cancer, Demystifying Pancreatic Cancer Therapies, Eradicating Minimal Residual Disease in AML<, Targeting Clonal Hematopoiesis to Prevent AML, The Data Science Hub
Alex K. Shalek, PhD, is a Core Member of the Institute for Medical Engineering and Science (IMES), an Associate Professor of Chemistry, and an Extramural Member of MIT’s Koch Institute for Integrative Cancer Research. He is also an Institute Member of the Broad Institute, a Member of the Ragon Institute, an Assistant in Immunology at MGH, and an Instructor in Health Sciences and Technology at HMS. Dr. Shalek received his bachelor’s degree summa cum laude from Columbia University and his PhD from Harvard University in chemical physics under the guidance of Hongkun Park, and performed postdoctoral training under Hongkun Park and Aviv Regev (Broad/MIT). His lab’s research is directed towards the development and application of new approaches to elucidate cellular and molecular features that inform tissue-level function and dysfunction across the spectrum of human health and disease. Dr. Shalek and his work have received numerous honors including a NIH New Innovator Award, a Beckman Young Investigator Award, a Searle Scholar Award, a Pew-Stewart Scholar Award, the Avant-Garde (DP1 Pioneer) Award from the National Institute for Drug Abuse (NIDA), and an Alfred P. Sloan Research Fellowship in Chemistry, as well as the 2019-2020 Harold E. Edgerton Faculty Achievement Award at MIT and the 2020 HMS Young Mentor Award.
Amy DeZern
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Amy DeZern is a hematologist and an Associate Professor of Oncology and Medicine at the Johns Hopkins University School of Medicine. Dr. DeZern’s primary clinical and research interests are focused on bone marrow failure disorders. She has expertise in the diagnosis and treatment of aplastic anemia (AA), myelodysplastic syndromes (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) as well as acute leukemias. All of these are disorders of clonal hematopoiesis. She is an active clinician scientist who specializes in clinical trials of diagnostics and therapeutics for these disorders. She has been the principle investigator for over 40 single-center and multicenter clinical trials in MDS and AA. These investigator-led initiatives focus is on transplant therapies in AA (including the upcoming BMT CTN upfront trial for SAA) and novel therapeutics (Phase 1-3 trials) in MDS and clonal cytopenias. Additionally, Dr. DeZern is the deputy co-chair of The National MDS Study.
Benjamin Ebert, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Benjamin Ebert is the Chair of Medical Oncology at the Dana-Farber Cancer Institute, the George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School, a Howard Hughes Medical Institute Investigator. The Ebert laboratory focuses on the molecular basis and treatment of hematologic malignancies and its non-malignant precursor conditions, with a particular focus on myelodysplastic syndromes (MDS) and clonal hematopoiesis. The Ebert laboratory demonstrated that lenalidomide, a derivative of thalidomide, binds the CRL4-CRBN E3 ubiquitin ligase and induces degradation of specific substrates. Subsequent research has examined novel mechanisms of drug-induced protein degradation that expand the spectrum of protein substrates that can be targeted pharmacologically. Dr. Ebert received a bachelor’s degree from Williams College and a doctorate from Oxford University. He completed an M.D. from Harvard Medical School, a residency in internal medicine at Massachusetts General Hospital, and a fellowship in hematology/oncology at the Dana-Farber Cancer Institute. He received the William Dameshek Prize from the American Society of Hematology, the Meyenburg Prize for Cancer Research, the Sjöberg Prize from the Royal Swedish Academy of Sciences, and the Korsmeyer Award from the American Society for Clinical Investigation.
Danielle Hammond, MD
The University of Texas MD Anderson Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Danielle Hammond, MD, is an Assistant Professor in the Department of Leukemia, Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center (MDACC). She received her M.D. degree from The University of Ottawa. She is a graduate of the University of Toronto Internal Medicine Core Residency and completed her Adult Hematology Residency at Queen’s University in Kingston, Canada. She is board-certified with The Royal College of Physicians and Surgeons of Canada in both Adult Hematology and Internal Medicine and subsequently completed a Leukemia Fellowship at the MDACC, serving as Chief Leukemia Fellow 2020-2021. Dr. Hammond is a member of the MDS Section at the MDACC, likely the largest clinical MDS program of its kind in the world. She is the co-leader of the Clonal Hematopoiesis and Leukemia Prevention Clinic there, which focuses on identifying, counseling, and investigating ways to prevent progression in individuals at highest risk of developing hematologic malignancies, particularly therapy related myeloid neoplasms. Dr. Hammond’s work also focuses on the intersection of chronic inflammation and the pathogenesis of progression of myeloid malignancies. She is the recent recipient of American Society of Hematology (ASH) and American Society of Clinical Oncology Abstract Achievement Awards. Dr. Hammond also enjoys medical education writing, serving for 3 years as an editor and contributor to The Microenvironment, a Canadian Hematology Society publication, and writing for the 2020 ASH News Daily.
Eytan M. Stein, MD
Memorial Sloan Kettering Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Eytan M. Stein, MD is the Chief of the Leukemia Service, Associate Attending Physician, Clinical Investigator, and Director of the Program for Drug Development in Leukemia on the Leukemia Service at Memorial Sloan Kettering Cancer Center. He conducts novel, phase I clinical trials of compounds that target the genetic and epigenetic basis of myeloid malignancies. Dr. Stein led the clinical studies of the IDH2 inhibitor Enasidenib and the IDH1 Inhibitor Ivosidenib in patients with relapsed and refractory AML that led to their FDA approval in 2017 and 2018, respectively. He also leads a variety of phase 1 clinical trials and serves as the lead investigator at Memorial Sloan Kettering for the BEAT AML master clinical trial. His current research focuses on elucidating mechanisms of resistance to IDH inhibitors and the use of Menin inhibitors in patients with MLL-rearranged acute leukemia. His work has been published in journals such as Nature, Nature Medicine, The New England Journal of Medicine, JAMA Oncology, Cancer Discovery and Blood. In addition, he serves on the Editorial Boards of Blood and Leukemia and Lymphoma.
Gabriel Ghiaur, MD, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Gabriel Ghiaur, M.D., PhD. is an Associate Professor of Oncology and Medicine with a strong fundamental research interest in hematopoiesis and a clinical focus on the biology of acute leukemia and minimal residual disease. Dr. Ghiaur has received his medical degree from UMF Carol Davila, Bucharest, Romania and his Ph.D. in Molecular and Developmental Biology from University of Cincinnati under the guidance of Dr. David Williams. After completing his clinical training in hematology at Johns Hopkins, he joined the Adult Leukemia Program at Johns Hopkins. The Ghiaur Laboratory is focused on investigating how the bone marrow microenvironment controls stem biology with an eye towards better understanding of normal stem cell behavior as well as persistence of minimal residual disease in hematological malignancies. Using a combination of cell biology techniques and single cell genomic and transcriptomic tools as well as access to primary human tissue and innovative patient derived xenograft models, the Ghiaur Lab aims to develop and test clinical tools that target the bone marrow microenvironment to mitigate hematopoietic aging and to improve outcomes hematological malignancies. Dr. Ghiaur has been the recipient of various honors, including the Passano Clinician Scientist Award and the American Society of Clinical Investigator Young Physician Scientist Award and he was elected as an Ambassador Alumni of UMF Carol Davila.
Gregory A. Abel, MD, MPH
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Gregory A. Abel, MD, MPH is an outcomes researcher and hematologic oncologist at Dana-Farber Cancer Institute (DFCI). His research applies health services methods to understand the experiences of patients with cancer, and to answer questions about the effectiveness of their care. He is also interested in evaluating how intensive cancer therapy affects quality of life; developing innovations to address disparities in care; and understanding the bioethics of cancer care delivery. He primarily focusses on the hematologic malignancies, studying the impact of these diseases and their treatment from diagnosis to the end of life. He also runs DFCI’s Older Adult Hematologic Malignancy (OHM) geriatric research program and serves as Chair of the DFCI Ethics Advisory Committee.
Jairo Matthews
The University of Texas MD Anderson Cancer Center
TeamLab(s): Eradicating Minimal Residual Disease in AML,Targeting Clonal Hematopoiesis to Prevent AML
Jairo Matthews is a Program Director of the MDACC leukemia tissue biorepository. He received his bachelor’s degree from the University of Michigan, and gained experience working in the U of M Cancer Center tissue bank for Head and Neck cancer. He later moved to Houston and has been with the Leukemia department under the guidance of Steven Kornblau for over a decade. He serves as a link between trial study managers, attending physicians, lab PIs and personnel, and leukemia sample bank personnel. He recently received an MDACC Division of Cancer Medicine award for Excellence in Clinical Research.
Jeffrey Molldrem, MD
The University of Texas MD Anderson Cancer Center
TeamLab(s): Eradicating Minimal Residual Disease in AML, Targeting Clonal Hematopoiesis to Prevent AML
Dr. Molldrem is a physician scientist and joined the Stem Cell Transplantation and Cellular Therapy Department of The University of Texas MD Anderson Cancer Center in 1997. He is a Professor of Medicine and Virginia H. Cockrell Distinguished Professor in Immunology, and Chair of the Department of Hematopoietic Biology and Malignancy. He also serves as Scientific Director of Oncology Research for Biologics and Immunotherapy Translation (ORBIT) platform and as Institute Director and Head of Evolution of Cancer, Leukemia, and Immunity Post Stem cEll transplant (ECLIPSE) platform. He received his medical degree from the University of Minnesota in 1990, trained in internal medicine at UCLA, and completed fellowship in hematology and medical oncology at the National Institutes of Health and Johns Hopkins. The long-term goals of his lab are to understand how adaptive immunity against hematopoietic malignancies is mediated and regulated, and to develop novel immunotherapies that target these malignancies. His laboratory has been working on T cell-mediated anti-leukemia GVL immunity for more than 25 years with continuous NIH funding. Leveraging a large longitudinal biorepository of transplant donor and recipients, his lab is studying the coevolution and clonal architecture of AML and adaptive immunity using next generation deep sequencing and multi-omic approaches.
Kelly Chien, MD
The University of Texas MD Anderson Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Kelly S. Chien, MD is an Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center and co-lead of the Clonal Hematopoiesis/Leukemia Prevention Clinic. She received her undergraduate degrees in chemical engineering and biology from the Massachusetts Institute of Technology and medical degree from Baylor College of Medicine, completed residency training at The University of Texas Southwestern Medical Center at Dallas, and graduated from hematology/medical oncology fellowship at MD Anderson. Her research is focused on not only clonal hematopoiesis and leukemia prevention, but also relapsed/refractory myelodysplastic syndrome after hypomethylating agent therapy. Dr. Chien was awarded the 2019 American Society of Clinical Oncology Conquer Cancer Foundation Young Investigator Award, 2020 Waun Ki Hong Award in Clinical Investigation at MD Anderson, 2020 Kimberly Patterson Fellowship in Leukemia Research at MD Anderson, and 2022 Waun Ki Hong Award for Excellence in Team Science as part of the Clonal Hematopoiesis Team at MD Anderson.
Ken Chen, PhD
The University of Texas MD Anderson Cancer Center
TeamLab(s): Eradicating Minimal Residual Disease in AML, Targeting Clonal Hematopoiesis to Prevent AML
Ken Chen, PhD, is a professor in Bioinformatics and Computational Biology, the Director of Bioinformatics of Institute of Personalized Cancer Therapy at the MD Anderson Cancer Center (MDACC), co-director of CPRIT single-cell genomics core. He also holds adjunct faculty position in Department of Systems Biology at MDACC and in Department of Computer Science at Rice University. He has a background in machine learning and statistical data analytics with extensive experience developing and applying computational tools to analyze large-scale high-throughput experimental data, towards detection, discovery, interpretation, modeling, and prediction. Over the past 18 years, he has led the development over 10 computational methods/tools such as BreakDancer, novoBreak (ranked #1 in DREAM 8.5 Challenges), Texomer, TransVar, Monovar, SCMER, and bindSC, which have been published in top journals such as Nature Methods, and have been widely used by computational biology, statistical genetics, single-cell, systems biology, and cancer personalized therapy communities. Meanwhile, He has been actively involved in major cancer research initiatives, such as 1000 Genomes, TCGA, ICGC, CTD2, HCA, and HTAN. His research group at MDACC is interested in developing cutting-edge data scientific capacity for quantitative characterization of cancer as a complex system and for identification of molecular targets useful for personalized diagnosis and medicine.
Koichi Takahashi, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Koichi Takahashi, MD, PhD, is an Associate Professor in the Departments of Leukemia and Genomic Medicine at The University of Texas MD Anderson Cancer Center. Dr. Takahashi received MD degree from Niigata University in Japan and PhD degree from Kyoto University Japan. He did internal medicine residency in Toranomon Hospital, Tokyo and Beth Israel Medical Center in New York. He completed Hematology and Oncology Fellowship at MD Anderson. He is board certified in Internal Medicine, Hematology, and Medical Oncology. He did research fellowship in Drs. Lynda Chin and Andrew Futreal Lab. His research focuses on studying etiology, pathogenesis and clinical phenotype of hematologic malignancies and pre-malignancies by understanding the underlying genetic underpinnings, heterogeneity and evolution through application of state-of-the-art genomics and single-cell technologies coupled with computational analytics. Dr. Takahashi is a recipient of ASH Scholar Award and LLS Scholar Award.
Lachelle Dawn Weeks, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Lachelle D. Weeks is a hematologist and scientist at Dana-Farber Cancer Institute in the division of hematologic malignancies and an Instructor of Medicine Harvard Medical School. She is a graduate of Case Western Reserve University School of Medicine where she earned her MD and PhD degrees. She completed her medical training at Brigham and Women’s Hospital Internal Medicine Residency and Dana-Farber Cancer Institute Hematology/Oncology Fellowship. Dr. Week performed her postdoctoral research in the laboratory of Dr. Benjamin L. Ebert where her work focused on three domains: (1) understanding the relationship between inflammatory disease phenotypes and clonal hematopoiesis; (2) developing clinically useful prognostic algorithms for CH which predict adverse clinical outcomes; and (3) clinical trials of therapeutic interventions in CH to prevent adverse malignant and non-malignant outcomes. Her work has led to the development of the clonal hematopoiesis risk score (CHRS), the first clinically validated prognostic model for CH. Dr. Weeks is also a champion of equity in hematology and has developed programming on health equity and anti-racism in medicine for the American Society of Hematology and Brigham and Women’s Hospital. Dr. Weeks’s work is supported by the Robert Wood Johnson Foundation Harold Amos Faculty Development Award, the Edward P. Evans Foundation and the Wood Foundation.
Lukasz Gondek, MD, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLab: Eradicating Minimal Residual Disease in AML and Targeting Clonal Hematopoiesis to Prevent AML
Lukasz Gondek, MD, PhD is an Assistant Professor of Oncology at the Johns Hopkins University School of Medicine in the Division of Hematologic Malignancies. Dr. Gondek received his medical degree from the University of Silesia, Poland and his Ph.D. from the University of Warsaw, Poland. Following his post-doctoral training at the Cleveland Clinic, he completed residency in internal medicine at the Cleveland Clinic and his fellowship training in hematology at the Johns Hopkins University. His academic research focuses on cancer genomics as well as cancer stem cell biology in bone marrow failures and myeloid malignancies. His most recent work is focused on the biology and clinical consequences of clonal hematopoiesis.
Martin Aryee, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Martin Aryee is an institute member of the Broad Institute of MIT and Harvard, an associate professor in the Department of Data Sciences at Dana-Farber Cancer Institute (DFCI), and director of hematologic malignancies, biostatistics and computational biology at DFCI. He holds a secondary appointment as an assistant professor in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health, where he teaches an introductory course in statistical genetics. Aryee is also a recipient of the Merkin Institute Fellowship at the Broad.
The Aryee lab develops statistical analysis methods for studying the genetic and epigenetic basis of cancer and other diseases. Most of their work has focused on improving our understanding of how aberrations in the physical and chemical structure of DNA within the nucleus are linked to cancer and other common diseases. Projects range from basic biology, to probing how DNA misfolds in cancer cells, to clinical applications aiming to develop blood tests for early detection of cancer. His lab also develops tools that aim to enable the safe translation of gene editing techniques such as CRISPR into human therapeutics.
Martin earned an M.Eng. in electronic engineering at Imperial College London, and an M.Sc. in neuroscience at King’s College London. He earned his Ph.D. in biostatistics from the Harvard T.H. Chan School of Public Health.
Maximilian Stahl, MD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Stahl is a member of the Adult Leukemia Group at Dana-Farber Cancer Institute and an Instructor of Medicine at Harvard Medical School. His research focus is on early phase clinical trials in myeloid malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
He authored and co-authored more than 60 peer reviewed publications and has presented his research in multiple national and international meetings. He has received the ASCO Conquer Cancer Foundation Young Investigator Award, the ASH HONORS Award and several ASH Abstract Achievement Awards. He is a member of the Editorial Board of Leukemia & Lymphoma and serves as an ad hoc reviewer for several journals including Blood, Blood Advances, Clinical Cancer Research, the British Journal of Haematology and Haematologica.
He graduated from Hannover Medical School in Hannover, Germany. He then received his internal medicine residency training at the Yale School of Medicine where he also served as a chief medical resident. He then completed his Hematology and Oncology fellowship training at the Memorial Sloan Kettering Cancer Center in New York City.
Omar Abdel-Wahab, MD
Memorial Sloan Kettering Cancer Center
TeamLab: Eradicating Minimal Residual Disease in AML and Targeting Clonal Hematopoiesis to Prevent AML
Omar Abdel-Wahab, MD, is the Edward P. Evans Chair in MDS at Memorial Sloan Kettering Cancer Center where he also serves as Chair of the Molecular Pharmacology Program in the Sloan Kettering Institute. His clinical areas of expertise are in myeloid malignancies, chronic lymphocytic leukemia, and rare forms of leukemias including hairy cell leukemia, CMML, BPDCN, and histiocytoses. Dr. Abdel-Wahab completed his undergraduate studies and M.D. at Duke University followed by Internal Medicine residency at the Massachusetts General Hospital. He then joined MSK in 2007 as a Fellow in Hematology/Medical Oncology and joined as independent faculty member in 2012. Over the last ten years, his laboratory has been focused on understanding alterations in the process of RNA splicing in cancer. Motivated by the discovery of high frequency mutations in the splicing machinery in leukemias and certain solid tumors, his lab’s work has led to the development of several therapeutic approaches for these genetic subtypes of cancer which are currently in phase 1/2 clinical trials. In addition, his laboratory has performed a number of studies of molecular genetics and genomics of blood cancers more broadly and used this information to develop novel therapeutic approaches for myeloid and lymphoid hematologic cancers. He has received several honors, including the Seldin-Smith Award for Pioneering Research from the American Society of Clinical Investigation, the Joanne Levy Memorial Award for Outstanding Achievement from the American Society of Hematology, and the Pershing Square Sohn Prize for Young Investigators in Cancer Research.
Roger Belizaire, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Roger Belizaire, MD, PhD is an Assistant Professor of Pathology at Harvard Medical School with appointments at the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Boston Children’s Hospital. He is an Associate Medical Director in the Division of Transfusion Medicine at the Brigham and Women’s Hospital. He obtained his bachelor’s degree from Princeton University and his MD and PhD in immunology from Washington University School of Medicine. He received his training in Clinical Pathology and Transfusion Medicine at Brigham and Women’s Hospital and Harvard Medical School. He performed his postdoctoral training in the laboratory of Benjamin Ebert, MD, PhD at the Dana-Farber Cancer Institute. He has received funding from the American Society of Hematology, the American Cancer Society, and the NIH/NCI. Dr. Belizaire is a laboratory-based investigator in the Department of Pathology at the Dana-Farber Cancer Institute where his research focuses on oncogenic signaling and targeted therapies in myeloid malignancies.
Simona Colla
The University of Texas MD Anderson Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Simona Colla is a tenured associate professor in MD Anderson Cancer Center’s Department of Leukemia, where she runs a research laboratory that includes 7 people. Her current research aims are to 1) dissect the biological mechanisms of MDS progression to acute myeloid leukemia; 2) discover novel therapeutic approaches to target MDS at the early stage; and 3) develop new therapeutic approaches to overcome anemia induced by SF3B1 mutations in MDS.
In the last 5 years, her studies have been published in extremely high-impact journals, including Cancer Cell, Nature Communications, Nature Medicine, Blood Cancer Discovery, and Cell Reports Medicine.
Wenbin Xiao, MD, PhD
Memorial Sloan Kettering Cancer Center
TeamLab: Eradicating Minimal Residual Disease in AML, Targeting Clonal Hematopoiesis to Prevent AML
Wenbin Xiao, MD, PhD, is an assistant Member and attending of the Department of Pathology and Laboratory Medicine at the MSKCC. Dr. Xiao received MD/PhD degree from Peking University and performed postdoctoral research at La Jolla Institute for Immunology. He then completed his residency training in Pathology at Case Western Reserve University and Hematopathology Fellowship training at the NCI under Elaine Jaffe before joining MSKCC as a faculty. His clinical research includes disease discovery, classification and risk stratification of acute myeloid leukemia (AML). His laboratory research focuses on the pathogenesis of RUNX1 mutations in myeloid neoplasm and the characterization of measurable residual disease (MRD) at single cell levels in AML. He is a recipient of NCI K08 award, Early Career Investigator Award from RUNX1 foundation, and Berard-Dorfman Founders Young Investigator Award from the Society for Hematopathology.
Zuzana Tothova, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Tothova is an Assistant Professor of Medicine at Harvard Medical School, Associate Member of the Broad Institute, Investigator in the Department of Medical Oncology and the Division of Hematologic Neoplasia at the Dana-Farber Cancer Institute, and principal faculty in the Harvard Stem Cell Institute. Dr. Tothova received her B.A. in Biology and Chemistry from Williams College, a doctorate in Genetics from Harvard University, and an M.D. from Harvard Medical School/MIT in the Health Sciences and Technology program. She completed residency training in internal medicine at the Brigham and Women’s Hospital and fellowship training in adult hematology and oncology at the Dana-Farber Cancer Institute and MGH Cancer Center. Dr. Tothova carried out her postdoctoral work in Dr. Benjamin Ebert’s laboratory at the Broad Institute where she studied mechanisms of cohesin mutations in myelodysplastic syndrome and acute myeloid leukemia. She started her own laboratory at the Dana-Farber Cancer Institute in July 2018. The primary focus of her group is investigation of the biology, genetics and treatment of myeloid malignancies, including the premalignant state of clonal hematopoiesis (CHIP), MDS and AML. In particular, Dr. Tothova’s lab aims to contribute to our understanding of the effect of chromatin organization on hematopoietic stem cell (HSC) transformation in the context of different epigenetic modulators recurrently mutated in myeloid malignancies with the goal to identify novel therapeutic targets that can be translated to true patient benefit in the future. She is a recipient of multiple career development awards from the American Society of Hematology, Leukemia and Lymphoma Society, the Conquer Cancer Foundation of the American Society of Clinical Oncology, RUNX1 Foundation/Alex’s Lemonade Stand, Doris Duke charitable Foundation, the Burroughs Wellcome Fund, and the National Institutes of Health.
MEET THE TEAM
The Targeting Clonal Hematopoiesis TeamLab comprises both rising stars and established thought leaders in the fields of hematology, bioinformatics, immunology, and cellular biology. Indeed, many of these researchers were involved in the original discovery of CH and the early investigations into its clinical and biological implications.
Together, they and their institutions have formed a robust clinical, basic science, and translational ecosystem with specific expertise in disease modeling, single cell technology, computational analytics, clinical identification and management of CH patients, community partnership and engagement, and clinical trials. Moreover, a planned collaboration with pharmaceutical industry partners will provide access to novel therapeutics with minimal toxicity for early intervention clinical trials.
We invite you to learn about the institutions and individual investigators driving this pioneering scientific and clinical research collaboration.
View Team
Alex K. Shalek, PhD
Amy DeZern
Benjamin Ebert, MD, PhD
Danielle Hammond, MD
Eytan M. Stein, MD
Gabriel Ghiaur, MD, PhD
Gregory A. Abel, MD, MPH
Jairo Matthews
Jeffrey Molldrem, MD
Kelly Chien, MD
Ken Chen, PhD
Koichi Takahashi, MD, PhD
Lachelle Dawn Weeks, MD, PhD
Lukasz Gondek, MD, PhD
Martin Aryee, PhD
Maximilian Stahl, MD
Omar Abdel-Wahab, MD
Roger Belizaire, MD, PhD
Simona Colla
Wenbin Xiao, MD, PhD
Zuzana Tothova, MD, PhD
Alex K. Shalek, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab(s): Conquering KRAS in Pancreatic Cancer, Demystifying Pancreatic Cancer Therapies, Eradicating Minimal Residual Disease in AML<, Targeting Clonal Hematopoiesis to Prevent AML, The Data Science Hub
Alex K. Shalek, PhD, is a Core Member of the Institute for Medical Engineering and Science (IMES), an Associate Professor of Chemistry, and an Extramural Member of MIT’s Koch Institute for Integrative Cancer Research. He is also an Institute Member of the Broad Institute, a Member of the Ragon Institute, an Assistant in Immunology at MGH, and an Instructor in Health Sciences and Technology at HMS. Dr. Shalek received his bachelor’s degree summa cum laude from Columbia University and his PhD from Harvard University in chemical physics under the guidance of Hongkun Park, and performed postdoctoral training under Hongkun Park and Aviv Regev (Broad/MIT). His lab’s research is directed towards the development and application of new approaches to elucidate cellular and molecular features that inform tissue-level function and dysfunction across the spectrum of human health and disease. Dr. Shalek and his work have received numerous honors including a NIH New Innovator Award, a Beckman Young Investigator Award, a Searle Scholar Award, a Pew-Stewart Scholar Award, the Avant-Garde (DP1 Pioneer) Award from the National Institute for Drug Abuse (NIDA), and an Alfred P. Sloan Research Fellowship in Chemistry, as well as the 2019-2020 Harold E. Edgerton Faculty Achievement Award at MIT and the 2020 HMS Young Mentor Award.
Amy DeZern
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Amy DeZern is a hematologist and an Associate Professor of Oncology and Medicine at the Johns Hopkins University School of Medicine. Dr. DeZern’s primary clinical and research interests are focused on bone marrow failure disorders. She has expertise in the diagnosis and treatment of aplastic anemia (AA), myelodysplastic syndromes (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) as well as acute leukemias. All of these are disorders of clonal hematopoiesis. She is an active clinician scientist who specializes in clinical trials of diagnostics and therapeutics for these disorders. She has been the principle investigator for over 40 single-center and multicenter clinical trials in MDS and AA. These investigator-led initiatives focus is on transplant therapies in AA (including the upcoming BMT CTN upfront trial for SAA) and novel therapeutics (Phase 1-3 trials) in MDS and clonal cytopenias. Additionally, Dr. DeZern is the deputy co-chair of The National MDS Study.
Benjamin Ebert, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Benjamin Ebert is the Chair of Medical Oncology at the Dana-Farber Cancer Institute, the George P. Canellos, MD and Jean S. Canellos Professor of Medicine at Harvard Medical School, a Howard Hughes Medical Institute Investigator. The Ebert laboratory focuses on the molecular basis and treatment of hematologic malignancies and its non-malignant precursor conditions, with a particular focus on myelodysplastic syndromes (MDS) and clonal hematopoiesis. The Ebert laboratory demonstrated that lenalidomide, a derivative of thalidomide, binds the CRL4-CRBN E3 ubiquitin ligase and induces degradation of specific substrates. Subsequent research has examined novel mechanisms of drug-induced protein degradation that expand the spectrum of protein substrates that can be targeted pharmacologically. Dr. Ebert received a bachelor’s degree from Williams College and a doctorate from Oxford University. He completed an M.D. from Harvard Medical School, a residency in internal medicine at Massachusetts General Hospital, and a fellowship in hematology/oncology at the Dana-Farber Cancer Institute. He received the William Dameshek Prize from the American Society of Hematology, the Meyenburg Prize for Cancer Research, the Sjöberg Prize from the Royal Swedish Academy of Sciences, and the Korsmeyer Award from the American Society for Clinical Investigation.
Danielle Hammond, MD
The University of Texas MD Anderson Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Danielle Hammond, MD, is an Assistant Professor in the Department of Leukemia, Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center (MDACC). She received her M.D. degree from The University of Ottawa. She is a graduate of the University of Toronto Internal Medicine Core Residency and completed her Adult Hematology Residency at Queen’s University in Kingston, Canada. She is board-certified with The Royal College of Physicians and Surgeons of Canada in both Adult Hematology and Internal Medicine and subsequently completed a Leukemia Fellowship at the MDACC, serving as Chief Leukemia Fellow 2020-2021. Dr. Hammond is a member of the MDS Section at the MDACC, likely the largest clinical MDS program of its kind in the world. She is the co-leader of the Clonal Hematopoiesis and Leukemia Prevention Clinic there, which focuses on identifying, counseling, and investigating ways to prevent progression in individuals at highest risk of developing hematologic malignancies, particularly therapy related myeloid neoplasms. Dr. Hammond’s work also focuses on the intersection of chronic inflammation and the pathogenesis of progression of myeloid malignancies. She is the recent recipient of American Society of Hematology (ASH) and American Society of Clinical Oncology Abstract Achievement Awards. Dr. Hammond also enjoys medical education writing, serving for 3 years as an editor and contributor to The Microenvironment, a Canadian Hematology Society publication, and writing for the 2020 ASH News Daily.
Eytan M. Stein, MD
Memorial Sloan Kettering Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Eytan M. Stein, MD is the Chief of the Leukemia Service, Associate Attending Physician, Clinical Investigator, and Director of the Program for Drug Development in Leukemia on the Leukemia Service at Memorial Sloan Kettering Cancer Center. He conducts novel, phase I clinical trials of compounds that target the genetic and epigenetic basis of myeloid malignancies. Dr. Stein led the clinical studies of the IDH2 inhibitor Enasidenib and the IDH1 Inhibitor Ivosidenib in patients with relapsed and refractory AML that led to their FDA approval in 2017 and 2018, respectively. He also leads a variety of phase 1 clinical trials and serves as the lead investigator at Memorial Sloan Kettering for the BEAT AML master clinical trial. His current research focuses on elucidating mechanisms of resistance to IDH inhibitors and the use of Menin inhibitors in patients with MLL-rearranged acute leukemia. His work has been published in journals such as Nature, Nature Medicine, The New England Journal of Medicine, JAMA Oncology, Cancer Discovery and Blood. In addition, he serves on the Editorial Boards of Blood and Leukemia and Lymphoma.
Gabriel Ghiaur, MD, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Gabriel Ghiaur, M.D., PhD. is an Associate Professor of Oncology and Medicine with a strong fundamental research interest in hematopoiesis and a clinical focus on the biology of acute leukemia and minimal residual disease. Dr. Ghiaur has received his medical degree from UMF Carol Davila, Bucharest, Romania and his Ph.D. in Molecular and Developmental Biology from University of Cincinnati under the guidance of Dr. David Williams. After completing his clinical training in hematology at Johns Hopkins, he joined the Adult Leukemia Program at Johns Hopkins. The Ghiaur Laboratory is focused on investigating how the bone marrow microenvironment controls stem biology with an eye towards better understanding of normal stem cell behavior as well as persistence of minimal residual disease in hematological malignancies. Using a combination of cell biology techniques and single cell genomic and transcriptomic tools as well as access to primary human tissue and innovative patient derived xenograft models, the Ghiaur Lab aims to develop and test clinical tools that target the bone marrow microenvironment to mitigate hematopoietic aging and to improve outcomes hematological malignancies. Dr. Ghiaur has been the recipient of various honors, including the Passano Clinician Scientist Award and the American Society of Clinical Investigator Young Physician Scientist Award and he was elected as an Ambassador Alumni of UMF Carol Davila.
Gregory A. Abel, MD, MPH
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Gregory A. Abel, MD, MPH is an outcomes researcher and hematologic oncologist at Dana-Farber Cancer Institute (DFCI). His research applies health services methods to understand the experiences of patients with cancer, and to answer questions about the effectiveness of their care. He is also interested in evaluating how intensive cancer therapy affects quality of life; developing innovations to address disparities in care; and understanding the bioethics of cancer care delivery. He primarily focusses on the hematologic malignancies, studying the impact of these diseases and their treatment from diagnosis to the end of life. He also runs DFCI’s Older Adult Hematologic Malignancy (OHM) geriatric research program and serves as Chair of the DFCI Ethics Advisory Committee.
Jairo Matthews
The University of Texas MD Anderson Cancer Center
TeamLab(s): Eradicating Minimal Residual Disease in AML,Targeting Clonal Hematopoiesis to Prevent AML
Jairo Matthews is a Program Director of the MDACC leukemia tissue biorepository. He received his bachelor’s degree from the University of Michigan, and gained experience working in the U of M Cancer Center tissue bank for Head and Neck cancer. He later moved to Houston and has been with the Leukemia department under the guidance of Steven Kornblau for over a decade. He serves as a link between trial study managers, attending physicians, lab PIs and personnel, and leukemia sample bank personnel. He recently received an MDACC Division of Cancer Medicine award for Excellence in Clinical Research.
Jeffrey Molldrem, MD
The University of Texas MD Anderson Cancer Center
TeamLab(s): Eradicating Minimal Residual Disease in AML, Targeting Clonal Hematopoiesis to Prevent AML
Dr. Molldrem is a physician scientist and joined the Stem Cell Transplantation and Cellular Therapy Department of The University of Texas MD Anderson Cancer Center in 1997. He is a Professor of Medicine and Virginia H. Cockrell Distinguished Professor in Immunology, and Chair of the Department of Hematopoietic Biology and Malignancy. He also serves as Scientific Director of Oncology Research for Biologics and Immunotherapy Translation (ORBIT) platform and as Institute Director and Head of Evolution of Cancer, Leukemia, and Immunity Post Stem cEll transplant (ECLIPSE) platform. He received his medical degree from the University of Minnesota in 1990, trained in internal medicine at UCLA, and completed fellowship in hematology and medical oncology at the National Institutes of Health and Johns Hopkins. The long-term goals of his lab are to understand how adaptive immunity against hematopoietic malignancies is mediated and regulated, and to develop novel immunotherapies that target these malignancies. His laboratory has been working on T cell-mediated anti-leukemia GVL immunity for more than 25 years with continuous NIH funding. Leveraging a large longitudinal biorepository of transplant donor and recipients, his lab is studying the coevolution and clonal architecture of AML and adaptive immunity using next generation deep sequencing and multi-omic approaches.
Kelly Chien, MD
The University of Texas MD Anderson Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Kelly S. Chien, MD is an Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center and co-lead of the Clonal Hematopoiesis/Leukemia Prevention Clinic. She received her undergraduate degrees in chemical engineering and biology from the Massachusetts Institute of Technology and medical degree from Baylor College of Medicine, completed residency training at The University of Texas Southwestern Medical Center at Dallas, and graduated from hematology/medical oncology fellowship at MD Anderson. Her research is focused on not only clonal hematopoiesis and leukemia prevention, but also relapsed/refractory myelodysplastic syndrome after hypomethylating agent therapy. Dr. Chien was awarded the 2019 American Society of Clinical Oncology Conquer Cancer Foundation Young Investigator Award, 2020 Waun Ki Hong Award in Clinical Investigation at MD Anderson, 2020 Kimberly Patterson Fellowship in Leukemia Research at MD Anderson, and 2022 Waun Ki Hong Award for Excellence in Team Science as part of the Clonal Hematopoiesis Team at MD Anderson.
Ken Chen, PhD
The University of Texas MD Anderson Cancer Center
TeamLab(s): Eradicating Minimal Residual Disease in AML, Targeting Clonal Hematopoiesis to Prevent AML
Ken Chen, PhD, is a professor in Bioinformatics and Computational Biology, the Director of Bioinformatics of Institute of Personalized Cancer Therapy at the MD Anderson Cancer Center (MDACC), co-director of CPRIT single-cell genomics core. He also holds adjunct faculty position in Department of Systems Biology at MDACC and in Department of Computer Science at Rice University. He has a background in machine learning and statistical data analytics with extensive experience developing and applying computational tools to analyze large-scale high-throughput experimental data, towards detection, discovery, interpretation, modeling, and prediction. Over the past 18 years, he has led the development over 10 computational methods/tools such as BreakDancer, novoBreak (ranked #1 in DREAM 8.5 Challenges), Texomer, TransVar, Monovar, SCMER, and bindSC, which have been published in top journals such as Nature Methods, and have been widely used by computational biology, statistical genetics, single-cell, systems biology, and cancer personalized therapy communities. Meanwhile, He has been actively involved in major cancer research initiatives, such as 1000 Genomes, TCGA, ICGC, CTD2, HCA, and HTAN. His research group at MDACC is interested in developing cutting-edge data scientific capacity for quantitative characterization of cancer as a complex system and for identification of molecular targets useful for personalized diagnosis and medicine.
Koichi Takahashi, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Koichi Takahashi, MD, PhD, is an Associate Professor in the Departments of Leukemia and Genomic Medicine at The University of Texas MD Anderson Cancer Center. Dr. Takahashi received MD degree from Niigata University in Japan and PhD degree from Kyoto University Japan. He did internal medicine residency in Toranomon Hospital, Tokyo and Beth Israel Medical Center in New York. He completed Hematology and Oncology Fellowship at MD Anderson. He is board certified in Internal Medicine, Hematology, and Medical Oncology. He did research fellowship in Drs. Lynda Chin and Andrew Futreal Lab. His research focuses on studying etiology, pathogenesis and clinical phenotype of hematologic malignancies and pre-malignancies by understanding the underlying genetic underpinnings, heterogeneity and evolution through application of state-of-the-art genomics and single-cell technologies coupled with computational analytics. Dr. Takahashi is a recipient of ASH Scholar Award and LLS Scholar Award.
Lachelle Dawn Weeks, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Lachelle D. Weeks is a hematologist and scientist at Dana-Farber Cancer Institute in the division of hematologic malignancies and an Instructor of Medicine Harvard Medical School. She is a graduate of Case Western Reserve University School of Medicine where she earned her MD and PhD degrees. She completed her medical training at Brigham and Women’s Hospital Internal Medicine Residency and Dana-Farber Cancer Institute Hematology/Oncology Fellowship. Dr. Week performed her postdoctoral research in the laboratory of Dr. Benjamin L. Ebert where her work focused on three domains: (1) understanding the relationship between inflammatory disease phenotypes and clonal hematopoiesis; (2) developing clinically useful prognostic algorithms for CH which predict adverse clinical outcomes; and (3) clinical trials of therapeutic interventions in CH to prevent adverse malignant and non-malignant outcomes. Her work has led to the development of the clonal hematopoiesis risk score (CHRS), the first clinically validated prognostic model for CH. Dr. Weeks is also a champion of equity in hematology and has developed programming on health equity and anti-racism in medicine for the American Society of Hematology and Brigham and Women’s Hospital. Dr. Weeks’s work is supported by the Robert Wood Johnson Foundation Harold Amos Faculty Development Award, the Edward P. Evans Foundation and the Wood Foundation.
Lukasz Gondek, MD, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLab: Eradicating Minimal Residual Disease in AML and Targeting Clonal Hematopoiesis to Prevent AML
Lukasz Gondek, MD, PhD is an Assistant Professor of Oncology at the Johns Hopkins University School of Medicine in the Division of Hematologic Malignancies. Dr. Gondek received his medical degree from the University of Silesia, Poland and his Ph.D. from the University of Warsaw, Poland. Following his post-doctoral training at the Cleveland Clinic, he completed residency in internal medicine at the Cleveland Clinic and his fellowship training in hematology at the Johns Hopkins University. His academic research focuses on cancer genomics as well as cancer stem cell biology in bone marrow failures and myeloid malignancies. His most recent work is focused on the biology and clinical consequences of clonal hematopoiesis.
Martin Aryee, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Martin Aryee is an institute member of the Broad Institute of MIT and Harvard, an associate professor in the Department of Data Sciences at Dana-Farber Cancer Institute (DFCI), and director of hematologic malignancies, biostatistics and computational biology at DFCI. He holds a secondary appointment as an assistant professor in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health, where he teaches an introductory course in statistical genetics. Aryee is also a recipient of the Merkin Institute Fellowship at the Broad.
The Aryee lab develops statistical analysis methods for studying the genetic and epigenetic basis of cancer and other diseases. Most of their work has focused on improving our understanding of how aberrations in the physical and chemical structure of DNA within the nucleus are linked to cancer and other common diseases. Projects range from basic biology, to probing how DNA misfolds in cancer cells, to clinical applications aiming to develop blood tests for early detection of cancer. His lab also develops tools that aim to enable the safe translation of gene editing techniques such as CRISPR into human therapeutics.
Martin earned an M.Eng. in electronic engineering at Imperial College London, and an M.Sc. in neuroscience at King’s College London. He earned his Ph.D. in biostatistics from the Harvard T.H. Chan School of Public Health.
Maximilian Stahl, MD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Stahl is a member of the Adult Leukemia Group at Dana-Farber Cancer Institute and an Instructor of Medicine at Harvard Medical School. His research focus is on early phase clinical trials in myeloid malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
He authored and co-authored more than 60 peer reviewed publications and has presented his research in multiple national and international meetings. He has received the ASCO Conquer Cancer Foundation Young Investigator Award, the ASH HONORS Award and several ASH Abstract Achievement Awards. He is a member of the Editorial Board of Leukemia & Lymphoma and serves as an ad hoc reviewer for several journals including Blood, Blood Advances, Clinical Cancer Research, the British Journal of Haematology and Haematologica.
He graduated from Hannover Medical School in Hannover, Germany. He then received his internal medicine residency training at the Yale School of Medicine where he also served as a chief medical resident. He then completed his Hematology and Oncology fellowship training at the Memorial Sloan Kettering Cancer Center in New York City.
Omar Abdel-Wahab, MD
Memorial Sloan Kettering Cancer Center
TeamLab: Eradicating Minimal Residual Disease in AML and Targeting Clonal Hematopoiesis to Prevent AML
Omar Abdel-Wahab, MD, is the Edward P. Evans Chair in MDS at Memorial Sloan Kettering Cancer Center where he also serves as Chair of the Molecular Pharmacology Program in the Sloan Kettering Institute. His clinical areas of expertise are in myeloid malignancies, chronic lymphocytic leukemia, and rare forms of leukemias including hairy cell leukemia, CMML, BPDCN, and histiocytoses. Dr. Abdel-Wahab completed his undergraduate studies and M.D. at Duke University followed by Internal Medicine residency at the Massachusetts General Hospital. He then joined MSK in 2007 as a Fellow in Hematology/Medical Oncology and joined as independent faculty member in 2012. Over the last ten years, his laboratory has been focused on understanding alterations in the process of RNA splicing in cancer. Motivated by the discovery of high frequency mutations in the splicing machinery in leukemias and certain solid tumors, his lab’s work has led to the development of several therapeutic approaches for these genetic subtypes of cancer which are currently in phase 1/2 clinical trials. In addition, his laboratory has performed a number of studies of molecular genetics and genomics of blood cancers more broadly and used this information to develop novel therapeutic approaches for myeloid and lymphoid hematologic cancers. He has received several honors, including the Seldin-Smith Award for Pioneering Research from the American Society of Clinical Investigation, the Joanne Levy Memorial Award for Outstanding Achievement from the American Society of Hematology, and the Pershing Square Sohn Prize for Young Investigators in Cancer Research.
Roger Belizaire, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Roger Belizaire, MD, PhD is an Assistant Professor of Pathology at Harvard Medical School with appointments at the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Boston Children’s Hospital. He is an Associate Medical Director in the Division of Transfusion Medicine at the Brigham and Women’s Hospital. He obtained his bachelor’s degree from Princeton University and his MD and PhD in immunology from Washington University School of Medicine. He received his training in Clinical Pathology and Transfusion Medicine at Brigham and Women’s Hospital and Harvard Medical School. He performed his postdoctoral training in the laboratory of Benjamin Ebert, MD, PhD at the Dana-Farber Cancer Institute. He has received funding from the American Society of Hematology, the American Cancer Society, and the NIH/NCI. Dr. Belizaire is a laboratory-based investigator in the Department of Pathology at the Dana-Farber Cancer Institute where his research focuses on oncogenic signaling and targeted therapies in myeloid malignancies.
Simona Colla
The University of Texas MD Anderson Cancer Center
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Simona Colla is a tenured associate professor in MD Anderson Cancer Center’s Department of Leukemia, where she runs a research laboratory that includes 7 people. Her current research aims are to 1) dissect the biological mechanisms of MDS progression to acute myeloid leukemia; 2) discover novel therapeutic approaches to target MDS at the early stage; and 3) develop new therapeutic approaches to overcome anemia induced by SF3B1 mutations in MDS.
In the last 5 years, her studies have been published in extremely high-impact journals, including Cancer Cell, Nature Communications, Nature Medicine, Blood Cancer Discovery, and Cell Reports Medicine.
Wenbin Xiao, MD, PhD
Memorial Sloan Kettering Cancer Center
TeamLab: Eradicating Minimal Residual Disease in AML, Targeting Clonal Hematopoiesis to Prevent AML
Wenbin Xiao, MD, PhD, is an assistant Member and attending of the Department of Pathology and Laboratory Medicine at the MSKCC. Dr. Xiao received MD/PhD degree from Peking University and performed postdoctoral research at La Jolla Institute for Immunology. He then completed his residency training in Pathology at Case Western Reserve University and Hematopathology Fellowship training at the NCI under Elaine Jaffe before joining MSKCC as a faculty. His clinical research includes disease discovery, classification and risk stratification of acute myeloid leukemia (AML). His laboratory research focuses on the pathogenesis of RUNX1 mutations in myeloid neoplasm and the characterization of measurable residual disease (MRD) at single cell levels in AML. He is a recipient of NCI K08 award, Early Career Investigator Award from RUNX1 foundation, and Berard-Dorfman Founders Young Investigator Award from the Society for Hematopathology.
Zuzana Tothova, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Targeting Clonal Hematopoiesis to Prevent AML
Dr. Tothova is an Assistant Professor of Medicine at Harvard Medical School, Associate Member of the Broad Institute, Investigator in the Department of Medical Oncology and the Division of Hematologic Neoplasia at the Dana-Farber Cancer Institute, and principal faculty in the Harvard Stem Cell Institute. Dr. Tothova received her B.A. in Biology and Chemistry from Williams College, a doctorate in Genetics from Harvard University, and an M.D. from Harvard Medical School/MIT in the Health Sciences and Technology program. She completed residency training in internal medicine at the Brigham and Women’s Hospital and fellowship training in adult hematology and oncology at the Dana-Farber Cancer Institute and MGH Cancer Center. Dr. Tothova carried out her postdoctoral work in Dr. Benjamin Ebert’s laboratory at the Broad Institute where she studied mechanisms of cohesin mutations in myelodysplastic syndrome and acute myeloid leukemia. She started her own laboratory at the Dana-Farber Cancer Institute in July 2018. The primary focus of her group is investigation of the biology, genetics and treatment of myeloid malignancies, including the premalignant state of clonal hematopoiesis (CHIP), MDS and AML. In particular, Dr. Tothova’s lab aims to contribute to our understanding of the effect of chromatin organization on hematopoietic stem cell (HSC) transformation in the context of different epigenetic modulators recurrently mutated in myeloid malignancies with the goal to identify novel therapeutic targets that can be translated to true patient benefit in the future. She is a recipient of multiple career development awards from the American Society of Hematology, Leukemia and Lymphoma Society, the Conquer Cancer Foundation of the American Society of Clinical Oncology, RUNX1 Foundation/Alex’s Lemonade Stand, Doris Duke charitable Foundation, the Burroughs Wellcome Fund, and the National Institutes of Health.
PROJECT SUMMARY
Much of the progress in decreasing cancer morbidity and mortality has come from early detection and prevention efforts. Detection of clonal hematopoiesis (CH), a pre-malignant state for AML, may offer the potential to identify individuals at greatest risk of developing the disease and to shift the paradigm of AML care towards prevention.
CH is caused by leukemogenic mutations in hematopoietic cells, leading to an expanded clone of blood cells and increased risk for blood cancers, in addition to other inflammatory disorders. Therefore, the team hypothesizes that if scientists can develop ways to halt expansion of—or even eradicate—premalignant clones, then AML risk could be significantly reduced. Residual CH following AML treatment, which is a harbinger of disease relapse, might also be reduced.
There are several hurdles to pursuing those goals. First, most CH-related mutations are not directly targetable for treatment. Second, there are currently no lab models of CH in humans, making it impossible to learn about CH cell biology. Third, researchers have not yet developed clearly defined surrogate endpoints for evaluating the effectiveness of early interventions targeting CH. Finally, there has not previously been a consortium of institutions with sufficiently large numbers of patients to effectively identify suitable candidate drugs for clinical trials.
This project seeks to address these hurdles by expeditiously identifying novel vulnerabilities created by factors such as CH cells’ genomic alterations, micro-environmental interactions, and immunologic signals. The researchers will then use novel lab models of human CH cells to target these vulnerabilities with potential therapeutic interventions intended to prevent AML; and they will leverage the clinical resources of four CH-focused clinical centers to build an effective cohort of patients to participate in powerful clinical trials.
The Targeting Clonal Hematopoiesis TeamLab is pursuing three primary aims.
The first aim focuses on the biology of CH: using genetic engineering technologies in human stem and progenitor cells—as well as an array of scientific approaches pioneered by TeamLab members—to develop and benchmark robust models of CH. The researchers will also use human cell models of CH to perform CRISPR/Cas9 screens that will help identify genetic dependencies in the condition.
The second aim seeks to understand and target immunologic alterations in CH. Building on the investigators’ previous discoveries of aberrant inflammation in CH patients, the project will examine the immune microenvironment in CH, determine immunologic mechanisms essential for CH expansion, and identify clone-specific novel antigens as potential therapeutic targets.
The third aim is to develop the resources necessary to support a Phase I trial of therapeutic intervention in high-risk CH. Leveraging the capacities of the collaborating institutions’ CH clinics, the researchers will prospectively collect samples from a representative population of patients with CH, creating a diverse and deeply annotated biobank. This resource will support validation of CH risk stratification models—as well as the project’s preclinical studies on CH biology and immunologic alternations. Leveraging the results of that work, a planned multi-institutional Phase I trial could determine the feasibility of systemic therapy designed to improve blood counts and to reduce clonal expansion in patients with high-risk CH.
Ultimately, the TeamLab’s pursuit of these aims will bridge critical gaps in the current understanding of the biologic and immunologic dependences of CH clonal evolution. And it will establish a diverse and representative patient cohort to enable the swift translation of preclinical findings into early detection and prevention clinical trials.
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