REVOLUTIONIZING GBM DRUG DEVELOPMENT THROUGH SERIAL BIOPSIES
The 5-year survival rate for Glioblastoma is dismal: <10% for the 13,000 GBM patients diagnosed each year in the United States. The only therapeutics for GBM approved by the FDA in the past 30 years have shown little to no survival benefit.
The 5-year survival rate for Glioblastoma is dismal: <10% for the 13,000 GBM patients diagnosed each year in the United States. The only therapeutics for GBM approved by the FDA in the past 30 years have shown little to no survival benefit.
PROJECT HIGHLIGHTS
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- Therapeutic development for glioblastoma (GBM) has been stunted following several large and expensive phase III clinical trials that failed, despite encouraging preliminary results.
- A central challenge is the complexity of the human brain, which cannot be modeled perfectly in the laboratory.
- The Revolutionizing GBM Drug Development Through Serial Biopsies project will demonstrate the safety and feasibility of carefully performed serial biopsies, while in parallel assessing how promising new therapies directly affect these brain tumors. The team will investigate whether samples of cerebrospinal fluid and/or blood from patients may provide surrogate markers of drug activity.
- The objective of the project is to establish a new paradigm of therapy development for GBM by utilizing longitudinal biopsies in the same patient to determine which therapies are successfully delivered to the tumor and exert an intended effect—two major hurdles which have historically hindered therapeutic advances.
- The extraordinary level of funding support from Break Through Cancer, highly unusual in GBM research, will be essential to overcoming many financial and logistical barriers to converting the vision of longitudinal tumor sampling into a reality.
MEET THE TEAM
Adrienne Boire, MD, PhD
Betty Kim, MD, PhD
Chetan Bettegowda, MD, PhD
Christopher Douville, PhD
David A. Reardon, MD
E. Antonio (Nino) Chiocca, MD, PhD
Emma Dyer, MS
Forest White, PhD
Franziska Michor, PhD
Jian Hu, PhD
Kadir Akdemir, PhD
Keith Ligon, MD, PhD
Kenny Yu, MBBS, PhD, FRCS
Manuel Schuerch, PhD
Mesut Unal, PhD
Michael J. Cima, PhD
Nathalie Y.R. Agar, PhD
Padmanee Sharma, MD, PhD
Rameen Beroukhim, MD, PhD
Ryuhjin Ahn, PhD
Sangeeta Goswami, MD, PhD
Shahab Sarmashghi, PhD
Shiao-Pei Weathers, MD
Siri Palreddy
Sreyashi Basu, PhD
Stuart Levine, PhD
Vinay K. Puduvalli, MD
Viviane Tabar, MD
Wen Jiang, MD, PhD
Adrienne Boire, MD, PhD
Memorial Sloan Kettering Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Adrienne Boire, MD, PhD is the Geoffrey Beene Junior Faculty Chair at Memorial Sloan Kettering Cancer Center in New York. As a neuro-oncologist, she cares for patients with metastasis to the central nervous system (CNS), with particular focus on leptomeningeal metastasis. As a scientist, she runs a laboratory-based research program focused on the biology of the leptomeningeal space. Her team employs multi-omic analysis of human samples to identify cell adaptations to the challenging microenvironment of the leptomeninges. Leveraging mouse models, the team uncovers the mechanistic implications of these discoveries to establish novel therapies for CNS malignancies.
Betty Kim, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Betty Kim, MD, PhD, is an Associate Professor in the Department of Neurosurgery at MD Anderson. Dr. Kim’s clinical interests include brain surgery for primary and secondary tumors. Her research focuses on the design of novel immune nanomedicine and immunotherapy strategies to engage innate immune cells. Her lab has also developed advanced bioimaging platforms that enable the tracking and characterization of specific immune interactions within the brain, in vivo. Her research has resulted in multiple patents. Her work has been published in numerous high-impact journals such as New England Journal of Medicine, Nature, Nature Nanotechnology, and Nature Biomedical Engineering. Her research is supported by the NIH and the Department of Defense.
Chetan Bettegowda, MD, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Chetan Bettegowda is the Jennison and Novak Families Professor of Neurosurgery at Johns Hopkins Medicine and the Vice Chair for Research for the Department of Neurosurgery. He is a surgeon scientist whose research is focused on understanding the genetic underpinnings of central nervous system (CNS) cancers. His clinical practice is dedicated to caring for individuals with brain tumors. He and his group have discovered several of the key driver genes involved in the pathogenesis of myriad of CNS cancers. Dr. Bettegowda has also been focused on translating these genetic discoveries for translational benefit by applying them for the earlier detection of cancers. He and his group have published several of the seminal papers in liquid biopsies including a landmark study demonstrating the wide applicability of circulating tumor DNA for the detection and monitoring of cancers throughout the body. He has also published extensively on non-plasma- based diagnostics for cancer detection.
Christopher Douville, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLabs: Revolutionizing GBM Drug Development Through Serial Biopsies
Christopher Douville, PhD finished his doctoral work under the direction of Dr. Rachel Karchin in the Department of Biomedical Engineering at Johns Hopkins. His graduate work focused on developing machine learning methods to interpret inherited and somatic genetic variation. He then completed a post-doctoral fellowship in the Ludwig Center at Johns Hopkins under the guidance of Drs Bert Vogelstein and Ken Kinzler where his research focused on designing novel molecular diagnostics for the earlier detection of cancer. Currently, his group combines machine learning and next generation sequencing to develop improved computational algorithms and molecular diagnostics. They have successfully applied their techniques for various earlier detection applications including multi-cancer early detection in blood, early detection of CNS cancers in cerebral spinal fluid, progression of Barrett’s esophagus, and progression of extraovarian lesions to ovarian cancer.
David A. Reardon, MD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
David Reardon, MD is the Clinical Director of Dana-Farber Cancer Institute’s Center for Neuro-Oncology. His research efforts focus on preclinical drug development and early clinical trials including first-in-man, as well as phase I and II studies. Dr. Reardon is particularly interested in evaluating promising agents for patients with newly diagnosed as well as recurrent primary and metastatic tumors of the central nervous system. His lab has concentrated on a broad spectrum of therapeutics, including molecular inhibitors against key mediators of cell signaling pathways regulating proliferation, survival, invasion, and angiogenesis of CNS tumors, cytotoxic agents, and immunotherapeutics. Dr. Reardon’s current preclinical and clinical trial efforts focus on a range of immunotherapy reagents including novel vaccine approaches and immune checkpoint inhibitors for neuro-oncology.
E. Antonio (Nino) Chiocca, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Chiocca is the Harvey Cushing Professor of Neurosurgery at Harvard Medical School and is the Chairman of Neurosurgery at the Brigham and Women’s Hospital. He was previously Chairman of the Department of Neurosurgery at The Ohio State University Medical Center. He has been continuously funded by the NIH since 1996. He has more than 250 peer-reviewed publications, some in journals such as Nature Medicine, Nature Biotechnology, Molecular Cell, and PNAS. He has elucidated how viruses with specific gene mutations will replicate selectively in tumors with a specific defect in a tumor suppressor pathway. He has also shown how modulation of innate immunity will improve replication of these tumor-selective viruses. More recently, he has elucidated how specific microRNAs (mir128 and mir451) regulate cellular target transcripts to permit tumor cell self-renewal and invasion into brain. He has been PI of three multi-institutional clinical trials of gene and viral therapies for malignant gliomas. He has been a permanent member of NIH study sections (NCI DT and NCI P01-D clinical studies), and a member of the federal recombinant DNA Advisory Committee (RAC/OBA) and of the NINDS Scientific Advisory Council. In 2013, he was elected Vice President of the Society for Neuro-Oncology (SNO). He was President of SNO from 2015-2017 and President of the American Academy of Neurological Surgery (2018-2019). He is currently the Secretary of the American Association of Neurological Surgery. He also serves on the scientific advisory board of several foundations (Sontag and American Brain Tumor Association). He received The Grass Award in 2007, the Farber Award in 2008, the Bittner Award in 2013, and the Gerlas Award in 2016. He was elected to the American Society for Clinical Investigation (2005), is an AAAS fellow (2005) and was also elected to the National Academy of Medicine (formerly Institute of Medicine) in 2014. In 2018, he received the Charles B. Wilson Career Achievement Award from the CNS/AANS Section on Tumors and the Victor Levin Award for Achievement in neuro-oncology from SNO. He also has served on multiple editorial boards and is the current Tumor Section Editor for Neurosurgery and Associate Editor for Neuro-oncology. He was on the editorial board of Journal of Neurosurgery from 2005 until 2012.
Emma Dyer, MS
Dana-Farber Cancer Institute
TeamLabs: Revolutionizing GBM Drug Development Through Serial Biopsies, The Data Science Hub
Emma C. Dyer is a PhD student in the Harvard Biological Sciences in Public Health program studying in the laboratory of Dr. Franziska Michor at the Dana Farber Cancer Institute. She received her Bachelor’s and Master’s degrees from The University of Chicago where she studied Biological Sciences and Bioinformatics. She completed her Master’s work under the supervision of Dr. Alexander Pearson with a focus in computational pathology. Her work applied deep learning models for biomarker identification and survival prediction of patients with head and neck cancers. Currently she applies spatial statistics and deep learning methods to spatial multi-omics datasets to study tumor evolution and heterogeneity.
Forest White, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Forest White, PhD is the Ned C. and Janet Bemis Rice Professor of Biological Engineering in the Department of Biological Engineering at the Massachusetts Institute of Technology (MIT). After receiving his PhD from Florida State University in 1997 and completing a post-doc at the University of Virginia from 1997-1999, he joined MDS Proteomics as a Senior Research Scientist and developed phosphoproteomics capabilities for the company. In July 2003 he joined the Department of Biological Engineering at MIT. Research in the White lab is focused on understanding how protein phosphorylation-mediated signaling networks regulate normal and pathophysiological cell biology. Specific applications include novel drug target discovery in glioblastoma and melanoma, analysis of mechanisms underlying therapeutic resistance and metastasis in cancer, and mechanisms underlying development of neurodegenerative diseases, as well as Type II diabetes. In addition to his appointment in the Department of Biological Engineering, Forest is a member of MIT’s Koch Institute for Integrative Cancer Research.
Franziska Michor, PhD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Michor is a Professor of Computational Biology in the Department of Data Science at Dana-Farber Cancer Institute, in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health, and in the Department of Stem Cell and Regenerative Biology at Harvard University. Dr. Michor obtained her undergraduate training in mathematics and molecular biology from the University of Vienna, Austria, and her PhD from the Department of Organismic and Evolutionary Biology at Harvard University. Afterwards, she was awarded a fellowship from the Harvard Society of Fellows. From 2007 until 2010, she was an Assistant Professor in the Computational Biology Program at Memorial Sloan-Kettering Cancer Center. Dr. Michor is the director of Dana-Farber Cancer Institute’s Center for Cancer Evolution. She has been the recipient of the Theodosius Dobzhansky Prize of the Society for the Study of Evolution, the Alice Hamilton Award, the Vilcek Prize for Creative Promise in Biomedical Science, the 36th Annual AACR Award for Outstanding Achievement in Cancer Research, and others. Dr. Michor’s laboratory investigates the evolutionary dynamics of cancer initiation, progression, response to therapy, and emergence of resistance.
Jian Hu, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Hu received his PhD from UNC Chapel Hill. He did his postdoctoral training with Dr. Ronald DePinho at Dana-Farber Cancer Institute. He is currently an associate professor in the Department of Cancer Biology at The University of Texas MD Anderson Cancer Center.
Kadir Akdemir, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Akdemir is a computational biologist in the departments of Neurosurgery and Genomic Medicine at The University fo Texas MD Anderson Cancer Center. His research focuses on investigating the chromatin organization and genomic instability in human cancer types.
Keith Ligon, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Ligon, MD, PhD is a principal investigator and neuropathologist at the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School. His laboratory is focused on understanding the biology of glioma treatment resistance and discovery of novel diagnostic approaches in cancer. His lab has specific expertise in analysis of patient tissue samples, patient derived models, and translational science of clinical trials.
Kenny Yu, MBBS, PhD, FRCS
Memorial Sloan Kettering Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Kenny Yu is a neurosurgeon-scientist at Memorial Sloan Kettering Cancer Center. He did his residency training in the United Kingdom and obtained a PhD from the University of Manchester in glioma associated macrophages, and was awarded a National Institute of Health Research (UK) clinical lectureship and starter grant by the Academy of Medical Sciences. He was subsequently awarded the Dowager Countess Eleanor Peel Travelling Tellowship to pursue post-doctoral research in the laboratory of Peter Dirks at the Hospital for Sick Children in Toronto, Canada. After obtaining his UK board certification, he went on to complete a research and clinical subspecialty fellowship in neurosurgical oncology at Memorial Sloan Kettering Cancer Center before joining the faculty in 2021. As a promising young investigator, he will be closely involved with the planning and execution of clinical and scientific GBM TeamLab projects for Break Through Cancer.
Manuel Schuerch, PhD
Dana-Farber Cancer Institute
TeamLabs: Revolutionizing GBM Drug Development Through Serial Biopsies, The Data Science Hub
Manuel Schuerch, PhD, is a Postdoctoral Fellow at Dana-Farber Cancer Institute in the Department of Data Science.
Manuel has a diverse background in Machine Learning, Statistics, and a range of biomedical applications. He earned his Bachelor’s degree in Computer Science and a Master’s in Statistics from ETH Zurich, Switzerland, followed by a PhD in Machine Learning from USI Lugano, Switzerland. Afterward, he pursued postdoctoral research at UZH and USZ Zurich, where he developed machine learning methods for personalized decision support in fields such as rheumatology, ICU care, diabetes, delirium, immunology, oncology, and solid organ transplantation. Currently, at Dana-Farber Cancer Institute, Manuel’s research focuses on designing advanced machine learning and AI models to analyze biomedical data, particularly for cancer progression models, perturbation effects, and multi-omics cancer data integration. His technical expertise and interest span probabilistic modeling, generative time series, counterfactual treatment effect estimation, uncertainty quantification, explainable AI, and foundational AI models in biomedicine. Manuel’s work is driven by the goal of advancing AI methods for personalized medicine, with applications in oncology, organ transplantation, and beyond.
Mesut Unal, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Mesut Unal, PhD, is a Postdoctoral Researcher in the departments of Genomic Medicine at The University of Texas MD Anderson Cancer Center. He received his bachelor’s degree from Middle East Technical University and his PhD from The University of Texas at Austin. His research focuses on investigating the chromatin organization and genomic instability in human cancer types with DNN models.
Michael J. Cima, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Michael J. Cima, PhD is a Professor of Materials Science and Engineering at the Massachusetts Institute of Technology and has an appointment at MIT’s Koch Institute for Integrative Cancer Research. He earned a BsS in chemistry in 1982 (Phi Beta Kappa) and a PhD in chemical engineering in 1986, both from the University of California at Berkeley. Dr. Cima joined the MIT faculty in 1986 as an Assistant Professor. He was promoted to full Professor in 1995. Professor Cima was elected to the National Academy of Engineering in 2011 and to the National Academy of Inventors in 2016. He now holds the David H. Koch Professor of Engineering at MIT. Professor Cima is author or co-author of over three hundred peer-reviewed scientific publications, fifty US patents, and is a recognized expert in the field of medical devices and materials processing. Professor Cima is actively involved in materials and engineered systems for improvement in human health, such as treatments for cancer, metabolic diseases, trauma, and urological disorders. His research concerns advanced forming technology such as for complex macro and micro devices, colloid science, MEMS, and other micro components for medical devices that are used for drug delivery and diagnostics, high-throughput development methods for formulations of materials and, pharmaceutical formulations.
Nathalie Y.R. Agar, PhD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Nathalie Y.R. Agar, PhD is the Daniel E. Ponton Distinguished Chair in Neurosurgery at Brigham and Women’s Hospital and Associate Professor of Neurosurgery and of Radiology at Harvard Medical School. Dr. Agar’s multidisciplinary training includes a BSc in Biochemistry, PhD in Chemistry, a postdoctoral fellowship in Neurology and Neurosurgery from McGill University, and further postdoctoral training in Neurosurgery at BWH/HMS. From this unique background, she has developed distinct skills to address unmet analytical needs in the clinical environment. Her research focuses on the development and implementation of integrated biomolecular and drug imaging of tissue specimens. Her laboratory focuses on the mass spectrometry imaging of drugs and metabolism from pre-clinical animal models and clinical trial specimens to study therapeutics for brain tumors. She is also developing and validating real time mass spectrometry approaches to support surgical decision making. Her overall goals are to enable surgeons and oncologists to tailor treatment from the time of surgery, support the development of new therapeutics, and allow precision cancer care using molecular imaging with mass spectrometry approaches.
Padmanee Sharma, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Sharma is a nationally and internationally renowned physician scientist whose research work is focused on investigating mechanisms and pathways within the immune system that facilitate tumor rejection or elicit resistance to immune checkpoint therapy. She is a Professor in the departments of Genitourinary Medical Oncology and Immunology, and the T.C. and Jeanette D. Hsu Endowed Chair in Cell Biology at The University of Texas MD Anderson Cancer Center. She is also the inaugural Scientific Director for the Immunotherapy Platform and the Co-director of the Parker Institute for Cancer Immunotherapy at The University of Texas MD Anderson Cancer Center. She is a member of the American Society for Clinical Investigation (ASCI). She received the Emil Frei III Award for Excellence in Translational Research in 2016, the Coley Award for Distinguished Research for Tumor Immunology in 2018, the Women in Science with Excellence (WISE) award in 2020, the Heath Memorial Award in 2021, and the Randall Prize for Excellence in Cancer Research in 2021. In 2006, Dr. Sharma designed and conducted the first neoadjuvant (pre-surgical) trial, also known as a window-of-opportunity trial, with immune checkpoint therapy (anti-CTLA-4, ipilimumab), which allowed her to establish safety of the neoadjuvant approach for immune checkpoint therapy as well as provide tumor tissues for translational research studies. She identified the ICOS/ICOSL pathway as a novel target for cancer immunotherapy strategies. The neoadjuvant clinical trial in 2006 was also the first trial with immune checkpoint therapy in patients with bladder cancer. The clinical data indicated that 25% of patients had significant anti-tumor responses with pathologic complete responses. These data led Dr. Sharma to conduct additional clinical trials with immune checkpoint therapy (anti-PD-1, nivolumab) for patients with bladder cancer, which enabled FDA-approval of nivolumab as treatment for patients with metastatic bladder cancer. Dr. Sharma also led the clinical trials with immune checkpoint therapy (nivolumab and nivolumab plus ipilimumab) in patients with metastatic renal cell carcinoma (RCC), which led to FDA-approval of these agents as treatment for patients with RCC. Dr. Sharma is the Principal Investigator for multiple immunotherapy clinical trials. Her studies have identified novel resistance mechanisms, including loss of interferon (IFN) signaling, VISTA+ immunosuppressive cells, increased EZH2 expression in T cells, TGFb signaling in bone metastases, and CD73+ myeloid cells in GBM. Her work continues to drive the development of immunotherapy strategies for the treatment of cancer patients.
Rameen Beroukhim, MD, PhD
Dana-Farber Cancer Institute
TeamLabs: Intercepting Ovarian Cancer, The Data Science Hub, and Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Beroukhim is a practicing neuro-oncologist whose research focus is to understand tumor evolution, with emphases on brain tumors and alterations in chromosome structure. This work spans computational methods development, genomic studies of human cancers, and experiments in model systems. In early work describing integrated genomic profiling of glioblastomas, he developed the Genomic Identification of Significant Targets In Cancer (GISTIC) method that is now widely used to analyze copy-number changes across a range of cancers. He has also contributed to the development of several other genomic analysis methods and has led integrated genomic profiling efforts in multiple cancer types, including pan-cancer analyses across thousands of tumors. This work has identified novel mechanisms by which cancers develop and progress, and novel cancer dependencies that have spurred the development of new cancer therapeutics.
Ryuhjin Ahn, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Using phosphoproteomics, systems and molecular biology approaches, Ryuhjin seeks to understand the balance between pro- and anti-tumorigenic immune responses that are regulated by the interplay of microglia and brain cancer.
Sangeeta Goswami, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Sangeeta Goswami is an Assistant Professor at MD, PhD Anderson Cancer Center with a background in medical oncology and immunology. She is involved in patient care, conducting clinical trials, as well as in translational and discovery science research. Her laboratory focuses on understanding the epigenetic regulation of immune suppression in the tumor microenvironment to develop rational combinatorial strategies of immunotherapies and epigenetic modulators in a tumor-specific manner.
Shahab Sarmashghi, PhD
Dana-Farber Cancer Institute
TeamLab(s): The Data Science Hub, Revolutionizing GBM Drug Development Through Serial Biopsies
Shahab Sarmashghi, PhD, is a Postdoctoral Associate at the Broad Institute of MIT and Harvard and a Research Fellow at Dana-Farber Cancer Institute and HMS. He earned his BS and MS degrees from Sharif University of Technology, Iran, and his PhD from UC San Diego in Electrical Engineering. During his PhD, he developed several methods to utilize low-pass whole genome sequencing to study eukaryotic genomes. In the Beroukhim lab, Dr. Sarmashghi is interested in developing computational methods to study the biology of tumors, in particular GBM, and identify novel therapeutic targets. His main focus is on understanding positive and negative selection in cancer using somatic copy number alterations. He is also interested in studying cancer dependencies caused by loss of chromosome arms. He also works on developing new copy number calling pipelines and deploying them to the cloud.
Shiao-Pei Weathers, MD
The University of Texas MD Anderson Cancer Center
TeamLab: Investigating Longitudinal Sampling in Glioblastoma
Dr. Weathers is a neuro-oncologist with clinical research experience in primary brain tumors, specifically gliomas, at The University of Texas MD Anderson Cancer Center in Houston, Texas. Her clinical background has afforded her the opportunity to treat a diverse primary brain tumor patient population. This exposure has provided her with a unique perspective on the integration of novel treatment strategies, both pharmacologic and non-pharmacologic, in the management of patients with gliomas. She has contributed to clinical research in gliomas by acting as either PI or co-investigator for a number of clinical trials for patients with newly diagnosed glioblastoma and recurrent glioblastoma. Aside from developing new protocol concepts with targeted therapies, immunotherapy including cellular therapies, or other rationale combination treatment strategies, she has also been involved and served as PI in conducting research evaluating symptom burden and quality of life in patients with gliomas. In her role as a clinical researcher, she collaborates with multiple researchers from different departments to develop unique, multidisciplinary treatment approaches to improve survival and quality of life for patients with gliomas. Dr. Weathers serves as the Director of the MD Anderson Neuro-Oncology Fellowship Program, Clinical Medical Director for the Brain and Spine Center, and Director of MD Anderson’s brain tumor support group named MD Anderson BEST (Brain tumor Education and Support Together).
Siri Palreddy
Dana-Farber Cancer Institute
TeamLabs: The Data Science Hub, Intercepting Ovarian Cancer,Revolutionizing GBM Drug Development Through Serial Biopsies, Conquering KRAS in Pancreatic Cancer, Demystifying Pancreatic Cancer Therapies
Siri Palreddy is a Clinical Research Coordinator for Dana-Farber Cancer Institute and works across the Break Through Cancer TeamLabs. She recently graduated magna cum laude from Amherst College, holding a BA in Biology and English.
Sreyashi Basu, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Sreyashi Basu, PhD is a Research Group Leader at MD Anderson Cancer Center. Dr Basu co-directs human immune monitoring group of Immunotherapy platform at MDACC under the guidance of Drs Padmanee Sharma and James Allison. She earned her doctorate degree in Immunology and completed her postdoctoral training at University of Connecticut Health Center. Dr Basu is an innovative biomedical scientist, passionate about newer technologies and implementing them in her research. Her research experience is in immunology, neuro-immuno-oncology and autoimmunity. Dr. Basu manages a group of scientists involved with immunogenomic profiling to study the changes in immune cell phenotypes in response to therapy and to identify predictive biomarkers of therapeutic benefit. Her group identified CD73+ immunosuppressive myeloid cells as a resistance mechanism to immune checkpoint therapy in GBM.
Stuart Levine, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab(s): Revolutionizing GBM Drug Development Through Serial Biopsies
, The Data Science Hub
Stuart S. Levine, PhD, is the director of the MIT BioMicro Center and co-leader of the Koch Institute Integrated Genomics and Bioinformatics core facility. Dr. Levine received his bachelor’s degree from MIT and his PhD from Harvard University under the guidance of Robert Kingston, and performed postdoctoral training under Richard Young (Whitehead Institute). The Integrated Genomics and Bioinformatics core provides MIT researchers with facilities for high-throughput data-intensive genomics and bioinformatic analysis, as well as large-scale database storage, management, data mining and data modeling required to fully implement systems approaches to investigate a broad spectrum of biological problems. Dr Levine is currently president of the Northeast Regional Laboratory Staff and Core Directors, a chapter of the Association of Biomolecular Resource Facilities.
Vinay K. Puduvalli, MD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Vinay K. Puduvalli is Professor and Chair of the Department of Neuro-Oncology at the University of Texas MD Anderson Cancer Center, and Co-Director of the MD Anderson Brain Tumor Center and holds the Beau Biden Endowed Chair in Brain Cancer Research. He serves as the leader of the MD Anderson Brain Cancer Core Grant Program and as co-leader of the GBM Moonshot Project. Dr. Puduvalli’s research focuses on patient-oriented research to develop new treatments for brain malignancies using a combined approach of targeted therapies, innovative clinical trial designs, and rational combinations of anticancer agents. His clinical expertise includes care of patients with brain and spine malignancies, as well as neurological complications of cancer. His laboratory research focuses on identifying vulnerabilities in gliomas that can overcome tumor heterogeneity in order to target these with novel agents using a variety of pre-clinical models. His team has also identified novel ways to target stress response and energy metabolism in gliomas to specifically target tumor cells while sparing normal ones. In a translational context, he has led several institutional and multicenter clinical studies involving epigenetic therapies and novel targeted agents. He has served as a mentor for students, residents, fellows, junior, and senior faculty over the past 2 decades. He serves in national leadership roles in the Society of Neurooncology and has served on advisory boards, review boards, and study sections for national and international federal and industry agencies.
Viviane Tabar, MD
Memorial Sloan Kettering Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Viviane Tabar, MD is the Chair of the Department of Neurosurgery and the Theresa C Feng Professor in Neurosurgical Oncology at Memorial Sloan Kettering Cancer Center in New York. She is a neurosurgeon with expertise in brain tumors, and a scientist with a focus on stem cell biology.
Dr. Tabar’s surgical practice is focused on primary brain tumors and tumors of the skull base. Her research includes the development of cell-based therapies for neurological disorders, using human pluripotent stem cells. This portfolio includes strategies for repairing radiation and chemotherapy induced brain injury and the development of human pluripotent stem cell-derived dopamine neurons for Parkinson’s disease, currently in a Phase I clinical trial. Her lab has also studies glioma biology and has pioneered the use of human embryonic stem cell-based models of brain tumors, with a focus on histone-mutant high grade glioma in the pediatric and young adult patients. She has received several honors and awards from the International Society for Stem Cell Research, the New York Academy of Medicine and the American Association of Neurological Surgeons and was elected to the membership of the American Society for Clinical Investigation and the Society of Neurological Surgeons. Dr. Tabar is also member of the National Academy of Medicine. She serves on the advisory board of Cell Stem Cell.
Wen Jiang, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Wen Jiang, MD, PhD is an Assistant Professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center. He received his PhD in Biomedical Engineering at the University of Toronto and MD from Stanford School of Medicine. He completed his residency training in Radiation Oncology at MD Anderson Cancer in 2018 and was recruited to UT Southwestern as a tenure-track Assistant Professor of Radiation Oncology and a CPRIT Scholar. He returned to MD Anderson in 2021, where he treats patients with primary and metastatic CNS tumors. As a physician scientist, Dr. Jiang’s laboratory research aims to identify ways to promote innate immunity as a new strategy to eliminate brain cancer. Dr. Jiang’s research is supported by multiple grant funding from the NCI, NINDS, DOD, CPRIT, and the Susan G. Komen Foundation.
MEET THE TEAM
See Team
Adrienne Boire, MD, PhD
Betty Kim, MD, PhD
Chetan Bettegowda, MD, PhD
Christopher Douville, PhD
David A. Reardon, MD
E. Antonio (Nino) Chiocca, MD, PhD
Emma Dyer, MS
Forest White, PhD
Franziska Michor, PhD
Jian Hu, PhD
Kadir Akdemir, PhD
Keith Ligon, MD, PhD
Kenny Yu, MBBS, PhD, FRCS
Manuel Schuerch, PhD
Mesut Unal, PhD
Michael J. Cima, PhD
Nathalie Y.R. Agar, PhD
Padmanee Sharma, MD, PhD
Rameen Beroukhim, MD, PhD
Ryuhjin Ahn, PhD
Sangeeta Goswami, MD, PhD
Shahab Sarmashghi, PhD
Shiao-Pei Weathers, MD
Siri Palreddy
Sreyashi Basu, PhD
Stuart Levine, PhD
Vinay K. Puduvalli, MD
Viviane Tabar, MD
Wen Jiang, MD, PhD
Adrienne Boire, MD, PhD
Memorial Sloan Kettering Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Adrienne Boire, MD, PhD is the Geoffrey Beene Junior Faculty Chair at Memorial Sloan Kettering Cancer Center in New York. As a neuro-oncologist, she cares for patients with metastasis to the central nervous system (CNS), with particular focus on leptomeningeal metastasis. As a scientist, she runs a laboratory-based research program focused on the biology of the leptomeningeal space. Her team employs multi-omic analysis of human samples to identify cell adaptations to the challenging microenvironment of the leptomeninges. Leveraging mouse models, the team uncovers the mechanistic implications of these discoveries to establish novel therapies for CNS malignancies.
Betty Kim, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Betty Kim, MD, PhD, is an Associate Professor in the Department of Neurosurgery at MD Anderson. Dr. Kim’s clinical interests include brain surgery for primary and secondary tumors. Her research focuses on the design of novel immune nanomedicine and immunotherapy strategies to engage innate immune cells. Her lab has also developed advanced bioimaging platforms that enable the tracking and characterization of specific immune interactions within the brain, in vivo. Her research has resulted in multiple patents. Her work has been published in numerous high-impact journals such as New England Journal of Medicine, Nature, Nature Nanotechnology, and Nature Biomedical Engineering. Her research is supported by the NIH and the Department of Defense.
Chetan Bettegowda, MD, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Chetan Bettegowda is the Jennison and Novak Families Professor of Neurosurgery at Johns Hopkins Medicine and the Vice Chair for Research for the Department of Neurosurgery. He is a surgeon scientist whose research is focused on understanding the genetic underpinnings of central nervous system (CNS) cancers. His clinical practice is dedicated to caring for individuals with brain tumors. He and his group have discovered several of the key driver genes involved in the pathogenesis of myriad of CNS cancers. Dr. Bettegowda has also been focused on translating these genetic discoveries for translational benefit by applying them for the earlier detection of cancers. He and his group have published several of the seminal papers in liquid biopsies including a landmark study demonstrating the wide applicability of circulating tumor DNA for the detection and monitoring of cancers throughout the body. He has also published extensively on non-plasma- based diagnostics for cancer detection.
Christopher Douville, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
TeamLabs: Revolutionizing GBM Drug Development Through Serial Biopsies
Christopher Douville, PhD finished his doctoral work under the direction of Dr. Rachel Karchin in the Department of Biomedical Engineering at Johns Hopkins. His graduate work focused on developing machine learning methods to interpret inherited and somatic genetic variation. He then completed a post-doctoral fellowship in the Ludwig Center at Johns Hopkins under the guidance of Drs Bert Vogelstein and Ken Kinzler where his research focused on designing novel molecular diagnostics for the earlier detection of cancer. Currently, his group combines machine learning and next generation sequencing to develop improved computational algorithms and molecular diagnostics. They have successfully applied their techniques for various earlier detection applications including multi-cancer early detection in blood, early detection of CNS cancers in cerebral spinal fluid, progression of Barrett’s esophagus, and progression of extraovarian lesions to ovarian cancer.
David A. Reardon, MD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
David Reardon, MD is the Clinical Director of Dana-Farber Cancer Institute’s Center for Neuro-Oncology. His research efforts focus on preclinical drug development and early clinical trials including first-in-man, as well as phase I and II studies. Dr. Reardon is particularly interested in evaluating promising agents for patients with newly diagnosed as well as recurrent primary and metastatic tumors of the central nervous system. His lab has concentrated on a broad spectrum of therapeutics, including molecular inhibitors against key mediators of cell signaling pathways regulating proliferation, survival, invasion, and angiogenesis of CNS tumors, cytotoxic agents, and immunotherapeutics. Dr. Reardon’s current preclinical and clinical trial efforts focus on a range of immunotherapy reagents including novel vaccine approaches and immune checkpoint inhibitors for neuro-oncology.
E. Antonio (Nino) Chiocca, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Chiocca is the Harvey Cushing Professor of Neurosurgery at Harvard Medical School and is the Chairman of Neurosurgery at the Brigham and Women’s Hospital. He was previously Chairman of the Department of Neurosurgery at The Ohio State University Medical Center. He has been continuously funded by the NIH since 1996. He has more than 250 peer-reviewed publications, some in journals such as Nature Medicine, Nature Biotechnology, Molecular Cell, and PNAS. He has elucidated how viruses with specific gene mutations will replicate selectively in tumors with a specific defect in a tumor suppressor pathway. He has also shown how modulation of innate immunity will improve replication of these tumor-selective viruses. More recently, he has elucidated how specific microRNAs (mir128 and mir451) regulate cellular target transcripts to permit tumor cell self-renewal and invasion into brain. He has been PI of three multi-institutional clinical trials of gene and viral therapies for malignant gliomas. He has been a permanent member of NIH study sections (NCI DT and NCI P01-D clinical studies), and a member of the federal recombinant DNA Advisory Committee (RAC/OBA) and of the NINDS Scientific Advisory Council. In 2013, he was elected Vice President of the Society for Neuro-Oncology (SNO). He was President of SNO from 2015-2017 and President of the American Academy of Neurological Surgery (2018-2019). He is currently the Secretary of the American Association of Neurological Surgery. He also serves on the scientific advisory board of several foundations (Sontag and American Brain Tumor Association). He received The Grass Award in 2007, the Farber Award in 2008, the Bittner Award in 2013, and the Gerlas Award in 2016. He was elected to the American Society for Clinical Investigation (2005), is an AAAS fellow (2005) and was also elected to the National Academy of Medicine (formerly Institute of Medicine) in 2014. In 2018, he received the Charles B. Wilson Career Achievement Award from the CNS/AANS Section on Tumors and the Victor Levin Award for Achievement in neuro-oncology from SNO. He also has served on multiple editorial boards and is the current Tumor Section Editor for Neurosurgery and Associate Editor for Neuro-oncology. He was on the editorial board of Journal of Neurosurgery from 2005 until 2012.
Emma Dyer, MS
Dana-Farber Cancer Institute
TeamLabs: Revolutionizing GBM Drug Development Through Serial Biopsies, The Data Science Hub
Emma C. Dyer is a PhD student in the Harvard Biological Sciences in Public Health program studying in the laboratory of Dr. Franziska Michor at the Dana Farber Cancer Institute. She received her Bachelor’s and Master’s degrees from The University of Chicago where she studied Biological Sciences and Bioinformatics. She completed her Master’s work under the supervision of Dr. Alexander Pearson with a focus in computational pathology. Her work applied deep learning models for biomarker identification and survival prediction of patients with head and neck cancers. Currently she applies spatial statistics and deep learning methods to spatial multi-omics datasets to study tumor evolution and heterogeneity.
Forest White, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Forest White, PhD is the Ned C. and Janet Bemis Rice Professor of Biological Engineering in the Department of Biological Engineering at the Massachusetts Institute of Technology (MIT). After receiving his PhD from Florida State University in 1997 and completing a post-doc at the University of Virginia from 1997-1999, he joined MDS Proteomics as a Senior Research Scientist and developed phosphoproteomics capabilities for the company. In July 2003 he joined the Department of Biological Engineering at MIT. Research in the White lab is focused on understanding how protein phosphorylation-mediated signaling networks regulate normal and pathophysiological cell biology. Specific applications include novel drug target discovery in glioblastoma and melanoma, analysis of mechanisms underlying therapeutic resistance and metastasis in cancer, and mechanisms underlying development of neurodegenerative diseases, as well as Type II diabetes. In addition to his appointment in the Department of Biological Engineering, Forest is a member of MIT’s Koch Institute for Integrative Cancer Research.
Franziska Michor, PhD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Michor is a Professor of Computational Biology in the Department of Data Science at Dana-Farber Cancer Institute, in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health, and in the Department of Stem Cell and Regenerative Biology at Harvard University. Dr. Michor obtained her undergraduate training in mathematics and molecular biology from the University of Vienna, Austria, and her PhD from the Department of Organismic and Evolutionary Biology at Harvard University. Afterwards, she was awarded a fellowship from the Harvard Society of Fellows. From 2007 until 2010, she was an Assistant Professor in the Computational Biology Program at Memorial Sloan-Kettering Cancer Center. Dr. Michor is the director of Dana-Farber Cancer Institute’s Center for Cancer Evolution. She has been the recipient of the Theodosius Dobzhansky Prize of the Society for the Study of Evolution, the Alice Hamilton Award, the Vilcek Prize for Creative Promise in Biomedical Science, the 36th Annual AACR Award for Outstanding Achievement in Cancer Research, and others. Dr. Michor’s laboratory investigates the evolutionary dynamics of cancer initiation, progression, response to therapy, and emergence of resistance.
Jian Hu, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Hu received his PhD from UNC Chapel Hill. He did his postdoctoral training with Dr. Ronald DePinho at Dana-Farber Cancer Institute. He is currently an associate professor in the Department of Cancer Biology at The University of Texas MD Anderson Cancer Center.
Kadir Akdemir, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Akdemir is a computational biologist in the departments of Neurosurgery and Genomic Medicine at The University fo Texas MD Anderson Cancer Center. His research focuses on investigating the chromatin organization and genomic instability in human cancer types.
Keith Ligon, MD, PhD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Ligon, MD, PhD is a principal investigator and neuropathologist at the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School. His laboratory is focused on understanding the biology of glioma treatment resistance and discovery of novel diagnostic approaches in cancer. His lab has specific expertise in analysis of patient tissue samples, patient derived models, and translational science of clinical trials.
Kenny Yu, MBBS, PhD, FRCS
Memorial Sloan Kettering Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Kenny Yu is a neurosurgeon-scientist at Memorial Sloan Kettering Cancer Center. He did his residency training in the United Kingdom and obtained a PhD from the University of Manchester in glioma associated macrophages, and was awarded a National Institute of Health Research (UK) clinical lectureship and starter grant by the Academy of Medical Sciences. He was subsequently awarded the Dowager Countess Eleanor Peel Travelling Tellowship to pursue post-doctoral research in the laboratory of Peter Dirks at the Hospital for Sick Children in Toronto, Canada. After obtaining his UK board certification, he went on to complete a research and clinical subspecialty fellowship in neurosurgical oncology at Memorial Sloan Kettering Cancer Center before joining the faculty in 2021. As a promising young investigator, he will be closely involved with the planning and execution of clinical and scientific GBM TeamLab projects for Break Through Cancer.
Manuel Schuerch, PhD
Dana-Farber Cancer Institute
TeamLabs: Revolutionizing GBM Drug Development Through Serial Biopsies, The Data Science Hub
Manuel Schuerch, PhD, is a Postdoctoral Fellow at Dana-Farber Cancer Institute in the Department of Data Science.
Manuel has a diverse background in Machine Learning, Statistics, and a range of biomedical applications. He earned his Bachelor’s degree in Computer Science and a Master’s in Statistics from ETH Zurich, Switzerland, followed by a PhD in Machine Learning from USI Lugano, Switzerland. Afterward, he pursued postdoctoral research at UZH and USZ Zurich, where he developed machine learning methods for personalized decision support in fields such as rheumatology, ICU care, diabetes, delirium, immunology, oncology, and solid organ transplantation. Currently, at Dana-Farber Cancer Institute, Manuel’s research focuses on designing advanced machine learning and AI models to analyze biomedical data, particularly for cancer progression models, perturbation effects, and multi-omics cancer data integration. His technical expertise and interest span probabilistic modeling, generative time series, counterfactual treatment effect estimation, uncertainty quantification, explainable AI, and foundational AI models in biomedicine. Manuel’s work is driven by the goal of advancing AI methods for personalized medicine, with applications in oncology, organ transplantation, and beyond.
Mesut Unal, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Mesut Unal, PhD, is a Postdoctoral Researcher in the departments of Genomic Medicine at The University of Texas MD Anderson Cancer Center. He received his bachelor’s degree from Middle East Technical University and his PhD from The University of Texas at Austin. His research focuses on investigating the chromatin organization and genomic instability in human cancer types with DNN models.
Michael J. Cima, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Michael J. Cima, PhD is a Professor of Materials Science and Engineering at the Massachusetts Institute of Technology and has an appointment at MIT’s Koch Institute for Integrative Cancer Research. He earned a BsS in chemistry in 1982 (Phi Beta Kappa) and a PhD in chemical engineering in 1986, both from the University of California at Berkeley. Dr. Cima joined the MIT faculty in 1986 as an Assistant Professor. He was promoted to full Professor in 1995. Professor Cima was elected to the National Academy of Engineering in 2011 and to the National Academy of Inventors in 2016. He now holds the David H. Koch Professor of Engineering at MIT. Professor Cima is author or co-author of over three hundred peer-reviewed scientific publications, fifty US patents, and is a recognized expert in the field of medical devices and materials processing. Professor Cima is actively involved in materials and engineered systems for improvement in human health, such as treatments for cancer, metabolic diseases, trauma, and urological disorders. His research concerns advanced forming technology such as for complex macro and micro devices, colloid science, MEMS, and other micro components for medical devices that are used for drug delivery and diagnostics, high-throughput development methods for formulations of materials and, pharmaceutical formulations.
Nathalie Y.R. Agar, PhD
Dana-Farber Cancer Institute
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Nathalie Y.R. Agar, PhD is the Daniel E. Ponton Distinguished Chair in Neurosurgery at Brigham and Women’s Hospital and Associate Professor of Neurosurgery and of Radiology at Harvard Medical School. Dr. Agar’s multidisciplinary training includes a BSc in Biochemistry, PhD in Chemistry, a postdoctoral fellowship in Neurology and Neurosurgery from McGill University, and further postdoctoral training in Neurosurgery at BWH/HMS. From this unique background, she has developed distinct skills to address unmet analytical needs in the clinical environment. Her research focuses on the development and implementation of integrated biomolecular and drug imaging of tissue specimens. Her laboratory focuses on the mass spectrometry imaging of drugs and metabolism from pre-clinical animal models and clinical trial specimens to study therapeutics for brain tumors. She is also developing and validating real time mass spectrometry approaches to support surgical decision making. Her overall goals are to enable surgeons and oncologists to tailor treatment from the time of surgery, support the development of new therapeutics, and allow precision cancer care using molecular imaging with mass spectrometry approaches.
Padmanee Sharma, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Sharma is a nationally and internationally renowned physician scientist whose research work is focused on investigating mechanisms and pathways within the immune system that facilitate tumor rejection or elicit resistance to immune checkpoint therapy. She is a Professor in the departments of Genitourinary Medical Oncology and Immunology, and the T.C. and Jeanette D. Hsu Endowed Chair in Cell Biology at The University of Texas MD Anderson Cancer Center. She is also the inaugural Scientific Director for the Immunotherapy Platform and the Co-director of the Parker Institute for Cancer Immunotherapy at The University of Texas MD Anderson Cancer Center. She is a member of the American Society for Clinical Investigation (ASCI). She received the Emil Frei III Award for Excellence in Translational Research in 2016, the Coley Award for Distinguished Research for Tumor Immunology in 2018, the Women in Science with Excellence (WISE) award in 2020, the Heath Memorial Award in 2021, and the Randall Prize for Excellence in Cancer Research in 2021. In 2006, Dr. Sharma designed and conducted the first neoadjuvant (pre-surgical) trial, also known as a window-of-opportunity trial, with immune checkpoint therapy (anti-CTLA-4, ipilimumab), which allowed her to establish safety of the neoadjuvant approach for immune checkpoint therapy as well as provide tumor tissues for translational research studies. She identified the ICOS/ICOSL pathway as a novel target for cancer immunotherapy strategies. The neoadjuvant clinical trial in 2006 was also the first trial with immune checkpoint therapy in patients with bladder cancer. The clinical data indicated that 25% of patients had significant anti-tumor responses with pathologic complete responses. These data led Dr. Sharma to conduct additional clinical trials with immune checkpoint therapy (anti-PD-1, nivolumab) for patients with bladder cancer, which enabled FDA-approval of nivolumab as treatment for patients with metastatic bladder cancer. Dr. Sharma also led the clinical trials with immune checkpoint therapy (nivolumab and nivolumab plus ipilimumab) in patients with metastatic renal cell carcinoma (RCC), which led to FDA-approval of these agents as treatment for patients with RCC. Dr. Sharma is the Principal Investigator for multiple immunotherapy clinical trials. Her studies have identified novel resistance mechanisms, including loss of interferon (IFN) signaling, VISTA+ immunosuppressive cells, increased EZH2 expression in T cells, TGFb signaling in bone metastases, and CD73+ myeloid cells in GBM. Her work continues to drive the development of immunotherapy strategies for the treatment of cancer patients.
Rameen Beroukhim, MD, PhD
Dana-Farber Cancer Institute
TeamLabs: Intercepting Ovarian Cancer, The Data Science Hub, and Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Beroukhim is a practicing neuro-oncologist whose research focus is to understand tumor evolution, with emphases on brain tumors and alterations in chromosome structure. This work spans computational methods development, genomic studies of human cancers, and experiments in model systems. In early work describing integrated genomic profiling of glioblastomas, he developed the Genomic Identification of Significant Targets In Cancer (GISTIC) method that is now widely used to analyze copy-number changes across a range of cancers. He has also contributed to the development of several other genomic analysis methods and has led integrated genomic profiling efforts in multiple cancer types, including pan-cancer analyses across thousands of tumors. This work has identified novel mechanisms by which cancers develop and progress, and novel cancer dependencies that have spurred the development of new cancer therapeutics.
Ryuhjin Ahn, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Using phosphoproteomics, systems and molecular biology approaches, Ryuhjin seeks to understand the balance between pro- and anti-tumorigenic immune responses that are regulated by the interplay of microglia and brain cancer.
Sangeeta Goswami, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Sangeeta Goswami is an Assistant Professor at MD, PhD Anderson Cancer Center with a background in medical oncology and immunology. She is involved in patient care, conducting clinical trials, as well as in translational and discovery science research. Her laboratory focuses on understanding the epigenetic regulation of immune suppression in the tumor microenvironment to develop rational combinatorial strategies of immunotherapies and epigenetic modulators in a tumor-specific manner.
Shahab Sarmashghi, PhD
Dana-Farber Cancer Institute
TeamLab(s): The Data Science Hub, Revolutionizing GBM Drug Development Through Serial Biopsies
Shahab Sarmashghi, PhD, is a Postdoctoral Associate at the Broad Institute of MIT and Harvard and a Research Fellow at Dana-Farber Cancer Institute and HMS. He earned his BS and MS degrees from Sharif University of Technology, Iran, and his PhD from UC San Diego in Electrical Engineering. During his PhD, he developed several methods to utilize low-pass whole genome sequencing to study eukaryotic genomes. In the Beroukhim lab, Dr. Sarmashghi is interested in developing computational methods to study the biology of tumors, in particular GBM, and identify novel therapeutic targets. His main focus is on understanding positive and negative selection in cancer using somatic copy number alterations. He is also interested in studying cancer dependencies caused by loss of chromosome arms. He also works on developing new copy number calling pipelines and deploying them to the cloud.
Shiao-Pei Weathers, MD
The University of Texas MD Anderson Cancer Center
TeamLab: Investigating Longitudinal Sampling in Glioblastoma
Dr. Weathers is a neuro-oncologist with clinical research experience in primary brain tumors, specifically gliomas, at The University of Texas MD Anderson Cancer Center in Houston, Texas. Her clinical background has afforded her the opportunity to treat a diverse primary brain tumor patient population. This exposure has provided her with a unique perspective on the integration of novel treatment strategies, both pharmacologic and non-pharmacologic, in the management of patients with gliomas. She has contributed to clinical research in gliomas by acting as either PI or co-investigator for a number of clinical trials for patients with newly diagnosed glioblastoma and recurrent glioblastoma. Aside from developing new protocol concepts with targeted therapies, immunotherapy including cellular therapies, or other rationale combination treatment strategies, she has also been involved and served as PI in conducting research evaluating symptom burden and quality of life in patients with gliomas. In her role as a clinical researcher, she collaborates with multiple researchers from different departments to develop unique, multidisciplinary treatment approaches to improve survival and quality of life for patients with gliomas. Dr. Weathers serves as the Director of the MD Anderson Neuro-Oncology Fellowship Program, Clinical Medical Director for the Brain and Spine Center, and Director of MD Anderson’s brain tumor support group named MD Anderson BEST (Brain tumor Education and Support Together).
Siri Palreddy
Dana-Farber Cancer Institute
TeamLabs: The Data Science Hub, Intercepting Ovarian Cancer,Revolutionizing GBM Drug Development Through Serial Biopsies, Conquering KRAS in Pancreatic Cancer, Demystifying Pancreatic Cancer Therapies
Siri Palreddy is a Clinical Research Coordinator for Dana-Farber Cancer Institute and works across the Break Through Cancer TeamLabs. She recently graduated magna cum laude from Amherst College, holding a BA in Biology and English.
Sreyashi Basu, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Sreyashi Basu, PhD is a Research Group Leader at MD Anderson Cancer Center. Dr Basu co-directs human immune monitoring group of Immunotherapy platform at MDACC under the guidance of Drs Padmanee Sharma and James Allison. She earned her doctorate degree in Immunology and completed her postdoctoral training at University of Connecticut Health Center. Dr Basu is an innovative biomedical scientist, passionate about newer technologies and implementing them in her research. Her research experience is in immunology, neuro-immuno-oncology and autoimmunity. Dr. Basu manages a group of scientists involved with immunogenomic profiling to study the changes in immune cell phenotypes in response to therapy and to identify predictive biomarkers of therapeutic benefit. Her group identified CD73+ immunosuppressive myeloid cells as a resistance mechanism to immune checkpoint therapy in GBM.
Stuart Levine, PhD
MIT’s Koch Institute for Integrative Cancer Research
TeamLab(s): Revolutionizing GBM Drug Development Through Serial Biopsies
, The Data Science Hub
Stuart S. Levine, PhD, is the director of the MIT BioMicro Center and co-leader of the Koch Institute Integrated Genomics and Bioinformatics core facility. Dr. Levine received his bachelor’s degree from MIT and his PhD from Harvard University under the guidance of Robert Kingston, and performed postdoctoral training under Richard Young (Whitehead Institute). The Integrated Genomics and Bioinformatics core provides MIT researchers with facilities for high-throughput data-intensive genomics and bioinformatic analysis, as well as large-scale database storage, management, data mining and data modeling required to fully implement systems approaches to investigate a broad spectrum of biological problems. Dr Levine is currently president of the Northeast Regional Laboratory Staff and Core Directors, a chapter of the Association of Biomolecular Resource Facilities.
Vinay K. Puduvalli, MD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Dr. Vinay K. Puduvalli is Professor and Chair of the Department of Neuro-Oncology at the University of Texas MD Anderson Cancer Center, and Co-Director of the MD Anderson Brain Tumor Center and holds the Beau Biden Endowed Chair in Brain Cancer Research. He serves as the leader of the MD Anderson Brain Cancer Core Grant Program and as co-leader of the GBM Moonshot Project. Dr. Puduvalli’s research focuses on patient-oriented research to develop new treatments for brain malignancies using a combined approach of targeted therapies, innovative clinical trial designs, and rational combinations of anticancer agents. His clinical expertise includes care of patients with brain and spine malignancies, as well as neurological complications of cancer. His laboratory research focuses on identifying vulnerabilities in gliomas that can overcome tumor heterogeneity in order to target these with novel agents using a variety of pre-clinical models. His team has also identified novel ways to target stress response and energy metabolism in gliomas to specifically target tumor cells while sparing normal ones. In a translational context, he has led several institutional and multicenter clinical studies involving epigenetic therapies and novel targeted agents. He has served as a mentor for students, residents, fellows, junior, and senior faculty over the past 2 decades. He serves in national leadership roles in the Society of Neurooncology and has served on advisory boards, review boards, and study sections for national and international federal and industry agencies.
Viviane Tabar, MD
Memorial Sloan Kettering Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Viviane Tabar, MD is the Chair of the Department of Neurosurgery and the Theresa C Feng Professor in Neurosurgical Oncology at Memorial Sloan Kettering Cancer Center in New York. She is a neurosurgeon with expertise in brain tumors, and a scientist with a focus on stem cell biology.
Dr. Tabar’s surgical practice is focused on primary brain tumors and tumors of the skull base. Her research includes the development of cell-based therapies for neurological disorders, using human pluripotent stem cells. This portfolio includes strategies for repairing radiation and chemotherapy induced brain injury and the development of human pluripotent stem cell-derived dopamine neurons for Parkinson’s disease, currently in a Phase I clinical trial. Her lab has also studies glioma biology and has pioneered the use of human embryonic stem cell-based models of brain tumors, with a focus on histone-mutant high grade glioma in the pediatric and young adult patients. She has received several honors and awards from the International Society for Stem Cell Research, the New York Academy of Medicine and the American Association of Neurological Surgeons and was elected to the membership of the American Society for Clinical Investigation and the Society of Neurological Surgeons. Dr. Tabar is also member of the National Academy of Medicine. She serves on the advisory board of Cell Stem Cell.
Wen Jiang, MD, PhD
The University of Texas MD Anderson Cancer Center
TeamLab: Revolutionizing GBM Drug Development Through Serial Biopsies
Wen Jiang, MD, PhD is an Assistant Professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center. He received his PhD in Biomedical Engineering at the University of Toronto and MD from Stanford School of Medicine. He completed his residency training in Radiation Oncology at MD Anderson Cancer in 2018 and was recruited to UT Southwestern as a tenure-track Assistant Professor of Radiation Oncology and a CPRIT Scholar. He returned to MD Anderson in 2021, where he treats patients with primary and metastatic CNS tumors. As a physician scientist, Dr. Jiang’s laboratory research aims to identify ways to promote innate immunity as a new strategy to eliminate brain cancer. Dr. Jiang’s research is supported by multiple grant funding from the NCI, NINDS, DOD, CPRIT, and the Susan G. Komen Foundation.
PROJECT SUMMARY
Outcomes for patients diagnosed with glioblastoma (GBM) have not significantly improved in decades. The current standard of care for GBM includes surgery, radiation and chemotherapy. Despite this treatment, GBM always recurs, usually within ten months from initial diagnosis, and remains incurable. The only therapies for GBM approved by the FDA in the past 30 years have shown only incremental survival benefit, and several recent, large, and expensive phase III clinical trials have failed to show meaningful improvements in outcome.
GBM is challenging in part because most cancer therapeutics fail to penetrate the tumor due to the protective effect of the blood-brain barrier. Therefore, clinicians are typically “flying blind” when treating GBM patients with novel chemotherapeutic, immunologic, or biologic agents. Although repeat biopsy (referred to as longitudinal sampling) has been routinely incorporated into the evaluation of promising oncology therapies for many other types of cancer, this has not been previously considered for brain tumors due to logistical and safety concerns. In addition, insurance companies do not yet cover the prohibitively high costs of repeated intracranial biopsies. Not only do these blind trials fail at stunningly high rates, but also this methodology effectively teaches us nothing about why the trial failed, leading to a futile cycle of repeated failure. Thus, without a platform for longitudinal sampling early in the clinical development of promising therapeutics for GBM, these large, costly, uninformative, and ultimately fruitless clinical trials will likely continue, providing no benefit to the hundreds of patients who are enrolled, nor to those who follow.
The breakthrough hypothesis of this project is that a novel early-stage GBM clinical trial platform providing critical information from sequential tumor biopsies, accompanied by peripheral liquid biopsies, will revolutionize our understanding of the effects of these therapies, thus transforming the approach to identifying effective therapeutic agents for GBM. This approach will fundamentally change how early GBM trials are conducted and will open this devastating disease to the kinds of breakthroughs that have transformed treatment of other cancers in the past few years.
The Break Through Cancer team will introduce a new paradigm that such longitudinal tumor sampling early in clinical trial testing should be critically considered for all therapies being developed for GBM patients. In addition, the body of knowledge created by analysis of longitudinal tumor samples over several drug and biologic agent trials will form the basis of new treatment hypotheses, and encourage pharmaceutical and biotechnology company investment in GBM.
Intracranial sampling is an invasive procedure that can now be performed with precision due to advances in neurosurgical and imaging technologies. However, its value must be irrefutably demonstrated if longitudinal sampling is to be adopted as a routine component of therapy development for GBM. As such, the initial goal of this team is to assess the safety, feasibility, and value of performing serial biopsies to determine if a therapeutic is being effectively delivered to the tumor and to obtain critical biological readouts of the effect of the drug on the tumor, with patient safety as an overriding concern. The initial trial will assess an oncolytic virus engineered to induce immune responses against GBM, which will be dosed intratumorally and on a repeated basis over time. This will provide an opportunity to safely take tumor samples each time the treatment is delivered. The team will use molecular profiling techniques such as genomic analysis, single cell RNA-sequencing, immune analyses, and sophisticated image analyses to investigate how cellular interactions and signaling in the tumor tissue are affected by the treatments.
Simultaneously, the team will also evaluate critical liquid biopsies for so-called surrogate markers of such treatment: first, using blood samples corresponding to the time of tumor interventions as well as through the course of therapy; and second, studying cerebrospinal fluid to assess for molecular changes that correspond to intertumoral sampling. If validated, these less invasive peripheral approaches to longitudinal sampling will reduce costs, improve safety further, and make this form of assessment more broadly available to physicians and patients.
Finally, this project will have an important discovery research component related to understanding how the immune response is blocked by GBM tumor cells. This will involve a series of experiments designed to identify genetic and cellular factors that are actively suppressing a more effective immune response against this disease. Another important component will assess drug effects in the laboratory using human tumor slice cultures – living pieces of human brain tumor tissue soon after they are removed from the operating room. These slice cultures can provide otherwise unknown insights into the effects of therapy on human GBM and could be scaled further to support novel therapeutic discovery in numerous ways.
MAKE A DIFFERENCE
Break Through Cancer was created in February 2021 with an extraordinary matching gift of $250,000,000. Every gift to the Foundation supports groundbreaking cancer research and helps us to meet our matching commitment.
For questions about giving please email Lisa Schwarz, Chief Philanthropy Officer at LMS@BreakThroughCancer.org