Dana-Farber Cancer Institute PS-OC

Dana-Farber Cancer Institute Physical Sciences-Oncology Center (PS-OC)

The principal mission of this PS-OC is to promote the understanding of cancer evolution and treatment responses utilizing approaches from the physical sciences intertwined with cancer biology and oncology.

It is investigating the treatment response of leukemic, brain and breast cancer cells and their microenvironments to classical and novel treatment approaches. It is developing novel mathematical frameworks describing the evolutionary dynamics of tumor progression and treatment response that are parameterized using the experimental systems, as well as predicting and validating optimum intervention strategies that will ultimately be implemented as prospective clinical trials. This approach is incorporating the spatio-temporal organization of evolving, heterogeneous tumor cell populations within their microenvironment.

Collaborations between physical and experimental scientists in the PS-OC will bridge the chasm between the physical sciences and oncology with the ultimate goal of uncovering novel biology and enhancing patient care.

Projects

Project 1: Prospective Clonal Dynamics Guiding Curative Therapies for Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a rapidly fatal disease that can quickly be brought into complete remission, but with high relapse rates. The genetic evolution of the disease has been defined, but the basis for resistance to therapy and effective strategies to overcome it are lacking.

This project is using well-defined murine models where an analogous form of highly lethal, human AML can be temporarily brought into remission by traditional chemotherapy agents. Combining these basic features with novel strategies for quantitatively assessing oncological behavior and cell growth patterns, this study is providing multidimensional datasets for mathematical modeling of disease progression and susceptibility to therapeutic approaches.

Ultimately, these models will be used to predict and test unique vulnerabilities of the disease that can be exploited therapeutically to reduce AML relapse.

Project 2: Intratumor Heterogeneity Determines Best Treatment Modalities in Brain Cancer

Glioblastomas (GBMs) are the most common and most malignant primary brain tumors and can be divided into several molecular subgroups. All subtypes demonstrate high insensitivity to standard therapeutic approaches and, unfortunately, recurrence inevitably occurs.

This project is advancing the understanding of particular subtypes of GBMs and optimizing intervention strategies. Additionally, it is elucidating the combined effects of chemotherapy and radiation treatment on proneural-GBMs , to maximize radiation therapy responses in mesenchymal-GBMs and improve overall GBM treatment strategies independent of tumor subtype.

Utilizing a multidisciplinary approach of basic biological and novel mathematical models, the PS-OC investigators are determining therapeutic dynamics of treatment response to ultimately provide optimized and novel intervention strategies for GBM and improve the standard of care for patients.

Project 3: Single Cell Analyses of Intra-Tumor Heterogeneity Identify Optimum Therapies for Breast Cancer

Breast cancer is the most commonly diagnosed cancer and is the main cause of cancer-related mortality in women worldwide. Achieving a meaningful global impact on breast cancer-associated morbidity and mortality requires a better understanding of drivers of metastatic progression and therapeutic resistance at the cellular and molecular level, a way to recognize these features in diagnostic patient samples, and early intervention and treatment strategies that prevent the emergence of metastatic and treatment-resistant tumors.

The goals of this project are to tackle these key clinical problems in breast cancer through a combined mathematical modeling and experimental approach utilizing single cell analyses and xenograft models to identify optimal therapeutic strategies to ultimately prevent metastatic outgrowth and treatment resistance. Ultimately, these models will be validated in clinical and xenograft samples and they will be utilized to combat primary tumor and metastases formation.

Cores

Core 1: Single Cell Profiling

This core is a virtual infrastructure led by Dr. Rong Fan. The core provides the capability of characterizing single cells at the omics level in order to dissect intra-clonal cellular heterogeneity, discover molecular correlates, and refine the parameters used to gauge tumor cell fitness in computational modeling. The core will support the PS-OC by offering services to measure the transcriptome, epigenome, and proteomic signatures in single cells.

While researchers in individual PS-OC projects will track clonal growth and molecular signature changes of each clone, the core will characterize cellular heterogeneity within individual clones, especially at the omics level. Additionally, the core is a technology innovation center that aims to develop new technology platforms to enable new opportunities of scientific discoveries. Thus, the core itself involves substantial engineering innovation and represents an important component of the PS-OC.

Education and Outreach Unit

This PS-OC is facilitating integrative science through education and outreach, as well as supporting career building opportunities and synergistic collaborations with clinicians, experimentalists, and physical scientists with diverse disciplinary background.

Our overarching goal is to expose scientists and students to a multidisciplinary environment, foster collaborative networks, and ensure career building opportunities.

Learn more about the Dana-Farber Cancer Institute PS-OC Education and Outreach Activities.

Investigators

Franziska Michor, Ph.D.
Dana-Farber Cancer Institute

Dr. Franziska Michor is the Principal Investigator of the PS-OC. She is a Professor of Computational Biology in the Department of Biostatistics and Computational Biology at the Dana-Farber Cancer Institute, and in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health. She obtained her undergraduate training in mathematics and molecular biology from the University of Vienna, Austria, and her Ph.D. from the Department of Organismic and Evolutionary Biology at Harvard University. After a fellowship at the Harvard Society of Fellows, she was an Assistant Professor in the Computational Biology Program at Memorial Sloan-Kettering Cancer Center.

Dr. Michor has been the recipient of numerous awards including the Leon Levy Young Investigator Award, the Alice Hamilton Award, and the Vilcek Prize for Creative Promise in Biomedical Science. Dr. Michor's laboratory investigates the evolutionary dynamics of cancer initiation, progression, response to therapy, and emergence of resistance.

Eric C. Holland, M.D., Ph.D.
Fred Hutchison Cancer Research Center

Dr. Eric Holland is the Senior Co-Investigator of the PS-OC. He is the Director of the Alvord Brain Tumor Center; Chap and Eve Alvord and Elias Alvord Chair in Neuro-Oncology; and Professor in the Department of Neurological Surgery at the University of Washington and he is the Director of the Division of Human Biology and Solid Tumor Translational Research at the Fred Hutchinson Cancer Research Center in Seattle. He received his Ph.D. from the University of Chicago in 1985 and his MD from Stanford University in 1990.

He is the recipient of numerous honorary degrees, awards and memberships in honorary societies and committees. Dr. Holland's research has centered on the development of genetically accurate mouse models of gliomas. He has used these models to study the biology of these tumors, the way they respond to current therapy, and the development of new therapeutic strategies for these tumors.

David Scadden, M.D.
Harvard University

Dr. David Scadden is the Gerald and Darlene Jordan Professor of Medicine at Harvard University. He is a practicing hematologist/oncologist who focuses on bringing stem cell biology to patient care. He founded and directs the Center for Regenerative Medicine at the Massachusetts General Hospital and with Douglas Melton, co-founded and co-directs the Harvard Stem Cell Institute and the Harvard University Department of Stem Cell and Regenerative Biology. He is a member of the Institute of Medicine of the National Academies of Science, the Board of External Experts for the National Heart, Lung and Blood Institute and a former member of the National Cancer Institute’s Board of Scientific Counselors.

Dr. Scadden received his M.D. from Case Western Reserve University School of Medicine. He has received multiple honorary degrees, awards and memberships in honorary societies. His work emphasizes targeting the stem cell niche to attain novel therapies for blood diseases.

Kornelia Polyak, M.D., Ph.D.
Dana-Farber Cancer Institute

Dr. Kornelia Polyak is a Professor of Medicine at Harvard Medical School and in the Department of Medical Oncology at the Dana-Farber Cancer Institute. She received her M.D. in 1991 from Albert Szent-Gyorgyi Medical University, Szeged, Hungary, and her Ph.D. in 1995 from Cornell University/Memorial Sloan-Kettering Cancer Center. She completed a research fellowship in oncology at the Johns Hopkins Oncology Center, Baltimore. Dr. Polyak joined the Dana-Farber Cancer Institute in 1998.

She is the recipient of multiple awards including the AACR Outstanding Investigator Award for Breast Cancer Research, the Paul Marks Award for Cancer Research, the 27th Annual Award for Outstanding Achievement in Cancer Research, and has served on multiple committees including the AACR Board of Directors form 2010-2013. Dr. Polyak’s laboratory is principally involved in basic laboratory research focusing on cancer genetics and the molecular basis of breast cancer.

Rong Fan, Ph.D.
Yale University

Dr. Rong Fan is an Associate Professor of Biomedical Engineering at Yale University. He received his Ph.D. in chemistry from University of California at Berkeley. His graduate work involves the development of novel nanofluidic transistors for single molecule detection and ion transport control. Afterwards, he went on to take a postdoctoral associate position in Professor Jim Heath’s laboratory in NanoSystems Biology Cancer Center at CalTech.

He is the recipient of numerous awards including the NSF Faculty Early Career Development, the Packard Fellowship for Science and Engineering, and the Bill & Melinda Gates Foundation GCE award and others. Dr. Fan's research focuses on combining single-cell analysis technology and systems biology to study cell-cell communication and cellular heterogeneity in human cancers and the immune system. Ultimately, the goal is to accelerate the translational development of these tools for informative immune monitoring or cancer diagnosis.