Dana-Farber Cancer Institute
Mark A. Murakami, MD

Mark A. Murakami, MD

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Contact Information

Office Phone Number

617-582-9171

Fax

779-212-7795

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Biography

Mark A. Murakami, MD

Dr. Murakami graduated from Washington University School of Medicine with an M.D. and M.A. in Biology and Biomedical Sciences in 2009. He trained in Internal Medicine at the Massachusetts General Hospital before pursuing subspecialty training in Hematology and Medical Oncology at the Dana-Farber/Partners CancerCare program. He has been an independent laboratory investigator in the Division of Hematologic Neoplasia at the Dana-Farber Cancer Institute since 2018. He devotes his clinical practice to patients with hematological malignancies, including leukemia and lymphoma and those undergoing hematopoietic stem cell transplantation. He contributes to early phase clinical trials through correlative science. 

Researcher

Physician

Scientific Director, Mantle Cell Lymphoma Center
Scientific Director, Follicular Lymphoma Center
Physician
Assistant Professor of Medicine, Harvard Medical School

Centers/Programs

Clinical Interests

Clinical genomics, Experimental therapeutics, Minimal residual disease, Precision medicine, Predictive Biomarkers

Board Certification

  • Hematology
  • Internal Medicine
  • Medical Oncology

Fellowship

  • Dana-Farber Cancer Institute
  • Dana-Farber/Partners CancerCare

Residency

  • Massachusetts General Hospital

Medical School

  • Washington University School of Medicine

Recent Awards

  • 2005-2007 Howard Hughes Medical Institute (HHMI) Research Training Fellowship
  • 2006 Merit Award, American Society of Hematology
  • 2009 Dr. Richard S. Brookings Prize for Meritorious Research, Washington University School of Medicine
  • 2015 Translational Research Training in Hematology, European Hematology Association and the America Society of Hematology

Research

    View Dr. Murakami’s Research

    Defining acquired vulnerabilities within minimal residual disease in leukemia and lymphoma
    The overarching goal of the Murakami laboratory is to advance new therapeutic strategies to overcome minimal residual disease (MRD) and cure patients with B-cell leukemias and lymphomas.
    Our investigations in BCR-ABL-rearranged B-cell acute lymphoblastic leukemia (B-ALL) integrate biophysical and molecular methodologies to reveal how tumor subclones adapt to oncogene withdrawal by entering a state of dormancy from which they later emerge to drive clinical progression. We model human tumor biology by utilizing primary samples from patients treated on an ongoing phase I clinical trial for which we lead the biological correlatives as well as patient-derived xenograft (PDX) models that we previously helped to generate and characterize (Cancer Cell 2016). We conduct in vivo trials of experimental therapeutics in these PDX models and isolate leukemia cells from the bone marrow of animals prior to treatment, on active treatment in deep remission, and at relapse. We sequence leukemias to identify mutational mechanisms of resistance and have found evidence of oncogenic signaling divergence at relapse involving either reactivation of STAT5 or acquired activation of ERK (Nature, 2020). In collaboration with colleagues at MIT, we measure single-cell mass and perform single-cell RNA sequencing to identify non-mutational molecular correlates of drug resistance as well (Nature Biotechnology, 2016). We recently identified several biological pathways highly upregulated within MRD, pharmacologic targeting of which reduces MRD in vivo.
    We seek to extend these findings into mantle cell lymphoma, another B-cell malignancy in which remissions are common but cures are rare. We contribute to a phase I/II clinical trial investigating a biologically informed combination of targeted therapies which will provide a valuable opportunity to study MRD in mantle cell lymphoma. With our collaborative research team, we are integrating serial molecular profiling of mantle cell lymphoma cells and the tumor microenvironment to define tumor-intrinsic biological programs as well as tumor-stromal interactions that are associated with tumor persistence, MRD, and ultimately relapse. We use these data to nominate new therapeutic strategies, which we evaluate with short-term, functional, ex vivo drug sensitivity tests, such as single-cell biophysical assessments and dynamic BH3 profiling.
    Finally, we also use DNA-based genomic approaches to define molecular correlates of therapeutic response and resistance in lymphomas. We are developing multiplexed molecular assays to detect not only individual molecular alterations of biological and/or clinical significance, but also integrative genomic signatures that enhance the precision of biological characterization, risk stratification, and therapeutic assignment of these disorders. A major goal of this work is to enable longitudinal tracking of tumors, even when the residual tumor is insufficient or inaccessible for repeat tissue-based sampling. We are developing a parallel circulating tumor DNA or liquid biopsy assay to evaluate many of the same molecular targets and integrative signatures as the tissue-based platform. We aim to implement these assays in the context of laboratory and translational research studies, then deploy them in the clinical setting for prospective clinical prognostication and therapeutic prediction. 

    Research Departments

    Publications

      View Dr. Murakami's Publications

      • High-throughput single-cell density measurements enable dynamic profiling of immune cell and drug response from patient samples. Nat Biomed Eng. 2025 May 20. View in: Pubmed

      • Asciminib plus dasatinib and prednisone for Philadelphia chromosome-positive acute leukemia. Blood. 2025 Feb 06; 145(6):577-589. View in: Pubmed

      • Mutation and cell state compatibility is required and targetable in Ph+ acute lymphoblastic leukemia minimal residual disease. bioRxiv. 2024 Jun 10. View in: Pubmed

      • Measuring single-cell density with high throughput enables dynamic profiling of immune cell and drug response from patient samples. bioRxiv. 2024 Apr 28. View in: Pubmed

      • Bone Marrow Harvest: A White Paper of Best Practices by the NMDP Marrow Alliance. Transplant Cell Ther. 2024 Jul; 30(7):663-680. View in: Pubmed

      • Comparison of whole-genome and immunoglobulin-based circulating tumor DNA assays in diffuse large B-cell lymphoma. Hemasphere. 2024 Apr; 8(4):e47. View in: Pubmed

      • Toward rational therapy for mantle cell lymphoma. Blood. 2023 11 02; 142(18):1504-1506. View in: Pubmed

      • Protein re-surfacing of E. coli L-Asparaginase to evade pre-existing anti-drug antibodies and hypersensitivity responses. Front Immunol. 2022; 13:1016179. View in: Pubmed

      • Distinction of lymphoid and myeloid clonal hematopoiesis. Nat Med. 2021 11; 27(11):1921-1927. View in: Pubmed

      • Signalling input from divergent pathways subverts B cell transformation. Nature. 2020 07; 583(7818):845-851. View in: Pubmed

      • Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models. Nat Commun. 2018 05 22; 9(1):2024. View in: Pubmed

      • Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma. Blood. 2018 05 24; 131(21):2345-2356. View in: Pubmed

      • Targeting minimal residual disease: a path to cure? Nat Rev Cancer. 2018 04; 18(4):255-263. View in: Pubmed

      • PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models. Cancer Res. 2017 11 01; 77(21):e62-e66. View in: Pubmed

      • Cancer models: The next best thing. Nature. 2017 09 07; 549(7670):39-41. View in: Pubmed

      • Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate. Nat Biotechnol. 2016 Nov; 34(11):1161-1167. View in: Pubmed

      • The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 07 11; 30(1):183. View in: Pubmed

      • An ED pilot intervention to facilitate outpatient acute care for cancer patients. Am J Emerg Med. 2016 Oct; 34(10):1934-1938. View in: Pubmed

      • The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 04 11; 29(4):574-586. View in: Pubmed

      • Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol. 2015 Sep; 16(9):1111-1122. View in: Pubmed

      • Activation of the unfolded protein response is associated with impaired granulopoiesis in transgenic mice expressing mutant Elane. Blood. 2011 Mar 31; 117(13):3539-47. View in: Pubmed

      • Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. Blood. 2007 Dec 15; 110(13):4179-87. View in: Pubmed

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