Photo of Sean Lawler,  PhD

Sean Lawler, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-5066
Fax: (617) 525-5067


slawler@partners.org

Sean Lawler, PhD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Neurosurgery, Harvard Medical School
  • Assistant Professor, Neurosurgery, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The overarching goal of my laboratory is to develop and optimize novel therapies for brain tumors through the use of advanced research tools, animal models and collaborative enterprise. The Lawler lab utilizes molecular biological approaches, high-throughput cell-based assays and preclinical immunocompetent and invasive mouse models of glioblastoma and collaborates extensively with investigators in bioinformatics, imaging, immunology, oncolytic viruses, virology and drug design. Our major goal is to provide the foundation to move new therapies forward from bench to bedside; for example clinicaltrials.gov NCT03576612, which was developed based on our data combining local immunostimulation with immune checkpoint blockade. The use of STING agonists would represent an exciting approach for GBM, and we have assembled a team with the strengths and qualities to investigate this in detail using the framework of tools developed in my research laboratory, and a clear path to patient application through our clinical connections at BWH and DFCI Neuro Oncology.

Publications from Harvard Catalyst Profiles

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  • Hofman L, Lawler SE, Lamfers MLM. The Multifaceted Role of Macrophages in Oncolytic Virotherapy. Viruses 2021. PubMed
  • Krenzlin H, Zdioruk M, Nowicki MO, Finkelberg T, Keric N, Lemmermann N, Skubal M, Chiocca EA, Cook CH, Lawler SE. Cytomegalovirus infection of glioblastoma cells leads to NF-κB dependent upregulation of the c-MET oncogenic tyrosine kinase. Cancer Lett 2021; 513:26-35. PubMed
  • von Spreckelsen N, Fadzen CM, Hartrampf N, Ghotmi Y, Wolfe JM, Dubey S, Yang BY, Kijewski MF, Wang S, Farquhar C, Bergmann S, Zdioruk M, Wasserburg JR, Scott B, Murrell E, Bononi FC, Luyt LG, DiCarli M, Lamfers MLM, Ligon KL, Chiocca EA, Viapiano MS, Pentelute BL, Lawler SE, Cho CF. Targeting glioblastoma using a novel peptide specific to a deglycosylated isoform of brevican. Adv Ther (Weinh) 2021. PubMed
  • Koch MS, Lawler SE, Chiocca EA. HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials. Cancers (Basel) 2020. PubMed
  • Fadzen CM, Wolfe JM, Zhou W, Cho CF, von Spreckelsen N, Hutchinson KT, Lee YC, Chiocca EA, Lawler SE, Yilmaz OH, Lippard SJ, Pentelute BL. A Platinum(IV) Prodrug-Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain. J Med Chem 2020. PubMed
  • Mineo M, Lyons SM, Zdioruk M, von Spreckelsen N, Ferrer-Luna R, Ito H, Alayo QA, Kharel P, Giantini Larsen A, Fan WY, Auduong S, Grauwet K, Passaro C, Khalsa JK, Shah K, Reardon DA, Ligon KL, Beroukhim R, Nakashima H, Ivanov P, Anderson PJ, Lawler SE, Chiocca EA. Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus. Mol Cell 2020; 78:1207-1223.e8. PubMed
  • Schregel K, Nowicki MO, Palotai M, Nazari N, Zane R, Sinkus R, Lawler SE, Patz S. Magnetic Resonance Elastography reveals effects of anti-angiogenic glioblastoma treatment on tumor stiffness and captures progression in an orthotopic mouse model. Cancer Imaging 2020; 20:35. PubMed
  • Lawler SE, Nowicki MO, Ricklefs FL, Chiocca EA. Immune Escape Mediated by Exosomal PD-L1 in Cancer. Adv Biosyst 2020. PubMed
  • Lawler SE, Chiocca EA, Cook CH. Cytomegalovirus Encephalopathy during Brain Tumor Irradiation. Clin Cancer Res 2020. PubMed
  • Alayo QA, Ito H, Passaro C, Zdioruk M, Mahmoud AB, Grauwet K, Zhang X, Lawler SE, Reardon DA, Goins WF, Fernandez S, Chiocca EA, Nakashima H. Glioblastoma infiltration of both tumor- and virus-antigen specific cytotoxic T cells correlates with experimental virotherapy responses. Sci Rep 2020; 10:5095. PubMed
  • Ricklefs FL, Maire CL, Matschke J, Dührsen L, Sauvigny T, Holz M, Kolbe K, Peine S, Herold-Mende C, Carter B, Chiocca EA, Lawler SE, Westphal M, Lamszus K. FASN Is a Biomarker Enriched in Malignant Glioma-Derived Extracellular Vesicles. Int J Mol Sci 2020. PubMed
  • Storey KM, Lawler SE, Jackson TL. Modeling Oncolytic Viral Therapy, Immune Checkpoint Inhibition, and the Complex Dynamics of Innate and Adaptive Immunity in Glioblastoma Treatment. Front Physiol 2020; 11:151. PubMed
  • Berger G, Marloye M, Lawler SE. Pharmacological Modulation of the STING Pathway for Cancer Immunotherapy. Trends Mol Med 2019; 25:412-427. PubMed
  • Nowicki MO, Hayes JL, Chiocca EA, Lawler SE. Proteomic Analysis Implicates Vimentin in Glioblastoma Cell Migration. Cancers (Basel) 2019. PubMed
  • Krenzlin H, Behera P, Lorenz V, Passaro C, Zdioruk M, Nowicki MO, Grauwet K, Zhang H, Skubal M, Ito H, Zane R, Gutknecht M, Griessl MB, Ricklefs F, Ding L, Peled S, Rooj A, James CD, Cobbs CS, Cook CH, Chiocca EA, Lawler SE. Cytomegalovirus promotes murine glioblastoma growth via pericyte recruitment and angiogenesis. J Clin Invest 2019; 130:1671-1683. PubMed
  • Marloye M, Lawler SE, Berger G. Current patent and clinical status of stimulator of interferon genes (STING) agonists for cancer immunotherapy. Pharm Pat Anal 2019; 8:87-90. PubMed
  • Berger G, Lawler SE. Novel non-nucleotidic STING agonists for cancer immunotherapy. Future Med Chem 2018; 10:2767-2769. PubMed
  • Berger G, Grauwet K, Zhang H, Hussey AM, Nowicki MO, Wang DI, Chiocca EA, Lawler SE, Lippard SJ. Anticancer activity of osmium(VI) nitrido complexes in patient-derived glioblastoma initiating cells and in vivo mouse models. Cancer Lett 2018; 416:138-148. PubMed
  • Schregel K, Nazari N, Nowicki MO, Palotai M, Lawler SE, Sinkus R, Barbone PE, Patz S. Characterization of glioblastoma in an orthotopic mouse model with magnetic resonance elastography. NMR Biomed 2018; 31:e3840. PubMed
  • Fadzen CM, Wolfe JM, Cho CF, Chiocca EA, Lawler SE, Pentelute BL. Perfluoroarene-Based Peptide Macrocycles to Enhance Penetration Across the Blood-Brain Barrier. J Am Chem Soc 2017; 139:15628-15631. PubMed
  • Lawler SE. Shifting the balance of power? The combination of oncolytic virotherapy and immune checkpoint blockade for glioblastoma treatment. 2017; 19:463-465. PubMed
  • Peruzzi P, Bronisz A, Nowicki MO, Wang Y, Ogawa D, Price R, Nakano I, Kwon CH, Hayes J, Lawler SE, Ostrowski MC, Chiocca EA, Godlewski J. MicroRNA-128 coordinately targets Polycomb Repressor Complexes in glioma stem cells. 2013. PubMed
  • Levesley J, Steele L, Taylor C, Sinha P, Lawler SE. ABT-263 enhances sensitivity to metformin and 2-deoxyglucose in pediatric glioma by promoting apoptotic cell death. PLoS ONE 2013; 8:e64051. PubMed
  • Alvarez-Breckenridge CA, Yu J, Price R, Wojton J, Pradarelli J, Mao H, Wei M, Wang Y, He S, Hardcastle J, Fernandez SA, Kaur B, Lawler SE, Vivier E, Mandelboim O, Moretta A, Caligiuri MA, Chiocca EA. NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors. Nat Med 2012; 18:1827-34. PubMed
  • Agudelo-Garcia PA, De Jesus JK, Williams SP, Nowicki MO, Chiocca EA, Liyanarachchi S, Li PK, Lannutti JJ, Johnson JK, Lawler SE, Viapiano MS. Glioma cell migration on three-dimensional nanofiber scaffolds is regulated by substrate topography and abolished by inhibition of STAT3 signaling. Neoplasia 2011; 13:831-40. PubMed
  • Williams SP, Nowicki MO, Liu F, Press R, Godlewski J, Abdel-Rasoul M, Kaur B, Fernandez SA, Chiocca EA, Lawler SE. Indirubins decrease glioma invasion by blocking migratory phenotypes in both the tumor and stromal endothelial cell compartments. Cancer Res 2011; 71:5374-80. PubMed
  • Godlewski J, Nowicki MO, Bronisz A, Nuovo G, Palatini J, De Lay M, Van Brocklyn J, Ostrowski MC, Chiocca EA, Lawler SE. MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell 2010; 37:620-32. PubMed
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