About

David Mooney is the Robert P. Pinkas Family Professor of Bioengineering at Harvard University and a core faculty member at the Wyss Institute for Biologically Inspired Engineering. His primary teaching area is bioengineering. His research focuses on cell and tissue engineering, biomaterials, applied physics, materials, biomechanics, and therapeutics. His work includes developing implantable living materials composed of engineered hydrogels and synthetically engineered bacteria, as well as advancing biomaterial-based cancer vaccines and safer orthopedic devices using pathogen-specific antigens. He is involved in research that aims to create safe, on-demand, living therapeutics and to improve the safety and efficacy of biomedical implants.

Research topics

• Biology
• Cell biology
• Cancer research
• Materials science
• Immunology
• Composite material
• Chemistry
• Nanotechnology
• Medicine
• Biochemistry
• Biophysics
• Internal medicine
• Genetics
• Biological system
• Biomedical engineering
• Computational biology

Selected publications

• STING activation promotes robust immune response and NK cell–mediated tumor regression in glioblastoma models

  Proceedings of the National Academy of Sciences · 2022 · 154 citations

  • Cancer research
  • Immunology
  • Medicine

  Immunotherapy has had a tremendous impact on cancer treatment in the past decade, with hitherto unseen responses at advanced and metastatic stages of the disease. However, the aggressive brain tumor glioblastoma (GBM) is highly immunosuppressive and remains largely refractory to current immunotherapeutic approaches. The stimulator of interferon genes (STING) DNA sensing pathway has emerged as a next-generation immunotherapy target with potent local immune stimulatory properties. Here, we investigated the status of the STING pathway in GBM and the modulation of the brain tumor microenvironment (TME) with the STING agonist ADU-S100. Our data reveal the presence of STING in human GBM specimens, where it stains strongly in the tumor vasculature. We show that human GBM explants can respond to STING agonist treatment by secretion of inflammatory cytokines. In murine GBM models, we show a profound shift in the tumor immune landscape after STING agonist treatment, with massive infiltration of the tumor-bearing hemisphere with innate immune cells including inflammatory macrophages, neutrophils, and natural killer (NK) populations. Treatment of established murine intracranial GL261 and CT-2A tumors by biodegradable ADU-S100-loaded intracranial implants demonstrated a significant increase in survival in both models and long-term survival with immune memory in GL261. Responses to treatment were abolished by NK cell depletion. This study reveals therapeutic potential and deep remodeling of the TME by STING activation in GBM and warrants further examination of STING agonists alone or in combination with other immunotherapies such as cancer vaccines, chimeric antigen receptor T cells, NK therapies, and immune checkpoint blockade.

  DOI

• Matrix viscoelasticity controls spatiotemporal tissue organization

  Nature Materials · 2022 · 265 citations

  Senior authorCorresponding
  • Cell biology
  • Biophysics
  • Materials science
  PublisherOA PDFDOI

• Mechanical checkpoint regulates monocyte differentiation in fibrotic niches

  Nature Materials · 2022 · 80 citations

  Senior authorCorresponding
  • Cell biology
  • Cancer research
  • Biology
  PublisherOA PDFDOI

• Viscoelastic surface electrode arrays to interface with viscoelastic tissues

  Nature Nanotechnology · 2021 · 299 citations

  Senior authorCorresponding
  • Materials science
  • Nanotechnology
  • Composite material
  DOI

• Effects of extracellular matrix viscoelasticity on cellular behaviour

  Nature · 2020 · 2125 citations

  • Materials science
  • Biophysics
  • Nanotechnology
  DOI

• Metabolic labeling and targeted modulation of dendritic cells

  Nature Materials · 2020 · 177 citations

  Senior authorCorresponding
  • Cell biology
  • Chemistry
  • Biology
  DOI

• Biomaterial-based scaffold for in situ chemo-immunotherapy to treat poorly immunogenic tumors

  Nature Communications · 2020 · 167 citations

  Senior authorCorresponding
  • Cancer research
  • Medicine
  • Biology

  Poorly immunogenic tumors, including triple negative breast cancers (TNBCs), remain resistant to current immunotherapies, due in part to the difficulty of reprogramming the highly immunosuppressive tumor microenvironment (TME). Here we show that peritumorally injected, macroporous alginate gels loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) for concentrating dendritic cells (DCs), CpG oligonucleotides, and a doxorubicin-iRGD conjugate enhance the immunogenic death of tumor cells, increase systemic tumor-specific CD8 + T cells, repolarize tumor-associated macrophages towards an inflammatory M1-like phenotype, and significantly improve antitumor efficacy against poorly immunogenic TNBCs. This system also prevents tumor recurrence after surgical resection and results in 100% metastasis-free survival upon re-challenge. This chemo-immunotherapy that concentrates DCs to present endogenous tumor antigens generated in situ may broadly serve as a facile platform to modulate the suppressive TME, and enable in situ personalized cancer vaccination.

  DOI

• Multifunctional biomimetic hydrogel systems to boost the immunomodulatory potential of mesenchymal stromal cells

  Biomaterials · 2020 · 65 citations

  Senior authorCorresponding
  • Cell biology
  • Materials science
  • Cancer research
  DOI

• Metabolic glycan labelling for cancer-targeted therapy

  Nature Chemistry · 2020 · 204 citations

  Senior authorCorresponding
  • Chemistry
  • Biochemistry
  • Computational biology
  DOI

• Extracellular matrix mechanics regulate transfection and SOX9-directed differentiation of mesenchymal stem cells

  Acta Biomaterialia · 2020 · 54 citations

  Senior authorCorresponding
  • Cell biology
  • Materials science
  • Biology
  DOI

Recent grants

• Biomaterial Cancer Vaccines that Generate Patient-Specific Antigen In Situ

  NIH · $426k · 2017–2022

• NIH Grant DP3DK108224

  NIH · $2.4M · 2019

• Tissue Engineering and Regeneration

  NIH · $18.1M · 1976–2027

• Administrative Core

  NIH · $16.4M · 2019–2025

• Viscoelasticity and T Cell Production

  NIH · $2.4M · 2022–2026

Frequent coauthors

• Joseph P. Vacanti

  Harvard University

  182 shared

• Byung‐Soo Kim

  Seoul National University

  113 shared

• Nathaniel Huebsch

  Washington University in St. Louis

  67 shared

• Hyun Joon Kong

  University of Illinois System

  66 shared

• Georg N. Duda

  Berlin Institute of Health at Charité - Universitätsmedizin Berlin

  64 shared

• Susan X. Hsiong

  Harvard University

  62 shared

• Stephen S. Kim

  Inova Children's Hospital

  59 shared

• Rosa Choi

  55 shared

Education

• PhD, Chemical Engineering

  Massachusetts Institute of Technology

  1992

• Bachelor of Science, Chemical Engineering

  University of Wisconsin Madison

  1987

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• JoAnn E Mansonh-359
• Randy L. Bucknerh-268
• Edward Giovannuccih-267
• Kristen Andersonh-263