Photo of David Kozono,  MD, PhD

David Kozono, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3591

David Kozono, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Radiation Oncology, Harvard Medical School
  • Radiation Oncologist, Radiation Oncology, Brigham And Women's Hospital
  • Radiation Oncologist, Radiation Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

My career goal as a radiation oncologist is to improve lung cancer outcomes through basic, translational and clinical investigation. I am currently dedicating 75% effort toward research and 25% in the clinic performing consultations and treating thoracic oncology patients.

My career goal is to improve treatment for patients with locally advanced non-small cell lung carcinoma (LA-NSCLC). Approximately 60,000 patients are diagnosed annually in the United States with LA-NSCLC, from which deaths exceed those from all stages of any other cancer. Standard treatment involves a combination of radiotherapy (RT), chemotherapy and/or surgery. The poor survival of patients with LA-NSCLC is in part due to an inability to give enough radiation to eradicate the tumor without damaging surrounding vital organs including the uninvolved lung, heart, esophagus and spinal cord. Despite advances in RT targeting technology, these organs cannot be fully spared due to tumor invading or coming near them. Efforts are therefore focused on increasing the ability of RT to selectively kill cancer cells using radiosensitizing drugs, or to protect the surrounding normal tissues. Other efforts include characterization of tumor molecular subtypes that indicate higher doses of radiation for locoregional control, or patient factors that correlate with higher toxicities.

Publications

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  • Kozono D, Li J, Nitta M, Sampetrean O, Gonda D, Kushwaha DS, Merzon D, Ramakrishnan V, Zhu S, Zhu K, Matsui H, Harismendy O, Hua W, Mao Y, Kwon CH, Saya H, Nakano I, Pizzo DP, VandenBerg SR, Chen CC. Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression. Proc Natl Acad Sci U S A 2015. PubMed
  • Kushwaha D, O'Leary C, Cron KR, Deraska P, Zhu K, D'Andrea AD, Kozono D. USP9X inhibition promotes radiation-induced apoptosis in non-small cell lung cancer cells expressing mid-to-high MCL1. Cancer Biol Ther 2015; 16:392-401. PubMed
  • Baldini EH, Richards WG, Gill RR, Goodman BM, Winfrey OK, Eisen HM, Mak RH, Chen AB, Kozono DE, Bueno R, Sugarbaker DJ. Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2015. PubMed
  • Mak RH, Hermann G, Lewis JH, Aerts HJ, Baldini EH, Chen AB, Colson YL, Hacker FH, Kozono D, Wee JO, Chen YH, Catalano PJ, Wong KK, Sher DJ. Outcomes by tumor histology and KRAS mutation status after lung stereotactic body radiation therapy for early-stage non-small-cell lung cancer. Clin Lung Cancer 2014; 16:24-32. PubMed
  • Gray PJ, Mak RH, Yeap BY, Cryer SK, Pinnell NE, Christianson LW, Sher DJ, Arvold ND, Baldini EH, Chen AB, Kozono DE, Swanson SJ, Jackman DM, Alexander BM. Aggressive therapy for patients with non-small cell lung carcinoma and synchronous brain-only oligometastatic disease is associated with long-term survival. Lung Cancer 2014; 85:239-44. PubMed
  • Parikh RB, Cronin AM, Kozono DE, Oxnard GR, Mak RH, Jackman DM, Lo PC, Baldini EH, Johnson BE, Chen AB. Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys 2014. PubMed
  • Li J, Zhu S, Kozono D, Ng K, Futalan D, Shen Y, Akers JC, Steed T, Kushwaha D, Schlabach M, Carter BS, Kwon CH, Furnari F, Cavenee W, Elledge S, Chen CC. Genome-wide shRNA screen revealed integrated mitogenic signaling between dopamine receptor D2 (DRD2) and epidermal growth factor receptor (EGFR) in glioblastoma. 2014; 5:882-93. PubMed
  • Gazula A, Baldini EH, Chen A, Kozono D. Comparison of once and twice daily radiotherapy for limited stage small-cell lung cancer. Lung 2014; 192:151-8. PubMed
  • Herter-Sprie GS, Korideck H, Christensen CL, Herter JM, Rhee K, Berbeco RI, Bennett DG, Akbay EA, Kozono D, Mak RH, Mike Makrigiorgos G, Kimmelman AC, Wong KK. Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models. Nat Commun 2014; 5:5870. PubMed
  • Coroller TP, Mak RH, Lewis JH, Baldini EH, Chen AB, Colson YL, Hacker FL, Hermann G, Kozono D, Mannarino E, Molodowitch C, Wee JO, Sher DJ, Killoran JH. Low incidence of chest wall pain with a risk-adapted lung stereotactic body radiation therapy approach using three or five fractions based on chest wall dosimetry. PLoS ONE 2014; 9:e94859. PubMed
  • Cron KR, Zhu K, Kushwaha DS, Hsieh G, Merzon D, Rameseder J, Chen CC, D'Andrea AD, Kozono D. Proteasome inhibitors block DNA repair and radiosensitize non-small cell lung cancer. PLoS ONE 2013; 8:e73710. PubMed
  • Morgan EA, Kozono DE, Wang Q, Mery CM, Butrynski JE, Baldini EH, George S, Nascimento AF, Raut CP. Cutaneous radiation-associated angiosarcoma of the breast: poor prognosis in a rare secondary malignancy. Ann Surg Oncol 2012; 19:3801-8. PubMed
  • Nehs MA, Lin CI, Kozono DE, Whang EE, Cho NL, Zhu K, Moalem J, Moore FD, Ruan DT. Necroptosis is a novel mechanism of radiation-induced cell death in anaplastic thyroid and adrenocortical cancers. Surgery 2011; 150:1032-9. PubMed
  • Sturla LM, Zinn PO, Ng K, Nitta M, Kozono D, Chen CC, Kasper EM. Src homology domain-containing phosphatase 2 suppresses cellular senescence in glioblastoma. Br J Cancer 2011; 105:1235-43. PubMed
  • Nitta M, Kozono D, Kennedy R, Stommel J, Ng K, Zinn PO, Kushwaha D, Kesari S, Furnari F, Hoadley KA, Chin L, DePinho RA, Cavenee WK, D'Andrea A, Chen CC. Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy. PLoS ONE 2010; 5:e10767. PubMed
  • Kahle KT, Kozono D, Ng K, Hsieh G, Zinn PO, Nitta M, Chen CC. Functional genomics to explore cancer cell vulnerabilities. Neurosurg Focus 2010; 28:E5. PubMed
  • Palanivelu DV, Kozono DE, Engel A, Suda K, Lustig A, Agre P, Schirmer T. Co-axial association of recombinant eye lens aquaporin-0 observed in loosely packed 3D crystals. J Mol Biol 2005; 355:605-11. PubMed
  • Lee JK, Kozono D, Remis J, Kitagawa Y, Agre P, Stroud RM. Structural basis for conductance by the archaeal aquaporin AqpM at 1.68 A. Proc Natl Acad Sci U S A 2005; 102:18932-7. PubMed
  • Liu K, Kozono D, Kato Y, Agre P, Hazama A, Yasui M. Conversion of aquaporin 6 from an anion channel to a water-selective channel by a single amino acid substitution. Proc Natl Acad Sci U S A 2005; 102:2192-7. PubMed
  • King LS, Kozono D, Agre P. From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol 2004; 5:687-98. PubMed
  • Agre P, Kozono D. Aquaporin water channels: molecular mechanisms for human diseases. FEBS Lett 2003; 555:72-8. PubMed
  • Kozono D, Ding X, Iwasaki I, Meng X, Kamagata Y, Agre P, Kitagawa Y. Functional expression and characterization of an archaeal aquaporin. AqpM from methanothermobacter marburgensis. J Biol Chem 2003; 278:10649-56. PubMed
  • Carbrey JM, Gorelick-Feldman DA, Kozono D, Praetorius J, Nielsen S, Agre P. Aquaglyceroporin AQP9: solute permeation and metabolic control of expression in liver. Proc Natl Acad Sci U S A 2003; 100:2945-50. PubMed
  • Ikeda M, Beitz E, Kozono D, Guggino WB, Agre P, Yasui M. Characterization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine 63. J Biol Chem 2002; 277:39873-9. PubMed
  • Hazama A, Kozono D, Guggino WB, Agre P, Yasui M. Ion permeation of AQP6 water channel protein. Single channel recordings after Hg2+ activation. J Biol Chem 2002; 277:29224-30. PubMed
  • Kozono D, Yasui M, King LS, Agre P. Aquaporin water channels: atomic structure molecular dynamics meet clinical medicine. J Clin Invest 2002; 109:1395-9. PubMed
  • Saparov SM, Kozono D, Rothe U, Agre P, Pohl P. Water and ion permeation of aquaporin-1 in planar lipid bilayers. Major differences in structural determinants and stoichiometry. J Biol Chem 2001; 276:31515-20. PubMed
  • Borgnia MJ, Kozono D, Calamita G, Maloney PC, Agre P. Functional reconstitution and characterization of AqpZ, the E. coli water channel protein. J Mol Biol 1999; 291:1169-79. PubMed
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