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 from Harvard Catalyst Profiles

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  • Bitterman DS, Selesnick P, Bredfeldt J, Williams CL, Guthier C, Huynh E, Kozono DE, Lewis JH, Cormack RA, Carpenter CM, Mak RH, Atkins KM. Dosimetric Planning Tradeoffs to Reduce Heart Dose Using Machine Learning-Guided Decision Support Software in Patients with Lung Cancer. Int J Radiat Oncol Biol Phys 2021. PubMed
  • Liu KX, Sierra-Davidson K, Tyan K, Orlina LT, Marcoux JP, Kann BH, Kozono DE, Mak RH, White A, Singer L. Surgical complications and clinical outcomes after dose-escalated trimodality therapy for non-small cell lung cancer in the era of intensity-modulated radiotherapy. Radiother Oncol 2021; 165:44-51. PubMed
  • Hensing TA, Wang X, Stinchcombe TE, Gao J, Knopp MV, Watson M, Dudek AZ, Graziano SL, Patel JD, Faller BA, Dragnev KH, Kozono D, Vokes EE. Alliance Foundation Trial 09: A Randomized, Multicenter, Phase 2 Trial Evaluating Two Sequences of Pembrolizumab and Standard Platinum-Based Chemotherapy in Patients With Metastatic NSCLC. JTO Clin Res Rep 2021; 2:100208. PubMed
  • Kozono DE, Stinchcombe TE, Salama JK, Bogart J, Petty WJ, Guarino MJ, Bazhenova L, Larner JM, Weiss J, DiPetrillo TA, Feigenberg SJ, Chen X, Sun Z, Nuthalapati I, Rosenwinkel L, Johnson EF, Bach BA, Luo Y, Vokes EE. Veliparib in combination with carboplatin/paclitaxel-based chemoradiotherapy in patients with stage III non-small cell lung cancer. Lung Cancer 2021; 159:56-65. PubMed
  • Talcott WJ, Miccio JA, Park HS, White AA, Kozono DE, Singer L, Sands JM, Sholl LM, Detterbeck FC, Mak RH, Decker RH, Kann BH. Rates of invasive disease and outcomes in NSCLC patients with biopsy suggestive of carcinoma in situ. Lung Cancer 2021; 157:17-20. PubMed
  • Sands JM, Mandrekar SJ, Kozono D, Oxnard GR, Hillman SL, Wigle DA, Govindan R, Carlisle J, Gray J, Salama JK, Raez L, Ganti A, Foster N, Malik S, Bradley J, Kelly K, Ramalingam SS, Stinchcombe TE. Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO). 2021; 13:727-734. PubMed
  • Atkins KM, Bitterman DS, Chaunzwa TL, Kozono DE, Baldini EH, Aerts HJWL, Tamarappoo BK, Hoffmann U, Nohria A, Mak RH. Mean Heart Dose Is an Inadequate Surrogate for Left Anterior Descending Coronary Artery Dose and the Risk of Major Adverse Cardiac Events in Lung Cancer Radiation Therapy. Int J Radiat Oncol Biol Phys 2021. PubMed
  • Branigan TB, Kozono D, Schade AE, Deraska P, Rivas HG, Sambel L, Reavis HD, Shapiro GI, D'Andrea AD, DeCaprio JA. MMB-FOXM1-driven premature mitosis is required for CHK1 inhibitor sensitivity. Cell Rep 2021; 34:108808. PubMed
  • Atkins KM, Chaunzwa TL, Lamba N, Bitterman DS, Rawal B, Bredfeldt J, Williams CL, Kozono DE, Baldini EH, Nohria A, Hoffmann U, Aerts HJWL, Mak RH. Association of Left Anterior Descending Coronary Artery Radiation Dose With Major Adverse Cardiac Events and Mortality in Patients With Non-Small Cell Lung Cancer. JAMA Oncol 2021; 7:206-219. PubMed
  • Atkins KM, Bitterman DS, Chaunzwa TL, Williams CL, Rahman R, Kozono DE, Baldini EH, Aerts HJWL, Tamarappoo BK, Hoffmann U, Nohria A, Mak RH. Statin Use, Heart Radiation Dose, and Survival in Locally Advanced Lung Cancer. 2021. PubMed
  • Meerman M, Driessen R, van Engeland NCA, Bergsma I, Steenhuijsen JLG, Kozono D, Aikawa E, Hjortnaes J, Bouten CVC. Radiation Induces Valvular Interstitial Cell Calcific Response in an Model of Calcific Aortic Valve Disease. Front Cardiovasc Med 2021; 8:687885. PubMed
  • Mueller R, Yasmin-Karim S, DeCosmo K, Vazquez-Pagan A, Sridhar S, Kozono D, Hesser J, Ngwa W. Increased carcinoembryonic antigen expression on the surface of lung cancer cells using gold nanoparticles during radiotherapy. 2020; 76:236-242. PubMed
  • Cai MY, Dunn CE, Chen W, Kochupurakkal BS, Nguyen H, Moreau LA, Shapiro GI, Parmar K, Kozono D, D'Andrea AD. Cooperation of the ATM and Fanconi Anemia/BRCA Pathways in Double-Strand Break End Resection. Cell Rep 2020; 30:2402-2415.e5. PubMed
  • Kamran SC, Coroller T, Milani N, Agrawal V, Baldini EH, Chen AB, Johnson BE, Kozono D, Franco I, Chopra N, Zeleznik R, Aerts HJWL, Mak R. The impact of quantitative CT-based tumor volumetric features on the outcomes of patients with limited stage small cell lung cancer. Radiat Oncol 2020; 15:14. PubMed
  • Li F, Kozono D, Deraska P, Branigan T, Dunn C, Zheng XF, Parmar K, Nguyen H, DeCaprio J, Shapiro GI, Chowdhury D, D'Andrea AD. CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress. Mol Cell 2020; 80:410-422.e6. PubMed
  • Mitra D, Chen YH, Li R, Hermann G, Atkins K, Kozono D, Baldini EH, Aizer A, Chukwueke U, Mak RH. EGFR mutant locally advanced non-small cell lung cancer is at increased risk of brain metastasis. Clin Transl Radiat Oncol 2019; 18:32-38. PubMed
  • Atkins KM, Rawal B, Chaunzwa TL, Lamba N, Bitterman DS, Williams CL, Kozono DE, Baldini EH, Chen AB, Nguyen PL, D'Amico AV, Nohria A, Hoffmann U, Aerts HJWL, Mak RH. Cardiac Radiation Dose, Cardiac Disease, and Mortality in Patients With Lung Cancer. J Am Coll Cardiol 2019; 73:2976-2987. PubMed
  • Chalubinska-Fendler J, Graczyk L, Piotrowski G, Wyka K, Nowicka Z, Tomasik B, Fijuth J, Kozono D, Fendler W. Lipopolysaccharide-Binding Protein Is an Early Biomarker of Cardiac Function After Radiation Therapy for Breast Cancer. Int J Radiat Oncol Biol Phys 2019. PubMed
  • Ishizuka JJ, Manguso RT, Cheruiyot CK, Bi K, Panda A, Iracheta-Vellve A, Miller BC, Du PP, Yates KB, Dubrot J, Buchumenski I, Comstock DE, Brown FD, Ayer A, Kohnle IC, Pope HW, Zimmer MD, Sen DR, Lane-Reticker SK, Robitschek EJ, Griffin GK, Collins NB, Long AH, Doench JG, Kozono D, Levanon EY, Haining WN. Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade. Nature 2019; 565:43-48. PubMed
  • Lim KS, Li H, Roberts EA, Gaudiano EF, Clairmont C, Sambel LA, Ponnienselvan K, Liu JC, Yang C, Kozono D, Parmar K, Yusufzai T, Zheng N, D'Andrea AD. USP1 Is Required for Replication Fork Protection in BRCA1-Deficient Tumors. Mol Cell 2018; 72:925-941.e4. PubMed
  • Deraska PV, O'Leary C, Reavis HD, Labe S, Dinh TK, Lazaro JB, Sweeney C, D'Andrea AD, Kozono D. NF-κB inhibition by dimethylaminoparthenolide radiosensitizes non-small-cell lung carcinoma by blocking DNA double-strand break repair. Cell Death Discov 2018; 4:10. PubMed
  • Diao K, Chen YH, Catalano PJ, Lee S, Milani N, Killoran JH, Baldini EH, Chen AB, Kozono DE, Mak RH. Radiation toxicity in patients with collagen vascular disease and intrathoracic malignancy treated with modern radiation techniques. Radiother Oncol 2017; 125:301-309. PubMed
  • Franco I, Chen YH, Chipidza F, Agrawal V, Romano J, Baldini E, Chen A, Colson Y, Hou Y, Kozono D, Wee J, Mak R. Use of frailty to predict survival in elderly patients with early stage non-small-cell lung cancer treated with stereotactic body radiation therapy. 2017. PubMed
  • Agrawal V, Coroller TP, Hou Y, Lee SW, Romano JL, Baldini EH, Chen AB, Kozono D, Swanson SJ, Wee JO, Aerts HJWL, Mak RH. Lymph node volume predicts survival but not nodal clearance in Stage IIIA-IIIB NSCLC. PLoS ONE 2017; 12:e0174268. PubMed
  • Agrawal V, Coroller TP, Hou Y, Lee SW, Romano JL, Baldini EH, Chen AB, Jackman DM, Kozono D, Swanson SJ, Wee JO, Aerts HJ, Mak RH. Radiologic-pathologic correlation of response to chemoradiation in resectable locally advanced NSCLC. Lung Cancer 2016; 102:1-8. PubMed
  • Mingos M, Howard S, Giacalone N, Kozono D, Jacene H. Systemic Immune Response to Vaccination on FDG-PET/CT. Nucl Med Mol Imaging 2016; 50:358-361. PubMed
  • Hou Y, Hermann G, Lewis JH, Aerts HJ, Baldini EH, Chen AB, Colson YL, Hacker FL, Killoran JH, Kozono DE, Wagar M, Wee JO, Mak RH. Clinical Outcomes After Lung Stereotactic Body Radiation Therapy in Patients With or Without a Prior Lung Resection. Am J Clin Oncol 2016. PubMed
  • Hou Y, Lee S, Agrawal V, Romano J, Baldini EH, Chen AB, Kozono DE, Killoran JH, Wagar M, Hacker FL, Aerts HJ, Lewis JH, Mak RH. Inter-scan and inter-observer tumour volume delineation variability on cone beam computed tomography in patients treated with stereotactic body radiation therapy for early-stage non-small cell lung cancer. J Med Imaging Radiat Oncol 2016. PubMed
  • Kais Z, Rondinelli B, Holmes A, O'Leary C, Kozono D, D'Andrea AD, Ceccaldi R. FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair. Cell Rep 2016; 15:2488-99. PubMed
  • Li R, Hermann G, Baldini E, Chen A, Jackman D, Kozono D, Nguyen P, Nohria A, Powell G, Mak R. Advanced nodal stage predicts venous thromboembolism in patients with locally advanced non-small cell lung cancer. Lung Cancer 2016; 96:41-7. PubMed
  • Zhang H, Kozono DE, O'Connor KW, Vidal-Cardenas S, Rousseau A, Hamilton A, Moreau L, Gaudiano EF, Greenberger J, Bagby G, Soulier J, Grompe M, Parmar K, D'Andrea AD. TGF-β Inhibition Rescues Hematopoietic Stem Cell Defects and Bone Marrow Failure in Fanconi Anemia. Cell Stem Cell 2016. PubMed
  • Dinh TK, Fendler W, Chałubińska-Fendler J, Acharya SS, O'Leary C, Deraska PV, D'Andrea AD, Chowdhury D, Kozono D. Circulating miR-29a and miR-150 correlate with delivered dose during thoracic radiation therapy for non-small cell lung cancer. Radiat Oncol 2016; 11:61. PubMed
  • 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
  • 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
  • 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
  • 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 2015; 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
  • 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
  • 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
  • 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 2006; 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
  • Liu KX, Chen YH, Kozono D, Mak RH, Boyle PJ, Janeway KA, Mullen EA, Marcus KJ. Phase I/II Study of Stereotactic Body Radiation Therapy for Pulmonary Metastases in Pediatric Patients. Adv Radiat Oncol ; 5:1267-1273. 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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