RADIOLOGICAL RESEARCH ACCELERATOR FACILITY (RARAF)

Summary

Principal Investigator: DAVID JONATHAN BRENNER
Affiliation: Columbia University
Country: USA
Abstract: The technology development component focuses on four areas which our users have identified as ripe for enhancement: improved accuracy, enhanced imaging capabilities, extension of the charged-particle microbeam to X rays; and development of a simple stand-alone microbeam that can be used without physics support and can be potentially exported to other labs. A highlight regarding improved accuracy and reliability is that we have just received a $2M NIH high-end equipment grant (plus institutional support) for a new particle accelerator, central to the microbeam facility, which will be installed under the auspices of this P-41 grant. Highlights regarding enhanced imaging and sensor technology will be an on-line custom multi-photon imaging system to allow time-lapse fluorescent imaging of early (scale of seconds to minutes) radiation events in individual live cells, a new imaging system based on quantitative phase microscopy to image live cells and cell nuclei without use of potentially cytotoxic stains, and a system for single-cell microsensors to monitor the flux of molecules such as oxygen and NO, in microbeam-irradiated individual cells. In collaboration with a variety of investigators from outside and within Columbia University, 20 collaborative and service-based research projects are described, which both drive and utilize the new resources. All are logical outgrowths of current federally funded research In addition to the ongoing training of undergraduates, graduate students, and post docs, training will be enhanced through formal programs for high school students, high school teachers, and undergraduates. In addition to dissemination of material through talks, our website, and peer-reviewed publications, we will run a 2nd International Workshop "Imaging and Probing Individual Cells: Application to Signaling, Structure and Function", as well as the biannual "International Workshop on Microbeam Probes of Cellular Radiation Response".
Funding Period: 1996-09-30 - 2009-08-31
more information: NIH RePORT

Top Publications

  1. pmc The role of mass spectrometry-based metabolomics in medical countermeasures against radiation
    Andrew D Patterson
    Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
    Mass Spectrom Rev 29:503-21. 2010
  2. pmc The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction
    David J Brenner
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Semin Radiat Oncol 18:234-9. 2008
  3. pmc Optofluidic cell manipulation for a biological microbeam
    Michael Grad
    Department of Mechanical Engineering, Columbia University, New York, New York 10027, USA
    Rev Sci Instrum 84:014301. 2013
  4. pmc UV microspot irradiator at Columbia University
    Alan W Bigelow
    Center for Radiological Research, Columbia University Medical Center, New York, NY, USA
    Radiat Environ Biophys 52:411-7. 2013
  5. pmc Simultaneous immersion Mirau interferometry
    Oleksandra V Lyulko
    Radiological Research Accelerator Facility, Columbia University, 136 S Broadway, Irvington, New York 10533, USA
    Rev Sci Instrum 84:053701. 2013
  6. pmc Microbeam irradiation of C. elegans nematode in microfluidic channels
    M Buonanno
    Radiological Research Accelerator Facility, Columbia University, 136 S Broadway, P O Box 21, Irvington, NY, 10533, USA
    Radiat Environ Biophys 52:531-7. 2013
  7. pmc Single-cell responses to ionizing radiation
    Brian Ponnaiya
    Center for Radiological Research, Columbia University, 630 West 168th Street, VC11 240, New York, NY, 10032, USA
    Radiat Environ Biophys 52:523-30. 2013
  8. pmc Cytoplasmic irradiation results in mitochondrial dysfunction and DRP1-dependent mitochondrial fission
    Bo Zhang
    Authors Affiliations Center for Radiological Research, College of Physicians and Surgeons Department of Radiation Oncology, Columbia University, New York, New York and Biochemistry Section, National Institute for Neurological Disorders and Stroke, NIH, Bethesda, Maryland
    Cancer Res 73:6700-10. 2013
  9. pmc A role for TRAIL/TRAIL-R2 in radiation-induced apoptosis and radiation-induced bystander response of human neural stem cells
    Vladimir N Ivanov
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA
    Apoptosis 19:399-413. 2014
  10. pmc What we know and what we don't know about cancer risks associated with radiation doses from radiological imaging
    D J Brenner
    Center for Radiological Research, Columbia University Medical Center, New York, NY, USA
    Br J Radiol 87:20130629. 2014

Scientific Experts

  • TOM HEI
  • Igor Shuryak
  • DAVID JONATHAN BRENNER
  • Vladimir N Ivanov
  • Yanping Xu
  • Giuseppe Schettino
  • Shanaz A Ghandhi
  • Sally A Amundson
  • Olga A Sedelnikova
  • Rainer Sachs
  • Alan Bigelow
  • Antonella Bertucci
  • G Garty
  • Charles R Geard
  • Brian Ponnaiya
  • E Fuks
  • H Datz
  • L Oster
  • Y S Horowitz
  • G Randers-Pehrson
  • Eric J Hall
  • Stephen A Marino
  • Bo Zhang
  • M Buonanno
  • Oleksandra V Lyulko
  • Michael Grad
  • M Grad
  • Y Horowitz
  • A Rosenfeld
  • Alexandre Mezentsev
  • M Hong
  • Andrew D Patterson
  • A Horowitz
  • S Marino
  • Gerhard Randers-Pehrson
  • Hongning Zhou
  • Burong Hu
  • Lubomir B Smilenov
  • Eli S Williams
  • G Jeff Sykora
  • L B Smilenov
  • Oleg V Belyakov
  • Aiping Zhu
  • Mykyta V Sokolov
  • Manuela Buonanno
  • Guy Garty
  • Chunxin Wang
  • Winsome F Walker
  • Daniel Attinger
  • O Hobert
  • M Gendrel
  • Mercy M Davidson
  • J Livingstone
  • M Rainer
  • D Attinger
  • J Xu
  • B K Jones
  • A Xu
  • Frank J Gonzalez
  • Z Yu
  • H Zhou
  • Jeffrey R Idle
  • Christian Lanz
  • R M Santella
  • L Wu
  • Adayabalam S Balajee
  • Yanrong Su
  • Bo Shen
  • M Margaliot
  • Mark S Akselrod
  • Jacob A Aten
  • M Salasky
  • Robert L Ullrich
  • Jeroen Essers
  • Martijn S Luijsterburg
  • Przemek M Krawczyk
  • Jan Stap
  • Susan M Bailey
  • W M Bonner
  • G J Ross
  • E J Hall
  • Stephen A Mitchell
  • Igor G Panyutin
  • Howard B Lieberman
  • William M Bonner
  • Corinne Leloup
  • Deep Parikh

Detail Information

Publications54

  1. pmc The role of mass spectrometry-based metabolomics in medical countermeasures against radiation
    Andrew D Patterson
    Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
    Mass Spectrom Rev 29:503-21. 2010
    ....
  2. pmc The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction
    David J Brenner
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Semin Radiat Oncol 18:234-9. 2008
    ..To date, there is no evidence of problems when the LQ model has been applied in the clinic...
  3. pmc Optofluidic cell manipulation for a biological microbeam
    Michael Grad
    Department of Mechanical Engineering, Columbia University, New York, New York 10027, USA
    Rev Sci Instrum 84:014301. 2013
    ..To the best of our knowledge, this is the first time that OET cell handling is successfully implemented in a biological microbeam...
  4. pmc UV microspot irradiator at Columbia University
    Alan W Bigelow
    Center for Radiological Research, Columbia University Medical Center, New York, NY, USA
    Radiat Environ Biophys 52:411-7. 2013
    ....
  5. pmc Simultaneous immersion Mirau interferometry
    Oleksandra V Lyulko
    Radiological Research Accelerator Facility, Columbia University, 136 S Broadway, Irvington, New York 10533, USA
    Rev Sci Instrum 84:053701. 2013
    ..The system design and production are described and images produced with the developed techniques are presented...
  6. pmc Microbeam irradiation of C. elegans nematode in microfluidic channels
    M Buonanno
    Radiological Research Accelerator Facility, Columbia University, 136 S Broadway, P O Box 21, Irvington, NY, 10533, USA
    Radiat Environ Biophys 52:531-7. 2013
    ..5-MeV proton microbeam irradiation induced DNA damage in wild-type C. elegans, as assessed by the formation of Rad51 foci that are essential for homologous repair of radiation-induced DNA damage. ..
  7. pmc Single-cell responses to ionizing radiation
    Brian Ponnaiya
    Center for Radiological Research, Columbia University, 630 West 168th Street, VC11 240, New York, NY, 10032, USA
    Radiat Environ Biophys 52:523-30. 2013
    ..This in turn points to the value of single-cell analyses. ..
  8. pmc Cytoplasmic irradiation results in mitochondrial dysfunction and DRP1-dependent mitochondrial fission
    Bo Zhang
    Authors Affiliations Center for Radiological Research, College of Physicians and Surgeons Department of Radiation Oncology, Columbia University, New York, New York and Biochemistry Section, National Institute for Neurological Disorders and Stroke, NIH, Bethesda, Maryland
    Cancer Res 73:6700-10. 2013
    ..Taken together, our results provide a mechanistic explanation for the extranuclear, nontargeted effects of ionizing radiation...
  9. pmc A role for TRAIL/TRAIL-R2 in radiation-induced apoptosis and radiation-induced bystander response of human neural stem cells
    Vladimir N Ivanov
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA
    Apoptosis 19:399-413. 2014
    ..Intercellular communication between cancer cells and NSC could potentially be involved in amplification of cancer pathology in the brain. ..
  10. pmc What we know and what we don't know about cancer risks associated with radiation doses from radiological imaging
    D J Brenner
    Center for Radiological Research, Columbia University Medical Center, New York, NY, USA
    Br J Radiol 87:20130629. 2014
    ..For lower dose examinations, we have very little data, and the situation is much less certain, however, the collective dose from these lower dose examinations is comparatively unimportant from a public health perspective. ..
  11. pmc Mechanism of genotoxicity induced by targeted cytoplasmic irradiation
    M Hong
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Br J Cancer 103:1263-8. 2010
    ..Although targeted cytoplasmic irradiation has been shown to induce mutations in mammalian cells, the precise mechanism(s) underlying the mutagenic process is largely unknown...
  12. pmc Regulation of early signaling and gene expression in the alpha-particle and bystander response of IMR-90 human fibroblasts
    Shanaz A Ghandhi
    Center for Radiological Research, Columbia University, VC11 215, 630 West 168th Street, New York, NY 10032, USA
    BMC Med Genomics 3:31. 2010
    ....
  13. doi Effects of radiation quality on interactions between oxidative stress, protein and DNA damage in Deinococcus radiodurans
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    Radiat Environ Biophys 49:693-703. 2010
    ..These results suggest that synergism between oxidative stress and DNA damage may play an important role not only during γ-ray exposure, but during high-LET radiation exposure as well...
  14. pmc Development of a method for assessing non-targeted radiation damage in an artificial 3D human skin model
    Giuseppe Schettino
    Centre Cancer Research and Cell Biology, Queen s University Belfast, Belfast, Northern Ireland, UK
    Int J Radiat Biol 86:593-601. 2010
    ..This manuscript describes the development of a reliable protocol to harvest cells from tissue samples and investigate the radiation damage induced on a single cell basis...
  15. pmc Radiation-induced bystander signaling pathways in human fibroblasts: a role for interleukin-33 in the signal transmission
    Vladimir N Ivanov
    Center for Radiological Research, Department of Radiation Oncology, Columbia University, New York, NY 10032, USA
    Cell Signal 22:1076-87. 2010
    ....
  16. pmc An accelerator-based neutron microbeam system for studies of radiation effects
    Yanping Xu
    Radiological Research Accelerator Facility, Columbia University, Irvington, NY 10533, USA
    Radiat Prot Dosimetry 145:373-6. 2011
    ..The imaging of the neutron beam was performed using novel fluorescent nuclear track detector technology based on Mg-doped luminescent aluminum oxide single crystals and confocal laser scanning fluorescent microscopy...
  17. pmc Radiation induced non-targeted response: mechanism and potential clinical implications
    Tom K Hei
    Center for Radiological Research, Department of Radiation Oncology, Columbia University Medical Center, Vanderbilt Clinic, New York, USA
    Curr Mol Pharmacol 4:96-105. 2011
    ..A better understanding of the mechanism of the non-targeted effects will be invaluable to assess its clinical relevance and ways in which the bystander phenomenon can be manipulated to increase therapeutic gain in radiotherapy...
  18. pmc Design of a novel flow-and-shoot microbeam
    G Garty
    RARAF, Columbia University, 136 S Broadway, Irvington, NY 10533, USA
    Radiat Prot Dosimetry 143:344-8. 2011
    ..g. lymphocytes), which is of great interest to many of the RARAF users. This study presents the design of a FAST microbeam and results of first tests of imaging and tracking as well as a discussion of the achievable throughput...
  19. pmc Thermoluminescence solid-state nanodosimetry--the peak 5A/5 dosemeter
    E Fuks
    Physics Department, Ben Gurion University, Beersheva, Israel
    Radiat Prot Dosimetry 143:416-26. 2011
    ....
  20. pmc Time-series clustering of gene expression in irradiated and bystander fibroblasts: an application of FBPA clustering
    Shanaz A Ghandhi
    Center for Radiological Research, Columbia University, New York, NY 10032, USA
    BMC Genomics 12:2. 2011
    ..We compared our results with those of an alternate clustering method, Short Time series Expression Miner (STEM)...
  21. pmc Radiation response and regulation of apoptosis induced by a combination of TRAIL and CHX in cells lacking mitochondrial DNA: a role for NF-κB-STAT3-directed gene expression
    Vladimir N Ivanov
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, USA
    Exp Cell Res 317:1548-66. 2011
    ....
  22. pmc Global gene expression responses to low- or high-dose radiation in a human three-dimensional tissue model
    Alexandre Mezentsev
    Center for Radiological Research, Columbia University Medical Center, New York, New York 10032, USA
    Radiat Res 175:677-88. 2011
    ..HNF4A protein levels and phosphorylation were found to increase in tissues and cells after low- but not high-dose irradiation...
  23. pmc A model of interactions between radiation-induced oxidative stress, protein and DNA damage in Deinococcus radiodurans
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th St, New York, NY 10032, USA
    J Theor Biol 261:305-17. 2009
    ..Our model of radiogenic oxidative stress is consistent with these data and can potentially be generalized to other organisms and lower radiation doses...
  24. pmc Protein kinase C epsilon is involved in ionizing radiation induced bystander response in human cells
    Burong Hu
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, 630 West, 168th Street, VC 11, Room 239, Columbia University, New York, NY 10032, USA
    Int J Biochem Cell Biol 41:2413-21. 2009
    ..Our novel study suggests the possibility that PKC signaling pathway may be a critical molecular target for suppression of ionizing radiation induced biological effects in bystander cells...
  25. pmc Mysteries of LiF TLD response following high ionisation density irradiation: nanodosimetry and track structure theory, dose response and glow curve shapes
    Y Horowitz
    Physics Department, Ben Gurion University, Beersheva, Israel
    Radiat Prot Dosimetry 145:356-72. 2011
    ....
  26. ncbi Extrapolating radiation-induced cancer risks from low doses to very low doses
    David J Brenner
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Health Phys 97:505-9. 2009
    ....
  27. ncbi DNA double-strand breaks are not sufficient to initiate recruitment of TRF2
    Eli S Williams
    Nat Genet 39:696-8; author reply 698-9. 2007
  28. ncbi Novel Al2O3:C,Mg fluorescent nuclear track detectors for passive neutron dosimetry
    G Jeff Sykora
    Landauer, Inc, Stillwater Crystal Growth Division, Stillwater, OK 74074, USA
    Radiat Prot Dosimetry 126:278-83. 2007
    ..A specially developed image processing technique allows for fast fluorescent track identification and counting. The readout method is non-destructive, and detectors can be reused after thermal annealing...
  29. ncbi DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models
    Olga A Sedelnikova
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 67:4295-302. 2007
    ..Thus, this study points to the importance of considering the indirect biological effects of radiation in cancer risk assessment...
  30. ncbi Testing the stand-alone microbeam at Columbia University
    G Garty
    Columbia University, Radiological Research Accelerator Facility, 136 S Broadway, Irvington, NY 10533, USA
    Radiat Prot Dosimetry 122:292-6. 2006
    ..It also makes the microbeam simple and cheap enough to be realised in any large lab. The Microbeam design as well as first tests of its performance, using an accelerator-based beam are presented here...
  31. ncbi Radiation-induced leukemia at doses relevant to radiation therapy: modeling mechanisms and estimating risks
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th St, New York, NY 10032, USA
    J Natl Cancer Inst 98:1794-806. 2006
    ..This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks...
  32. ncbi A microbeam study of DNA double-strand breaks in bystander primary human fibroblasts
    L B Smilenov
    Center for Radiological Research, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Radiat Prot Dosimetry 122:256-9. 2006
    ..The delay and persistence of the bystander response suggests a different mechanism of DSB induction in bystander cells than in directly irradiated cells...
  33. pmc Differential impact of mouse Rad9 deletion on ionizing radiation-induced bystander effects
    Aiping Zhu
    Center for Radiological Research, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Radiat Res 164:655-61. 2005
    ..Results are presented in the context of defining the function of Rad9 in the cellular response to radiation and its differential effects on individual bystander end points...
  34. ncbi Ionizing radiation induces DNA double-strand breaks in bystander primary human fibroblasts
    Mykyta V Sokolov
    Department of Nuclear Medicine, Clinical Center, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Oncogene 24:7257-65. 2005
    ..These studies show that H2AX phosphorylation is an early step in the bystander effect and that the DNA DSBs underlying gamma-H2AX focus formation may be responsible for its downstream manifestations...
  35. pmc Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away
    Oleg V Belyakov
    Center for Radiological Research, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 102:14203-8. 2005
    ....
  36. pmc Second cancers after fractionated radiotherapy: stochastic population dynamics effects
    Rainer K Sachs
    Departments of Mathematics and of Physics, University of California, 970 Evans Hall, MC 3840, Berkeley, CA 94720, USA
    J Theor Biol 249:518-31. 2007
    ....
  37. ncbi Reducing second breast cancers: a potential role for prophylactic mammary irradiation
    David J Brenner
    Center for Radiological Research, Department of Radiation Oncology, Columbia University Medical Center, New York, NY, USA
    J Clin Oncol 25:4868-72. 2007
  38. ncbi Biophysical models of radiation bystander effects: 1. Spatial effects in three-dimensional tissues
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, New York, New York 10032, USA
    Radiat Res 168:741-9. 2007
    ..These assumptions are implemented by a mathematical formalism and computational algorithms. The model adequately describes data on bystander responses in the 3D system using a small number of adjustable parameters...
  39. pmc Reduction of the secondary neutron dose in passively scattered proton radiotherapy, using an optimized pre-collimator/collimator
    David J Brenner
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Phys Med Biol 54:6065-78. 2009
    ....
  40. pmc A new view of radiation-induced cancer: integrating short- and long-term processes. Part I: approach
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    Radiat Environ Biophys 48:263-74. 2009
    ....
  41. pmc A new view of radiation-induced cancer: integrating short- and long-term processes. Part II: second cancer risk estimation
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    Radiat Environ Biophys 48:275-86. 2009
    ..Potentially, the model can be incorporated into radiotherapy treatment planning algorithms, adding second cancer risk as an optimization criterion...
  42. pmc Is there a place for quantitative risk assessment?
    Eric J Hall
    Columbia University Medical Center, New York, NY, USA
    J Radiol Prot 29:A171-84. 2009
    ..These three examples, where uncertainties in quantitative risk estimates result in important practical problems, will be discussed...
  43. pmc Advances in radiobiological studies using a microbeam
    Tom K Hei
    Center for Radiological Research, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
    J Radiat Res 50:A7-A12. 2009
    ..The identification of specific signaling pathways provides mechanistic insight on the nature of the bystander process...
  44. pmc Microbeam irradiation of the C. elegans nematode
    Antonella Bertucci
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    J Radiat Res 50:A49-54. 2009
    ..GFP expression was enhanced after 24 hours in a number dependent manner at distances > 100 microm from the site of irradiation...
  45. pmc Expanding the question-answering potential of single-cell microbeams at RARAF, USA
    Alan Bigelow
    Center for Radiological Research, Columbia University, Irvington, New York 10533 0021, USA
    J Radiat Res 50:A21-8. 2009
    ..Additionally, an update on the status of the other biology oriented microbeams in the Americas is provided...
  46. pmc Microbeam-integrated multiphoton imaging system
    Alan W Bigelow
    Center for Radiological Research, Columbia University, New York, New York 10032, USA
    Rev Sci Instrum 79:123707. 2008
    ..Design details and biology applications using this enhanced 3D-imaging technique at RARAF are reviewed...
  47. pmc Investigation of the ionisation density dependence of the glow curve characteristics of LIF:MG,TI (TLD-100)
    Y S Horowitz
    Physics Department, Ben Gurion University of the Negev, Beersheva, Israel
    Radiat Prot Dosimetry 131:406-13. 2008
    ....
  48. ncbi Stress-specific signatures: expression profiling of p53 wild-type and -null human cells
    Sally A Amundson
    Gene Response Section, Center for Cancer Research, NCI, Bethesda, MD 20892, USA
    Oncogene 24:4572-9. 2005
    ..A set of 16 genes did exhibit a robust p53-dependent pattern of induction in response to all nine DNA-damaging agents, however...