Prof. Brenda Laster

Prof. Brenda Laster Profile

Associate Professor


Director of the Jerry L. Cohen Radio-biology Laboratory

Department : Unit of Nuclear Engineering
Room :
Phone :
Email : blaster@bgu.ac.il
Office Hours :  

Education

  • Professor Laster received her B.S. in biology from Stern College for Women, New York, NY and her graduate studies were carried out at Memorial/Sloan Kettering, New York NY, where her major was Diagnostic Cytology. Her Ph.D. studies in experimental pathology and radiation biology were carried out at the State University of New York at Stony Brook, Stony Brook, NY and the Union Institute, Cincinnati, Ohio. Her thesis was on “Binary Systems for the Improvement of Cancer Radiotherapy” and her thesis advisor was Victor P. Bond, M.D., Ph.D. Before joining the faculty of Ben Gurion University, Professor Laster was a scientist in the Medical Department of Brookhaven National Laboratory in Upton, N.Y. and an Assistant Professor in the Department of Radiation Oncology in the School of Medicine at the State University of New York at Stony Brook. She served as a visiting professor in the Department of Radiation Physics at the University of Lund, Lund, Sweden, and in the Social Dimensions of Science, Project WISE, at the State University of New York at Stony Brook, Stony Brook, N.Y.

Research Interests

    • Research Projects

      1. Preventing the Immortality of Cancerous Cells by Enhancing the Radiation Dose to Tumors and Inhibiting the Activation of the Telomerase Enzyme.
      2. This program is progressing through the collaborative efforts of Professor Laster of the Nuclear Engineering Department and Professor Joseph Kost, of the Chemical Engineering Department, and who is currently Dean of BGU’s Faculty of Engineering. Our project involves the physiological targeting of a pharmaceutical, tagged with a stable high Z atom that binds to DNA. The pharmaceutical we use is a DNA binding porphyrin, TMPyP4, tagged with a palladium (Pd) atom (PdTMPyP4). This molecule has been polymerized with a slow, long-term release compound. After a single implantation into malignant tumors growing on the thighs of mice, the pharmaceutical is released for thirty (30) days, as the polymer degrades.
      3. The enzyme, telomerase, is activated during radiotherapy and chemotherapy. Its activation prevents the telomeric ends of DNA from shortening and thereby confers immortality to the cancer cell. Tumor cells use the activation of telomerase as a survival mechanism to retain the length of DNA and prevent their succumbing to treatments that will cause them to die. Therefore, an important feature of our pharmaceutical is its ability to prevent the activation of telomerase.
      4. The long term release of the Pd tag offers another advantage to the use of PdTMPyP4. Photons from radiation sources, whose energies are appropriate to induce a photoelectric effect in the Pd atom, elicit the emission of low-energy, short-range, Auger electrons. These electrons cause the highly local and dense ionization of the DNA in tumor cells, which results in its fragmentation and limited ability to repair itself. The energies emitted by permanently implanted, iodine-125 brachytherapy seeds, are highly suited for inducing Auger electron emission. Finely-tuned monochromatic photons from medical synchrotron beams will also induce the effect.
      5. B. H. Laster, C. Isaacson, E. Perets, M. Msamra, E. Priel, J. Kalef-Ezra, J. Kost, Keeping those telomeres short! An innovative intratumoral long-term drug delivery system. Journal of Cancer Research and Clinical Oncology (2014)
      6. Evaluating the Biological Efficacy of Ingesting Low, Non-toxic Concentrations of Hydrogen Peroxide (H2O2) to Control the Immune System’s Response to Reactive Oxygen Species (ROS).
      7. This project was undertaken when it became clear to us, that H2O2 plays multiple roles in the inflammatory and immune systems. The Inflammation and immunology literature is replete with studies that use H2O2 as representative of ROS to evaluate their impact on the body. ROS are produced when ionizing radiation interacts with body water. ROS are also produced by phagocytic cells responding to body threats from pathogens. A major ROS specie, superoxide, is rapidly and enzymatically dismutated to H2O2, we began to investigate what happens to cells when they are exposed to graded concentrations of H2O2. We observed that high concentrations of H2O2 were lethal to cells, but they were able to recover from medium concentrations. Low concentrations did not have any affect at all. However, when we gave mice a low concentration of H2O2 in their drinking water and measured their differential blood counts weekly, we observed that, after 3 weeks of drinking H2O2, there was an immune response. This response was temporary and blood values returned to normal shortly thereafter. This suggested to us that the random molecular damage patterns caused by H2O2, may have been transmitted to the adaptive immune system. If so, much like this system remembers, rapidly responds, and protects us from the varicella zoster virus (chicken pox) upon a second encounter, H2O2 may act similarly. In fact, varicella is associated with the production of ROS, including H2O2. We are currently investigating the possibility that the ingestion of low concentrations of H2O2 may be useful in preventing an uncontrolled immune response.
      8. The Physiological Response of the Body to Radiation and to Pathogens is essentially the same.
      9. (MS in preparation)
      10. Exploring the Influence of Dietary Proteins in Cancer Development.
      11. This project is being carried out in collaboration with Professor David Eichler of the BGU Physics Department. We are evaluating the effects of a low protein diet compared to a high protein diet on the appearance and growth rate of tumors implanted on the thighs of mice.

        Publications and funding summary / representative publications and grants

        Refereed Publications:

        ·         Azagury, A., Amar-Lewis, E., Yudilevitch, Y., Isaacson, C., Laster, B., and Kost, J. Ultrasound effect on cancerous vs. non-cancerous cells. Ultrasound in Medicine and Biology 2016 (accepted for publication) 

        ·         B. H. Laster, C. Isaacson, E. Perets, M. Msamra, E. Priel, J. Kalef-Ezra & J. Kost. Keeping those telomeres short! An innovative intratumoral long-term drug delivery system. Journal of Cancer Research and Clinical Oncology 141: 23-34 2015

        ·         Laster, B.H., Dixon, D. W., Novick, S., Feldman, J. P., Seror, V., Goldbart, Z. I., Kalef Ezra, J.A. Photon activation therapy and brachytherapy. Brachytherapy,  8(3) 324-330 2009

        ·         Laster, B. and Gopas, J., Monoclonal Antibodies. Wiley Encyclopedia of Medical Devices and Instrumentation; John G. Webster, editor.  University of Wisconsin-Madison Press. Second Edition: p. 597-608  2007

        ·         Novick, S., B. Laster, and M.R. Quastel, Positive cooperativity in the cellular uptake of a boronated porphyrin. Int J Biochem Cell Biol. 38(8): p. 1374-81 2006.

        ·         Swenson, D.H., B.H. Laster, and R.L. Metzger, Synthesis and evaluation of a boronated nitroimidazole for boron neutron capture therapy. J Med Chem, 39(7): p. 1540-4 1996.

        ·         Laster, B.H., Shani, G., Kahl, S. B., Warkentien, L. The biological effects of Auger electrons compared to alpha-particles and Li ions. Acta Oncol, . 35(7): p. 917-23 1996

        ·         Liu, H.B., Brugger, R. M., Laster, B. H., Greenberg, D. D., Gordon, C. R., Warkentien, L. S. Physical and biological doses produced from neutron capture in a 235U foil. Med Phys, 22(5): p. 591-5 1995.

        ·         Bond, V.P., B.H. Laster, and L. Wielopolski, The equal effectiveness ratio: a quantitative approach to the evaluation of compounds for boron neutron capture therapy. Radiat Res, 141(3): p. 287-93 1995

        ·         Slatkin D.N., Micca P.L., Laster B.H., Fairchild R.G. Distribution of sulfhydryl boranes in mice and rats. In: Workshop on Neutron Capture Therapy. Reports BNL-S1994. Edited by R. G. Fairchild and V. P. Bond. Upton, NY: Brookhaven National Laboratory, pp. 173-177 1986

        ·         Laster, B.H., W.C. Thomlinson, and R.G. Fairchild, Photon activation of iododeoxyuridine: biological efficacy of Auger electrons. Radiat Res, 133(2): p. 219-24 1993.

        ·         Laster, B.H., Kahl, S. B., Popenoe, E. A., Pate, D. W., Fairchild, R. G., Biological efficacy of boronated low-density lipoprotein for boron neutron capture therapy as measured in cell culture. Cancer Res, 51(17): p. 4588-93 1991

        ·         Saraf, S.K., Kalef-Ezra, J., Fairchild, R. G., Laster, B. H., Fiarman, S., Ramsey, E.  Epithermal beam development at the BMRR: dosimetric evaluation. Basic Life Sci, 54:307-16 1990

        ·         Laster, B.H., Popenoe, E. A., Wielopolski, L., Commerford, S. L., Gahbauer, R., Goodman, J., Meek, A., Fairchild, R. G., Analysis of 5-iodo-2'-deoxyuridine incorporation in murine melanoma for photon activation therapy. Radiother Oncol,19(2): p. 169-78 1990

        ·         Goodman, J.H., Gahbauer, R. A., Kanellitsas, C., Clendenon, N. R., Laster, B. H., Fairchild, R. G.. Theoretical basis and clinical methodology for stereotactic interstitial brain tumor irradiation using iododeoxyuridine as a radiation sensitizer and 145Sm as a brachytherapy source. Stereotact Funct Neurosurg54-55: p. 531-4 1990

        ·         Fairchild, R.G., Saraf, S. K., Kalef-Ezra, J., Laster, B. H., Comparison of measured parameters from a 24-keV and a broad spectrum epithermal neutron beam for neutron capture therapy: an identification of consequential parameters. Med Phys 17(6): p. 1045-52 1990

        ·         Fairchild, R.G., Kalef-Ezra, J., Saraf, S. K., Fiarman, S., Ramsey, E., Wielopolski, L., Laster, B. H., Wheeler, F. J.  Installation and testing of an optimized epithermal neutron beam at the Brookhaven Medical Research Reactor (BMRR). Basic Life Sci 54:p.185-99  1990

        ·         Fairchild, R.G., Kahl, S. B., Laster, B. H., Kalef-Ezra, J., Popenoe, E. A. In vitro determination of uptake, retention, distribution, biological efficacy, and toxicity of boronated compounds for neutron capture therapy: a comparison of porphyrins with sulfhydryl boron hydrides. Cancer Res, 50(16): p. 4860-5 1990

        ·         Slatkin, D.N., Joel, D. D., Fairchild, R. G., Micca, P. L., Nawrocky, M. M., Laster, B. H., Coderre, J. A., Finkel, G. C., Poletti, C. E., Sweet, W. H.,  Distributions of sulfhydryl borane monomer and dimer in rodents and monomer in humans: boron neutron capture therapy of melanoma and glioma in boronated rodents. Basic Life Sci, 50: p. 179-91 1989.

        ·         Slatkin, D.N., Finkel, G. C., Micca, P. L., Laster, B. H., Poletti, C. E., Sweet, W. H.  Distribution of boron in two (B12H11SH)2--infused patients with malignant glioma. Strahlenther Onkol, 165(2-3): p. 244-6 1989

        ·         Slatkin, D.N., Miura, M., Gabel, D., Fairchild, R. G., Laster, B. H., Warkentien, L. S.,  Synthesis and in vivo studies of a carboranyl porphyrin. Strahlenther Onkol, 165(2-3): p. 131-4 1989

        ·         Slatkin, D.N., Finkel G.C., Micca, P.L, Laster B.H., Poletti C.E., Sweet W.H. Distribution of  boron in two (B2HnSH)"2-infused patients with malignant gliomas. Strahlentherapie und Onkologie,165, 244-246 1989

        ·         Laster, B.H., Kahl, S. B., Popenoe, E. A., Gordon, C., Kalef-Ezra, J., Fairchild, R. G., Survival assays with a boronated porphyrin as measured with hamster V-79 cells in culture. Basic Life Sci, 50: p. 213-8 1989

        ·         Laster, B.H. Kahl, S. B., Kalef-Ezra, J., Popenoe, E. A., Fairchild, R. G. Biological efficacy of a boronated porphyrin as measured in cell culture. Strahlenther Onkol, 165(2-3): p. 203-5 1989

        ·         Kahl, S.B., Laster, B. H., Koo, M. S., Warkentien, L. S., Fairchild, R. G.,  Distribution of a boronated porphyrin in murine tumors. Basic Life Sci, 50: p. 205-12 1989

        ·         Kahl, S.B., Koo, M. S., Laster, B. H., Fairchild, R. G., Boronated porphyrins in NCT: results with a new potent tumor localizer. Strahlenther Onkol, 165(2-3): p. 134-7 1989

        ·         Gahbauer, R., Kanellitsas, C., Blue, T., Wang, C., Clendenon, N., Fairchild, R., Laster, B., McGregor, J., Goodman, J., Dose bracketing in boron neutron capture therapy. Strahlenther Onkol, 165(2-3): p. 229-30 1989

        ·         Fairchild, R.G., Wheeler, F., Slatkin, D. N., Coderre, J., Micca, P., Laster, B., Kahl, S. B., Som, P., Fand, I. Recent developments in neutron capture therapy. Strahlenther Onkol 165(4): p. 343-7 1989

        ·         Fairchild, R.G., Slatkin, D. N., Coderre, J. A., Micca, P. L., Laster, B. H., Kahl, S. B., Som, P., Fand, I., Wheeler, F. Optimization of boron and neutron delivery for neutron capture therapy. Pigment Cell Res 2(4): p. 309-18 1989

        ·         Fairchild, R.G., Coderre, J. A., Packer, S., Greenberg, D., Laster, B. H. Therapeutic effects of S-35-thiouracil in BALB/c mice carrying Harding-Passey melanoma. Int J Radiat Oncol Biol Phys 17(2): p. 337-43 1989

        ·         Slatkin D.N., Joel D.D., Fairchild R.G., Micca P.L., Nawrocky M.M., Laster B.H., Coderre J.A., Finkel G.C., Poletti C.E., Sweet W.H. Distributions of sulfhydryl borane monomer and dimer in rodents and monomer in humans: boron neutron capture therapy of melanoma and glioma in boronated rodents. In: Clinical Aspects of Neutron Capture Therapy. Edited by R. G. Fairchild, V. P. Bond and A. D. Woodhead. New York and London: Plenum Press, pp. 179-191 1989

        ·         Slatkin D.N., Stoner R.D., Rosander K.M., Kalef-ezra J.A., Laissue J.A. Central nervous system radiation syndrome in mice from preferential l0B(n,a)7Li irradiation of brain vasculature. Proceedings of the National Academy of Sciences of the USA, 85, 4020-4024 1988

        ·         Fairchild, R.G., Kalef-Ezra, J., Packer, S., Wielopolski, L., Laster, B. H., Robertson, J. S., Mausner, L., Kanellitsas, C., Samarium-145: a new brachytherapy source. Phys Med Biol 32(7):p. 847-58 , 1987

        ·         Fairchild, R.G., Gabel, D., Laster, B. H., Greenberg, D., Kiszenick, W., Micca, P. L. Microanalytical techniques for boron analysis using the 10B(n,alpha)7Li reaction. Med Phys 13(1): p. 50-6 1986

        ·         Coderre, J.A., Packer, S., Fairchild, R. G., Greenberg, D., Laster, B., Micca, P., Fand, I.  Iodothiouracil as a melanoma localizing agent. J Nucl Med, 27(7): p. 1157-64 1986