Kathryn D. Held, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-8161
Fax: (617) 724-8320


kheld@partners.org

Kathryn D. Held, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Radiation Oncology, Harvard Medical School
  • Associate Radiation Biologist, Radiation Oncology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our research covers two related areas: cellular responses to localized oxidative stress and mechanisms for stress-induced bystander effects. The studies on localized oxidative stress involve a team approach for use of state-of-the-art methods such as ionizing radiation microbeams, in collaboration with a group in the UK, and subcellularly localized photosensitizers to study biochemical pathways involved in triggering of apoptosis, mutagenesis, and DNA damage and repair after subcellularly localized stress induction, e.g., in nuclear versus non-nuclear regions including plasma membranes and mitochondria. Cells containing genetic mutations or knock-downs in apoptosis and DNA repair pathways are used, and cellular responses are followed, among other approaches, by use of sophisticated time-lapse microscopy. The studies on stress-induced bystander effects involve investigation of the signaling pathways whereby a cell that is damaged by ionizing radiation, photosensitizers or other oxidative stresses sends a signal to neighboring undamaged cells which then show a biological response. These studies include use of a unique heavy ion irradiation facility at Brookhaven National Laboratory.

Publications

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  • Liu Q, Ghosh P, Magpayo N, Testa M, Tang S, Gheorghiu L, Biggs P, Paganetti H, Efstathiou JA, Lu HM, Held KD, Willers H. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation. Int J Radiat Oncol Biol Phys 2015; 91:1081-9. PubMed
  • Liu Q, Wang M, Kern AM, Khaled S, Han J, Yeap BY, Hong TS, Settleman J, Benes CH, Held KD, Efstathiou JA, Willers H. Adapting a Drug Screening Platform to Discover Associations of Molecular Targeted Radiosensitizers with Genomic Biomarkers. Mol Cancer Res 2015. PubMed
  • Kesler CT, Kuo AH, Wong HK, Masuck DJ, Shah JL, Kozak KR, Held KD, Padera TP. Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells. Angiogenesis 2014; 17:419-27. PubMed
  • Liu Q, Xu C, Kirubakaran S, Zhang X, Hur W, Liu Y, Kwiatkowski NP, Wang J, Westover KD, Gao P, Ercan D, Niepel M, Thoreen CC, Kang SA, Patricelli MP, Wang Y, Tupper T, Altabef A, Kawamura H, Held KD, Chou DM, Elledge SJ, Janne PA, Wong KK, Sabatini DM, Gray NS. Characterization of Torin2, an ATP-Competitive Inhibitor of mTOR, ATM, and ATR. Cancer Res 2013; 73:2574-2586. PubMed
  • Held KD. Summary: achievements, critical issues, and thoughts on the future. Health Phys 2012; 103:681-4. PubMed
  • Butterworth KT, McGarry CK, Clasie B, Carabe-Fernandez A, Schuemann J, Depauw N, Tang S, McMahon SJ, Schettino G, O'Sullivan JM, Lu HM, Kooy H, Paganetti H, Hounsell AR, Held KD, Prise KM. Relative biological effectiveness (RBE) and out-of-field cell survival responses to passive scattering and pencil beam scanning proton beam deliveries. Phys Med Biol 2012; 57:6671-80. PubMed
  • Wakatsuki M, Magpayo N, Kawamura H, Held KD. Differential bystander signaling between radioresistant chondrosarcoma cells and fibroblasts after x-ray, proton, iron ion and carbon ion exposures. Int J Radiat Oncol Biol Phys 2012; 84:e103-8. PubMed
  • Yang H, Magpayo N, Held KD. Targeted and non-targeted effects from combinations of low doses of energetic protons and iron ions in human fibroblasts. Int J Radiat Biol 2011; 87:311-9. PubMed
  • Purschke M, Rubio N, Held KD, Redmond RW. Phototoxicity of Hoechst 33342 in time-lapse fluorescence microscopy. Photochem Photobiol Sci 2010; 9:1634-9. PubMed
  • Held KD. Basic Clinical Radiobiology. Int J Radiat Biol 2010. PubMed
  • Zhang Y, Zhou J, Baldwin J, Held KD, Prise KM, Redmond RW, Liber HL. Ionizing radiation-induced bystander mutagenesis and adaptation: quantitative and temporal aspects. Mutat Res 2009; 671:20-5. PubMed
  • Rosenstein BS, Held KD, Rockwell S, Williams JP, Zeman EM. American Society for Radiation Oncology (ASTRO) survey of radiation biology educators in U.S. and Canadian radiation oncology residency programs. Int J Radiat Oncol Biol Phys 2009; 75:896-905. PubMed
  • Rubio N,Rajadurai A,Held KD,Prise KM,Liber HL,Redmond RW. Real-time imaging of novel spatial and temporal responses to photodynamic stress. Free Radic Biol Med 2009; 47:283-90. PubMed
  • Chakraborty A, Held KD, Prise KM, Liber HL, Redmond RW. Bystander effects induced by diffusing mediators after photodynamic stress. Radiat Res 2009; 172:74-81. PubMed
  • Kuhnert VM,Kachnic LA,Li L,Purschke M,Gheorghiu L,Lee R,Held KD,Willers H. FANCD2-deficient human fibroblasts are hypersensitive to ionising radiation at oxygen concentrations of 0% and 3% but not under normoxic conditions. Int J Radiat Biol 2009; 85:523-31. PubMed
  • Held KD. Effects of low fluences of radiations found in space on cellular systems. Int J Radiat Biol 2009; 85:379-90. PubMed
  • Zhang Y, Zhou J, Held KD, Redmond RW, Prise KM, Liber HL. Deficiencies of double-strand break repair factors and effects on mutagenesis in directly gamma-irradiated and medium-mediated bystander human lymphoblastoid cells. Radiat Res 2008; 169:197-206. PubMed
  • Shao C,Folkard M,Held KD,Prise KM. Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation. BMC Cancer 2008; 8:184. PubMed
  • Lawenda BD, Smith DE, Xu L, Niemierko A, Silverstein JR, Boucher Y, Kashiwagi S, Held KD, Jain RK, Loeffler JS, Eisenberg DM, Blumberg JB. Do the dietary supplements epigallocatechin gallate or vitamin e cause a radiomodifying response on tumors in vivo? A pilot study with murine breast carcinoma. J Soc Integr Oncol 2007; 5:11-7. PubMed
  • Yang H, Anzenberg V, Held KD. The time dependence of bystander responses induced by iron-ion radiation in normal human skin fibroblasts. Radiat Res 2007; 168:292-8. PubMed
  • Willers H, Held KD. Introduction to clinical radiation biology. Hematol Oncol Clin North Am 2006; 20:1-24. PubMed
  • Muckova K, Duffield JS, Held KD, Bonventre JV, Sheridan AM. cPLA2-interacting protein, PLIP, causes apoptosis and decreases G1 phase in mesangial cells. Am J Physiol Renal Physiol 2005; 290:F70-9. PubMed
  • Prise KM, Schettino G, Folkard M, Held KD. New insights on cell death from radiation exposure. Lancet Oncol 2005; 6:520-8. PubMed
  • Yang H, Asaad N, Held KD. Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts. Oncogene 2005; 24:2096-103. PubMed
  • Schettino G, Folkard M, Prise KM, Vojnovic B, Held KD, Michael BD. Low-dose studies of bystander cell killing with targeted soft X rays. Radiat Res 2003; 160:505-11. PubMed
  • Biaglow JE, Lee I, Donahue J, Held K, Mieyal J, Dewhirst M, Tuttle S. Glutathione depletion or radiation treatment alters respiration and induces apoptosis in R3230Ac mammary carcinoma. Adv Exp Med Biol 2003; 530:153-64. PubMed
  • White SM, Held KD, Palmer MR, Yanch JC. Biological dosimetry for epithermal neutron beams. Radiat Res 2001; 155:778-84. PubMed
  • Tartier L, McCarey YL, Biaglow JE, Kochevar IE, Held KD. Apoptosis induced by dithiothreitol in HL-60 cells shows early activation of caspase 3 and is independent of mitochondria. Cell Death Differ 2001; 7:1002-10. PubMed
  • Biaglow JE, Donahue J, Tuttle S, Held K, Chrestensen C, Mieyal J. A method for measuring disulfide reduction by cultured mammalian cells: relative contributions of glutathione-dependent and glutathione-independent mechanisms. Anal Biochem 2000; 281:77-86. PubMed
  • Tuttle S, Horan AM, Koch CJ, Held K, Manevich Y, Biaglow J. Radiation-sensitive tyrosine phosphorylation of cellular proteins: sensitive to changes in GSH content induced by pretreatment with N-acetyl-L-cysteine or L-buthionine-S,R-sulfoximine. Int J Radiat Oncol Biol Phys 1998; 42:833-8. PubMed
  • Manevich Y, Held KD, Biaglow JE. Coumarin-3-carboxylic acid as a detector for hydroxyl radicals generated chemically and by gamma radiation. Radiat Res 1997; 148:580-91. PubMed
  • Hagan MP, Hopcia KL, Sylvester FC, Held KD. Caffeine-induced apoptosis reveals a persistent lesion after treatment with bromodeoxyuridine and ultraviolet-B light. Radiat Res 1997; 147:674-9. PubMed
  • Kachur AV, Held KD, Koch CJ, Biaglow JE. Mechanism of production of hydroxyl radicals in the copper-catalyzed oxidation of dithiothreitol. Radiat Res 1997; 147:409-15. PubMed
  • Biaglow JE, Manevich Y, Uckun F, Held KD. Quantitation of hydroxyl radicals produced by radiation and copper-linked oxidation of ascorbate by 2-deoxy-D-ribose method. Free Radic Biol Med 1997; 22:1129-38. PubMed
  • Held KD. Radiation-induced apoptosis and its relationship to loss of clonogenic survival. Apoptosis 2003; 2:265-82. PubMed
  • Biaglow JE, Held KD, Manevich Y, Tuttle S, Kachur A, Uckun F. Role of guanosine triphosphate in ferric ion-linked Fenton chemistry. Radiat Res 1996; 145:554-62. PubMed
  • Held KD, Sylvester FC, Hopcia KL, Biaglow JE. Role of Fenton chemistry in thiol-induced toxicity and apoptosis. Radiat Res 1996; 145:542-53. PubMed
  • Hopcia KL, McCarey YL, Sylvester FC, Held KD. Radiation-induced apoptosis in HL60 cells: oxygen effect, relationship between apoptosis and loss of clonogenicity, and dependence of time to apoptosis on radiation dose. Radiat Res 1996; 145:315-23. PubMed
  • Held KD, Biaglow JE. Mechanisms for the oxygen radical-mediated toxicity of various thiol-containing compounds in cultured mammalian cells. Radiat Res 1994; 139:15-23. PubMed
  • Held KD, Biaglow JE. Role of copper in the oxygen radical-mediated toxicity of the thiol-containing radioprotector dithiothreitol in mammalian cells. Radiat Res 1993; 134:375-82. PubMed
  • Held KD, Tuttle SW, Biaglow JE. Role of the pentose cycle in oxygen radical-mediated toxicity of the thiol-containing radioprotector dithiothreitol in mammalian cells. Radiat Res 1993; 134:383-9. PubMed
  • Held KD, Hopcia KL. Role of protein thiols in intrinsic radiation protection of DNA and cells. Mutat Res 1993; 299:261-9. PubMed
  • Awad S, Henderson GB, Cerami A, Held KD. Effects of trypanothione on the biological activity of irradiated transforming DNA. Int J Radiat Biol 1992; 62:401-7. PubMed
  • Biaglow JE, Mitchell JB, Held K. The importance of peroxide and superoxide in the X-ray response. Int J Radiat Oncol Biol Phys 1992; 22:665-9. PubMed
  • Held KD, Epp ER, Awad S, Biaglow JE. Postirradiation sensitization of mammalian cells by the thiol-depleting agent dimethyl fumarate. Radiat Res 1991; 127:75-80. PubMed
  • Harrop HA, Held KD, Michael BD. The oxygen effect: variation of the K-value and lifetimes of O2-dependent damage in some glutathione-deficient mutants of Escherichia coli. Int J Radiat Biol 1991; 59:1237-51. PubMed
  • Held KD, Awad S. Effects of polyamines and thiols on the radiation sensitivity of bacterial transforming DNA. Int J Radiat Biol 1991; 59:699-710. PubMed
  • Kochevar IE, Walsh AA, Held KD, Gallo RL, Mirro J. Mechanism for 193-nm laser radiation-induced effects on mammalian cells. Radiat Res 1990; 122:142-8. PubMed
  • Biaglow JE, Varnes ME, Epp ER, Clark EP, Tuttle SW, Held KD. Role of glutathione in the aerobic radiation response. Int J Radiat Oncol Biol Phys 1989; 16:1311-4. PubMed
  • Epp ER, Held KD, Clark EP, Biaglow JE. Effect of varying the concentration of damage restituting species in the radical repair model. Int J Radiat Oncol Biol Phys 1989; 16:1219-23. PubMed
  • Biaglow JE, Varnes ME, Epp ER, Clark EP, Tuttle SW, Held KD. Role of glutathione and other thiols in cellular response to radiation and drugs. Drug Metab Rev 1988; 20:1-12. PubMed
  • Held KD, Epp ER, Clark EP, Biaglow JE. Effect of dimethyl fumarate on the radiation sensitivity of mammalian cells in vitro. Radiat Res 1988; 115:495-502. PubMed
  • Held KD. Models for thiol protection of DNA in cells. Pharmacol Ther 1987; 39:123-31. PubMed
  • Biaglow JE, Varnes ME, Epp ER, Clark EP, Tuttle S, Held KD. Cellular protection against damage by hydroperoxides: role of glutathione. Basic Life Sci 1987; 49:567-73. PubMed
  • Held KD. Interactions of oxygen and sulfhydryls with free radicals in irradiated mammalian cells. Basic Life Sci 1987; 49:441-8. PubMed
  • Held KD, Melder DC. Toxicity of the sulfhydryl-containing radioprotector dithiothreitol. Radiat Res 1987; 112:544-54. PubMed
  • Held KD, Bren GD, Melder DC. Interactions of radioprotectors and oxygen in cultured mammalian cells. II. Effects of dithiothreitol on radiation-induced DNA damage and comparison with cell survival. Radiat Res 1986; 108:296-306. PubMed
  • Held KD, Bren GD. DNA damage measured using the alkaline elution assay depends on time between subculturing of cells and irradiation. Radiat Res 1986; 105:211-8. PubMed
  • Biaglow JE, Jacobson B, Varnes ME, Held KD. Cellular oxygen utilization and hypoxia: interaction of dithiols with cellular electron transfer systems. Adv Exp Med Biol 1985; 200:591-601. PubMed
  • Michael BD, Davies S, Held KD. Ultrafast chemical repair of DNA single and double strand break precursors in irradiated V79 cells. Basic Life Sci 1985; 38:89-100. PubMed
  • Held KD, Harrop HA, Michael BD. Pulse radiolysis studies of the interactions of the sulfhydryl compound dithiothreitol and sugars. Radiat Res 1985; 103:171-85. PubMed
  • Held KD. Interactions of radioprotectors and oxygen in cultured mammalian cells. I. Dithiothreitol effects on radiation-induced cell killing. Radiat Res 1985; 101:424-33. PubMed
  • Held KD, Harrop HA, Michael BD. Effects of oxygen and sulphydryl-containing compounds on irradiated transforming DNA. II. Glutathione, cysteine and cysteamine. Int J Radiat Biol Relat Stud Phys Chem Med 1984; 45:615-26. PubMed
  • Held KD, Harrop HA, Michael BD. Effects of oxygen and sulphydryl-containing compounds on irradiated transforming DNA. III. Reaction rates. Int J Radiat Biol Relat Stud Phys Chem Med 1984; 45:627-36. PubMed
  • Held KD, Harrop HA, Michael BD. Effects of oxygen and sulphydryl-containing compounds on irradiated transforming DNA. Part I. Actions of dithiothreitol. Int J Radiat Biol Relat Stud Phys Chem Med 1981; 40:613-22. PubMed
  • Michael BD, Harrop HA, Held KD. Photoreactivation of Escherichia coli after exposure to ionizing radiation: the role of U.V. damage by concomitant Cerenkov light. Int J Radiat Biol Relat Stud Phys Chem Med 1981; 39:577-83. PubMed
  • Held KD, Powers EL. Sensitization to X-rays of transforming DNA by Ag+. Int J Radiat Biol Relat Stud Phys Chem Med 1980; 38:293-307. PubMed
  • Held KD, Powers EL. Protection of transforming DNA from X-irradiation-induced damage by .OH scavengers. Int J Radiat Biol Relat Stud Phys Chem Med 1979; 36:665-9. PubMed
  • Held KD, Powers EL. Effects of varying O2 concentration on the X-ray sensitivity of transforming DNA. Int J Radiat Biol Relat Stud Phys Chem Med 1979; 36:613-9. PubMed
  • Held KD, Synek RW, Powers EL. Radiation sensitivity of transforming DNA. Int J Radiat Biol Relat Stud Phys Chem Med 1978; 33:317-24. PubMed
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