Biosketch
Dr. Winters earned his PhD from The Ohio State University College of Medicine’s Department of Medical Microbiology and Immunology where he studied the human herpes simplex virus (1 & 2) encoded DNA repair enzyme uracil-DNA glycosylase as a potential target for the development of antiviral chemotherapeutic agents. He also holds a Bachelor of Science degree in microbiology from Michigan State University. Dr. Winters’ postgraduate training includes a fellowship in radiation biology with Georgetown University School of Medicine’s Department of Radiation Medicine, during which he investigated the mechanisms responsible for radiation-induced DNA single-strand break formation and the human DNA repair enzymology responsible for its repair. Dr. Winters also held an American Cancer Society Fellowship in radiation biology and DNA repair while at Georgetown University. He was also an Intramural Research Training Award Fellow studying DNA double-strand break induction and repair with NCI’s Radiation Oncology Branch before joining Dr. Ronald D. Neumann’s nuclear medicine research team in the Clinical Center.
As a staff scientist in the Radiopharmaceutical Development Laboratory, Dr. Winters is responsible for investigating the DNA repair mechanisms responsible for human biological responses to DNA double-strand break damage created by anti-gene targeted radionuclide decay, specifically that of Auger electron-emitting radionuclides. His research in this area has resulted in the first high-resolution molecular analysis of the highly complex and cytotoxic double-strand break structures formed by the decay of Auger electron-emitting radionuclides in close proximity to DNA. This work has contributed to a better understanding of the radiologic mechanisms by which Auger electron-emitting radionuclides create DNA damage, thus, based upon the ability to predict the DNA damage formed, this work may aid in the selection of radionuclides for use in DNA targeted radiopharmaceuticals. Also, knowledge of the molecular structures associated with the complex DNA double-strand breaks created by Auger-emitter decay has led to the identification of a specific radiation-induced configuration of DNA double-strand break damage that is the least reparable by the primary human DNA double-strand break repair pathway, and therefore, may represent an important highly cytotoxic subtype of radiation-induced DNA damage. Dr. Winters’ studies in this area have also recently identified specific enzymes in the human DNA double-strand break repair pathway that may be directly inhibited by complex radiation-induced DNA double-strand breaks, and thus may have a role in causing the cytotoxic effects associated with this form of DNA damage.
Selected Publications
Kamal Datta, Ronald D. Neumann, and Thomas A. Winters. Base damage immediately upstream from a DNA double-strand break end is a more severe impediment to nonhomologous end joining by human cell extracts than blocked 3’-ends. (2008) (Submitted).
Cynthia Hendrickson, Elzbieta Pastwa, Nadia Kulshina, Ronald D. Neumann, and Thomas A. Winters. Coincident In Vitro Analysis of DNA-PK-Dependent and -Independent Nonhomologous End Joining. (2008) (Submitted).
Kamal Datta, Michael Weinfeld, Ronald D. Neumann, and Thomas A. Winters. Determination and Analysis of Site-Specific 125I Decay-Induced DNA Double-Strand Break End-Group Structures. (2007) Radiat. Res. 167: 152-166.
Kamal Datta, Ronald D. Neumann, and Thomas A. Winters. An in vitro Non-homologous End-joining Assay Using Linear Duplex Oligonucleotides. (2006) Anal. Bioch. 358(1): 155-157.
Kamal Datta, Pawel Jaruga, Miral Dizdaroglu, Ronald D. Neumann, and Thomas A. Winters. Molecular Analysis of Base Damage Clustering Associated with a Site-Specific Radiation-Induced DNA Double-Strand Break. (2006) Radiat. Res. 166: 767-781.
Kamal Datta, Ronald D. Neumann, and Thomas A. Winters. Characterization of Complex AP-Site Clustering Associated with an Authentic Radiation-Induced DNA Double-Strand Break. (2005) Proc. Natl. Acad. Sci. U. S. A. 102(30): 10569-10574.
Kamal Datta, Ronald D. Neumann, and Thomas A. Winters. Characterization of a Complex 125I-induced DNA Double-Strand Break: Implications for Repair. (2005) Int. J. Radiat. Biol. 81(1): 13-21.
Elzbieta Pastwa, Erin Lubner, Katherina Mezhevaya, Ronald D. Neuman, and Thomas A. Winters. DNA Uptake and Repair Enzyme Access to Transfected DNA is Under Reported by Gene Expression. (2003) Biochem. Biophys. Res. Comm. 306: 421-429.
Elzbieta Pastwa, Ronald D. Neumann, Katherina Mezhevaya, and Thomas A. Winters. Repair of Radiation Induced DNA Double-Strand Breaks is Dependent Upon Radiation Quality and DSB Structural Complexity. (2003) Radiat. Res. 159: 251-261.
Thomas A. Winters, Elzbieta Pastwa, Kamal Datta, and Ronald D. Neumann. Rational Drug Development Using Gene-Targeted Agents and Their Application in Anti-Gene Radiotherapy. (2003) Curr. Genomics 4: 275-294.
Kamal Datta, Ronald D Neumann and Thomas A Winters. A protocol for separation and isolation of small and/or large DNA fragments with high yield using CL4B sepharose. (2003) Anal. Bioch. 317: 284-287.
Shubhadeep Purkayastha, Kamal Datta, Ronald D. Neumann, and Thomas A. Winters. Positional effect of base damage clustering on the processing of complex DNA double strand breaks by non-homologous end-joining. (In Preparation).
