• 34424 Citations
  • 94 Scopus h-Index
1976 …2020

Research output per year

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Personal profile

Research interests

As an oncologist and pharmacologist, my overall research goal is to improve the therapy of neoplastic diseases, with an emphasis on hematological malignancies that dates back to the mid-1980s and research on ovarian cancer that dates to 1994 when I moved to the Mayo Clinic.  Over the past 30 years my laboratory group has performed basic studies examining the biochemistry and biology of apoptosis, a cell death process that is triggered by a variety of anticancer treatments in susceptible cells.  We are continuing that work with an increasing emphasis on ovarian cancer. In addition, we have performed preclinical and translational studies on a variety of chemotherapeutics, including topoisomerase I poisons, gemcitabine, modulators of platinum sensitivity, and checkpoint kinase inhibitors, all of which have been investigated as potential therapeutics for ovarian cancer.  For example, our work on PARP inhibitors, which builds on studies of PARP biology that began in my laboratory in 1985, has over the past six years started to provide exciting new insight into the action of this exciting new class of agents. In particular, our studies have not only emphasized the role of alterations in particular repair pathways on sensitivity to PARP inhibitors, but also  demonstrated that PARP inhibitors sensitize homologous recombination-proficient cells to a variety of anticancer agents through several different mechanisms, including inhibition of base excision repair (sensitization to floxuridine), trapping of PARP1 on DNA to prevent DNA repair (sensitization to topotecan) and altered binding of transcription factors to promoters (sensitization to TRAIL and Fas ligand). 

As a practicing oncologist, I have tried whenever possible to use my laboratory's findings to guide the investigation of new therapies.  These efforts have led to several clinical trials, including single-agent rucaparib for platinum sensitive ovarian cancer (the ARIEL2 trial originally designed in collaboration with Elizabeth Swisher), topotecan + veliparib for platinum-resistant ovarian cancer, temsirolimus for mantle cell lymphoma, topotecan + carboplatin + veliparib for transformed myeloproliferative neoplasms, tipifarnib for relapsed T cell lymphoma, and tipifarnib + etoposide for relapsed AML.

Research interests

As an oncologist and pharmacologist, my overall research goal is to improve the therapy of neoplastic diseases, with an emphasis on hematological malignancies that dates back to the mid-1980s and research on ovarian cancer that dates to 1994 when I moved to the Mayo Clinic.  Over the past 30 years my laboratory group has performed basic studies examining the biochemistry and biology of apoptosis, a cell death process that is triggered by a variety of anticancer treatments in susceptible cells.  We are continuing that work with an increasing emphasis on ovarian cancer. In addition, we have performed preclinical and translational studies on a variety of chemotherapeutics, including topoisomerase I poisons, gemcitabine, modulators of platinum sensitivity, and checkpoint kinase inhibitors, all of which have been investigated as potential therapeutics for ovarian cancer.  For example, our work on PARP inhibitors, which builds on studies of PARP biology that began in my laboratory in 1985, has over the past six years started to provide exciting new insight into the action of this exciting new class of agents. In particular, our studies have not only emphasized the role of alterations in particular repair pathways on sensitivity to PARP inhibitors, but also  demonstrated that PARP inhibitors sensitize homologous recombination-proficient cells to a variety of anticancer agents through several different mechanisms, including inhibition of base excision repair (sensitization to floxuridine), trapping of PARP1 on DNA to prevent DNA repair (sensitization to topotecan) and altered binding of transcription factors to promoters (sensitization to TRAIL and Fas ligand). 

As a practicing oncologist, I have tried whenever possible to use my laboratory's findings to guide the investigation of new therapies.  These efforts have led to several clinical trials, including single-agent rucaparib for platinum sensitive ovarian cancer (the ARIEL2 trial originally designed in collaboration with Elizabeth Swisher), topotecan + veliparib for platinum-resistant ovarian cancer, temsirolimus for mantle cell lymphoma, topotecan + carboplatin + veliparib for transformed myeloproliferative neoplasms, tipifarnib for relapsed T cell lymphoma, and tipifarnib + etoposide for relapsed AML.

Keywords

  • RM Therapeutics. Pharmacology
  • Molecular pharmacology
  • Anticancer drug resistance
  • Apoptosis
  • Death receptor
  • Mitochondrial pathway
  • BCL2 proteins
  • Topoisomerases
  • DNA repair inhibitors
  • Signal transduction inhibitors
  • PARP inhibitors
  • Platinum compounds
  • R Medicine (General)
  • Medical oncology
  • Ovarian cancer
  • Hematology
  • Follicular lymphoma
  • Acute myeloid leukemia
  • Acute lymphoblastic leukemia

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Projects

  • Poisoning of PARP and Topoisomerase I to Treat Ovarian Cancer

    Kaufmann, S. H., Cliby, W. A., Bible, K. C., Goode, E. L., Galanis, E., Knutson, K. L., Hartmann, L. C., Oberg, A. L., Couch, F. J., Fields, A. P., Haluska, P. R. J., Long, H., Bell, D., Keeney, G., Lengyel, E., Keeney, G., Shridhar, V., Cliby, W. A., Goode, E. L., Peng, K., Hartmann, L. C. & Lingle, W. L.

    National Institutes of Health

    10/1/088/31/20

    Project: Research project

  • Research Output

    53BP1 as a potential predictor of response in PARP inhibitor-treated homologous recombination-deficient ovarian cancer

    Hurley, R. M., Wahner Hendrickson, A. E., Visscher, D. W., Ansell, P., Harrell, M. I., Wagner, J. M., Negron, V., Goergen, K. M., Maurer, M. J., Oberg, A. L., Meng, X. W., Flatten, K. S., De Jonge, M. J. A., Van Herpen, C. D., Gietema, J. A., Koornstra, R. H. T., Jager, A., den Hollander, M. W., Dudley, M., Shepherd, S. P. & 2 others, Swisher, E. M. & Kaufmann, S. H., Jan 1 2019, (Accepted/In press) In : Gynecologic Oncology.

    Research output: Contribution to journalArticle

  • 4 Scopus citations

    A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease

    Litzow, M. R., Wang, X. V., Carroll, M. P., Karp, J. E., Ketterling, R. P., Zhang, Y., Kaufmann, S. H., Lazarus, H. M., Luger, S. M., Paietta, E. M., Pratz, K. W., Tun, H. W., Altman, J. K., Broun, E. R., Rybka, W. B., Rowe, J. M. & Tallman, M. S., Jan 2019, In : American journal of hematology. 94, 1, p. 111-117 7 p.

    Research output: Contribution to journalArticle

  • 3 Scopus citations

    BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

    Lin, K. K., Harrell, M. I., Oza, A. M., Oaknin, A., Ray-Coquard, I., Tinker, A. V., Helman, E., Radke, M. R., Say, C., Vo, L. T., Mann, E., Isaacson, J. D., Maloney, L., O'Malley, D. M., Chambers, S. K., Kaufmann, S. H., Scott, C. L., Konecny, G. E., Coleman, R. L., Sun, J. X. & 5 others, Giordano, H., Brenton, J. D., Harding, T. C., McNeish, I. A. & Swisher, E. M., Feb 1 2019, In : Cancer discovery. 9, 2, p. 210-219 10 p.

    Research output: Contribution to journalArticle

    Open Access
  • 26 Scopus citations

    Effect of CHK1 Inhibition on CPX-351 Cytotoxicity in vitro and ex vivo

    Vincelette, N. D., Ding, H., Huehls, A. M., Flatten, K. S., Kelly, R. L., Kohorst, M. A., Webster, J., Hess, A. D., Pratz, K. W., Karnitz, L. M. & Kaufmann, S. H., Dec 1 2019, In : Scientific reports. 9, 1, 3617.

    Research output: Contribution to journalArticle

    Open Access
  • 1 Scopus citations

    Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women

    Grant, D. J., Manichaikul, A., Alberg, A. J., Bandera, E. V., Barnholtz-Sloan, J., Bondy, M., Cote, M. L., Funkhouser, E., Moorman, P. G., Peres, L. C., Peters, E. S., Schwartz, A. G., Terry, P. D., Wang, X. Q., Keku, T. O., Hoyo, C., Berchuck, A., Sandler, D. P., Taylor, J. A., O’Brien, K. M. & 70 others, Velez Edwards, D. R., Edwards, T. L., Beeghly-Fadiel, A., Wentzensen, N., Pearce, C. L., Wu, A. H., Whittemore, A. S., McGuire, V., Sieh, W., Rothstein, J. H., Modugno, F., Ness, R., Moysich, K., Rossing, M. A., Doherty, J. A., Sellers, T. A., Permuth-Way, J. B., Monteiro, A. N., Levine, D. A., Setiawan, V. W., Haiman, C. A., LeMarchand, L., Wilkens, L. R., Karlan, B. Y., Menon, U., Ramus, S., Gayther, S., Gentry-Maharaj, A., Terry, K. L., Cramer, D. W., Goode, E. L., Larson, M. C., Kaufmann, S. H., Cannioto, R., Odunsi, K., Etter, J. L., Huang, R. Y., Bernardini, M. Q., Tone, A. A., May, T., Goodman, M. T., Thompson, P. J., Carney, M. E., Tworoger, S. S., Poole, E. M., Lambrechts, D., Vergote, I., Vanderstichele, A., Van Nieuwenhuysen, E., Anton-Culver, H., Ziogas, A., Brenton, J. D., Bjorge, L., Salvensen, H. B., Kiemeney, L. A., Massuger, L. F. A. G., Pejovic, T., Bruegl, A., Moffitt, M., Cook, L., Le, N. D., Brooks-Wilson, A., Kelemen, L. E., Pharoah, P. D. P., Song, H., Campbell, I., Eccles, D., DeFazio, A., Kennedy, C. J. & Schildkraut, J. M., May 2019, In : Cancer medicine. 8, 5, p. 2503-2513 11 p.

    Research output: Contribution to journalArticle

    Open Access
  • 1 Scopus citations