• 34864 Citations
  • 95 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

  • Medical Scientist Training Program at Mayo Clinic

    Isaya, G., Rodriguez, M., Rodriguez, M., Lee, K. H. & Kaufmann, S. H.

    National Institutes of Health

    7/1/036/30/18

    Project: Research project

  • Research Output

    FAM111A protects replication forks from protein obstacles via its trypsin-like domain

    Kojima, Y., Machida, Y., Palani, S., Caulfield, T. R., Radisky, E. S., Kaufmann, S. H. & Machida, Y. J., Dec 1 2020, In : Nature communications. 11, 1, 1318.

    Research output: Contribution to journalArticle

    Open Access
  • Rare BRIP1 missense alleles confer risk for ovarian and breast cancer

    Moyer, C. L., Ivanovich, J., Gillespie, J. L., Doberstein, R., Radke, M. R., Richardson, M. E., Kaufmann, S. H., Swisher, E. M. & Goodfellow, P. J., Feb 15 2020, In : Cancer research. 80, 4, p. 857-867 11 p.

    Research output: Contribution to journalArticle

  • 2 Scopus citations

    Selective Inhibition of BFL1: It's All about Finding the Right Partner

    Dai, H., Meng, X. W. & Kaufmann, S. H., Jun 18 2020, In : Cell Chemical Biology. 27, 6, p. 639-642 4 p.

    Research output: Contribution to journalArticle

  • Therapeutic options for mucinous ovarian carcinoma

    Gorringe, K. L., Cheasley, D., Wakefield, M. J., Ryland, G. L., Allan, P. E., Alsop, K., Amarasinghe, K. C., Ananda, S., Bowtell, D. D. L., Christie, M., Chiew, Y. E., Churchman, M., DeFazio, A., Fereday, S., Gilks, C. B., Gourley, C., Hadley, A. M., Hendley, J., Hunter, S. M., Kaufmann, S. H. & 20 others, Kennedy, C. J., Köbel, M., Le Page, C., Li, J., Lupat, R., McNally, O. M., McAlpine, J. N., Pyman, J., Rowley, S. M., Salazar, C., Saunders, H., Semple, T., Stephens, A. N., Thio, N., Torres, M. C., Traficante, N., Zethoven, M., Antill, Y. C., Campbell, I. G. & Scott, C. L., Mar 2020, In : Gynecologic oncology. 156, 3, p. 552-560 9 p.

    Research output: Contribution to journalArticle

    Open Access
  • 1 Scopus citations

    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., Apr 2019, In : Gynecologic oncology. 153, 1, p. 127-134 8 p.

    Research output: Contribution to journalArticle

  • 5 Scopus citations