Projects per year
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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Collaborations and top research areas from the last five years
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Project 2: Next Generation TOP1 Inhibition for the Treatment of Ovarian Cancer
Kaufmann, S. H. & Kaufmann, S. S. H.
9/1/21 → 8/31/24
Project: Research project
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Mayo Clinic Ovarian Cancer SPORE
Kaufmann, S. H., Bell, D. A., Bible, K. C., Cliby, W. A., Couch, F. J., Fields, A. P., Galanis, E., Goode, E. L., Haluska, P. R. J., Hartmann, L. C., Karnitz, L. M., Keeney, G., Knutson, K. L., Lengyel, E., Lingle, W. L., Long, H. J., Sherman, M. E., Moriarity, B. S., Block, M. S., Oberg, A. L., Peng, K., Shridhar, V. & Weroha, S.
9/1/09 → 8/31/24
Project: Research project
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Career Enhancement Program
Houtman, J. C. D. & Kaufmann, S. H.
9/1/17 → 6/30/22
Project: Research project
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Deubiquitinases in regulation of BRCA1 pathway
Lou, Z., Kaufmann, S. H. & Yuan, J. N.
4/1/16 → 3/31/21
Project: Research project
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AMPK inhibition sensitizes acute leukemia cells to BH3 mimetic-induced cell death
Jia, J., Ji, W., Saliba, A. N., Csizmar, C. M., Ye, K., Hu, L., Peterson, K. L., Schneider, P. A., Meng, X. W., Venkatachalam, A., Patnaik, M. M., Webster, J. A., Smith, B. D., Ghiaur, G., Wu, X., Zhong, J., Pandey, A., Flatten, K. S., Deng, Q., Wang, H., & 2 others , 2024, (Accepted/In press) In: Cell Death and Differentiation.Research output: Contribution to journal › Article › peer-review
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Author Correction: Apoptotic stress causes mtDNA release during senescence and drives the SASP (Nature, (2023), 622, 7983, (627-636), 10.1038/s41586-023-06621-4)
Victorelli, S., Salmonowicz, H., Chapman, J., Martini, H., Vizioli, M. G., Riley, J. S., Cloix, C., Hall-Younger, E., Machado Espindola-Netto, J., Jurk, D., Lagnado, A. B., Sales Gomez, L., Farr, J. N., Saul, D., Reed, R., Kelly, G., Eppard, M., Greaves, L. C., Dou, Z., Pirius, N., & 19 others , Jan 18 2024, In: Nature. 625, 7995, p. E15Research output: Contribution to journal › Comment/debate › peer-review
Open Access -
Erratum: Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer (Cell (2023) 186(16) (3476–3498.e35), (S0092867423007377), (10.1016/j.cell.2023.07.004))
Chowdhury, S., Kennedy, J. J., Ivey, R. G., Murillo, O. D., Hosseini, N., Song, X., Petralia, F., Calinawan, A., Savage, S. R., Berry, A. B., Reva, B., Ozbek, U., Krek, A., Ma, W., da Veiga Leprevost, F., Ji, J., Yoo, S., Lin, C., Voytovich, U. J., Huang, Y., & 27 others , Feb 15 2024, In: Cell. 187, 4, p. 1016 1 p.Research output: Contribution to journal › Comment/debate › peer-review
Open Access -
Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort
Emiloju, O. E., Yin, J., Koubek, E., Reid, J. M., Borad, M. J., Lou, Y., Seetharam, M., Edelman, M. J., Sausville, E. A., Jiang, Y., Kaseb, A. O., Posey, J. A., Davis, S. L., Gores, G. J., Roberts, L. R., Takebe, N., Schwartz, G. K., Hendrickson, A. E. W., Kaufmann, S. H., Adjei, A. A., & 2 others , Feb 2024, In: Investigational New Drugs. 42, 1, p. 127-135 9 p.Research output: Contribution to journal › Article › peer-review
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A BAK subdomain that binds mitochondrial lipids selectively and releases cytochrome C
Dai, H., Peterson, K. L., Flatten, K. S., Meng, X. W., Venkatachalam, A., Correia, C., Ramirez-Alvarado, M., Pang, Y. P. & Kaufmann, S. H., Mar 2023, In: Cell Death and Differentiation. 30, 3, p. 794-808 15 p.Research output: Contribution to journal › Article › peer-review