Scott H. Kaufmann, M.D., Ph.D.

Location

Contact

SUMMARY

Scott H. Kaufmann, M.D., Ph.D., is an oncologist at Mayo Clinic who also conducts research to study what happens when cancer cells are treated with targeted anti-cancer agents. Research in Dr. Kaufmann's Anticancer Drug Action Laboratory focuses on two major questions: 1) What is the biochemical basis for cell killing when it occurs, and 2) What can happen to cancer cells to make them resistant to these treatments. Within the context of these broad questions, Dr. Kaufmann's lab applies a wide range of biochemistry, cell biology and molecular biology approaches to a series of projects.

Focus areas

• Many targeted agents induce the death process known as apoptosis. In this process, the pro-apoptotic proteins BAK and BAX breach the mitochondrial membrane to trigger cytochrome c release and caspase activation. Dr. Kaufmann's lab showed that BAK undergoes concentration-dependent autoactivation and is now studying the mechanism of BAK-induced mitochondrial permeabilization and the pathways that restrain activated BAK.
• Dr. Kaufmann's lab recently showed that certain kinase inhibitors — particularly inhibitors of the kinases CHK1, ATR and WEE1 — activate expression of ligands that trigger the extrinsic or death receptor pathway of apoptosis. This pathway also plays a role in killing by immune effector cells. Dr. Kaufmann's ongoing studies are designed to improve understanding of the regulation of this pathway and particularly its inhibition by oncogenes in cancer cells.
• Additional work is examining how other targeted agents, including inhibitors of the enzymes MTOR, PARP1, NEDD8-activating enzyme (NAE), TOP1 and DNA methyltransferases, engage the apoptotic machinery to induce cell death.
• At the same time, Dr. Kaufmann's lab is studying mechanisms of resistance to these agents. For example, building on Dr. Kaufmann's earlier work that contributed to the development of PARP inhibitors for ovarian cancer, he is studying PARP inhibitor resistance in ovarian cancer cell lines, patient-derived xenografts and clinical ovarian cancer, with a goal of devising strategies to overcome this resistance.
• With the realization that the risk of acute myelogenous leukemia is increased in patients with ovarian cancer who receive carboplatin therapy and increased further still by PARP inhibitor maintenance therapy, Dr. Kaufmann's lab is characterizing these PARP inhibitor-emergent myeloid neoplasms and attempting to identify new therapies for treating them.

Significance to patient care

Collectively, studies in Dr. Kaufmann's lab are designed to improve the therapy of cancer. These studies simultaneously provide new insight into the action of targeted anti-cancer agents and identify biochemical features that contribute to treatment sensitivity or resistance.

Professional Highlights

• Funding recipient, The Eric and Wendy Schmidt Fund for AI Research and Innovation, 2023.
• Helen C. Levitt Professorship in Cancer Research, 2001.