Sally J. York, MD, PhD

Department / Division:
Medicine / Medical Oncology

Address:
DUMC 3813
Durham, NC 27705

Appointment Telephone:
919-668-6688

Office Telephone:
919-681-6178

Fax Telephone:
919-681-9567

• MD, Washington University in St. Louis School of Medicine (Missouri), 1996

• Internal Medicine, Duke University Medical Center, 1996-1999

• Hematology/Medical Oncology, Duke University Medical Center, 1999-2001

• PhD, Molecular and Cellular Biology, Washington University (Missouri), 1996

Clinical Interests:
Lung cancer (small-cell and non-small-cell), supportive care for patients

Research Interests:
Medical oncologists administer chemotherapy to kill malignant cells and improve both patient survival and quality of life.  Many conventional chemotherapy agents cause DNA damage; unfortunately this damage occurs in both normal and tumor cells. While toxicity to normal tissues is predictable and dose-dependent, tumor responses vary widely, from complete involution of tumor to continued growth. Despite increasingly detailed molecular characterization of tumor cells, oncologists lack the tools to predict whether any individual patient will benefit from a specific cytotoxic agent, in large part due to a limited understanding of how DNA damage leads to cell death.  

My lab is studying the initial recognition and processing of chemotherapy-induced DNA damage by DNA mismatch repair (MMR), a genomic stability pathway defective in many sporadic and familial tumors.  MMR is involved in mediating cytotoxicity to a number of antineoplastic agents, including temozolomide and cisplatin.  Paradoxically, damage recognition by MMR does not lead to repair of damage, but instead to activation of the cell cycle checkpoint kinases, ATR and ATM, and apoptosis.  MMR-defective cells are chemoresistant and continue to grow despite accumulation of DNA lesions.  We are utilizing biochemical, cell biological and genetic approaches to understand the role of MMR in the DNA damage response.  Defining this role will shed insight into the regulation of the cell cycle checkpoint and the biological behavior of MMR-defective tumors.

Representative Publications:
York SJ, Modrich P. Mismatch Repair-dependent Iterative Excision at Irreparable O6-Methylguanine Lesions in Human Nuclear Extracts. J Biol Chem. 2006 Aug 11;281(32):22674-83. (2006) Abstract

York SJ, Armbruster BN, Greenwell P, Petes TD, York JD. Inositol diphosphate signaling regulates telomere length. J Biol Chem. 2005 Feb 11;280(6):4264-9. (2005) Abstract

York SJ, Arneson LS, Gregory WT, Dahms NM, Kornfeld S. The rate of internalization of the mannose 6-phosphate/insulin-like growth factor II receptor is enhanced by multivalent ligand binding. J Biol Chem. 1999 Jan 8;274(2):1164-71. (1999) Abstract