Alan E. Senior, Ph.D.

Alan E. Senior, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, NY 14642

Office: (585) 275-6645
Fax: (585) 271-2683

Research Bio

Multi drug resistance in cancer; ATP synthesis in bacteria and mitochondria.



(1) Multidrug resistance in cancer. Cancer chemotherapy often fails because the tumor develops resistance to multiple drugs simultaneously. The culprit is multidrug-resistance protein (mdr) also known as P-glycoprotein. It is located in plasma membranes, and uses ATP to transport drugs out of cells. We have generated a cell line which greatly overexpresses mdr, from which enriched plasma membranes and purified protein are readily obtained. The long-term goal is to learn ways to disable or circumvent mdr protein in cancer cells.

(2) ATP synthesis and hydrolysis in F1Fo-ATP synthase. ATP synthase is the smallest known rotary motor. It uses subunit rotation to drive ATP synthesis, and ATP hydrolysis to drive subunit rotation. The subunit rotation is linked in turn to utilization or generation of a membrane proton gradient. We are using a variety of probes to study the mechanism of catalysis and to elucidate the molecular linkage between catalysis and subunit rotation. We use the E. coli enzyme and a range of molecular genetics, biochemical and biophysical techniques. In recent work we have focussed on application of fluoroscent probes of cataytic sites which have yielded rapid and sensitive information about mechanism.

Recent Journal Articles

Showing the 5 most recent journal articles. 197 available »

2012 Aug 31
Senior AE. "Two ATPases." The Journal of biological chemistry.. 2012 Aug 31; 287(36):30049-62. Epub 2012 Jul 20.
2011 Sep 13
Senior AE. "Reaction chemistry ABC-style." Proceedings of the National Academy of Sciences of the United States of America.. 2011 Sep 13; 108(37):15015-6. Epub 2011 Aug 26.
2009 Apr 17
Li W, Brudecki LE, Senior AE, Ahmad Z. "Role of {alpha}-subunit VISIT-DG sequence residues Ser-347 and Gly-351 in the catalytic sites of Escherichia coli ATP synthase." The Journal of biological chemistry.. 2009 Apr 17; 284(16):10747-54. Epub 2009 Feb 23.
2008 Feb 29
Lee JY, Urbatsch IL, Senior AE, Wilkens S. "Nucleotide-induced structural changes in P-glycoprotein observed by electron microscopy." The Journal of biological chemistry.. 2008 Feb 29; 283(9):5769-79. Epub 2007 Dec 19.
2007 Jul 27
Senior AE. "ATP synthase: motoring to the finish line." Cell.. 2007 Jul 27; 130(2):220-1.

Current Appointments

Professor Emeritus - Department of Biochemistry and Biophysics (SMD) - Primary

Education

PhD | Pharmacology | UK-Med Sch U Newcastle-On-Tyne1967
BS | Physiology | UK-Med Sch U Newcastle-On-Tyne1964