Iain Buxton was born in Buckinghamshire England in 1950 to David and Lesley Buxton who met in North Africa while both served in the Royal Air Force during WWII. Together with his family, Iain emigrated from England to the United States in 1962 on the Queen Mary. Iain grew up in Cambria California and later attended the University of California, San Diego where he was an undergraduate research assistant with Dr. Gordon Sato whose research in hormone-dependent cell growth was important in our early understanding of breast and prostate cancer. Iain presented his first research abstract at the age of nineteen.
After graduating from the University of California San Diego, Iain was appointed as research assistant at the Salk Institute for Biological Studies in La Jolla and worked in the laboratory of Nobel laureate Dr. Robert Holley exploring cellular growth control and differentiation. The years at the Salk were particularly influential on Iain who would sit in Growth Control Group meetings with Salk regulars Renato Dulbecco (Nobel 1975) and Roger Guillemin (Nobel 1977) and summer visitors like James Watson (Nobel 1962), Genard Matrone among many others. While a lowly research assistant at the time, these experiences were inspiring to Iain. Iain's talents as an experimentalist were noticed by Gennard Matrone, Chair of Biochemistry at North Carolina State University in Raleigh and he recruited Iain to come to the graduate program at NCSU for his PhD training.
Iain left the Salk Institute to study protein chemistry and enzyme kinetics with Dr. A. R. Main in the Biochemistry Department at North Carolina State University in Raleigh. Main had done his postdoctoral training with E.C. Webb at Cambridge and was trying to purify an enzyme, cholinesterase to homogeneity. As a graduate student, Iain assisted in the first report of the purification of this enzyme critical to the regulation of the nervous system (Biochem J. 1974, 143(3):733-44). By this time Buxton's research interests had made him acutely aware of the field of pharmacology, the study of the actions of drugs and chemicals on the human body. Buxton attended the University of the Pacific School of Pharmacy and Pharmacology graduating in 1978. Dr. Buxton returned to San Diego where he was a clinical resident at the Veterans Affairs Medical Center and later, Director of the Investigational Drug Studies program at the same institution. In 1981, Dr. Buxton joined the Department of Medicine, as a fellow in cardiovascular pharmacology. This was, frankly a prestigious opportunity as the position was reserved for MD fellows.
In 1984, Dr. Buxton received a National Institutes of Health New Investigator Award (R23) and joined the faculty at the University of California San Diego as an Assistant Research Pharmacologist. In 1985, Dr. Buxton joined the Department of Pharmacology at the University of Nevada as an Assistant Professor. Dr. Buxton was immediately successful in Nevada and rose rapidly to become a tenured Associate professor in 1989 and Full professor in 1995. In 2008, Dr. Buxton was named UNR Outstanding Researcher of the Year and in 2011 was named Regents Professor. In 2013, Dr. Buxton was named Foundation Professor. Today, Buxton is Professor and Chair of Pharmacology, jointly appointed in the Department of Obstetrics & Gynecology as Clinical Professor. As Chair of the Department of Pharmacology, Dr. Buxton manages the pharmacy operation for the school. In this role he serves as a member of the practice plan executive committees and is a member of the board of the ICS Practice Plan Governance Group. Dr. Buxton's laboratory is NIH-funded and has attracted numerous extramural grant for groups such as the March of Dimes, the American Heart Association and the Bill and Melinda Gates Foundation. Dr. Buxton' research into the causes of preterm labor in women, and therapeutic approaches for the treatment of breast cancer has earned international recognition.
The Buxton lab is exploring contraction-relaxation coupling in the uterine myometrium in order to better understand and develop treatments for the the problem of preterm labor. Preterm delivery of an underdeveloped fetus is a global problem. Babies delivered prior to full development at term have multiple medical problems that plague these individuals throughout their lifetime. Prematurity explains 75% of all fetal morbidity and mortality. Thus, beyond the tragic and costly fact of their prematurity, is the major impact on individuals and societies long-term. There are no effective (or FDA-approved) medications that prevent contractions of the uterus in patients who enter labor preterm (PTL). What is used is ineffective at allowing the fetus to remain in the womb until term. Drugs employed to prevent PTL (tocolytics) are only evaluated for an ability to prevent labor for 48 hours, a time during which treatments can ready the fetus to breath air. PTL leads to preterm delivery (PTD) in over 50% of cases. Spontaneous PTL (no explanation such as infection) accounts for the majority of PTL.
The approach to sPTL we are pursuing is based on the non-canonical pathway by which NO relaxes myometrium. Our approach hypothesizes specific S-nitrosation differences in the protein fingerprint of sPTL compared with laboring myometrium. What is needed to investigate sPTL is to know the specific proteins that are post-translationally S-nitrosated and their abundance and/or unique presence and the impact of their S-nitrosation in pregnancy, labor and sPTL.
We have discovered particular unique proteins that are deferentially S-nitrosated and are pursuing their role in mediating relaxation on pregnancy and labor. One such protein is a channel called TREK-1. This channel is stretch-activated. We discovered genetic variants of the channel associated with PTL. Electrophysiological measurement of these gene variant channels suggests that their expression in women may constitute a mechanism to explain PTL in these patients. Drug discovery is in process to generate therapeutics to treat this form of PTL.
In a second thrust, the Buxton lab is looking for therapeutic targets in breast cancer. Tumor cells migrate to distant sites in the body before they are capable of forming aggressive metastases and thus remain dormant. We do not know the cellular behavior of disease we label latent but attracting a blood supply may be an early property that precedes and is required for those lesions that become malignant in women. Breast cancer specific mortality is almost exclusively a function of metastasis. Growth of tumor cells as metastases dictates that tumor cells must first develop a capillary blood supply or risk necrosis. Metastatic tumor cells have already attracted a blood supply, a hallmark of cancer. What activates dormant cells at metastatic sites to move from a quiescent to aggressive phenotype is not known. It is critical to determine the effect of a kinase we discovered to be released from cancer cells because every indication is that it produces a blood supply for cells that can later become malignant, an event that cannot take place unless a blood supply is available. Our current experiments are focused on the actions of the kinase that permit intravasation and extravasation of tumor cells that permit their passage to distant sites in the body where they can lodge and remain undetected for years. We have developed an inhibitor of the kinase and hope to demonstrate its potential a breast cancer prophylactic.