Iain L. O. Buxton
Department: Pharmacology and Obstetrics & Gynecology
Academic Unit: School of Medicine
Professional degrees (Degree, year, Institution): Pharm.D., University of the Pacific, 1978
Mail Stop: 318
Biophysics, Cancer, Cell Biology, Biochemistry, Pharmacology
Regulation of uterine contraction leading to parturition. The goal of this research is to investigate the action of biological signals that regulate uterine contraction uniquely, at the time of labor in humans. We are funded by NIH grant (RO1 HD-053028). This research proposes that the current understanding of uterine function based on studies in other smooth muscles is incorrect. Our research objective is to determine the signal transduction mechanisms that are unique to, or altered in the human myometrium in preterm labor because this is presently unknown and because current treatments for premature labor (PTL) are wholly inadequate. No matter the varied causes of PTL (fetal or maternal) in any given woman, in unexplained cases, changes will inevitably be found in myometrial signaling pathways or the timing of their activation/inactivation. We are taking experimental approaches in human and guinea pig myometrial cells and tissues that will converge in an understanding of the smooth muscle mechanisms of prematurity and provide one or more therapeutic targets not previously known.
Stretch-activated 2-pore Potassium Channels in Preterm Labor. In 2006 we discovered for the first time the expression of a stretch-activated channel TRAAK, in human myometrium and demonstrated that this channel may be gestationally regulated. We are funded for this work by the March of Dimes for the proposal entitled, "Role of the Stretch-Activated 2-Pore Potassium Channels TREK-1 and TRAAK in Preterm Labor". The objective of this research is to contribute to an understanding of the probable cause(s) of preterm labor in some women that may possess a dysfunctional channel. Preterm birth remains a significant health issue in industrialized nations accounting for 11.5% of all live births in the United States and 85% of all perinatal complications and death. The incidence of preterm birth is unacceptably high. Tocolytic agents do not work. Prematurity costs 26 billion annually and causes unacceptable morbidity and mortality. We must better understand the physiological mechanisms of pregnancy in women if we are to discover new approaches to the treatment of preterm labor.
Regulation of Breast Cancer-mediated Angiogenesis. The goal of our research is to delineate the role of extracellular Nucleotide Diphosphate Kinase-B (NDPK-B) and its regulation of ATP levels in human breast cancer angiogenesis. Human breast cancer cells secrete a factor that supports the growth, differentiation, and permeability of endothelial cells in vitro consistent with a pro-angiogenic potential that subserves metastasis. We have identified a pharmacophore for the development of inhibitors of this enzyme factor (NDPK) and find these compounds to be anti-angiogenic. Learning how secreted NDPK-B and its regulation of extracellular ATP, blocked by catechin gallates, can induce breast cancer angiogenesis will reveal new therapeutic targets in the treatment of breast cancer and its lethal metastatic spread. Extracellular purine nucleotides (e.g., ATP) have recently emerged as a novel class of proliferative agents with a putative role in cancer and angiogenesis. We show that P2Y receptor activation promotes a significant pro-angiogenic response. Coupled with our discovery of the generation and action of nucleotides in the blood stream, The Nucleotide Axis Hypothesis, progress on the aims described here may help explain aspects of cancer metastasis heretofore unrecognized.
Current Graduate Students
Nucharee Yokdang GSIII
Craig Ulrich GSI
Faculty by research area
- Mastick, C
- Mastick C.
- Mastick G.
- Van der Linden
- von Bartheld
- von Bartheld