Kristine Wiren, Ph.D.
PositionsProfessor Emeritus, Behavioral Neuroscience
androgen receptor; androgen; estrogen; alcohol abuse; alcohol withdrawal; neurotoxicity; osteoporosis; osteoblast, medical
Summary of Current Research
One broad aim in my laboratory is characterization of molecular mechanisms underlying neuroadaptation to chronic ethanol exposure, focusing on changes in gene expression in various brain regions observed during ethanol exposure/withdrawal in both genders. We are also interested in the behavioral consequences of alcohol abuse in animal models. Current studies are carried out in males and females using both seizure-prone or seizure-resistant selected lines of mice and in inbred strains to identify sex specific changes in after chronic exposure and withdrawal and after a period of abstinence. The laboratory is using a molecular biological approach that includes microarray analyses and real-time qPCR to identify and characterize regulated transcripts. Our analyses of sex-specific responses in gene expression have revealed increased vulnerability for brain damage in females, consistent with some controversial clinical literature. The sex-specific differences in transcriptional response may reflect changes in circulating sex steroids. The role of glia in mediating neuroadaptation and neurotoxicity after chronic alcohol exposure is also being evaluated. The goal of these studies is to better understand how neuroadaptation, through changes in gene expression, may underlie physical dependence and relapse potential, and the detrimental consequences that result from withdrawal from ethanol or other drugs of abuse.
A second area of research in my laboratory is the characterization of mechanisms underlying alterations in skeletal function mediated by steroid hormones, in particular through androgen action. Generally, steroid alterations are brought about at the molecular level by specific regulation of gene transcription, controlled by the steroid hormone receptors after ligand binding. My laboratory studies focus on characterizing the sequelae to androgen exposure in osteoblasts or stromal lineage cells that can form bone, cartilage, fat and muscle. The in vivo consequence of overexpression of androgen receptor in the osteoblast lineage is being evaluated in two AR-transgenic mouse models. Another model system that is employed uses normal osteoblasts grown in vitro that eventually develop a mineralized bone matrix. These cultures are exposed to sex steroids, and regulation of osteoblast gene expression during normal proliferation and differentiation is characterized at the RNA and protein level. In a broad sense, studies in my laboratory have the long-term goal of developing a better understanding of mechanisms that underlie the beneficial and/or detrimental effects of sex steroids on skeletal health and how they influence body composition.
Please visit Dr. Wiren's PubMed Listing
B.A. (1974) Oregon State University
Ph.D. (1985) University of Connecticut Health Center
Research Fellow in Medicine (1984-1988) Harvard Medical School and Massachusetts General Hospital