FACULTY
Zhengui Xia, PhD, MS
Professor, Env. and Occ. Health Sciences
Adjunct Professor, Pharmacology
I am an Professor in the Toxicology Program and an Adjunct Professor in the department of Pharmacology. I am also a Faculty member of the two interdisciplinary graduate programs at U. of Washington- the Neurobiology Graduate Program and the Molecular and Cell Biology (MCB) Graduate Program. My laboratory is generally interested in mechanisms that regulate apoptosis especially in relation to neurodegeneration, cancer, and toxin-induced damage. We are also interested in mechanisms of neurogenesis during development. Our lab is a medium sized lab that consists of post-doctoral fellows and students who are bright, motivated, collegial and friendly.
Contact Information
Box 3572341959 NE Pacific Street
Seattle, WA 98195
Tel: 206-616-9433
zxia@u.washington.edu
Links
Molecular & Cellular Biology Program
Neurobiology & Behavior Program
Research Interests
Mechanisms for regulation of apoptosis in animal cells; Mechanisms of neurogenesis
Education
PhD, Pharmacology, University of Washington 1991
MS, Biochemistry, Wuhan University (China) 1985
Projects
1. Mechanisms for regulation of apoptosis in animal cells:
Our laboratory is interested in molecular mechanisms and signal transduction pathways that control neuronal survival and cell death. We are particularly interested in elucidating transcriptional mechanisms for programmed cell death or apoptosis. Up to 50 % of the neurons produced during neurogenesis eventually die during development. During development, apoptosis serves as a prominent force in sculpting tissues, to remove cells that are produced in excess, no longer needed, or have developed improperly. In adults, apoptosis is used for homeostasis to remove cells that are potentially dangerous, such as viral infected cells, genetically damaged cells, or toxin-damaged cells. Abnormal apoptosis may be deleterious and can cause or contribute to various diseases. For example, abnormal apoptosis is associated with cancer, autoimmune disorders, neurodegenerative disorders including Huntington's disease, Alzheimer's disease, and stroke. It has become increasingly evident that many environmental toxicants exert their toxic effects by inducing apoptosis. Environmental toxicants might contribute to the development of neurodegenerative disorders including Parkinson's disease and ALS. For example, although genetic studies have linked some neurodegeneration to genetic predisposition, most cases of neurodegenerative diseases are sporadic and their etiology remains largely undefined. Environmental factors and gene-environmental interaction may play a large role in neurodegeneration. The discovery of a link between the neurotoxic substance MPTP and the development of Parkinson's disease in human provided the first evidence supporting this hypothesis. There is a complex balance between survival and apoptotic pathways in neurons derived from the central nervous system (CNS) that is distinct from non-neuronal cells or non-CNS neurons. The overall objective of our research is to identify signaling pathways that regulate neuronal apoptosis induced by various disease models as well as environmental toxicants. Because apoptosis also plays a key role in cancer, we are also interested in elucidating apoptotic mechanisms related to cancer biology. It is our hope that these mechanistic studies may ultimately lead to the development of pharmacological interventions and clinical strategies for treatment of various neurodegenerative disorders and cancer. These studies may also provide insights concerning the relationships between environmental toxicants and the etiology of neurodegenerative disorders.
2. Mechanisms of Neurogenesis
We are also interested in signal transduction mechanisms that regulate neurogenesis, i.e. what makes a neural stem cell proliferate and differentiate into neurons during development. Development of the mammalian central nervous system (CNS) requires the production of many types of neurons and glia at the correct numbers and appropriate locations. The controlled proliferation, differentiation and migration of multipotent neural progenitor cells give rise to these diverse cell types and are critical for proper CNS development. Abnormalities in these processes have been implicated in microcephaly and in several forms of mental disorders including mental retardation, depression, and schizophrenia. Furthermore, stem cell-based cell replacement therapy offers enormous potential for the treatment of a variety of developmental, psychiatric, neurodegenerative and aging related diseases for which there are currently no cures. The elucidation of molecular mechanisms that regulate neural progenitor cell proliferation and differentiation into neurons is important for an understanding of human developmental and neurodegenerative diseases. Furthermore, environmental toxicants may cause developmental neurotoxicity by perturbing these signaling mechanisms that regulate neurogenesis.
