Ying-Hui Fu, Ph.D.
Associate Professor in Residence of Neurology

Contact Information:
ying-hui.fu@ucsf.edu
Tel: (415) 502-2948
Fax: (415) 502-5641
1550 4th Street
Rock Hall, Room 546
Box 2922
Mission Bay Campus

Links:
lab website
Biomedical Sciences
Neuroscience

Publications

Human genetics in neurodegenerative diseases

We are interested in understanding the mechanisms of various diseases involving the nervous system. In particular, there are two classes of neurodegenerative diseases that we are focusing on: polyglutamine diseases and demyelinating degenerative diseases. In addition, we are also interested in the Human circadian rhythmicity. Our group has been using human genetic tools to identify genes involved in these disorders. Studying the disease mechanisms following the discovery of the genes will lead to unraveling of the pathogenesis of these disorders.
Polyglutamine diseases: Over the past decade, expanded TNR sequences have been recognized as a significant source of mutation in the human genome. More than a dozen neurodegenerative diseases are known to contain repeat expansions within their associated genes. One class of mutation, the expansion of a CAG repeat encoding a polyglutamine (polyQ) tract, has been associated with at least eight different neurodegenerative disorders. Spinocerebellar ataxia (SCA) is a heterogeneous group of diseases that fall into this category. The repeat tracts within these genes display common size ranges for both normal as well as mutant alleles. This has led to the hypothesis that expanded polyQ tracts may be toxic to cells in the CNS. Like other TNR expansion diseases, anticipation is present in the SCAs and intranuclear inclusions (INIs) are seen in affected cells from SCA patients. There are two forms of SCAs that we are working on: 1) Spinocerebellar Ataxia 7, 2) Spinocerebellar Ataxia 4.

Multiple Sclerosis: Multiple sclerosis is a common, often severe neurologic disorder for which the cause, cure and prevention are unknown and for which no specific diagnostic test exists. We are currently working on two projects that relate to demyelinating degenerative diseases of the nervous system. 1) Autosomal dominant leukodystrophy (ADLD) is clinically similar to the chronic progressive form of MS. Misdiagnosis of ADLD patients as having MS is common although ADLD and MS are readily distinguishable at autopsy. 2) Multiple Sclerosis Associated with a Chromosomal Translocation This phenotype is co-segregating with a balanced chromosome translocation. My long-term goal is to understand molecular mechanism of dysmyelination in these diseases (and of myelin synthesis, degeneration, and regeneration in general).

Human Circadian Rhythm Genetics
Another area of my research interest is in the study of circadian rhythm. Circadian rhythm is one of the best models for studying human behavior. When we say “Genetics is everything”, it may not be so far-fetched in truth if we come to recognize how much our behaviors are impacted by our genetic composition. Many of our physiological processes including heart beat, blood pressure, body temperature, and endocrine functions are subject to circadian regulation. However, the regulation of the overall behavior of an organism is the most overt and intriguing manifestation of circadian rhythmicity. The pursuit of the genetic and molecular basis of behavior is extremely complex because of the wide variation in “normal” individuals. Furthermore, behaviors such as sleep are confounded by social and familio-cultural influences that frequently lead us to override our biological clock and stay up later or to wake up earlier than we otherwise would. Various agents including caffeine and alcohol also confound one’s ability to understand the inherent rhythms dictating humans’ activities. We are in the process of identifying mutations that are involved in regulation of human rhythmicity. My long-term goal for this particular project is that as we find more mutations that are affecting human sleep pattern, we will characterizing these mutations to assist us understand human circadian clock.