Assistant Professor, Departments of Molecular and Human Genetics and Biochemistry & Molecular Biology
B.S., Fudan University, 1988
Ph.D., Baylor College of Medicine, 1997
Postdoctoral Fellow, Massachussetts Institute of Technology, 2001
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RESEARCH
INTERESTS:
Chromosome Segregation: Interaction
Between Spindle and Kinetochores
Chromosome segregation is a highly conserved process among eukaryotes. During
mitosis, cells assemble a sophisticated apparatus - the spindle, using microtubule
fibers. Spindle microtubules capture chromosomes and pull them apart via a specialized
protein complex on each chromosome called kinetochore. The mystery of how cells
precisely segregate sister chromosome has long fascinated cell biologists and
its molecular mechanisms just begin to be unraveled. Understanding how normal
cells segregate chromosome precisely is also essential for us to determine which
step of the process may go awry in cases of human diseases such as tumors that
lead to abnormal chromosome number, which is believed to contribute to tumorigenesis.
Research in my laboratory aims at a specific aspect of chromosome segregation,
namely, how the proper interaction between spindle microtubules and kinetochores
is established and maintained. We reason that the interface between microtubule
and kinetochore ought to be the focal point where various mitotic regulatory
elements exert their impact on chromosome segregation. We wish to identify what
proteins on the kinetochore mediate its affinity to microtubules; and further
to understand how this affinity is regulated to accommodate distinct motion patterns
of kinetochores at different stages of the cell cycle. We also wish to understand
how sister kinetochore pairs attach to the spindle in the correct configuration
that ensures the duplicated chromosomes are segregated into two equal sets.
Our model organism is the fission yeast, Schizosacchromyces pombe. We
currently focus our effort on kinetochores. Our short term goal is to dissect
the protein composition of the kinetochore in fission yeast to provide the structural
basis for functional study. Taking advantage of the extensive technical amenability
of the fission yeast, we employ multi-disciplinary approaches. Using genetic
approaches, we isolated mutants that specifically disrupt kinetochore functions.
By identifying the mutated proteins, we hope to find specific proteins that function
in establishing or maintaining kinetochore/spindle interaction. We also take
the biochemical approach to purify and analyze kinetochore proteins that are
of minute amount in the cell. Multiple specific kinetochore proteins have been
identified thus far by the biochemical approach. We wish to identify more novel
kinetochore proteins and further to understand the assembly pattern and the functional
role of these proteins within the kinetochore.
SELECTED PUBLICATIONS:
1. Liu X, McLeod I, Anderson S, Yates
J. III, He X (2005). Molecular
analysis of the kinetochore architecture in fission yeast. EMBO
J. 24: 2919-2930.
2. Rines DR, He X, Sorger PK (2002). Quantitative microscopy of green fluorescent protein-label yeast. Methods Enzymol. 351: 16-34.
3. Jones MH, He X, Winey M (2001). Yeast Dam1p has a role in kinetochore function. Proc. Natl. Acad. Sci. USA 98: 13675-13680.
4. He X, Rines DR, Espelin CW, Sorger PK (2001). Molecular Analysis of Kinetochore-Microtubule Attachment in Budding Yeast. Cell 106: 195-206.
5. He X, Asthana S, Sorger PK (2000). Transient sister chromatid separation and elastic deformation of chromosomes during mitosis in budding yeast. Cell 101: 763-775.
6. He X, Jones MH, Winey M, Sazer S (1998). Mph1, a member of the mps1-like family dual specificity protein kinases is required for the spindle checkpoint in S. pombe. J. Cell Science 111: 1635-1647.
7. He X, Hayashi N, Walcott N, Azuma Y, Patterson TE, Nishimoto T, Sazer S (1998). The identification of sbp1, encoding a spi1-GTP binding protein, and other cDNAs that affect the mitosis-to-anaphase transition in Schizosaccharomyces pombe. Genetics 148: 645-656.
8. He X, Patterson TE, Sazer S (1997). The S. pombe spindle checkpoint protein mad2p blocks anaphase initiation by inhibiting APC. Proc. Natl. Acad. Sci. USA 94: 7965-7797.
For more publications, see listing on Pub Med.