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Molecular and Human Genetics

Houston, Texas

Department of Molecular and Human Genetics
Department of Molecular and Human Genetics
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Xiangwei He, Ph.D

Xiangwei He, Ph.D

Assistant Professor, Department of Molecular and Human Genetics

Other Positions

Assistant Professor, Department of Biochemistry & Molecular Biology; Program in Cell and Molecular Biology

Education

B.S., Fudan University, 1988
Ph.D., Baylor College of Medicine, 1997
Postdoctoral Fellow, Massachusetts Institute of Technology, 2001

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.

Fission yeast cells

Fission yeast cells undergoing normal mitosis and defective mitosis due to a mutation in a kinetochore protein (From left to right).

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. Pidoux AL, Choi ES, Abbott JK, Liu X, Kagansky A, Castillo AG, Hamilton GL, Richardson W, Rappsilber J, He X, Allshire RC (2009). Fission yeast Scm3: A CENP-A receptor required for integrity of subkinetochore chromatin. Mol. Cell. 33(3): 299-311. [Pub Med]
  2. Song JS, Liu X, Liu XS, He X (2008). A high-resolution map of nucleosome positioning on a fission yeast centromere. Genome Res. 18(7): 1064-72. [Pub Med]
  3. Joglekar AP, Bouck D, Finley K, Liu X, Wan Y, Berman J, He X, Salmon ED, Bloom KS (2008). Molecular architecture of the kinetochore-microtubule attachment site is conserved between point and regional centromeres. J. Cell Biol. 181(4): 587-94. [Pub Med]
  4. Yao J, He X (2008). Kinetochore assembly: building a molecular machine that drives chromosome movement. Mol. BioSyst. 4 (10): 987-92. [Pub Med]
  5. Liu X, McLeod I, Anderson S, Yates J. III, He X (2005). Molecular analysis of the kinetochore architecture in fission yeast. EMBO J. 24 (16): 2919-30. [Pub Med]
  6. Rines DR, He X, Sorger PK (2002). Quantitative microscopy of green fluorescent protein-label yeast. Methods Enzymol. 351: 16-34. [Pub Med]
  7. Jones MH, He X, Winey M (2001). Yeast Dam1p has a role in kinetochore function. Proc. Natl. Acad. Sci. USA 98 (24): 13675-13680. [Pub Med]
  8. He X, Rines DR, Espelin CW, Sorger PK (2001). Molecular Analysis of Kinetochore-Microtubule Attachment in Budding Yeast. Cell 106(2): 195-206.. [Pub Med]
  9. He X, Asthana S, Sorger PK (2000). Transient sister chromatid separation and elastic deformation of chromosomes during mitosis in budding yeast. Cell 101(7): 763-75. [Pub Med]
  10. 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( Pt 12): 1635-47. [Pub Med]
  11. 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(15): 7965-7797. [Pub Med]

More Publications (PubMed)

Contact Information

Xiangwei He Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.

Phone: 713-798-2093
Fax: 713-798-8142
E-mail:

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