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Cell and Molecular Biology Graduate Group

Tim J. Yen Ph.D

Tim J. Yen Ph.D.
Senior Member, Fox Chase Cancer Center
Adjunct Associate Professor, Dept of Genetics

Cell Biology and Physiology Program


Fox Chase Cancer Center
7701 Burholme Ave
Philadelphia, PA 19111

Office tel.: 215 728-2590
Lab tel.: 215 728-4311
Fax: 215 728-2412
E-mail: tj_yen@fccc.edu


Dr. Yen's Fox Chase Cancer Center page

Dr. Yen's Lab page


  • We are interested in understanding the structure and function of kinetochores as a means to elucidate mechanisms of chromosome alignment and mitotic checkpoint control.

Key words: Mitosis, Cancer, Chromosomes, Checkpoints.


Search PubMed for articles


Growth of multicellular organisms is critically dependent on the ability of individual cells to duplicate and separate their genomes during cell division. Defects in DNA replication and chromosome segregation can lead to significant human health problems that include cancer, birth defects and infertility. The mechanisms that are responsible for replicating the genome and to segregate the resultant chromosomes during mitosis can be viewed as mechanical events because the proteins involved in these functions are molecular machines. Superimposed on the mechanical processes are regulatory mechanisms called checkpoints that monitor the molecular machines to ensure that their tasks are accomplished accurately and in a timely manner. Thus, checkpoints play an essential role in maintaining genome stability by ensuring that errors in DNA replication and chromosome segregation are corrected before cells are allowed to divide.

Our laboratory is focused on understanding the mechanical and regulatory mechanisms that ensure that chromosomes are properly attached and segregated by the spindle during mitosis. We have focused our attention on characterizing the molecular composition and function of the kinetochore, as this is the structure on the chromosome that establishes and monitors connections with microtubules. We have identified molecular motors and checkpoint proteins that reside at kinetochores and are interested in understanding how these proteins interact with each other to carry out complex kinetochore functions. Our research is particularly relevant to cancer research as drugs that inhibit mitosis are a major modality for anti-cancer therapy. Current drugs however, lack specificity as they target microtubules that provide functions that not only are critical for mitosis but also for other essential cellular processes such as vesicle transport, cell shape and locomotion. Our studies of how chromosomes segregate have revealed novel proteins that provide functions that are critical only during mitosis. As such, these proteins should be ideal candidates for the development of highly specific anti-mitotic drugs.


Daniel, R., Kao, G., Taganov, K., Greger, J., Favorova, O., Merkel, G., Yen, T.J., Katz, R.A., Skalka, A.M. Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response. Proc. Natl. Acad. Sci. U.S.A. 100:4778-4783, 2003.

Fletcher L, Yen TJ, Muschel RJ. Related Articles, Links Abstract DNA damage in HeLa cells induced arrest at a discrete point in G2 phase as defined by CENP-F localization. Radiat Res. 159:604-11, 2003.

Kao, G.D., McKenna, W.G., Guenther, M.G., Muschel, R.J., Lazar, M.A., Yen,T.J. Histone Deacetylase 4 interacts with 53BP1 to mediate the DNA damage response. J.Cell Biol. 160:1017-1027, 2003.

Liu, S.T., Hittle, J.C., Jablonski, S.A., Campbell, M.S., Yoda, K., Yen, T.J. Human CENP-I specifies localization of CENP-F, MAD1 and MAD2 to kinetochores and is essential for mitosis. Nat. Cell Biol. 5:341-345, 2003.

Liu, S.T., Hittle, J.C., Lees, E., Yen, T.J., Human MPS1 kinase is required for mitotic arrest induced by the loss of CENP-E from kinetochores. Mol. Biol. Cell. 14: 1638-1651, 2003.



Dividing cells rely on three basic mechanisms to maintain genome stability. Two of these mechanisms, duplication of the genome by DNA replication and the segregation of each genome copy into dividing cells during mitosis, are mechanical in nature. These two bioengineering tasks require a large number of structural proteins that function together as complex machines. Superimposed on these two mechanical systems is a third component of quality control that monitors the integrity of the genome to ensure its accurate replication and distribution. Defects in any one of these three fundamental cellular processes lead to the accumulation of mutations in the genome that result in cell death or uncontrolled cell growth. An understanding of the biochemical basis of the three mechanisms that maintain genome stability is of utmost importance in developing new methods of cancer detection and treatment.

Our laboratory is focused on studying two of the three essential processes that involve:

  1. Studying the biomechanical events that segregate chromosomes between two daughter cells during mitosis
  2. Characterizing the mechanism of the mitotic checkpoint to prevent aneuploidy
  3. Studying a checkpoint system to monitor radiation-induced DNA damage.
Lab personnel:
Sandra Jablonski, Ph.D. - Staff Scientist
Valery Sudakin, Ph.D. - Research Associate
Song-Tao Liu, Ph.D. - Postdoctoral Fellow
Nadia Ladygina, Graduate Student
James Hittle, B.S. - Technical Specialist
Beatrice J. Conner - Scientific Technician
Nadia Tikhmyanova, M.A. - Scientific Technician
Dina Matheos, Ph.D - Postdoctoral Fellow
Jie Feng, Ph.D. - Postdoctoral Fellow
last updated 9/2003
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