Assistant Researcher, Medicine
School of Medicine

Polycystic Kidney disease, DNA damage response and repair, Cell cycle regulation

Research in my laboratory focuses on the molecular and cellular basis of mitosis during cell division and the pathogenesis of polycystic kidney diseases (PKD). Coordination of cell cycle checkpoint control and DNA repair machinery is important for stability of the genome. DNA repair processes can eliminate genetic alterations such as point mutations, chromosomal loss, deletion, duplication, and translocation, all of which contribute fundamentally to the accumulation of more mutations. This progressive accumulation of mutations is the fundamental mechanism by which cancer develops and progresses. Polycystic kidney diseases affect up to 1 in 400-1000 people in the general population. Patients with PKD usually develop chronic renal failure and end-stage renal disease. Molecular genetic analysis of the available mouse models, kat and kat2J mice, has identified the Nek1 locus to be involved in PKD pathogenesis. Through research conducted in my laboratory and through detailed examination of kat2J -/- and +/- mice, I’ve discovered renal cyst formation and late tumor formation in multiple organs of kat2J +/- mice. These phenotypes strongly suggest that Nek1-mutated, kat2J mice suffer from genomic instability. Using Nek1-deficient cells and comparing them to identical cells from wild type littermates, I’ve also been able to demonstrate accelerated genomic instability in the telescoped setting of multiply passaged cells. My lab has also demonstrated that Nek1 is involved in an early DNA damage response, and that cells without functional Nek1 are hypersensitive to DNA damage. The current projects in my laboratory include further exploration of the roles of Nek1 in DNA damage response/repair pathways and in apoptosis and will provide further understanding of the molecular pathogenesis of polycystic kidney disease and tumor development.

Chen Y, Chen C-F, Riley DJ, Allred DC, Chen P-L, Von Hoff D, Osborne CK, and Lee W-H: Aberrant Subcellular Localization of BRCA1 in Breast Cancer. Science, 270: 789-791 (1995).
Chen Y, Riley DJ, Chen P-L, and Lee W-H: HEC, a Novel Nuclear Protein Rich in Leucine Heptad Repeats Specifically Involved in Mitosis. Mol. & Cell. Biol., 17: 6049-6056 (1997).
Zhong Q, Chen C-F, Li S, Chen Y, Wang C-C, Xiao J, Chen P-L, Sharp ZD, and Lee W-H: Association of BRCA1 with the hRad50-hMre11-p95 Complex and the DNA Damage Response. Science, 285: 747-750 (1999).
Polci R, Peng A, Chen PL, Riley DJ, Chen Y. NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response. Cancer Res 2004 Dec;64(24):8800-8803.
Chen Y**, Chen PL, Chen CF, Jiang X, Riley DJ: Never-in-Mitosis Related Kinase 1 Functions in DNA Damage Response and Checkpoint Control. Cell Cycle. 7(20): 3194 - 3201 (2008)
33. Chen Y**, Craigen W. and Riley DJ: Nek1 regulates cell death and mitochondrial membrane permeability through phosphorylation of VDAC1. Cell Cycle. 8(2): 257-267 (2009)
Chen Y**, Gaczynska M, Osmulski P, Polci R, Riley DJ. Phosphorylation by Nek1 regulates the opening and closing of voltage dependent anion channel 1, Biochem Biophys Res Commun. 2010 Apr 9;394(3):798-803. Epub 2010 Mar 15.

NIH-NIDDK, RO1 DK67339, Pathogenic mechanism of Polycystic Kidney Disease

Assistant Professor
UTHSCSA 2000—2009

Link to this profile
https://faculty.uci.edu/profile/?facultyId=5753

Last updated
08/03/2010