Li Lan, MD, PhD

Assistant Professor


Dr. Lan

Contact

412-623-3228
Fax: 412-623-7761

2.6 Hillman Cancer Center

5117 Centre Avenue

Pittsburgh, PA 15213-1862

Education

MD, Tohuku University, Sendai (Japan)

PhD, Tohuku University, Sendai (Japan)

Research Summary

My major research field is in DNA damage and repair. We developed several novel methods for producing various type of DNA damage in situ including using laser combined with confocal microscope. By using these novel methods, we successfully revealed the dynamic damage response of DNA repair proteins to DNA damage in cells. We are also interested in studying how chromatin remodeling and histone modifications affect each distinct repair pathway, such as repair of single-strand breaks (SSB), double-strand breaks (DSB) and nucleotide excision repair (NER). We found specific ATPase dependent chromatin remodeling factors, ACF and SNF2H, which are necessary for repair of DSB; we established an in vitro system to show ubiquitination of histone H2A destabilizes nucleosome and facilitates the initiation of NER. Our goal is to determine the specific chromatin remodeling factors, which are necessary for distinct repair pathway by siRNA screening, we will study the mechanisms using in vivo and in vitro approaches. This study will greatly advance our understanding of mechanisms of maintenance of genome instability and would be extremely useful for understanding mechanisms for neurodegenerative diseases and establishing novel targets for cancer chemotherapy.

Research Lab Affiliation

Publications

Lan, L; Nakajima, S; Wei, L; Sun, L; Hsieh, C.L; Sobol, R.W; Bruchez, M; Van Houten, B; Yasui, A and Levine, A.S. (2013) Novel method for site-specific induction of oxidative DNA damage reveals differences in recruitment of repair proteins to heterochromatin and euchromatin. Nucleic Acids Res. [Epub ahead of print] |  View Abstract

Lan, L; Nakajima, S; Kapetanaki, M. G; Hsieh, C. L; Fagerburg, M; Thickman, K; Rodriguez-Collazo, P; Leuba, S. H; Levine, A. S; and Rapic-Otrin, V. (2012) Monoubiquitinated histone H2A destabilizes photolesion-containing nucleosomes with concomitant release of UV-damaged DNA-binding protein E3 ligase. J Biol Chem. 287: 12036-12049. |  View Abstract

Lan, L; Ui, A; Nakajima, S; Hatakeyama, K; Hoshi, M; Watanabe, R; Janicki, S. M; Ogiwara, H; Kohno, T; Kanno, S; and Yasui, A. (2010) The ACF1 complex is required for DNA double-strand break repair in human cells. Mol Cell. 40: 976-987. |  View Abstract

Wei, L; Lan, L; Hong, Z; Yasui, A; Ishioka, C; and Chiba, N. (2008) Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80. Mol Cell Biol. 28: 7380-7393. |  View Abstract

Kamath-Loeb, A. S; Lan, L; Nakajima, S; Yasui, A; and Loeb, L. A. (2007) Werner syndrome protein interacts functionally with translesion DNA polymerases. Proc Natl Acad Sci USA. 104: 10394-10399. |  View Abstract

Yoshimura, M; Kohzaki, M; Nakamura, J; Asagoshi, K; Sonoda, E; Hou, E; Prasad, R; Wilson, S. H; Tano, K; Yasui, A; Lan, L; Seki, M; Wood, R. D; Arakawa, H; Buerstedde, J. M; Hochegger, H; Okada, T; Hiraoka, M; and Takeda, S. (2006) Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA damage. Mol Cell. 24: 115-125. |  View Abstract

Lan, L; Nakajima, S; Komatsu, K; Nussenzweig, A; Shimamoto, A; Oshima, J; and Yasui, A. (2005) Accumulation of Werner protein at DNA double-strand breaks in human cells. J Cell Sci. 118: 4153-4162. |  View Abstract