Molecular Biology

Demonstrated that cell surface receptor molecules not only mediate traditional chemical signals activating proliferation but also travel to the nucleus, where they can act on genes and other nuclear proteins to regulate transcription, DNA repair, and DNA synthesis.

Lin SY, Makino K, Xia W, Matin A, Wen Y, Kwong KY, Bourguignon L, Hung MC. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol. 2001;3(9):802-808.

Wang SC, Nakajima Y, Yu YL, Xia W, Chen CT, Yang CC, McIntush EW, Li LY, Hawke DH, Kobayashi R, Hung MC. Tyrosine phosphorylation controls protein stability of PCNA. Nature Cell Biol. 2006;8(12):1359-1368.

Lo HW, Hsu SC, Ali-Seyed M, Gunduz M, Xia W, Wei Y, Bartholomeusz G, Shih JY, Hung MC. Nuclear interaction of EGFR and STAT3 in the activation of iNOS/NO pathway. Cancer Cell. 2005;7(6):575-589.

Discovered MTA1s (metastatic tumor antigen 1, short version), a protein that is required for estrogen to exert its effects, including promotion of breast cancer, and demonstrated its abnormal activity in breast cancers.

Kumar R, Wang RA, Mazumdar A, Talukder AH, Mandal M, Yang Z, Bagheri-Yarmand R, Sahin A, Hortobagyi G, Adam L, Barnes CJ, Vadlamudi RK. A naturally occurring MTA1 variant sequesters estrogen receptor-alpha in the cytoplasm. Nature. 2002;418(6898):654-657.

Discovered Osterix, a molecule that binds to DNA and activates the expression of genes required for bone formation.

Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108(1):17-29.

Koga T, Matsui Y, Asagiri M, Kodama T, de Crombrugghe B, Nakashima K, Takayanagi H. NFAT and Osterix cooperatively regulate bone formation. Nat Med. 2005;11(8):880-885.

Discovered a mechanism that enables cells to detect and degrade non-functional RNA, preventing these defective RNA molecules from encoding truncated and ineffective proteins.

Chang YF, Imam JS, Wilkinson MF. The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem. 2007; 76: 51-74.

Chan WK, Huang L, Gudikote JP, Chang YF, Imam JS, MacLean JA, Wilkinson MF. An alternative branch of the nonsense-mediated decay pathway. EMBO J. 2007;26(7):1820-1830.

Gudikote JP, Imam JS, Garcia RF, Wilkinson MF. RNA splicing promotes translation and RNA surveillance. Nat Struct Mol Biol. 2005;12(9):801-809.

Discovered that EGFR, a receptor tyrosine kinase frequently overexpressed in human cancers, enhances the ability of cancer cells to utilize glucose.  This novel activity empowers cancer cell survival under poor nutritional conditions and suggests that treatment may be enhanced by knocking down both kinase activity and glucose-related activity of EGFR.

Weihua Z, Tsan R, Huang WC, Wu Q, Chiu CH, Fidler IJ, Hung MC. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell. 2008;13(5):385-393.