Professor
Daniel and Lori Efroymson Professor of Oncology

Department of Biochemistry and Molecular Biology
Indiana University School of Medicine
John D. Van Nuys Medical Science Building
635 Barnhill Drive, Room 0051D
Indianapolis, Indiana 46202-5122

Phone: (317) 278-0920
Facsimile: (317) 274-4686
E-mail: hualu@iupui.edu
Dr. Lu's Web Site

MB (US MD equivalent), 1983, Jiangxi Medical College, Nanchang, China
MS, 1986, Chinese Academy of Medical Sciences, Beijing, China,
Ph.D., 1993, Rutgers University / UMDNJ-RWJMS, Piscataway, NJ
Postdoctoral Fellow, Department of Molecular Biology, 1997, Princeton University, Princeton, New Jersey

Area of Study

Molecular dissection of the p53 and c-Myc networks in controlling cell growth, death, differentiation and tumorigenesis.  More details...

Selected Recent Publications

Zeng X.Y., Chen L., Jost C.A., Maya R., Kaelin W.G., Oren M., Chen J., and Lu H. (1999) MDM2 suppresses p73 function without promoting p73 degradation. Mol. Cell. Biol. 19:3257-3266.

Zeng X.Y, Li X, Miller A, Yuan Z, Yuan W, Kwok RP, Goodman R, Lu H. (2000) The N-terminal domain of p73 interacts with the CH1 domain of p300/CREB binding protein and mediates transcriptional activation and apoptosis. Mol Cell Biol. 20: 1299-310.

Kobet E, Zeng X, Zhu Y, Keller D and Lu H. (2000) MDM2 Inhibits p300-mediated p53 Acetylation and Activation by Forming a Ternary Complex with Two Proteins. Proc. Natl. Acad. Sci. USA. 97:12547-12552 4.,

Keller D, Zeng XY, Wang Y, Zhang Q, Kapoor M, Zhao YM, Goodman R, Lozano G, and Lu H. (2001) A DNA damage responsive p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Mol. Cell. 7: 283.

Zeng SX, Dai MS, Keller D, and Lu H. (2002) SSRP1 functions as a co-activator of the transcriptional activator p63. EMBO J. 21, 5487-5497.

Jin YT, Lee, HJ, Zeng SX, Dai, MS, and Lu H (2003) MDM2 promotes p21^waf1/cip1 proteasomal turnover independently of ubiquitylation. EMBO J. 22, 6365-6377.

Dai MS, Zeng SX, Jin YT, Sun XX, David L, and Lu H (2004). Ribosomal protein L23 activates p53 by abrogating MDM2 function in response to ribosomal perturbation but not to translation inhibition. Mol. Cell. Biol. 24, 7654-7668.

Dai MS, Jin Y, Gallegos JR, Lu H. Balance of Yin and Yang: ubiquitylation-mediated regulation of p53 and c-Myc. Neoplasia. 2006 Aug;8(8):630-44 (review article).

Lee HJ, Zeng SX, and Lu H. (2006) UV induces p21 rapid turnover independent of ubiquitin and skp2. J. Biol. Chem. 281, 26876-83.

Dai MS, Shi D, Jin Y, Sun XX, Zhang Y, Grossman SR, Lu H. Regulation of the MDM2-p53 Pathway by Ribosomal Protein L11 Involves a Post-ubiquitination Mechanism. J Biol Chem. 2006 Aug 25;281(34):24304-13. Epub 2006 Jun 27.

Yu Y, Maggi Jr. LB, Kim H, Dai M-S, Lu H, and Weber JD. Nucleophosmin is a rate-limiting nuclear export factor for the ribosome. Mol. Cell. Biol.(2006)

Ding Y, Lee JF, Lu H, Lee MH, and Yan DH. Interferon-inducible IFIXa1, a novel HDM2-interacting protein, destabilizes HDM2 by promoting its ubiquitination. Mol. Cell. Biol. (2006)

Landais I, Lee HJ, and Lu H. Coupling caspase cleavage and ubiquitin-proteasome dependent degradation of SSRP1 during apoptosis. Cell Death & Differentiation. (2006)

Jin Y, Dai MS, Lu SZ, Xu Y, Luo Z, Zhao Y, Lu H. 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J. 2006 Mar 22;25(6):1207-18.

Li YP, Zeng SX, Landais I, and Lu H. (2007) Human SSRP1 has Spt16-dependent and independent roles in gene transcription. J. Biol. Chem. 282, 6936-6945.

Sun XX, Dai MS, and Lu H. (2007) 5-Fluorouracil activation of p53 involves an MDM2-ribosomal protein interaction. J. Biol. Chem. 282, 8052-8059.

Dai MS, Arnold H, Sun XX, Sears R, Lu H. Inhibition of c-Myc activity by ribosomal protein L11. EMBO J. 2007 Jul 25;26(14):3332-45.

Dai MS, Sears R, and Lu H (2007) Feedback regulation of c-Myc by ribosomal protein L11. Cell Cycle. 6, 2735-41. 

Dai MS, Gallegos J and Lu H. (2007) The p53 tumor suppressor opens gateways for cancer therapy. In Gene therapy: Therapeutic mechanisms and strategies. Third edition. Nancy Smyth Templeton, Ed. Marcel Dekker, Inc. In press.

Gallegos J, Litersky J, Lee HJ, Sun Y, Nakayama K, Nakayama K, and Lu H. (2008) bTrCP activates and ubiquitylates TAp63g. JBC. 283, 66-75. 

Jin YT, Zeng SX, Sun XX, Lee H, Blattner C, Xiao ZX, and Lu H. (2008) MDMX promote proteasomal turnover of p21 during cell cycle independently of, but in cooperation with, MDM2. Mol Cell. Biol. 28, 1218-29.

Sun XX, Dai MS, and Lu H. (2008) Mycophenolic acid activation of p53 requires ribosomal proteins L5 and L11. JBC. 283, 12387-92.

Dai MS, Sun XX, and Lu H. (2008) Abnormal expression of Nucleostemin activates p53 activity and induces cell cycle arrest via inhibition of MDM2. Mol. Cell. Biol. 28, 4365-76.

MacPatlin MM, Zeng SX, and Lu H. (2008) Posphorylation and stabilization of TAp63g by IkB kinase-b. JBC. 283, 15754-61.

Khan A, and Lu H. (2008) Inhibition of MDM2-p53 feedback loop by various small molecules for potential cancer therapy? Cancer Biology & Therapy. 7, 6.

Dai MS, and Lu H. (2008) Crosstalk between c-Myc and ribosome in ribosomal biogenesis and cancer. J. Cell Biochem. In press.

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Research Interests

The Lu laboratory is interested in understanding the molecular and biochemical basis that underlies physiological and pathological signaling pathways (growth, hypoxia, or DNA damage signals), which lead to gene expression and subsequent cell growth arrest, differentiation, or apoptosis. The abnormal alterations of these pathways may result in carcinogenesis. A typical example of the carcinogenic abnormality is the alternation of the components in the stress signaling pathway that is mediated by the p53 tumor suppressor protein and its negative regulators such as MDM2 and MDMX. Genetic studies show that MDM2 and MDMX are the physiological feedback regulators of p53 and these proteins play important roles in tumorigenesis. MDM2 and MDMX repress p53 function by mediating its degradation and directly suppressing its activity. Various signals including ribosomal stress signals lead to p53 activation by blocking this feedback regulation. Another example of the cancerous abnormality is the overexpression of oncogenes, such as c-myc. Our recent studies show that ribosomal proteins also regulate c-Myc activity. To understand the molecular and biochemical mechanisms for cell proliferation and tumorigenesis involving the p53 and c-Myc pathways, my laboratory focuses on the following projects:

1). To understand the biochemical mechanism underlying the regulation of MDM2 by ribosomal proteins, leading p53 activation, and the role of these ribosomal proteins in cell cycle regulation and tumorigenesis;

2). To elucidate molecular mechanisms for the 14-3-3gamma regulation of MDMX, leading p53 activation, in response to hypoxia and DNA damage signals, and also the role of 14-3-3gamma in tumorigenesis;

3). To determine the role of SSRP1 in mitosis of normal and cancer stem cells and to dissect the molecular and biochemical mechanisms underlying SSRP1 regulation of mitosis;

4). To illustrate the role of ribosomal proteins in regulating c-Myc activity and tumorigenesis;

Diverse approaches including quantitative and analytical protein biochemistry, proteomics, gene microarray, molecular and cellular biological methods as well as genetic methods (such as animal models) will be employed in these studies. We will also pursue translational research by screening anti-cancer drugs targeting the above pathways and examining molecular alternations of these pathways in human cancers stemmed from the digestion system. The effort will be complemented by collaborating with other groups on and off the campus.