Research Interests: Regulation of tumor cell growth and metabolism by protein phosphorylation
The overall research interest in my laboratory is to understand how protein phosphorylation regulates cell growth and metabolism, and how its alteration causes diseases such as cancer and metabolic disorders. Our ongoing research focuses on characterization of AMP-activated protein kinase and Raf kinase, both of which have been implicated in cancer and other disorders.
AMPK serves as a fuel-sensing enzyme that is activated by binding of 5’ AMP to the? gamma subunit and phosphorylation of the catalytic subunit at Thr 172 by upstream kinases such as LKB1 and CaMKK. The activation of AMPK has been shown to improve metabolic syndrome and to be implicated in control of cancer cell growth. One of our research interests is to test the hypothesis that AMPK functions as a metabolic tumor suppressor. Using microarray and proteomic approaches, we have identified several target molecules regulated by AMPK and are currently evaluating their functional relationship with AMPK and biological relevance.
Raf kinases, consisting of three isoforms, Raf-1, B-Raf and A-Raf, act as immediate downstream effectors of Ras. They are implicated in tumorigenesis, inasmuch as activating mutations of the ras genes have been found in 20-30% of overall human cancers and activated mutants of B-Raf frequently reported in human cancers. Although the linear relationship of the Ras/Raf/MEK/Erk signaling pathway has been delineated, the mechanism of Raf activation still remains elusive. We have a long standing interest in characterizing phosphorylation of Raf for its activation, and identifying kinases responsible for these phosphorylation events and downstream targets in addition to MEK1/2.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- Boston Medical Center
- Jiangxi University of Traditional Chinese Medicine, MD
- Albert Einstein College of Medicine, PhD
- Sun Yat-sen University, MSc
- Published on 8/25/2017
Lin H, Ying Y, Wang YY, Wang G, Jiang SS, Huang D, Luo L, Chen YG, Gerstenfeld LC, Luo Z. AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation. Biochim Biophys Acta. 2017 12; 1864(12):2369-2377. PMID: 28847510.
- Published on 3/28/2016
He H, Liu D, Lin H, Jiang S, Ying Y, Chun S, Deng H, Zaia J, Wen R, Luo Z. Phosphatidylethanolamine binding protein 4 (PEBP4) is a secreted protein and has multiple functions. Biochim Biophys Acta. 2016 Jul; 1863(7 Pt A):1682-9. PMID: 27033522.
- Published on 2/2/2016
Huang D, He X, Zou J, Guo P, Jiang S, Lv N, Alekseyev Y, Luo L, Luo Z. Negative regulation of Bmi-1 by AMPK and implication in cancer progression. Oncotarget. 2016 Feb 02; 7(5):6188-200. PMID: 26717043.
- Published on 12/30/2015
Li NS, Zou JR, Lin H, Ke R, He XL, Xiao L, Huang D, Luo L, Lv N, Luo Z. LKB1/AMPK inhibits TGF-ß1 production and the TGF-ß signaling pathway in breast cancer cells. Tumour Biol. 2016 Jun; 37(6):8249-58. PMID: 26718214.
- Published on 10/13/2015
Yang Z, Xie C, Xu W, Liu G, Cao X, Li W, Chen J, Zhu Y, Luo S, Luo Z, Lu N. Phosphorylation and inactivation of PTEN at residues Ser380/Thr382/383 induced by Helicobacter pylori promotes gastric epithelial cell survival through PI3K/Akt pathway. Oncotarget. 2015 Oct 13; 6(31):31916-26. PMID: 26376616.
- Published on 9/30/2015
Lin H, Li N, He H, Ying Y, Sunkara S, Luo L, Lv N, Huang D, Luo Z. AMPK Inhibits the Stimulatory Effects of TGF-ß on Smad2/3 Activity, Cell Migration, and Epithelial-to-Mesenchymal Transition. Mol Pharmacol. 2015 Dec; 88(6):1062-71. PMID: 26424816.
- Published on 4/13/2015
Luo L, Jiang S, Huang D, Lu N, Luo Z. MLK3 phophorylates AMPK independently of LKB1. PLoS One. 2015; 10(4):e0123927. PMID: 25874865.
- Published on 3/1/2015
He H, Ke R, Lin H, Ying Y, Liu D, Luo Z. Metformin, an old drug, brings a new era to cancer therapy. Cancer J. 2015 Mar-Apr; 21(2):70-4. PMID: 25815846.
- Published on 11/4/2013
He G, Zhang YW, Lee JH, Zeng SX, Wang YV, Luo Z, Dong XC, Viollet B, Wahl GM, Lu H. AMP-activated protein kinase induces p53 by phosphorylating MDMX and inhibiting its activity. Mol Cell Biol. 2014 Jan; 34(2):148-57. PMID: 24190973.
- Published on 9/5/2012
Luo L, Huang W, Tao R, Hu N, Xiao ZX, Luo Z. ATM and LKB1 dependent activation of AMPK sensitizes cancer cells to etoposide-induced apoptosis. Cancer Lett. 2013 Jan 1; 328(1):114-9. PMID: 22960274.
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