My research area focuses on neuronal tissue regeneration and how cancers develop and. In particular, I am studying how critical extracellular signaling molecules such as Wnt, TGFbeta, and Hedgehog direct normal tissue to change into cancers or promote tissue regeneration. These signaling molecules interact with receptors that control cell growth. Abnormalities in the receptors or other proteins they interact with either directly or indirectly result in malignancies or neuron degeneration. As a result of my research, I have established a state of the art high throughput, high content screening platform and identified compounds that modulate the activity of these receptors. These compounds will have the potential to become new therapeutic agents to treat refractory as well as stroke and other neuronal degenerative diseases. Recently we identified a novel Wnt inhibitor and its IND is approved by US FDA for colon cancer treatment
Three representative publications:
1) Chen W, Berge DT, Brown J, Ahn S, Hu LA, Miller WE, Caron MG, Barak LS, Nusse R, Lefkowitz RJ. Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4. Science. 2003;301:1391-4. PMID: 12958364.
2) Chen W, Kirkbride KC, How T, Nelson CD, Mo J, Frederick JP, Wang X-F, Lefkowitz RJ, Blobe GC. Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor and down-regulation of its signaling. Science. 2003;301:1394-7. PMID: 12958365.
3) Wang J, Lu J, Bond MC, ChenM, Ren X, Lyerly HK, Barak LS, Chen W. Identification of select glucocorticoids as Smoothened agonists: potential utility for regenerative medicine Proc Natl Acad Sci U S A. 2010 107(20):9323-8. PMID: 20439738
Currently we are interested in employing high throughput screen approaches to identify small molecules and antibodies targeting Wnt signaling, Hedgehog and HER3 for brain injury and regeneration. In addition finding natural compounds from traditional Chinese medicine and their application in treating stroke and brain tumor disease is one of our current research focuses.
Award and honors
1. Elsa Jiler-ACS Professors Meeting, American Cancer Society, Florida, 2009
2. Markey Cancer Center, University of Kentucky, 2011
3. 1st HEALING International Meeting on Hedgehog-Gli Signalling, Kolymbari, Crete, Greece, 2011
4. Pediatric Neuro-Oncology Basic and Translational Research Conference, Florida. 2013
5. FABES:: "G Protein-coupled Receptor Kinases: From Molecules to Disease" , Steamboat, Colorado 2014
Selected peer-reviewed publications (in chronological order)
1 Pan C, Liu HD, Gong Z, Yu X, Hou XB, Xie DD, Zhu XB, Li HW, Tang JY, Xu YF, Yu JQ, Zhang LY, Fang H, Xiao KH, Chen YG, Wang JY, Pang Q, Chen W*, Sun JP*. Cadmium is a potent inhibitor of PPM phosphatases and targets the M1 binding site. Sci Rep. 2013;3:2333. PMID:23903585
2. Minyong Chen, Akhil Hegde, Yeon Ho Choi, Barbara S Theriot, Richard T Premont1, Wei Chen*, Julia K L Walker* . Genetic Deletion of β-arrestin-2 Mitigates Established Airway Hyperresponsiveness in a Murine Asthma Model. Am. J. Respir. Cell Mol 2015 (accepted for publication).
3. Ren X, Wang J, Osada T, Mook R, Morse M, Lyerly K, Chen W. Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth. Breast cancer research. 2015 15;17:20. PMID: 25849870;
4. Pironti G, Strachan RT, Abraham D, Mon-Wei Yu S, Chen M, Chen W, Hanada K, Mao L, Watson LJ, Rockman HA. Exosomes Induced by Cardiac Pressure Overload Contain Functional Angiotensin II Type 1Circulating Receptors. Circulation. 2015 131(24):2120-30. PMID: 25995315
5. Robert A. Mook, Jr., Jiangbo Wang, Xiu-Rong Ren, Minyong Chen, Ivan Spasojevic, Larry S. Barak, H. Kim Lyerly, and Wei Chen. Structure-Activity studies of Wnt/-betacatenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure Bioorganic & Medicinal Chemistry 2015 23(17):5829-38. PMID: 26272032