Xin-Hua Feng, Ph.D.
General Surgery Division of the Michael E. DeBakey Department of Surgery
Department of Molecular and Cellular Biology
- Ph.D., University of Maryland - College Park
- Postdoctoral, University of California - San Francisco
- Research Achievement Award, The W.M. Keck Foundation (2002)
- American Cancer Society Research Scholar (2003-2007)
- Leukemia and Lymphoma Society Scholar (2003-2008)
My research is aimed at elucidating the underlying mechanisms and interplays among protein modifications, signaling pathways and gene transcription as well as understanding their roles in cell proliferation, tissue differentiation and pathogenesis of human diseases. Our current research projects include:
- Phosphatome - genome-wide investigation of protein dephosphorylation: Signal transduction pathways are often regulated by dynamic interplay between protein kinases and phosphatases. We have constructed a cDNA cloneset containing all human protein serine/threonine phosphatases. This tool enables us to systematically investigating dephosphorylation of key proteins involved in cell signaling, cell cycle regulation and transcription.
- SUMO, ubiquitin and control of protein turnover/functions: We examine posttranslational modifications, particularly ubiquitination and SUMOylation of transcriptional factors in normal and cancer cells. We study the substrate specificity of ubiquitin and SUMO E3 ligases, and seek to understand the molecular mechanism how the ubiquitination/proteasome and SUMOylation systems are connected with protein functions. Our study will provide insights into the relationship of protein deregulation with human cancers or abnormal development.
- TGF-ß signal transduction: SMADs are evolutionarily conserved signal transducers and transcription factors controlling functions of TGF-ß/BMP. A large number of inactivating mutations on SMADs have been linked with human cancers and genetic diseases. The functions of SMADs are defined by specific SMAD-protein and SMAD-DNA interactions. We address these molecular interactions, requirement and functionality of SMADs in TGF-ß/BMP responses using genomic and proteomic approaches. We study how SMADs mediate transcriptional control of key cell cycle regulators such as CDK inhibitors p15 and p21, and oncogene c-Myc. We also investigate how SMAD tumor suppressors interplay with oncogenic pathways, and we are particularly interested in dissecting SMAD signaling pathway in pancreatic and breast cancers using in vitro and in vivo model systems.
- Genetic screens, BMP/TGF-ß signaling, and ES cells: We are taking genome-wide approaches (e.g. genetic screens using lentiviral RNAi library) to identify novel TGF-ß signal modifiers or regulators involved in stem cell differentiation. Novel molecules that control TGF-ß/BMP signaling or participate in human ES cell self-renewal and differentiation will be further studied in vitro and in model organisms to define their physiological roles in tissue differentiation and organ development.
- Immune suppression by TGF-ß: TGF-ß is a major anti-inflammatory cytokine, but the mechanism how TGF-ß exerts this action is unclear. We are interested in investigating the signaling interactions between TGF-ß pathway and pro-inflammatory pathways (such as TNF-alpha and IL-1 pathways). This area of research may lead to drug discovery for cancer and inflammatory diseases.
- Lin X, Liang M and Feng X-H. (2000) Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in TGF-ß signalling. J. Biol. Chem. 275:36818-36822.
- Feng X-H, Liang Y-Y, Liang M, Zhai W and Lin X. (2002) Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-ß-mediated induction of the CDK inhibitor p15. Molecular Cell 9:133-143.
- Lin X, Liang M, Liang Y-Y, Brunicardi FC, Melchior F and Feng X-H. (2003) Activation of TGF-ß signaling by SUMO modification of tumor suppressor Smad4/DPC4. J. Biol. Chem., 278:18714-18719.
- Liang Y-Y, Lin X, Liang M, Brunicardi FC, ten Dijke P, Chen Z, Choi K and Feng X-H. (2003) dSmurf, the Drosophila homolog of mammalian Smurf1, is responsible for Mad degradation and its ectopic expression disrupts wing development. J. Biol. Chem., 278: 26307-26310.
- Lin X, Sun B, Liang M, Liang Y-Y, Gast A, Hildebrand J, Brunicardi FC, Melchior F and Feng X-H. (2003) Opposed regulation of CtBP corepressor function by SUMOylation and PDZ binding. Molecular Cell, 11:1389-1396.
- Lin X, Liang Y-Y, Sun B., Liang M, Shi YJ, Brunicardi FC, Shi Y and Feng X-H. (2003). Smad6 recruits transcription corepressor CtBP to repress BMP-induced transcription. Mol. Cell. Biol., 23: 9081-9093.
- Liang M, Melchior F, Feng X-H and Lin X. (2004). Regulation of Smad4 sumoylation and TGF-ß signaling by Protein Inhibitor of Activated STAT1. J. Biol. Chem., 279: 22857-22865.
- Liang M, Y-Y. Liang, Wrighton K, Ungermannova D, Wang X, Brunicardi FC, X. Liu, Feng X-H and Lin X.. (2004). Ubiquitination and proteolysis of cancer-derived Smad4 mutants by SCFSkp2. Mol. Cell. Biol., 24: 7524-7537.
- Feng X-H and R. Derynck. (2005). Specificity and versatility of TGF-ß signaling through Smads. Annu. Rev. Cell Dev. Biol. 12: 659-693.
- Lin X *, Duan X*, Liang Y-Y*, Su Y*, Wrighton K, Hu M, Long J, Davis C, Wang J, Brunicardi FC, Shi Y, Chen YG, Meng A, and Feng X-H. (2006). PPM1A functions a Smad phosphatase to terminate TGF-ß signaling. Cell, 125: 915-928. (*equal contribution)