Xuelian Luo, Ph.D. Adjunct Associate Professor Associate Professor School Medical School Department Pharmacology | Biophysics Graduate Programs Molecular Biophysics Biography Dr. Xuelian ‘Sue’ Luo received her undergraduate degree in Chemistry from Peking University. She received her Ph.D. in Biochemistry from Tufts University School of Medicine. Her graduate work was mostly focused on biochemical and structural studies of the DNA-binding domain of the SV40 T-antigen and characterization of its interactions with the SV40 origin. During her postdoctoral work with Gerhard Wagner at Harvard Medical School, Dr. Luo determined the atomic structure of the key spindle checkpoint protein Mad2 by NMR. Due to family reason, she later moved to UT Southwestern and continued her postdoctoral work with Jose Rizo-Rey. Using both NMR and X-ray crystallography, Dr. Luo determined the atomic structures of the multiple conformers of Mad2 and Mad2 in complex with its inhibitor p31comet and showed that a regulated conformational switch of Mad2 is crucial for spindle checkpoint activation. These studies have contributed significantly to our understanding of the mechanisms of chromosome segregation. Dr. Luo joined the faculty of UT Southwestern in the fall of 2006. Her laboratory is interested in understanding the molecular mechanisms of intracellular signal transduction pathways using a combination of biochemical, structural, and cellular approaches. Her current research efforts focus on the regulation of the Hippo pathway, which controls organ size and maintains tissue homeostasis. Dysregulation of this pathway drives tumor formation in flies, mice, and humans. Dr. Luo’s research has provided critical insights into the activation mechanisms of the core MST-LATS kinase cascade and TEAD-YAP regulation. Her work defines the mechanisms by which MOB1 mediates MST-dependent LATS activation, a central event during Hippo signaling. Her lab recently shows that SAV1 promotes MST kinase activation through antagonizing the STRIPAK PP2A phosphatase. Her research also establishes that TEAD transcription factors undergo functionally important auto-palmitoylation. The discovery that TEAD has enzyme-like activity indicates that TEAD-YAP, which has previously been thought to be undruggable, is in fact an attractive molecular target for cancer therapy. Dr. Luo’s research is aimed to advance our fundamental understanding of the regulation of the Hippo signaling network, and may also uncover novel ways of exploiting defects in the Hippo pathway to treat human diseases. Education Undergraduate Peking University (1990), Chemistry Graduate School Tufts University (1997), Biochemistry Research Interest Biochemistry Mechanism of Signaling Pathways NMR and X-ray Crystallography Signal Transduction Structural Biology Publications Featured Publications SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK. Bae SJ, Ni L, Osinski A, Tomchick DR, Brautigam CA, Luo X Elife 2017 Oct 6 Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway. Chan P, Han X, Zheng B, DeRan M, Yu J, Jarugumilli GK, Deng H, Pan D, Luo X, Wu X Nat. Chem. Biol. 2016 Feb Structure of an intermediate conformer of the spindle checkpoint protein Mad2. Hara M, Özkan E, Sun H, Yu H, Luo X Proc. Natl. Acad. Sci. U.S.A. 2015 Aug Structural basis for Mob1-dependent activation of the core Mst-Lats kinase cascade in Hippo signaling. Ni L, Zheng Y, Hara M, Pan D, Luo X Genes Dev. 2015 Jun Structural basis for autoactivation of human Mst2 kinase and its regulation by RASSF5. Ni L, Li S, Yu J, Min J, Brautigam CA, Tomchick DR, Pan D, Luo X Structure 2013 Oct 21 10 1757-68 Structural analysis of human Cdc20 supports multisite degron recognition by APC/C. Tian W, Li B, Warrington R, Tomchick DR, Yu H, Luo X Proc. Natl. Acad. Sci. U.S.A. 2012 Nov 109 45 18419-24 Structure of human Mad1 C-terminal domain reveals its involvement in kinetochore targeting. Kim S, Sun H, Tomchick DR, Yu H, Luo X Proc. Natl. Acad. Sci. U.S.A. 2012 Apr 109 17 6549-54 Structural and functional analysis of the YAP-binding domain of human TEAD2. Tian W, Yu J, Tomchick DR, Pan D, Luo X Proc. Natl. Acad. Sci. U.S.A. 2010 Apr 107 16 7293-8 Protein metamorphosis: the two-state behavior of Mad2. Luo X, Yu H Structure 2008 Nov 16 11 1616-25 p31comet blocks Mad2 activation through structural mimicry. Yang M, Li B, Tomchick DR, Machius M, Rizo J, Yu H, Luo X Cell 2007 Nov 131 4 744-55 Results 1-10 of 26 1 2 3 Next Last Honors & Awards CPRIT Individual Investigator Research Awards (2013) National Cancer Institute Howard Temin Award (2003-2008) American Cancer Society ACS-IRG award (2002) National Institutes of Health (NIH) Postdoctoral Fellowship (1998-2001) Giovanni Armenise-Harvard Foundation Postdoctoral FellowHarvard Medical School (1997) Professional Associations/Affiliations American Society of Biochemistry and Molecular Biology (2015-2019) Chinese Biological Investigators Society (2005-2018)