Biography

Dr. Hu received  his Bachelor degree in pharmaceutical science and Master degree in medicinal  chemistry from the School of Pharmaceutical Sciences, Peking University. Then he  studied in the School of Life Sciences, Tsinghua University and received his  Doctoral degree in biology in 2014. In 2015, he joined Prof. Kevan Shokat’s lab  in the University of California, San Francisco for postdoctoral training. He  received Damon Runyon Fellowship Award in 2015. His PhD research focused on the  molecular mechanism for activation of caspase-9 by the Apaf-1 apoptosome. His  postdoctoral work is to develop small molecule inhibitors of cancer-associated  mutant Gαs. He has published several research papers on journals such  as Cell, Nature, PNAS and Cell  Research. 

Research

The study in  the Hu lab will focus on protein palmitoylation. As a type of protein  lipidation, protein palmitoylation is the attachment of a palmitoyl group to a  cysteine residue via a thioester bond. Because of its high reversibility,  protein palmitoylation participates in the rapid regulation of many cell  signaling pathways. Protein palmitoylation is catalyzed by  palmitoyltransferases, also known as DHHC enzymes. A total of 23 human DHHC  enzymes have been identified to catalyze the palmitoylation of nearly 1000 human  proteins. It’s not clear how the activities of these enzymes are regulated. The  lack of effective and selective DHHC inhibitors impedes the study of protein  palmitoylation. The Hu lab will combine biological and chemical tools to  understand the molecular mechanism underlying the function of DHHC enzymes and  will develop small molecules to regulate DHHC-related signaling pathways.

Representative  Publications

1.  Hu,  Q., Shokat, K. (2018). Disease-causing mutations in the G  protein Gαs subvert the roles of GDP and GTP. Cell 173, 1254–1264.

2.  Li, Y.#, Zhou, M.#, Hu,  Q.#,  Bai, X.-C., Huang, W., Scheres, S.H.W., and Shi, Y. (2017). Mechanistic insights  into caspase-9 activation by the structure of the apoptosome holoenzyme. Proc Natl Acad  Sci U S A 114, 1542–1547. (# co-first author)

3.  Zhou, M., Li, Y., Hu,  Q., Bai, X.-C., Huang, W., Yan, C., Scheres, S.H.W., and Shi, Y.  (2015). Atomic structure of the apoptosome: mechanism of cytochrome c- and  dATP-mediated activation of Apaf-1. Genes Dev 29, 2349–2361

4.  Wang, J., Yan, C., Li, Y., Hirata, K., Yamamoto, M., Yan, N.*, and Hu,  Q.* (2014). Crystal structure of a bacterial homologue of SWEET  transporters. Cell Res 24, 1486-1489. (*  co-corresponding author)

5.  Hu,  Q.#, Wu, D.#, Chen, W., Yan, Z., Yan, C., He, T., Liang, Q., and  Shi, Y. (2014). Molecular determinants of caspase-9 activation by the Apaf-1  apoptosome. Proc Natl Acad Sci U S A 111,  16254-16261. (# co-first author)

6.  Hu,  Q.#, Wu, D.#, Chen, W., Yan, Z., and Shi, Y. (2013). Proteolytic  processing of the caspase-9 zymogen is required for apoptosome-mediated  activation of caspase-9. J Biol Chem 288, 15142-15147. (#  co-first author)

7.  Wu, D.#, Hu,  Q..#,  Yan, Z.#, Chen, W., Yan, C., Huang, X., Zhang, J., Yang, P., Deng, H., and Wang,  J., et al. (2012). Structural basis of ultraviolet-B perception by UVR8. Nature 484, 214-219. (# co-first  author)

8.  Hu,  Q., Nie, A., Welsh, K., Pinacho, C.F., Zhu, X., Li, Z., An, J.,  Reed, J.C., Zhang, L., and Huang, Z. (2011). Novel X-linked inhibitor of  apoptosis protein inhibitors as probes of apoptosis in biology and medicine.  Exp  Biol Med (Maywood) 236, 247-251.

9.  Wang, F., Mei, Z., Qi, Y., Yan, C., Hu,  Q., Wang, J., and Shi, Y. (2011). Structure and mechanism of the  hexameric MecA-ClpC molecular machine. Nature 471, 331-335.

10.  Qi, S., Pang, Y., Hu,  Q.,  Liu, Q., Li, H., Zhou, Y., He, T., Liang, Q., Liu, Y., and Yuan, X., et al.  (2010). Crystal structure of the Caenorhabditis elegans apoptosome reveals an  octameric assembly of CED-4. Cell 141, 446-457.