Xiaofeng Qi, Ph.D.

Dr. Xiaofeng Qi obtained his Ph.D. degree in Genetics from the Chinese Academy of Sciences, China. He joined UT Southwestern in 2017 as a Postdoctoral Researcher in Dr. Xiaochun Li’s lab in the Department of Molecular Genetics. In 2023, Dr. Qi transitioned to the Department of Molecular Biology as an Assistant Professor.

During his postdoctoral training, Dr. Qi focused on two signaling pathways closely associated with cancer: the Hedgehog (HH) pathway and the Wnt pathway. By determining the cryogenic electron microscopy (cryo-EM) structures of key components in HH signaling pathways, such as HH, Patched-1 and Smoothened, Dr. Qi uncovered the mechanism of HH signal transduction from the extracellular space to the cell. In the Wnt signaling pathway, Dr. Qi identified Calreticulin as a novel binding partner of the Wnt protein and elucidated the mechanisms underlying Wnt morphogen biogenesis.

Currently, Dr. Qi’s lab continues to concentrate on signaling pathways, particularly those involved in immune regulation in the tumor microenvironment (TME) and conduct cutting-edge studies on essential protein complexes using biophysical and cell biological approaches. Leveraging techniques such as cryo-EM and AlphaFold, Dr. Qi aims to identify new regulators in the TME by analyzing protein complexes purified endogenously from natural sources. The results of this proposed research hold significant promise for enhancing our understanding of cancer biology and facilitating the development of new reagents for cancer therapies.

Dr. Qi is a Michael L. Rosenberg Scholar in Medical Research and was named one of the 2023 CPRIT Scholars in the First-Time, Tenure-Track Faculty Member program.

• Cancer
• Drug Discovery
• Membrane Protein
• Structural Biology

Featured Publications

Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling.

Qi X, Hu Q, Elghobashi-Meinhardt N, Long T, Chen H, Li X, Cell 2023 Oct

Mechanisms and inhibition of Porcupine-mediated Wnt acylation.

Liu Y, Qi X, Donnelly L, Elghobashi-Meinhardt N, Long T, Zhou RW, Sun Y, Wang B, Li X, Nature 2022 Jul

Regulated degradation of HMG CoA reductase requires conformational changes in sterol-sensing domain.

Chen H, Qi X, Faulkner RA, Schumacher MM, Donnelly LM, DeBose-Boyd RA, Li X, Nat Commun 2022 Jul 13 1 4273

Molecular basis of cholesterol efflux via ABCG subfamily transporters.

Sun Y, Wang J, Long T, Qi X, Donnelly L, Elghobashi-Meinhardt N, Esparza L, Cohen JC, Xie XS, Hobbs HH, Li X, Proc Natl Acad Sci U S A 2021 Aug 118 34

Sterols in an intramolecular channel of Smoothened mediate Hedgehog signaling.

Qi X, Friedberg L, De Bose-Boyd R, Long T, Li X, Nat. Chem. Biol. 2020 Sep

Mechanistic Insights into the Generation and Transduction of Hedgehog Signaling.

Qi X, Li X, Trends Biochem. Sci. 2020 May 45 5 397-410

Cryo-EM structure of oxysterol-bound human Smoothened coupled to a heterotrimeric G_i.

Qi X, Liu H, Thompson B, McDonald J, Zhang C, Li X, Nature 2019 Jun

Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex.

Qi X, Schmiege P, Coutavas E, Li X Science 2018 Aug

Structures of human Patched and its complex with native palmitoylated sonic hedgehog.

Qi X, Schmiege P, Coutavas E, Wang J, Li X Nature 2018 Jul

Structure and mechanism of a group-I cobalt energy coupling factor transporter.

Bao Z, Qi X, Hong S, Xu K, He F, Zhang M, Chen J, Chao D, Zhao W, Li D, Wang J, Zhang P Cell Res. 2017 Mar

 Featured Books

Expression, Purification and Structure Determination of Human PTCH1-HH-N Complexes. In Methods in Molecular Biology: Hedgehog Signaling

Qi, X., Schmiege, P., Esparza, L., Li, X. (2022). Humana New York, NY

• CPRIT First-Time, Tenure-Track Faculty Member
  (2023)
• Life Sciences Research Foundation Fellow
  (2019-2023)