Professor Lan Wang earned her Ph.D. from Harvard University in the lab of Professor Gregory Verdine, where she discovered the structural basis of the lesion searching mechanism by the DNA repair protein MutY. Upon completion of her Ph.D., Lan went on to join Professor Peter Walter’s lab at UCSF, where she made a series of discoveries on different aspects of cellular protein homeostasis. Lan’s postdoctoral work earned her a few recognitions and awards including the Damon Runyon Cancer Research Foundation Fellowship Award and the UCSF PBBR Postdoc Independent Research Award.

Research Question

Molecular mechanism of mitochondrial quality control

The long-term goal of the lab is to understand the molecular mechanisms that govern mitochondrial form and function. A mitochondrion is an organelle universal to all eukaryotes. Its health is closely linked to neurodegenerative, muscle, and other diseases. The health of this organelle is a function of its quality control, both in terms of the proteins and of the genome. Despite the importance of the quality control pathways, we know very little about them: how mitochondria control the protein homeostasis on its membranes, or how it selects for healthy DNA. Combining the power of structural biology and cell biology, we aim at understanding how mitochondria maintain the quality of its protein and genome, and how the dysfunction of the quality control mechanisms leads to human diseases.

Representative Publications

1. Wang L, Myasnikov A, Pan X, Walter P: Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction eLife 2020;9:e54031*
   *Recommended by F1000Prime: https://f1000.com/prime/737285485?bd=1
2. Wang L^#,*, Toutkoushian H*, Belyy V, Kokontis C, Walter P^#: Conserved structural elements specialize  ATAD1 as a membrane protein extraction machine. eLife 11:e73941
3. Schoof M*, Wang L*, Lawrence R, Cogan Z, Walter P: Viral Evasion of the Integrated Stress Response Through eIF2-P Mimicry Nat. Commun. (2021)12:7103
4. Wang L, Walter P: Msp1/ATAD1 in Protein Quality Control and Regulation of Synaptic Plasticity Annu. Rev. Cell Dev. Biol. 2020, 36:141-164
5. Subramanian A*, Wang L*, Moss T, Voorhies M, Sangwan S, Stevenson E, Pulido E H, Kwok S, Chalkley R J, Li K H, Krogan N J, Swaney D L, Burlingame A L, Floor S N, Sil A, Walter P^# and Mukherjee S^#. A Legionella toxin exhibits tRNA mimicry and glycosyl transferase activity to target the translation machinery and trigger a ribotoxic stress response. Nat Cell Biol. 2023, 25, 1600-1615
   Featured by media of the UCSF Quantitative Bioscience Institute (https://www.youtube.com/watch?v=51fttPlGil0) and also Phys.org (https://phys.org/news/2023-12-pathogenic-bacterium-molecular-mimicry-compromise.html)