Position title: Professor of Bacteriology
6478 Microbial Sciences
1550 Linden Drive
Madison, WI 53706
I was born in China and obtained an undergraduate background in physics from McGill University in Canada, and obtained graduate training in biochemistry from Jonathan Weissman at UCSF by characterizing the molecular chaperone GroEL via directed evolution. As a postdoc in Alan Grossman’s lab I developed a genomic method to monitor DNA replication in B. subtilis. I started my independent research at Baylor College of Medicine in 2007 and moved to University of Wisconsin Madison in 2012. Combining genetic, genomic, biochemical, and computational methods, my laboratory elucidates how bacteria deal with stress through nucleotide signaling and evolution.
Start and Promotion Dates
- Assistant Professor: 2012
- Associate Professor: 2013
- Full Professor: 2017
Ph.D., Biochemistry, University of California, San Francisco, 2002
Postdoctoral Research: Massachusetts Institute of Technology
We currently focus on three major directions:
The interface between DNA replication and the cellular environment. We are testing the hypothesis that multiple small molecules, induced by a spectrum of stresses, regulate DNA replication robustly. Our previous discovery of a novel regulatory mechanism of replication elongation by a small molecule, (p)ppGpp, established such a precedent. We are currently investigating the molecular mechanism of this regulation and expanding this theme to include a spectrum of other small molecules and protein regulators.
The physiological role of the nucleotide (p)ppGpp in stress response. (p)ppGpp is ubiquitously present in bacteria and is crucial for their survival and virulence. How (p)ppGpp ensures survival of Gram-positive bacteria upon stress remains elusive. We had made progress in finding answers to this question. We have identified components of (p)ppGpp metabolism aided by whole-genome sequencing. Taking advantage of this knowledge and applying genetic and genomic methods, we are building a new model of (p)ppGpp function.
Prevention of transcription/replication conflict. There is a genome-wide conflict between replication and transcription, with important consequences to cellular fitness and genome integrity. Bacteria have developed diverse mechanisms to deal with this conflict. The conflict between replication and transcription can be prevented by a genome-wide strand bias to encode genes in the leading strand. In addition, a functional analog of the eukaryotic transcription factor TFIIS is crucial for prevention of this conflict. Our discoveries laid the foundation for addressing the following questions: How do transcription factors prevent the conflict between transcription and replication? What is the physical nature of the transcription barrier and how it is formed in response to stress? What are the evolutionary consequences? We are combining biochemical, genetic and genomic approaches to answer these questions.
Microbiology 470: Microbial Genetics and Molecular Machines
Trainer, Microbiology Doctoral Training Program
Trainer, Genetics Training Program
Trainer, Cellular and Molecular Biology Program
Trainer, Biotechnology Training Program
- 2022, Vilas Associate Award
- 2017, Romnes Faculty Fellowship Award
- 2016, Howard Hughes Medical Institute Faculty Scholar
- 2011, The American Society for Microbiology Branch Lectureship
- 2010, Michael E. DeBakey, M.D., Excellence in Research Award, Baylor College of Medicine
- 2010, Rosalind Franklin Young Investigator Award
- 2008, NIH Director’s New Innovator Award