Nan Hao

Research

Living organisms respond to a wide variety of environmental cues and initiate physiological responses through complex signaling and gene regulatory networks. The era of genomic sequencing has generated a huge body of knowledge regarding the molecular components and interactions within these regulatory networks. However, little is known about how these molecular network systems operate in time and space to transmit environmental information and carry out diverse cellular functions. Our laboratory aims to obtain a quantitative and predictive understanding of how complex biological systems operate and function. We use two complementary approaches: systems biology analysis to deconstruct natural systems and synthetic biology to build orthogonal artificial systems analogous to natural systems.

In particular, our laboratory focuses on the following research themes:

Encoding and decoding information in signal dynamics

Cells could transmit environmental information and control cellular behaviors through regulating the temporal dynamics of signaling activities. In an oft-cited example, epidermal growth factor induces transient activation of the mitogen activated protein kinase ERK and leads to cell proliferation, whereas nerve growth factor elicits sustained ERK activation and results in cell differentiation. In S.cerevisiae, we have recently discovered that the general stress responsive transcription factor Msn2 encodes both the identity and strength of external stimuli into dynamic patterns of its nuclear translocation. We further developed a synthetic system to control the dynamics of transcription factor translocation and revealed that these dynamic patterns can be decoded to generate selective gene expression. Our current work focuses on understanding: (1) how the environmental information is encoded into distinct signal dynamics and (2) how the dynamic patterns of extracellular or intracellular signals are decoded through genetic networks to control cell fate decisions.

The logic and design principles of biological networks

Mechanistic understanding of biological functions has been hindered by the daunting complexity of related regulatory networks. Our laboratory uses synthetic biology to build simple orthogonal systems analogous to the core parts of natural systems and aims to uncover the key design principles of biological functions that are buried in sophisticated network connections. We have recently employed this synthetic biology strategy to reveal how modular design of transcription factors enables tunable signal processing functions to track, filter or integrate dynamic signaling inputs. Our current work focuses on understanding the design principles of complex signal processing circuits and cell fate decision systems.

Metabolic control of cell signaling, gene regulation and aging

Cells survive in their natural habitats by instantly altering cellular behaviors in response to nutrient or metabolic changes. Our current work focuses on understanding how cells coordinate complex cellular functions based on their intracellular metabolic status. In particular, we combine single-cell imaging, microfluidic technology and computational modeling to investigate how the dynamic interplay between extracellular nutrient conditions and intracellular metabolic status regulates cell signaling, gene regulation and aging.

Publications

  • Nan Hao, Bogdan Budnik, Jeremy Gunawardena, Erin K. O’Shea (2013). Tunable signal processing through modular control of transcription factor translocation. Science 339:460-464.
  • Nan Hao, Necmettin Yildirim, Michal J. Nagiec, Stephen Parnell, Beverly Errede, Henrik G. Dohlman, Timothy C. Elston (2012). Combined computational and experimental analysis reveals MAP kinase-mediated feedback phosphorylation as a mechanism for signaling specificity. Mol. Biol. Cell 23:3899-3910.
  • Nan Hao, Erin K. O’Shea (2012). Signal-dependent dynamics of transcription factor translocation controls gene expression. Nature Struc. Mol. Biol. 19: 31-39.
  • Nan Hao, Sujata Nayak, Marcelo Behar, Ryan Shanks, Michal Nagiec, Beverly Errede, Jeffrey Hasty, Timothy C. Elston, Henrik G. Dohlman (2008). Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5. Mol. Cell 30: 649-656.
  • Nan Hao, Marcelo Behar, Stephen C. Parnell, Matthew P. Torres, Christoph H. Borchers, TimothyC. Elston, Henrik G. Dohlman (2007). A systems-biology analysis of feedback inhibition in the Sho1 osmotic-stress response pathway. Curr. Biol. 17: 659-667.

Biography

Nan Hao received his Ph.D in Biochemistry and Biophysics from the University of North Carolina at Chapel Hill. He was a postdoctoral fellow with Timothy Elston at the University of North Carolina and a postdoctoral fellow with Erin O’Shea at Harvard University/Howard Hughes Medical Institute.