Assistant Professor

* B.S. Nankai University, 1990
* Ph.D. Yale University, 1998

Research Interests:

Kidney development
Polycystic kidney disease (PKD)
Size control
Zebrafish genetics

Honors:

* John Spangler Nicholas Prize for outstanding doctoral candidate in Experimental Zoology, 1999, Yale University
* Mallinckrodt Scholar, 2005, Edward Mallinckrodt, JR. Foundation

Current Research:

We use zebrafish to study kidney development and diseases. Currently, we are focusing on polycystic kidney disease (PKD). PKD is characterized by the formation of multiple kidney cysts thought to result from over-proliferation of epithelial cells. Understanding PKD is of profound medical importance. Striking one in 1000 live births, autosomal dominant form of PKD (ADPKD) is among the most common monogenetic disorders in humans. Recently, cilia have been linked to PKD. The cilium is a cell surface organelle containing a membrane bound microtubule axoneme in the center. In renal tubes, the cilium protrudes from the apical surface of epithelial cells into the lumen. Multiple PKD gene products have been found on cilia. Cilia are therefore proposed to be sensory organelles involved in the control of cell proliferation. However, the link between cilia and PKD is largely based on “guilty by association” arguments. Additionally, the signal sensed by cilia remains controversial and the signaling pathway that couples cilia to cell proliferation is almost completely unknown.

Through a forward genetic screen in zebrafish carried out in Dr. Nancy Hopkins’ laboratory at MIT, we identified multiple novel genes involved in PKD. Based on preliminary analyses on these mutants, we proposed a revised model in which cilia function as sensors for lumen size of epithelial tubes. Defects in cilia formation or function lead to uncontrolled expansion of lumen size and eventually cyst formation in local areas.

Using mutants isolated in the screen as entry points, we now start to unravel the genetic network that regulates the size of renal tubes. We are particularly interested in, but not limited to the following three questions: First, how is the cilium built during development? Second, what is the signal sensed by cilia? Third, how does signal from cilia eventually regulate tube size? We believe addressing these questions will help us understand size control during development and molecular etiology of PKD

Kidney cyst in a Zebrafish embryo:

Cilia in Zebrafish pronephric duct:

G. Golling, A. Amsterdam, Z. Sun, M. Antonelli, E. Maldonado, W. Chen, S. Burgess, M. Haldi, K. Artzt, S. Farrington, S.-Y. Lin, R. M. Nissen and N. Hopkins. 2002.