Postdoctoral Position Available

Zheng-Zheng Bao, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Cell Biology
   Endocrinology
   Medicine

Other Affiliation(s):
   Cell Dynamics Group
   Center for AIDS Research
   Interdisciplinary Graduate Program
   Program in Neuroscience

Axon Growth, Guidance and Regeneration

Establishment of precise neural network during embryonic development is critical for the function of the mature nervous systems.  Understandings of the fundamental mechanisms involved in neuronal differentiation and connectivity can help uncover the causes of developmental neural disorders and neurodegenerative diseases, and provide important information for studies of neural regeneration and stem cell therapy.  

We are interested in molecular and cellular mechanisms of axon growth and guidance, key processes in the establishment of neural network. Particularly, we are interested in regulation and function of membrane trafficking and cytoskeleton organization during axon growth and guidance.  We use retinal ganglion cell (RGC) axon as a model system and combine molecular, genetic and cell biology approaches.  In the past several years, we have identified a number of molecules that play important roles in RGC axon pathfinding, including Sonic Hedgehog (Shh), Zic3 and Slit-1. Our recent work demonstrates that macropinocytosis-mediated membrane trafficking plays a critical role in negative guidance factor-induced repulsive axon turning. 

Current projects in this laboratory include: (a) Investigation of noncanonical Shh signaling pathways involved in axon growth and guidance; (b) Molecular characterization of macropinocytosis-based membrane trafficking in neuronal cells; (c) Screening of small molecules for promotion of adult nerve regeneration in mouse models of neurodegeneration.

Figures

Figure 1. Retinal ganglion axons grew preferentially on stripes coated with low concentrations of Shh protein (lo), and avoided those coated with high concentrations of Shh protein (hi).

Figure 2. The projection patterns of the retinal ganglion axons appeared abnormal in the samples with overexpression of Zic3.

Representative Publications

Kopak, A., Jiang, J., Guo, D., Standley, C., Bellve, K., Forgarty, K., Bao, Z. Z. (2009).  Negative guidance factor-induced macropinocytosis in the growth cone plays a critical role in repulsive axon turning.  J. Neurosci.  29:10488-98.

Bao, Z. Z. (2008).  Intraretinal projection of retinal ganglion cell axon as a model system for studying axon navigation.  Brain Res. 1192:165-177.

Chau, M., Tuft, R., Fogarty, K., Bao, Z. Z. (2006).  Notch signaling plays a key role in cardiac differentiation.  Mech. Dev.  123:626-640.

Bao, Z. Z. and Jin, Z. (2006).  Sema3D and Sema7A have distinct expression patterns in chick embryonic development.  Dev. Dyn.  235:2282-2289.

Jin, Z., Chau, M., Bao, Z. Z. (2006).  Sema3D, Sema3F, and Sema5A are expressed in overlapping distinct patterns in chick embryonic heart.  Dev. Dyn. 235:163-169.

Kolpak, A., Zhang, J., Bao, Z. Z. (2005). Sonic hedgehog has a dual effect on the growth of retinal ganglion axons depending on its concentration.  J. Neurosci. 25(13): 3432-41.  With accompanying Editor’s highlight.

Zhang, J., Jin, Z., Bao, Z. Z. (2004). Disruption of gradient expression of Zic3 resulted in aberrant projection of the retinal ganglion axons to the optic disc.  Development,131: 1553-1562. 

Jin, Z., Zhang, J., Klar, A., Chédotal, A., Rao, Y., Cepko, C., Bao, Z. Z. (2003). Irx4-mediated regulation of Slit1 expression contributes to the definition of early axonal paths inside the retina.  Development, 130: 1037-1048.

Bruneau, B. G., Bao, Z. Z., Fatkin, D., Georgakopoulos, D., Kass, D. A., Mudd, J. O., Schoen, F. J., de Bold, A. J., Cepko,, C. L., Seidman, J. G., Seidman, C. E. (2001). Irx4 -targeted mice reveal a novel pathway for cardiomyopathy and ventricle-specific gene expression. Mol. Cell Biol. 21: 1730-1736.

Wang, G. F., Nikovits, W., Bao, Z. Z., Stockdale, F. E. (2001).  Irx4 Forms an Inhibitory Complex with the Vitamin D and Retinoic X Receptor to Regulate Chamber-Specific Slow MyHC3 Expression. J. Biol. Chem. 276: 28835-28841.

Bruneau, B. G., Bao, Z. Z., Tanaka, M., Schott, J.-J., Izumo, S., Cepko, C. L., Seidman, C., Seidman, J. G. (2000) Cardiac expression of the ventricle-specific homeobox gene Irx4 is regulated by Nkx2-5- and Hand2-dependent pathways.  Dev. Biol. 217: 266-277.

Furukawa, T., Mukherjee, S., Bao, Z. Z., Morrow, E. and Cepko, C. L. (2000). Rax , Hes1, and Notch1 promote the formation of Müller glia by postnatal retinal progenitor cells.  Neuron. 26: 383-394

Bao, Z. Z., Bruneau, B. G., Seidman, J. G., Seidman, C. E., and Cepko, C. L.. (1999). Regulation of chamber-specific gene expression in the developing heart by Irx4. Science, 283, 1161-1164.

Potential Rotation Projects

1. Investigate Shh signaling pathway that mediates its effect on the growing axons. 
2. identify genes involved in membrane trafficking process including membrane insertion, retrieval and movement during axon guidance; 
3. Study signaling pathways involved in membrane trafficking.

Laboratory Staff

Academic Background

Z. Z. Bao received her BS from Fudan University in China and her PhD from University of Illinois at Urbana-Champaign. She was a postdoctoral fellow at Harvard Medical School in the laboratoty of Dr. Constance Cepko. She joined the faculty of the University of Massachusetts Medical School in 2001.

Office: LRB #221
Phone: (508) 856-3202
E-mail: Zheng-Zheng.Bao@umassmed.edu
Keywords: Neurobiology, Genetics, Signal Transduction, Cell Biology, Developmental Biology

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Bao for additional details.