Signal Transduction in Mammal Development and Pathogenesis
The focus of Zhang's lab is to understand the molecular basis of signal transducer and activator of transcription (STAT) proteins during mammalian development and pathogenesis. STAT were originally identified and isolated using cell culture systems that respond to cytokines such as interferon. It is well established that the STAT proteins have a range of essential functions for generation and function of the immune system. It is also widely accepted that STAT proteins co-evolved with the innate and adaptive immunity that occurred in the transition from lower to higher organisms. Tissue specific STAT3 disruption causes several phenotypes related to human diseases such as Crohn's disease-like pathogenesis, heart failure, and severe inflammation. Growing experimental evidences that STAT pathways are also involved in many other aspects of vertebrate development. It has been found that several STAT proteins are active during early mammalian development. Recently we show that STAT3 mediated signaling is crucial for the inhibitory function of CNTF during rod photoreceptor development. Activation of STAT3 keeps the undifferentiation status of postnatal precursors in retina. STAT3 is also critical for retina Muller glial reactivation in response to stresses. These indicated that STAT as common factors have specific roles on specific cell types. To understand their tissue specific functions, we use retina as a model to study STAT function in neuron and glia cells.

Systems Biology of Neural Development and Functions
The retina is a well-defined portion of the central nervous system (CNS) that has long been used as a model for CNS developmental and functional studies. It is susceptible to a variety of diseases that can lead to vision loss or complete blindness. Most of the unique functions of the retina depend upon its tissue-specific transcripts, suggesting that a systematic definition of retinal transcripts would be an invaluable approach to understanding retinal cell identities and functions. Traditional method allows functional relationship only among few genes, the development of microarray techniques changes the way to understand a biological process as a whole among the major genes played. We have generated a comprehensive mouse retina transcriptome based on 81,000 murine retina transcripts from whole mouse ESTs. About 33,000 sequence-unique retina transcript clusters (RTCs) have been identified and the highest-grade retina-enriched pool covered almost all the known genes in phototransduction processes that involved in human retina diseases, suggesting the potential of gene discoveries for human retina disorders. We have also generated mouse retina specific cDNA microarray that represented about 10,000 UniGene clusters for studying the biological process during retina development or downstream network alternatives by gene targeting in mouse retina. Integrated biological and computational methods, our goal is to understand the gene regulation network during retina development and pathogenesis.