Abstract: Fueled by the fast-growing genomics information, the next challenge is to characterize protein functionality and understand how cell functions on the systems level. To undertake this change, my group has developed functional protein arrays to facilitate analyses of various biochemical activities of proteins on the proteome level. In this presentation, I will present two recently accomplished projects to highlight the power of protein arrays in understanding transcription regulations in humans. I will also discuss our recent invention of the virion display (VirD) technology with focus on human transmembrane proteins. Finally, we will touch base on biomarker identification using the HuProt array approaches.
Biography: Dr. Heng Zhu received his Ph.D. degree in Genetics at Clemson University, South Carolina, with the focus on genetic analysis of the rice blast fungus and physical map construction using BAC clones in 1999. From 1999 to 2004, Dr. Zhu performed his postdoctoral research in Dr. Michael Snyder's group at Yale University. During this period of time Dr. Zhu and colleagues developed the proteome chip technology in the budding yeast. In 2004, Dr. Zhu joined the faculty of the Johns Hopkins University School of Medicine. Dr. Zhu has a solid track record with technology development. The highlights are the inventions of the proteome microarraysand virion display (VirD) technologies. His group constructed the world-largest proteome array, each comprised of 20,240 individual purified human proteins in full-length. Recently, Dr. Zhu and colleagues invented the VirD array technology that enables biochemistry analyses of mutlipass membrane proteins folded in their native environment. In parallel, his group has developed a series of biochemical assays to characterize biochemistry activities of proteins. Moreover, Dr. Zhu and colleagues have made some groundbreaking discoveries in biology. For example, they challenged the traditional view that sequence-specific DNA-binding activity is restricted to TFs. In a 2009 Cell paper they demonstrated that one of these hits, Erk2, part of the MAPK/ERK pathway, is able to bind directly to promoters and act as a transcriptional repressor in vivo. More recently, Dr. Zhu’s group disputed the paradigm that DNA methylation in cis-regulatory elements causes gene silencing. They systematically demonstrated that many human TFs preferentially bind to methylated DNA motifs. Their in-depth studies showed that one such factor, KLF4, binds to methylated promoters in human embryonic stem cells and that R458 residue of KLF4 was responsible for mCpG-dependent transcriptional activation.