Congratulations to Dr. Brian Strahl who was promoted to full professor effective April 25, 2014.
Brian Strahl’s laboratory has been at the forefront of understanding how histones and their covalent modifications regulate chromatin structure and function, with a particular emphasis on how chromatin impacts gene regulation. His career began at the University of North Carolina (UNC) at Greensboro, where he majored in Biology and Chemistry. He then obtained his doctorate degree in Biochemistry from North Carolina State University in 1998, where he provided new insights into the transcriptional regulation of the Follicle Stimulating Hormone-ß (FSHß) gene. His curiosity in transcriptional regulation led him to pursue his postdoctoral studies in the laboratory of Dr. C. David Allis at the University of Virginia. In David’s lab, he made a number of seminal discoveries in the area of histone methylation and histone function. In particular, Dr. Strahl identified new sites of histone lysine methylation and linked this chromatin modification to gene regulation using the model organism Tetrahymena. His work also helped to identify the first lysine-specific histone methyltransferase in humans and several others in the budding yeast S. cerevisiae. Dr. Strahl, with David Allis, also coined the idea of the histone code – a highly influential review that has been cited well over 5000 times.
In December of 2001, Dr. Strahl initiated his lab at UNC-Chapel Hill, where he has now been promoted to the rank of Full Professor in the Department of Biochemistry & Biophysics. Dr. Strahl is also the Director of Graduate Studies and is the Faculty Director of the UNC High-Throughput Peptide Synthesis and Arraying Core Faculty.
With his colleagues, his group has been at the forefront of determining how small chemical additions or molecular “tags” on histone proteins regulate the accessibility of DNA and the genetic information it contains. Histones are central to the organization of our DNA in cells. These proteins come in a variety of types or isoforms – defined as histone H3, H4, H2A and H2B, and they associate with themselves as a means to package our DNA within the small nuclei of cells. Two copies each of each histone type come together to form what is called an octamer, which wraps approximately 147 base pairs of DNA around it. This structure (histones + DNA) makes up the fundamental building block of chromatin – the nucleosome. Strings of nucleosomes make up the chromatin fiber, and they organize into higher-order structures that are poorly defined but allow large genomes (e.g., ~3 billion base pairs making up the human genome) to fit in the confines of a 2-10 micron nucleus. With all this compaction, a fundamental question Brian Strahl’s group has been addressing is how our genome is made accessible at the right place and time for all of the fundamental processes that occurs with DNA (e.g., gene expression, DNA repair and replicating the genome).
Dr. Strahl’s UNC group has made a number of key contributions into the role of these chemical tags or modifications on histones (e.g., methylation and ubiquitylation), and more recently, DNA methylation. Using budding yeast as a model system, his lab has helped to show how histone-modifying enzymes “hitch a ride” with RNA polymerase II (RNAPII) during gene transcription, and how the modifications they put on histones contributes to the transcription process.
More recently, the Strahl group has focused on how patterns of histone modifications (i.e., the ‘histone code’) regulate the structure and function of chromatin. To understand how patterns of histone modifications function, they developed a high-throughput peptide microarray platform, where hundreds of synthetic histone peptides that are combinatorially modified with distinct chemical modifications are arrayed on glass slides. With this technology, the lab has been interrogating chromatin-associated proteins that are critical for cell growth and development, and/or are dysregulated in human cancer. One such protein his lab has recently been focused on is UHRF1, an E3 ubiquitin ligase essential for DNA methylation. Dr. Strahl’s lab showed that this protein binds to a particular pattern of histone modification to regulate the maintenance of DNA methylation in human cells. They are continuing these lines of studies to address how the chromatin-machinery engages histones and DNA, and how these factors influence fundamental processes in the cell such as gene transcription.
Work in Dr. Strahl’s lab is funded by the National Institutes of Health (NIH), the Keck Foundation and the National Science Foundation (NSF).
Learn more about the Strahl Lab here.
-Brian Strahl, PhD