Dr. Brian David Strahl – Bio and Research Into Histone Modifications

Dr. Brian David Strahl is presently an Associate Professor in the Department of Biochemistry and Biophysics in the School of Medicine at the University of North Carolina at Chapel Hill (UNC-Chapel Hill). He also holds a secondary faculty appointment in UNC’s Lineberger Comprehensive Cancer Center, and is currently the Faculty Director of the High-Throughput Peptide Synthesis and Arraying core facility (UNC HTPSA) and act as the Director of Graduate Studies in his home department.

Brian Strahl studied at the University of North Carolina at Greensboro where he finished his two bachelor’s degrees in Chemistry and Biology in 1993. It was in his college years where he became interested in biological research and became involved in several undergraduate research studies in the Chemistry and Biology Departments. In Chemistry, he studied under the mentorship Dr. Bruce Banks, where he investigated the enzymatic properties of lipase in organic solvents while in Biology, he was mentored by Dr. Julian Lombardi. In Dr. Julian Lombardi’s lab, he discovered a new approach and method to examine the dry mass content of extremely small volumes of biological fluid using a state-of-the-art ultra microbalance. This method allowed the evaluation of nutrients contained in the small volumes of embryonic fluid found in live bearing sharks to study their developmental regulation – for which little was known at the time.

In 1993, Brian Strahl enrolled in the Department of Biochemistry at North Carolina State University to complete his doctorate degree. He studied under the mentorship of Dr. William L. Miller and in his lab Brian sought to understand how the Follicle-Stimulating Hormone-Beta (FSHß) gene is regulated at the transcriptional level. His efforts resulted in a new understanding for how the transcription factor AP-1 mediates FSHß gene activation through PKC.  His work also showed that Gonadotropin Releasing Hormone (GnRH) functions to control FSHß gene activation through PKC and AP-1.  His work provided new insights into the regulation of this critical hormone.  In 1998, Dr. Brian Strahl completed his doctorate degree and then moved on to perform his postdoctoral studies under the mentorship of Dr. C. David Allis at the University of Virginia’s Department of Biochemistry and Molecular Genetics. He contributed to the identification and characterization of lysine and arginine histone methyltransferases.  In addition, Dr. Strahl, together with David Allis, coined the ‘Histone Code’ hypothesis – which aimed to provide an explanation for how multiple histone modifications function together to regulate chromatin structure and function.

In December of 2001, Dr. Strahl started his own laboratory at University of North Carolina. His lab is focused on deciphering the role of histone modifications – such as lysine methylation, lysine ubiquitination and lysine acetylation – in chromatin function. Using yeast and human cells as model systems, together with his colleagues, they are determining the role of a number of histone-modifying enzymes and how they contribute to gene regulation and heterochromatin formation.  His recent work has discovered how histone H3 lysine 9 methylation is critical for the maintenance of DNA methylation in human cells.  Moreover, the Strahl laboratory demonstrated that UHRF1, a E3 ubiquitin ligase, binds to methylated histone H3 using several of its histone-interacting domains to help recruit the DNA maintenance methylase DNMT1.  These studies have led to new insights into how combinatorial histone modifications contribute to chromatin function.

Understanding Chromatin Structure and Function With Dr. Brian Strahl

Brian D. 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.

Brian Strahl’s career began at the University of North Carolina (UNC) at Greensboro, where he majored in Biology and Chemistry. Brian 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, Brian 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 is also well known for coining the histone code hypothesis with David Allis – a highly influential review that has been cited over 4000 times.

Brian Strahl Professor

In December of 2001, Dr. Strahl began his independent scientific career at UNC Chapel Hill, where he is now an Associate Professor in the Department of Biochemistry & Biophysics.
He also holds a second faculty appointment in the UNC Lineberger Comprehensive Cancer Center. In addition to training undergraduate, graduate and postdoctoral fellows to be independent scientist and teachers, Dr. Strahl is also the Director of Graduate Studies in his home Department and is also the Faculty Director of the High-Throughput Peptide Synthesis and Arraying Core Faculty at UNC.

Over the course of his career, Dr. Strahl has made a number of significant contributions to the chromatin, epigenetics and transcription fields, with over 75 publications in top-tier journals. These discoveries have gained him wide recognition and have been recognized with a number of prestigious awards. In 2009, UNC honored Brian with the Ruth and Phillip Hettleman Prize for Artistic and Scholarly Achievement. In 2008, Dr. Strahl received an Exceptional, Unconventional Research Enabling Knowledge Acceleration Award (EUREKA) from the National Institute of Health (NIH) to study the histone code. In 2005, Dr. Strahl was given the prestigious ASBMB Schering-Plough Research Institute Award, an important honor that is only given once a year. Dr. Strahl was also named a Pew Scholar in the Biomedical Sciences in 2004, and in 2003, he was honored at the White House with a Presidential Early Career Award for Scientists and Engineers (PECASE).

Brian Strahl

Brian D. Strahl holds membership in the American Society for Microbiology, the American Society for Biochemistry and Molecular Biology, and the American Association for the Advancement of Science. He also is on the Editorial Board of Molecular & Cellular Biology and Epigenetics and Chromatin and serves to review papers from a wide-number of journals.

Work in Brian Strahl’s UNC lab is funded by NIH, the Keck Foundation and the NSF.

Associate Professor Brian David Strahl, PhD

Brian Strahl, associate professor of Biochemistry & Biophysics, has been studying the role of histone post-translational modifications (PTMs) in chromatin structure and function. To date, a striking number of histone PTMs have been identified (e.g., lysine acetylation and methylation), yet how they work together to regulate fundamental aspects of DNA-based functions in chromatin (e.g., transcription and DNA repair) is poorly understood.  To address this, the Strahl lab has been studying the protein machinery that modify histones, in addition to examining the effector proteins that associate or bind to histone modifications.

Brian Strahl bio

Over the years, Brian Strahl’s group has made seminal contributions into the role of histone methylation and ubiquitylation, and more recently, DNA methylation.  Using budding yeast as a model system, Brian’s lab has helped to show how histone-modifying enzymes “piggyback” with RNA polymerase II (RNAPII) during gene transcription.  Specifically, Dr. Strahl’s lab showed that enzymes like Set2, Set1 and Rad6/Bre1 are recruited via the C-terminal domain of RNAPII, or through the association of other RNAPII-associated factors (i.e., PAF).  More recently, Dr. Strahl’s lab has identified an important role for the histone chaperone Spt6 in the regulation of RNAPII CTD modification – generating a feed-forward circuit that drives transcriptional elongation. Together, these studies have shown that chromatin modifiers, as well as histone chaperones, play a crucial role in the transcription process, and also aid in transcription fidelity.

Brian Strahl Prof.

In addition to his work in budding yeast, Brian Strahl’s lab has also focused on how histone modifications regulate the presumed ‘histone code’.  As a postdoctoral fellow with Dr. C. David Allis, Brian and David coined the ‘histone code’ hypothesis.  However, information regarding how combinations of histone PTMs work together to regulate chromatin function is still lacking.  To address this, Brian’s lab developed a high-throughput proteomics peptide microarray platform, where hundreds of synthetic histone peptides that are combinatorially modified with distinct histone PTMs (i.e., the histone code) are arrayed on glass slides.  With this technology, the Strahl lab has been interrogating a wide number of chromatin-associated proteins that are critical for cell growth and development, and/or are dysregulated in human cancer.  One such protein Brian’s 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 H3 lysine 9 methylation to regulate the maintenance of DNA methylation in human cells, and further, that multiple histone-interaction domains in this protein “read” a specific histone signature on H3 to do so.  These studies define how histones, as well as their PTMs, drive fundamental epigenetic processes in the cell such as DNA methylation.  They also reveal fundamental insight into therapeutic targets that can be exploited for drug development – which is ongoing with Dr. Stephen Frye in the UNC Center for Drug Discovery.  Current efforts are aimed at defining how other multi domain-containing chromatin-associated proteins engage their histone targets and potentially read the histone code.

Brian Strahl’s lab is funded by the National Institutes of Health (NIH), the Keck Foundation and the National Science Foundation (NSF).