Research Interests
Genetics, Molecular Biology, Transcriptional memory and cellular identity in mouse embryonic stem cells
Research Focus Teams
Cancer, Cardiovascular
Departments
Biochemistry & Molecular Biology
Contact
Email: sheila.teves@ubc.ca
Office Phone: phone: 604–827–2044
Publications
Lab Website
Prior to joining the UBC’s Biochemistry and Molecular Biology Department as an assistant professor, I was a postdoctoral fellow in Dr. Robert Tjian’s laboratory at the University of California, Berkeley. I received my Ph.D. from the University of Washington MCB program where I conducted graduate research with Dr. Steven Henikoff at the Fred Hutchinson Cancer Research Center.
My graduate research with Dr. Steven Henikoff explored how transcriptional regulation occurs in the context of chromatin. Funded by the National Science Foundation Graduate Research Fellowship Program, my work examined the question of how nucleosomes impact transcription and vice versa, and led to several publications as highlighted in my curriculum vitae, as well as the Harold M. Weintraub Graduate Student Award, a national award recognizing outstanding achievement during graduate studies in the biological sciences. During my postdoctoral training, I studied how transcription programs are maintained and regulated during the cell cycle as a fellow in Dr. Robert Tjian’s laboratory. This work, funded by the Jane Coffin Childs Postdoctoral Fellowship, has combined my expertise in genomics with cutting edge technologies on genome editing and live-cell imaging, with a focus on super-resolution single particle tracking, to challenge conventional wisdom on the mechanisms of transcription maintenance through mitosis.
2022 Tier 2 Canada Research Chair
2019 Michael Smith Health Research Foundation Scholar Award
2014 Jane Coffin Childs Foundation Postdoctoral Fellowship Award
2013 Harold M. Weintraub Graduate Student Award
2010 NSF Graduate Research Fellowship Award
2010 Best Poster Award. FASEB Conference: Transcriptional Regulation During Cell Growth, Differentiation and Development
2009 Honorable Mention, NSF GRF
2005 Post-Baccalaureate Cancer Research Training Award
2005 Magna Cum Laude
Our lab studies how transcription is maintained and altered over time using the model system of mouse embryonic stem cells. Our research combines cutting-edge technologies including CRISPR/Cas9-mediated gene editing, genomics, and single molecule live-cell imaging to explore the mechanisms of transcriptional memory.
Our long term goal is to understand the mechanisms governing transcriptional memory over multiple time scales. By focusing on the underlying mechanisms, we hope to generate models for how cells maintain self-identity over time, how cells change their identity over time, and how the next generation of the organism is borne from the old. These important questions touch on the cornerstone of multi-cellularity and propagation.
A dynamic mode of mitotic bookmarking by transcription factors
Each cell type in an organism has a specific function that is tied to its identity. Cell identity is determined primarily by the specific set of genes that are active in that cell type while silencing the rest. More importantly, the cell type specific gene program must be maintained throughout the lifetime of the organism.
This type of ‘transcriptional memory’ is potentially compromised every time a cell divides. When cells divide to form new cells, the DNA is condensed and gene activity is mostly turned off. However, each dividing cell also has to ‘remember’ the program of genes that specifies its identity. After division, how do the new daughter cells ‘know’ which genes to turn on and which ones to keep off?
One way that cells can regulate their genes is by using cell type specific transcription factors that can bind and regulate cell type specific target genes. Previous studies over the last 2 decades have shown that the transcription factors bound to DNA were all detached and become excluded from mitotic chromosomes during cell division, presenting a potential challenge to re-establishing the original gene program. Through studies in mouse embryonic stem cells that combined gene editing, genomics, and single molecule live cell imaging, we have shown that this finding is largely an artifact of the methods used to study the process. Movie 1 shows that the transcription factor Sox2 starts as highly enriched on mitotic chromosomes, but upon the addition of formaldehyde for fixation, most Sox2 molecules detach from DNA. In fact, many transcription factors still bind to and interact with DNA during cell division. This provides an efficient way for the newly formed cells to quickly reset to the pattern of gene activity appropriate for their cell type.