Steven B. Haase, Associate Professor
Our group is broadly interested in understanding the biological clock mechanisms that control the timing of events during the cell division cycle. In 2008, the Haase group proposed a new model in which a complex network of sequentially activated transcription factors regulates the precise timing of gene expression during the cell-cycle, and functions as a robust time-keeping oscillator. Greater than a thousand genes are expressed at distinct phases of the cycle, and the control network itself consists of ~20 components, so this dynamical system is far too complex to understand simply by biological intuition. We rely heavily on the expertise of the Harer group (Dept. of Mathematics, Duke University) for the analysis of complex data, and their understanding of dynamical systems. Using a collection of tools, including molecular genetics, genomics, mathematical models, and statistical inference, our groups aim to understand how the cell division clock works, how it might be perturbed in proliferative diseases such as cancer, and how the clock components might be targeted for new anti-tumor therapies. Qualitatively, the clock networks that control the yeast cell cycle look much like the networks controlling circadian rhythms in a variety of organisms. More recently, we have been using our experimental and quantitative approaches to investigate the function of circadian clocks, as well as clocks that control the division and development of pathogenic organisms such as P. falciparum and P. vivax, the causative agents of malaria.
Ph.D., Stanford University, 1993
B.S., Colorado State University at Fort Collins, 1985
Office Location: 4316 French, Durham, NC 27708
Office Phone: (919) 613-8205
Email Address: firstname.lastname@example.org
Web Page: http://www.biology.duke.edu/haaselab/index.html
Additional Web Page: http://sites.duke.edu/haaselab
Cell and Molecular Biology
Research Categories: Control of cell cycle, DNA replication, and centrosome duplication in budding yeast
Research Description: In order to divide, cells must first duplicate their entire contents, and then segregate the duplicated contents equally into two daughter cells. The duplication and segregation events of the cell division cycle must be triggered in a strict temporal order to insure that each new daughter cell is identical to the original mother cell. Using the budding yeast, Saccharomyces cerevisiae, as a model system, we are investigating the role of a highly conserved family of cell cycle regulatory proteins, called cyclin-dependent kinases (Cdks), in maintaining the ordered sequence of events during cell division. Our lab utilizes a variety of molecular, genetic, genomic and cell imaging approaches to address three fundamental questions: 1. What are the mechanisms that initiate the ordered progression of the cell cycle? 2. How do Cdk activities insure that DNA sequences are replicated once and only once during each cell cycle? 3. How do Cdk activities insure that centrosomes/ spindle pole bodies are duplicated once and only once during each cell cycle? We have found that cells lacking mitotic Cdk activities undergo successive rounds of budding, DNA replication, and spindle pole body (centrosome) duplication without intervening mitoses. Our findings suggest that mitotic Cdk activities are essential not only for promoting mitosis, but also for preventing the re-initiation of duplication events until the completion of mitosis. Several lines of evidence suggest that failure to properly coordinate cell cycle events may lead to genome instability, a driving force in tumorigenesis. The goal of our research is to understand how Cdk activities normally maintain order during the cell cycle, and how perturbation of Cdk activities may contribute to genome instability.
- Kelliher, CM; Haase, SB, Connecting virulence pathways to cell-cycle progression in the fungal pathogen Cryptococcus neoformans., Current Genetics (March, 2017) [doi] [abs].
- Kelliher, CM; Leman, AR; Sierra, CS; Haase, SB, Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans., PLoS genetics, vol. 12 no. 12 (December, 2016), pp. e1006453 [doi] [abs].
- McGoff, KA; Guo, X; Deckard, A; Kelliher, CM; Leman, AR; Francey, LJ; Hogenesch, JB; Haase, SB; Harer, JL, The Local Edge Machine: inference of dynamic models of gene regulation., Genome Biology: biology for the post-genomic era, vol. 17 no. 1 (October, 2016), pp. 214 [abs].
- Perea, JA; Deckard, A; Haase, SB; Harer, J, SW1PerS: Sliding windows and 1-persistence scoring; discovering periodicity in gene expression time series data., BMC Bioinformatics, vol. 16 (August, 2015), pp. 257 [doi] [abs].
- Leman, AR; Bristow, SL; Haase, SB, Analyzing transcription dynamics during the budding yeast cell cycle, Methods in molecular biology (Clifton, N.J.), vol. 1170 (January, 2014), pp. 295-312 [doi] [abs].