Steven B. Haase

Associate Professor of Biology

Office: 
4316 French, Durham, NC 27708
Campus Box: 
90338
Phone: 
(919) 613-8205
Fax: 
613-8177

Lab Site: http://www.biology.duke.edu/haaselab/index.html

Research Interests: 

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.

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.

Education

  • Ph.D. 1993, Stanford University

  • B.S. 1985, Colorado State University at Fort Collins

Papers Published

B-cyclin/CDKs regulate mitotic spindle assembly by phosphorylating kinesins-5 in budding yeast., 05-06-2010
MK Chee, SB Haase, PLoS Genet. (05-06-2010) 6 vol. (5); pp. e1000935

Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans., 12, 2016
Kelliher, CM; Leman, AR; Sierra, CS; Haase, SB, PLoS genetics. 12 vol. (12); pp. e1006453

The Local Edge Machine: inference of dynamic models of gene regulation., 10, 2016
McGoff, KA; Guo, X; Deckard, A; Kelliher, CM; Leman, AR; Francey, LJ; Hogenesch, JB; Haase, SB; Harer, JL, Genome Biology: biology for the post-genomic era. 17 vol. (1); pp. 214

SW1PerS: Sliding windows and 1-persistence scoring; discovering periodicity in gene expression time series data., 8, 2015
Perea, JA; Deckard, A; Haase, SB; Harer, J, BMC Bioinformatics. 16 pp. 257

Analyzing transcription dynamics during the budding yeast cell cycle, 1, 2014
Leman, AR; Bristow, SL; Haase, SB, Methods in molecular biology (Clifton, N.J.). 1170 pp. 295-312

Analyzing transcription dynamics during the budding yeast cell cycle., 1, 2014
Leman, AR; Bristow, SL; Haase, SB, Methods in molecular biology (Clifton, N.J.). 1170 pp. 295-312

Cell cycle-regulated transcription: effectively using a genomics toolbox., 1, 2014
Bristow, SL; Leman, AR; Haase, SB, Methods in molecular biology (Clifton, N.J.). 1170 pp. 3-27

Topology and control of the cell-cycle-regulated transcriptional circuitry., 1, 2014
Haase, SB; Wittenberg, C, Genetics. 196 vol. (1); pp. 65-90

Branching process deconvolution algorithm reveals a detailed cell-cycle transcription program., 3, 2013
Guo, X; Bernard, A; Orlando, DA; Haase, SB; Hartemink, AJ, Proc Natl Acad Sci U S A. 110 vol. (10); pp. E968-E977

Errata to Cyclin-dependent kinases are regulators and effectors of oscillations driven by a transcription factor network [Molecular Cell, 45 (2012) 669-679], 0, 2013
Kovacs, LAS; Mayhew, MB; Orlando, DA; Jin, Y; Li, Q; Huang, C; Reed, SI; Mukherjee, S; Haase, SB, Molecular Cell. 49 vol. (6); pp. 1177-1179

New and Redesigned pRS Plasmid Shuttle Vectors for Genetic Manipulation of Saccharomycescerevisiae., 5, 2012
Chee, MK; Haase, SB, G3 (Bethesda). 2 vol. (5); pp. 515-526

Parametric modeling of cellular state transitions as measured with flow cytometry, April, 2012
Ho, HJ; Lin, TI; Chang, HH; Haase, SB; Huang, S; Pyne, S, BMC Bioinformatics. (April, 2012) 13 pp. S5

Cyclin-dependent kinases are regulators and effectors of oscillations driven by a transcription factor network., 3, 2012
Simmons Kovacs, LA; Mayhew, MB; Orlando, DA; Jin, Y; Li, Q; Huang, C; Reed, SI; Mukherjee, S; Haase, SB, Mol Cell. 45 vol. (5); pp. 669-679

Close encounters of the collaborative kind, 0, 2012
Mayhew, MB; Guo, X; Haase, SB; Hartemink, AJ, Computer. 45 vol. (3); pp. 24-30

Design and Analysis of Large-Scale Biological Rhythm Studies: A Comparison of Algorithms for Detecting Periodic Signals in Biological Data, 0, 2012
Deckard, A; Anafi, RC; Hogenesch, JB; Haase, SB; Harer, J, Bioinformatics. 29 vol. (24); pp. 3174-3180

Parametric modeling of cellular state transitions as measured with flow cytometry., 0, 2012
HJ Ho, TI Lin, HH Chang, SB Haase, S Huang, S Pyne, BMC Bioinformatics. 13 Suppl 5 pp. S5

A generalized model for multi-marker analysis of cell cycle progression in synchrony experiments., 7, 2011
Mayhew, MB; Robinson, JW; Jung, B; Haase, SB; Hartemink, AJ, Bioinformatics. 27 vol. (13); pp. i295-i303

Parametric modeling of cellular state transitions as measured with flow cytometry, 0, 2011
Pyne, S; Haase, SB; Ho, HJ; Lin, TI, 2011 IEEE 1st International Conference on Computational Advances in Bio and Medical Sciences, ICCABS 2011. pp. 147-152

B-cyclin/CDKs regulate mitotic spindle assembly by phosphorylating kinesins-5 in budding yeast., 5, 2010
Chee, MK; Haase, SB, Cell Cycle. 6 vol. (5); pp. e1000935

Cohesin: it's not just for chromosomes anymore., 5, 2010
Simmons Kovacs, LA; Haase, SB, Cell Cycle. 9 vol. (9); pp. 1750-1753

B-cyclin/CDKs regulate mitotic spindle assembly by phosphorylating kinesins-5 in budding yeast., May, 2010
Chee, MK; Haase, SB, PLoS Genet. (May, 2010) 6 vol. (5); pp. e1000935

A branching process model for flow cytometry and budding index measurements in cell synchrony experiments., Winter, 2009
Orlando, DA; Iversen, ES; Hartemink, AJ; Haase, SB, The annals of applied statistics. (Winter, 2009) 3 vol. (4); pp. 1521-1541

A BRANCHING PROCESS MODEL FOR FLOW CYTOMETRY AND BUDDING INDEX MEASUREMENTS IN CELL SYNCHRONY EXPERIMENTS., 0, 2009
DA Orlando, ES Iversen Jr, AJ Hartemink, SB Haase, Ann Appl Stat. 3 vol. (4); pp. 1521-1541

Transcription network and cyclin/CDKs: The yin and yang of cell cy, 9, 2008
Kovacs, LAS; Orlando, DA; Haase, SB, Cell Cycle. 7 vol. (17); pp. 2626-2629

Transcription networks and cyclin/CDKs: the yin and yang of cell cycle oscillators., 9, 2008
Simmons Kovacs, LA; Orlando, DA; Haase, SB, Cell Cycle. 7 vol. (17); pp. 2626-2629

Transcription networks and cyclin/CDKs: the yin and yang of cell cycle oscillators., 9, 2008
LA Simmons Kovacs, DA Orlando, SB Haase, Cell Cycle. 7 vol. (17); pp. 2626-9

Intrinsic and cyclin-dependent kinase-dependent control of spindle pole body duplication in budding yeast., 8, 2008
Simmons Kovacs, LA; Nelson, CL; Haase, SB, Molecular Biology of the Cell. 19 vol. (8); pp. 3243-3253

Global control of cell-cycle transcription by coupled CDK and network oscillators., 6, 2008
Orlando, DA; Lin, CY; Bernard, A; Wang, JY; Socolar, JES; Iversen, ES; Hartemink, AJ; Haase, SB, Nature. 453 vol. (7197); pp. 944-947

Global control of cell-cycle transcription by coupled CDK and network oscillators., 6, 2008
DA Orlando, CY Lin, A Bernard, JY Wang, JE Socolar, ES Iversen, AJ Hartemink, SB Haase, Nature. 453 vol. (7197); pp. 944-7

Microtubule organization: cell shape is destiny., 4, 2007
Haase, SB; Lew, DJ, Curr Biol. 17 vol. (7); pp. R249-R251

Microtubule organization: cell shape is destiny., 4, 2007
SB Haase, DJ Lew, Curr Biol. 17 vol. (7); pp. R249-51

A probabilistic model for cell cycle distributions in synchrony experiments., 2, 2007
Orlando, DA; Lin, CY; Bernard, A; Iversen, ES; Hartemink, AJ; Haase, SB, Cell Cycle. 6 vol. (4); pp. 478-488

A probabilistic model for cell cycle distributions in synchrony experiments., February, 2007
D. A. Orlando and C. Y. Lin and A. Bernard and E. S. Iversen and A. J. Hartemink and S. B. Haase, Cell Cycle. (February, 2007) 6 vol. (4); pp. 478-88

Distinct mechanisms control the stability of the related S-phase cyclins Clb5 and Clb6., March, 2006
Jackson, LP; Reed, SI; Haase, SB, Mol Cell Biol. (March, 2006) 26 vol. (6); pp. 2456-2466

Cell cycle analysis of budding yeast using SYTOX Green., 11, 2004
Haase, SB, Current Protocols in Cytometry. Chapter 7 pp. Unit-7.23

Cell Cycle Analysis of Budding Yeast Using SYTOX Green, 10, 2003
S. Haase, pp. 7.23.1-7.23.5

Improved flow cytometric analysis of the budding yeast cell cycle., 1, 2003
SB Haase, SI Reed, Cell Cycle. 1 vol. (2); pp. 132-6

Improved flow cytometric analysis of the budding yeast cell cycle., 0, 2002
Haase, SB; Reed, SI, Cell cycle (Georgetown, Tex.). 1 vol. (2); pp. 132-136

A festival of cell-cycle controls., 11, 2001
SB Haase, DJ Clarke, Trends Cell Biol. 11 vol. (11); pp. 445-6

A festival of cell-cycle controls, 0, 2001
Haase, SB; Clarke, DJ, Trends in Cell Biology. 11 vol. (11); pp. 445-446

Multi-step control of spindle pole body duplication by cyclin-dependent kinase, 0, 2001
Haase, SB; Winey, M; Reed, SI, Nature Cell Biology. 3 vol. (1); pp. 599-607

Multi-step control of spindle pole body duplication by cyclin-dependent kinase, 0, 2001
Haase, SB; Winey, M; Reed, SI, Nat Cell Biol. 3 vol. (1); pp. 38-42

Functions of fission yeast orp2 in DNA replication and checkpoint control., 2, 2000
J Kiely, SB Haase, P Russell, J Leatherwood, Genetics. 154 vol. (2); pp. 599-607

Functions of fission yeast Orp2 in DNA replication and checkpoint control, 0, 2000
Kiely, J; Haase, SB; Russell, P; Leatherwood, J, Genetics. 154 vol. (2); pp. 599-607

Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle., 9, 1999
SB Haase, SI Reed, Nature. 401 vol. (6751); pp. 394-7

Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle, 0, 1999
Haase, SB; Reed, SI, Nature. 401 vol. (6751); pp. 394-397

Flow cytometric analysis of DNA content in budding yeast., 0, 1997
Haase, SB; Lew, DJ, Methods Enzymol. 283 pp. 322-332

Transcription inhibits the replication of autonomously replicating plasmids in human cells, 0, 1994
Haase, SB; Heinzel, SS; Calos, MP, Mol Cell Biol. 14 vol. (4); pp. 2516-2524

Replication control of autonomously replicating human sequences, 0, 1991
Haase, SB; Calos, MP, Nucleic Acids Res. 19 vol. (18); pp. 5053-5058

Isolation of human sequences that replicate autonomously in human cells, 0, 1989
Krysan, PJ; Haase, SB; Calos, MP, Mol Cell Biol. 9 vol. (3); pp. 1026-1033

Improved EBV shuttle vectors, 0, 1989
Haase, SB; Heinzel, SS; Krysan, PJ; Calos, MP, Mutat Res. 220 vol. (2-3); pp. 125-132

Papers Submitted

Checkpoints couple transcription network oscillator dynamics to cell-cycle progression in Genome Biology 0, 2014
Bristow, SL; Leman, AR; Simmons Kovacs, LA; Deckard, A; Harer, J; Haase, SB