PAUL S. MADDOX, Ph.D.
- Principal Investigator, Mitotic Mechanisms and Chromosome Dynamics research unit, Institute for Research in Immunology and Cancer
- Assistant Professor, Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal
AWARDS & HONOURS
- Canada Research Chair in Cell Division and Chromosomal Organization, 2007-
- Fayez Sarofim Postdoctoral Fellow, Damon Runyon Cancer Research Foundation, 2004-2007
- Harold M. Weintraub Award, Outstanding Graduate Student
TRAINING
- Postdoctoral training with Arshad Desai at the Ludwig Institute for Cancer Research, University of California, San Diego, 2003-2007
- Ph.D., University of North Carolina, Chapel Hill, 1996-2003
- B.S. Biology Major, Chemistry Minor, University of North Carolina, Chapel Hill, 1991-1995
RESEARCH SUPPORT
- Canada Foundation for Innovation
- Canadian Cancer Society Research Institute
- Canadian Institutes of Health Research
For over a century, researchers have been captivated by watching cells divide. From these observations, we know that during cell division, chromosomes condense to form small genomic packages which are separated to the daughter cells by the mitotic spindle generating two cells containing identical copies of the genome. Regulating the mechanical formation of chromosomes and their interaction between the spindle is critical to life, but key questions remain unanswered.
Just prior to cell division, chromosomes rapidly reorganize via unknown mechanisms and a specialized protein structure, the kinetochore, is constructed to mediate attachment to microtubules of the mitotic spindle. Kinetochores are complex structures containing many proteins, a subset of which bind directly to microtubules and generate forces which are used to move chromosomes to the daughter cells during segregation. Importantly, each chromosome must construct one and only one kinetochore. To ensure fidelity, kinetochores are assembled at discrete loci on chromosomes called centromeres. How centromeres are defined is an unanswered question, however a specialized histone variant, CENP-A is central.
In Dr. Maddox research unit, we study three discrete mechanisms of the mitotic chromosome. 1) How are chromosomes formed in mitosis? 2) What are the underlying mechanisms which govern specification of centromeres? 3) How do kinetochores produce forces to move the chromosomes? Our work focuses on the use of the light microscope to determine the fundamental properties underlying each of these mechanisms. Specifically, we image events in living cells where individual proteins can be specifically removed thus illuminating the molecular basis of cellular events. We use the small soil nematode C. elegans as well as cultured human cells are models for these fundamental, conserved events. Importantly, cancer is a disease of misregulated cell division, therefore understanding basic mechanisms of cell division will provide critical information and potential chemotherapeutic targets.
SELECTED PUBLICATIONS
Portier N, Audhya A, Maddox PS, Green RA, Dammermann A, Desai A, Oegema K (2007) A microtubule-independent role for centrosomes and aurora a in nuclear envelope breakdown. Dev Cell 12:515-529
Maddox PS, Hyndman F, Monen J, Oegema K, Desai A (2007) Functional genomics identifies a Myb domain-containing protein family required for assembly of CENP-A chromatin. J Cell Biol 176:757-763
Maddox PS, Portier N, Desai A, Oegema K (2006) Molecular analysis of mitotic chromosome condensation using a quantitative time-resolved fluorescence microscopy assay. Proc Natl Acad Sci U S A 103:15097-15102
Monen J, Maddox PS, Hyndman F, Oegema K, Desai A (2005) Differential role of CENP-A in the segregation of holocentric C. elegans chromosomes during meiosis and mitosis. Nat Cell Biol 7:1248-1255
Maddox PS, Oegema K, Desai A, Cheeseman IM (2004) "Holo"er than thou: chromosome segregation and kinetochore function in C. elegans. Chromosome Res 12:641-653
Pearson CG, Maddox PS, Zarzar TR, Salmon ED, Bloom K (2003) Yeast kinetochores do not stabilize Stu2p-dependent spindle microtubule dynamics. Mol Biol Cell 14:4181-4195
Maddox PS, Stemple JK, Satterwhite L, Salmon ED, Bloom K (2003) The minus end-directed motor Kar3 is required for coupling dynamic microtubule plus ends to the cortical shmoo tip in budding yeast. Curr Biol 13:1423-1428
Maddox P, Straight A, Coughlin P, Mitchison TJ, Salmon ED (2003) Direct observation of microtubule dynamics at kinetochores in Xenopus extract spindles: implications for spindle mechanics. J Cell Biol 162:377-382
Canman JC, Cameron LA, Maddox PS, Straight A, Tirnauer JS, Mitchison TJ, Fang G, Kapoor TM, Salmon ED (2003) Determining the position of the cell division plane. Nature 424:1074-1078
Maddox PS, Bloom KS, Salmon ED (2000) The polarity and dynamics of microtubule assembly in the budding yeast Saccharomyces cerevisiae. Nat Cell Biol 2:36-41
Top
<< Back to Investigators List
