Academic Background

Dan McCollum received his B.S. in Biochemistry from the University of Illinois in 1987, and his Ph.D., from the University of California at San Diego in 1993.  He did his postdoctoral training in Dr. Kathleen Gould's lab at Vanderbilt University.  Dr. McCollum joined the faculty at the Worcester Foundation for Biomedical Research in 1996, and then joined the University of Massachusetts Medical School in the department of Molecular Genetics and Microbiology in 1997.  Dr. McCollum is also a member of the Program in Cell Dynamics.

Molecular Mechanisms which Regulate Cytokinesis

The primary interest of my lab is understanding the molecular mechanisms which coordinate mitosis with cell division (cytokinesis).  Proper regulation of cytokinesis is critical for a number of reasons.  Normally cytokinesis is tightly coupled to the completion of mitosis.  If cells either loose this coupling, or have defects in cytokinesis, genetic instability can result, often leading to genetic defects and cancer.  We have chosen the fission yeast, Schizosaccharomyces pombe, as a model system for these studies because of the powerful molecular genetics available in S. pombe and the fact that the mechanisms of cytokinesis and cell cycle control are highly conserved between S. pombe and higher eukaryotic cells.

Through the combined use of genetic biochemical and cytological techniques, we have identified a novel signal transduction pathway which functions to coordinate cell division and mitosis.  This pathway (the SIN pathway) includes 4 protein kinases and one small GTPase, and functions to transmit a signal from the spindle poles to the cell division site causing initiation of cell division.  Recent studies have characterized the order of function of the proteins in the pathway and revealed key mechanisms by which signaling through the pathway is regulated to ensure that cytokinesis is coupled to the other events of mitosis.  For example, we recently showed that the Dma1 protein is required to inhibit the SIN in response to mitotic spindle defects to ensure that cytokinesis does not take place when chromosomes are unable to be segregated.  Interestingly a human homolog of Dma1 (CHFR) is deleted in a large percent of tumors suggesting that regulation of an analogous pathway may be important to inhibit tumor formation.