Du, Quansheng, Ph.D., D.Sc.
Member, Molecular Oncology and Biomarkers
Associate Professor, Neurology
Associate Professor, Graduate Studies
GRU Cancer Center
Research interests: Cell polarity, symmetric and asymmetric cell division, cell fate determination, epithelia morphogenesis and cell migration
BSc 1989 Wuhan University, Wuhan, China
MSc 1995 Wuhan University, Wuhan, China
PhD 1998 Wuhan University, Wuhan, China
Dr. Quansheng Du’s studies of cell polarity in MCG’s Institute of Molecular Medicine and Genetics bear on cancer in two ways: cell division and cell migration. Understanding how these activities work first in normal cells, then in cancer cells, can present opportunities to intervene and block cancer’s growth.
Cells normally divide in a controlled way. In the case of cancer, that control is disrupted, and the resulting rapid growth can become life-threatening. He is trying to understand the role certain molecules play in this process.
Cell division is a multi-step process, one people can watch under a microsope. Before a cell splits in two, its chromosomes are duplicated, forming sister chromatids. As division progresses, the chromatids begin to separate within the cell, pulled to one end or the other of the cell by a bipolar, spindle-shaped structure made of filamentous microtubules. Spindle microtubules interact with sister chromatids as well as the cell cortex to generate pulling forces that segregate chromosomes into daughter cells.
Cell division is usually symetrical, resulting in twin daughter cells, but in some cases, especially in stem cells, it could be asymmetrical.
To achieve self renewal and differentiation in one step, stem cells utilize asymmetric cell division, such that one daughter cell remains a stem cell and the other eventually evolves into another type of cell, such as that found in bone, muscle, blood or nerves.
Cell polarity may be a factor in determining which daughter cell stays a stem cell and which differentiates into another type of cell, says Dr. Du. Specifically, he is interested in how cell polarization directs mitotic spindle orientation to achieve asymmetrical division of the cell.
Mistakes here may contribute to disrupting the mechanisms that control growth and lead to cancer.
Cell polarity may also explain cell migration — for example, how one of the immune system’s T cells migrates to a lymph node to fight infection or how a cancer cell migrates (metastasizes) to another site. Such activity can present more opportunities for drug intervention to block cancer. “But whether cell polarity is tightly linked to cancer metastatics, we don’t know yet,” he says.
A BS in virology was awarded to Dr. Du in 1989 by Wuhan University. He earned an MS in 1995, followed by a PhD in 1998, both in virology and both from Wuhan. He has collaborated on 16 articles published in peer-reviewed professional journals.
The genetic materials that control the behavior of a cell are contained within its DNA, which is packaged into structures called chromosomes. During cell division, duplicated chromosomes must be precisely segregated to allow each daughter cell to inherit the same genetic information. Abnormal chromosome segregation is common in cancer cells and is believed to promote the growth and progression of a tumor. Chromosome segregation is driven by a complex microtubule-based bipolar structure called the spindle. Astral microtubles A subgroup of spindle microtubules, called astral microtubules, extends toward and interacts with the periphery of the cell, called the cell cortex. Astral microtubules contribute to the forces that separate the chromosomes.
Cell fate determinants.
The interaction between astral microtubules and the cell cortex also contributes to the positioning of the spindle, which determines the direction of chromosome segregation and the subsequent cleavage plane of the mother cell.
Spindle positioning is essential for one specific type of cell division called asymmetric cell division, which allows the daughter cells to inherit the same genetic material but different molecules that can affect the fate of cells, a process that is crucial for stem cell function. Perturbation of asymmetric cell division may lead to the transformation of normal stem cells to so-called tumor stem cells which are responsible for cancer progression and metastasis.
Identifying therapeutic targets.
Our long-term goal is to understand the molecular mechanisms that control chromosome segregation, spindle positioning and cell fate determination. Towards this aim, we recently identified several molecules that appear to mediate the interaction between astral microtubules and the cell cortex. We are using combined biochemical, genetic and live cell imaging approaches to determine how those molecules we identified form the physical link between astral microtubules and the cell cortex, contributing to chromosome segregation, spindle positioning and cell fate determination. Ultimately, we hope that results from our research will advance the understanding of how cancer is developed and help to identify targets for future therapeutic purpose.
- American Cancer Society, Inc.: “Interaction Between Astral Microtubules and the Cell Cortex” 2007-2011
- National Institutes of Health, General Medical Sciences “Mechanisms of Mitotic Spindle Orientation in Mammalian Cells” 2007-2012.
Grant information is updated quarterly.
Hao Y, Du Q, Chen X, Zheng Z, Balsbaugh JL, Maitra S, Shabanowitz J, Hunt DF, Macara IG. Par3 controls epithelial spindle orientation by aPKC-mediated phosphorylation of apical Pins. Curr Biol. 2010 Oct 26;20(20):1809-18.
Cho SG, Du Q, Huang S, Dong Z. Drp1 dephosphorylation in ATP depletion-induced mitochondrial injury and tubular cell apoptosis. Am J Physiol Renal Physiol. 2010 Jul;299(1):F199-206.
Zheng Z, Zhu H, Wan Q, Liu J, Xiao Z, Siderovski DP, Du Q. LGN regulates mitotic spindle orientation during epithelial morphogenesis. J Cell Biol. 2010 Apr 19;189(2):275-88.
Ying XB, Dong L, Zhu H, Duan CG, Du QS, Lv DQ, Fang YY, Garcia JA, Fang RX, Guo HS. RNA-dependent RNA polymerase 1 from Nicotiana tabacum suppresses RNA silencing and enhances viral infection in Nicotiana benthamiana. Plant Cell. 2010 Apr;22(4):1358-72.
Luo SW, Zhang C, Zhang B, Kim CH, Qiu YZ, Du QS, Mei L, Xiong WC. Regulation of heterochromatin remodelling and myogenin expression during muscle differentiation by FAK interaction with MBD2. EMBO J. 2009 Sep 2;28(17):2568-82.
Willard FS, Zheng Z, Guo J, Digby GJ, Kimple AJ, Conley JM, Johnston CA, Bosch D, Willard MD, Watts VJ, Lambert NA, Ikeda SR, Du Q, Siderovski DP. A point mutation to Galphai selectively blocks GoLoco motif binding: direct evidence for Galpha.GoLoco complexes in mitotic spindle dynamics. J Biol Chem. 2008 Dec 26;283(52):36698-710.
Publications are updated quarterly. For a complete listing, see Dr. Du’s work on PubMed.
- Associate Professor, Neurology, College of Graduate Studies, Georgia Regents University
- Member, American Society of Cell Biology
- Member, Chinese Biological Investigator Society
Du Q*, Stukenberg PT, Macara IG. A mammalian partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nat Cell Biol. 2001Dec;3(12):1069-1075.
Du Q*, Taylor L, Compton DA, Macara IG. LGN blocks the ability of NuMA to bind and stabilize microtubules: a mechanism for mitotic spindle assembly regulation. Curr Biol. 2002 Nov 19;12(22):1928-33.
Du Q, Macara IG. Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell. 2004 Nov 12;119(4):503-16.
Kisurina-Evgenieva O, Mack G, Du Q, Macara I, Khodjakov A, Compton DA. Multiple mechanisms regulate NuMA dynamics at spindle poles. J Cell Sci. 2004 Dec 15;117(Pt 26):6391-400.
Sans N, Wang PY, Du Q, Petralia RS, Wang YX, Nakka S,Blumer JB, Macara IG, Wenthold RJ. mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression. Nat Cell Biol. 2005 Dec;7(12):1179-90.
Bowman SK, Neumüller RA, Novatchkova M, Du Q, Knoblich JA. The Drosophila NuMA Homolog Mud Regulates Spindle Orientation in Asymmetric Cell Division. Dev Cell. 2006 Jun;10(6):731-42.
Zhu X-J, Wang C-Z, Dai P-G, Xie Y, Song N-N, Liu Y, Du Q, Mei L, Ding Y-Q, Xiong WC. Myosin X regulates netrin
receptors and functions in axonal path-finding. Nat Cell Biol. 2007 Feb;9(2):184-92.
* denotes corresponding author.