Professor, Baylor College of Medicine
B.S., Fudan University, Shangai, China, 1988
Ph.D., Baylor College of Medicine, 1994
Postdoc, Massachusetts Institute of Technology, Cambridge, 1995-2001
Molecular genetic studies of clearance of apoptotic cells in C. elegans
During an animal’s development and adulthood many unwanted cells are eliminated by a process called “programmed cell death” or “apoptosis”. Such cells undergo specific changes in appearance, die, and are quickly engulfed and digested by other cells. The engulfment step is important because dead cells can contain material that, if released, could harm neighboring cells. Both inefficient engulfment of apoptotic cells and incorrect engulfment of cells that should normally live could result in human diseases. The engulfment process utilizes mechanisms that remain largely unknown to regulate cell-cell signaling, cell-cell interaction, and cytoskeletal reorganization. These mechanisms are likely to be utilized by many other biological processes such as cell migration. Therefore, understanding the mechanisms that control engulfment has important meanings to biological and medical research.
My laboratory is investigating how engulfment of apoptotic cells is controlled. We are working to answer the following questions:
- How do engulfing cells recognize the apoptotic cells, their specific targets? What is the molecular nature of the “eat me” signal(s) presented by the apoptotic cells?
- What are the signaling pathways that trigger and regulate the polarized extension of engulfing cell surfaces that embrace the apoptotic cells? How are the plasma membrane and the actin cytoskeleton underneath it rearranged during cell-surface extension?
- How is an apoptotic cell efficiently degraded inside the engulfing cell?
We are studying these questions using a small round worm, the nematode Caenorhabditis elegans, a simple organism in which apoptotic cells are easily recognizable and genetic manipulations are well-established. Because many genes that have been identified in C. elegans resemble genes that perform analogous functions in humans, it is likely that what is learned from studying this worm will enhance the understanding of how human genes work. In C. elegans, apoptotic cells are rapidly engulfed and digested by their neighboring, living cells. Previous genetic analyses have identified six genes that control engulfment by acting in two partially redundant pathways: ced-1, -6, -7 in one, and ced-2, -5, and -10 in the other (ced: cell death abnormal). Mutations in these genes result in defects in the engulfment of apoptotic cells and persistent “cell corpses” remain in the worm’s body.
Yu X, Odera S, Chuang CH, Lu N, Zhou Z (2006) C. elegans Dynamin mediates the signaling of phagocytic receptor CED-1 for the engulfment and degradation of apoptotic cells. Developmental Cell 10:743-757.
Venegas V, Zhou Z (2007) Two alternative mechanisms that regulate the presentation of apoptotic cell engulfment signal in Caenorhabditis elegans. Molecular Biology of the Cell 18:3180-3192.
Mangahas PM, Yu X, Miller KG, Zhou Z (2008) The small GTPase Rab2 functions in the removal of apoptotic cells in Caenorhabditis elegans. Journal of Cell Biology 180:357-373.
Yu X, Lu N, Zhou Z (2008) Phagocytic receptor CED-1 initiates a signaling pathway for degrading engulfed apoptotic cells. PLoS Biology 6:e61.
Zhou Z, Yu X (2008) Phagosome maturation during the removal of apoptotic cells: receptors lead the way. Trends in Cell Biology 18:474-485.
He B, Lu N, Zhou Z (2009) Cellular and nuclear degradation during apoptosis. Current Opinion in Cell Biology 21:900-912.
Lu N, Yu X, He X, Zhou Z (2009) Detecting apoptotic cells and monitoring their clearance in the nematode Caenorhabditis elegans. Methods in Molecular Biology 559:357-370.
He B, Yu X, Margolis M, Liu X, Leng X, Etzion Y, Zheng F, Lu N, Quiocho FA, Danino D, Zhou Z (2010) Live-cell imaging in Caenorhabditis elegans reveals the distinct roles of dynamin self-assembly and guanosine triphosphate hydrolysis in the removal of apoptotic cells. Molecular Biology of the Cell 21:610-629.
Lu N, Shen Q, Mahoney TR, Liu X, Zhou Z (2011) Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling. Molecular Biology of the Cell 22:354-374.
Lu N, Shen Q, Mahoney TR, Neukomm LJ, Wang Y, Zhou Z (2012) Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic waves of phagosomal PtdIns(3)P critical for the degradation of apoptotic cells. PLoS Biology 10:e1001245.
Lu N, Zhou Z (2012) Membrane trafficking and phagosome maturation during the clearance of apoptotic cells. International Review of Cell and Molecular Biology 293:269-309.
Zheng Zhou, Ph.D.
Department of Biochemistry and Molecular Biology
Baylor College of Medicine
One Baylor Plaza 322B
Houston, Texas 77030, U.S.A.
Tel: (713) 798-6489
Fax: (713) 798-9438