Dr. William Saunders

Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
W. Saunders
B. Stronach
S. Tonsor
R. Wood

Microbiology
J. Boyle
G. Hatfull
R. Hendrix
J. Lawrence
J. Pipas
M. Popa
R.L. Duda
S. Godfrey
V. Oke

Molecular Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh

Plant Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw

Science Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg

Structural Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark

Former Faculty

Photo of Dr.
Saunders

Segregation of Chromosomes During Mitosis

Associate Professor

Dr. Saunders received his Ph.D. in 1990 from the Johns Hopkins University, performed his postdoctoral studies with M.A. Hoyt at Johns Hopkins University, and joined the Department in 1994.

Currently, Dr. Saunders is accepting graduate students in his laboratory. Dr. Saunders is accepting undergraduate researchers, and does sponsor students in other laboratories.

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of William Saunders

Multipolar spindles The research of the Saunders lab is focused on the study of cell division and the origin of divisional defects in cancer cells. When cells divide, it is essential that the components of the cell are separated such that both daughters will inherit the necessary starting material to propagate as healthy cells. During tumorigenesis, cells often divide irregularly with missegregation of chromosomes and microtubule organizing centers or centrosomes. Our interests are to define pathways required for normal division and determine how these pathways are altered in human disease.

Currently, we are focused on three types of abnormal division in tumor cells. These are multipolar spindles, anaphase bridges and failed cytokinesis.

Multipolar spindles happen when the cell tries to divide the chromosomes into more than two groups. This is a result of amplification of the number of centrosomes in the cell. Centrosomes organize the microtubules into a spindle to separate the chromosomes into two groups. Extra centrosomes can form more than two microtubule foci resulting in abnormal separation of the chromosomes into three or more groups. In cancer cells, multipolarity is accompanied by interference with the microtubule motor called cytoplasmic dynein. Dynein is not visible on cancer cell spindles and inhibition of dynein can greatly increase the multipolarity resulting from centrosomal amplification. In some tumor cells, dynein is inhibited by overexpression of another spindle motor called NuMA [1]. Current work in the lab is directed towards studying the mechanism of NuMA inhibition of dynein in vitro.

A related question is how the centrosomes get amplified in the first place. Currently, two models are proposed. One is that centrosomes are amplified by increased replication, the other is that centrosomes are amplified by failed cell division or cytokinesis. We have examined this question in cancer cells using live-cell imaging. In the cell lines examined, centrosomal amplification was associated with failure of cytokinesis. Recent work in the lab has shown that cytokinesis in cancer cells is due to a reduction of myosin heavy chain phosphorylation.

The third divisional defects of cancer cells we study is anaphase bridges. These structures form following DNA double-strand breaks and result in a tug-of-war between two dividing cells for a single chromosome [2]. Our focus is to identify the DNA repair pathways required for bridge formation. There are two known double-strand break repair pathways, nonhomologous end joining and homologous recombination, and we are testing mutants and siRNA knockdown of both pathways to examine their role in bridge induction.

A specialized type of cell division that is also defective in disease is meiosis. We study meiotic division in the model organism Saccharomyces cerevisiae, or budding yeast. We have used functional genomic analysis of a large collection of single gene deletion mutants created by a consortium of labs to identify many of the genes required for meiosis. Currently, we are examining the relationship between these gene products to define the pathways used to signal the start of meiosis. Defects in this pathway may contribute to birth defects in humans.

Publication Archive
32 Citations
32 Abstracts
24 PDFs

Recent Publications of William Saunders

Parikh, R.A., J.S. White, X. Huang, D.W. Schoppy, B.E. Baysal, R. Baskaran, C.J. Bakkenist, W.S. Saunders, L.C. Hsu, M. Romkes, and S.M. Gollin (2007) Loss of distal 11q is associated with DNA repair deficiency and reduced sensitivity to ionizing radiation in head and neck squamous cell carcinoma. Gene Chromosome Canc. 46:761-775

Acilan, C., D.M. Potter, and W.S. Saunders (2007) DNA repair pathways involved in anaphase bridge formation. Gene Chromosome Canc. 46:522-531

Reshmi, S.C., S. Roychoudhury, Z. Yu, E. Feingold, D. Potter, W.S. Saunders, and S.M. Gollin (2007) Inverted duplication pattern in anaphase bridges confirms the breakage-fusion-bridge (BFB) cycle model for 11q13 amplification. Cytogenet. Genome Res. 116:46-52

Reshmi, S.C., X. Huang, D.W. Schoppy, R.C. Black, W.S. Saunders, D.I. Smith, and S.M. Gollin (2007) Relationship between FRA11F and 11q13 gene amplification in oral cancer. Gene Chromosome Canc. 46:143-154

Mondal, G., S. Sengupta, C.K. Panda, C.K. Gollin, W.S. Saunders, and S. Roychoudhury (2007) Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Carcinogenesis 28:81-92

Saunders, W. (2005) Centrosomal amplification and spindle multipolarity in cancer cells. Semin. Cancer Biol. 15:25-32 (PDF Reprint: 138 kb)

Sproul, L.R., D.J. Anderson, A.T. Mackey, W.S. Saunders, and S.P. Gilbert (2005) Cik1 targets the minus-end kinesin depolymerase Kar3 to microtubule plus ends. Curr. Biol. 15:1420-1427 (PDF Reprint: 641 kb)

Quintyne, N.J., J.E. Reing, D.R. Hoffelder, S.M. Gollin, and W.S. Saunders (2005) Spindle multipolarity is prevented by centrosomal clustering. Science 307:127-129 (PDF Reprint: 573 kb)

Luo, L.Z., K.M. Werner, S.M. Gollin, and W.S. Saunders (2004) Cigarette smoke induces anaphase bridges and genomic imbalances in normal cells. Mutat. Res. 554:375-385 (PDF Reprint: 317 kb)

Reing, J.E., S.M. Gollin, and W.S. Saunders (2004) The occurrence of chromosome segregational defects is an intrinsic and heritable property of oral squamous cell carcinoma cell lines. Cancer Genet. Cytogenet. 150:57-61 (PDF Reprint: 579 kb)

Hoffelder, D.R., L. Luo, N.A. Burke, S.C. Watkins, S.M. Gollin, and W.S. Saunders (2004) Resolution of anaphase bridges in cancer cells. Chromosoma 112:389-397 (PDF Reprint: 473 kb)

Reshmi, S.C., W.S. Saunders, D.M. Kudla, C.R. Ragin, and S.M. Gollin (2004) Chromosomal instability and marker chromosome evolution in oral squamous cell carcinoma. Gene Chromosome Canc. 41:38-46 (PDF Reprint: 217 kb)

Saunders, W. (2003) Bridging mitotic defects and clinical diagnoses. Cancer Biol. Ther. 2:253-255

Enyenihi, A.H., and W.S. Saunders (2003) Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae. Genetics 163:47-54 (PDF Reprint: 343 kb)

How to Contact William Saunders

US Mail
University of Pittsburgh
Department of Biological Sciences
264A Crawford Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 624-4320
Lab : (412) 624-4309
FAX : (412) 624-4759
Email : wsaund+@pitt.edu
Web :

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