Christopher L. Sansam, Ph.D.
Cell Cycle & Cancer Biology Research Program
Before cells divide, they run through a checklist to make sure everything is OK. If something is missing, malformed or otherwise wrong, the cell division stops. That’s important because when cells divide incorrectly, it can lead to birth defects and cancer.
In my lab, we study genes that ensure that DNA is not broken or incompletely replicated before cells divide. We are interested in how these genes sense that DNA is damaged and how they stop cell division. We are also interested in the consequences of losing the function of these genes in the developing embryo.
We discovered a new gene that is part of the system that senses and responds to damaged DNA. We have named this gene TICRR. We’ve found that in cells with a mutated version of TICRR, cell division continues even under circumstances when it should stop. For instance, when intense radiation blasts a cell and breaks the DNA, a cell should not divide. But when it’s missing TICRR, the division goes ahead. This has catastrophic consequences for a dividing cell, and embryos lacking the TICRR gene die during development.
Our lab mainly uses two experimental systems to study cell cycle control. We use human cells grown in culture because these cells can be easily manipulated and monitored. We also use zebrafish embryos because their cell cycle control genes are very similar to humans; but unlike humans, they develop externally, so we can watch cells dividing in a living embryo.
By better understanding cell cycle control genes like TICRR, we hope to find ways to predict and prevent the occurrence of birth defects, understand the genesis of some cancers and possibly find a way to make cancer treatments more effective with fewer side effects.
1997 B.S., James Madison University, Harrisonburg, VA (summa cum laude)
2004 Ph.D., Vanderbilt University School of Medicine, Nashville, TN
2010 Postdoc, Laboratories of Nancy Hopkins and Jacqueline Lees, Massachusetts Institute of Technology
Honors and Awards
1997 Outstanding Student Award, Integrated Science and Technology Program, James Madison University
1997 Dan May Summer Research Scholarship in Cardiology, Vanderbilt University
1997-2004 Harold Sterling Vanderbilt Graduate Scholarship
2001-2004 NIH Ruth L. Kirschstein Predoctoral National Research Service Award
2004 Anna Fuller Postdoctoral Fellowship
2004-2010 NIH Ruth L. Kirschstein Postdoctoral National Research Service Award NIH/NIGMS
Joined OMRF Scientific Staff in 2010
My laboratory is interested in how the cell cycle is regulated during embryonic development and in the DNA damage response. In all eukaryotes, signal transduction pathways called checkpoints monitor the genome and slow cell cycle progression when DNA is damaged or DNA replication is perturbed. These pathways ensure normal development of the vertebrate embryo, and disruption of DNA damage checkpoints is associated with numerous inherited human developmental disorders. In the adult, DNA damage checkpoints are needed to suppress tumorigenesis, and tumors develop as these checkpoint pathways become partially inactivated. Checkpoints are also important factors in the chemotherapy response, since nearly all commonly used chemotherapeutic drugs work by causing DNA damage or inhibiting DNA replication. Checkpoint pathways are broadly medically important, and we are interested in elucidating their mechanisms and their roles in both embryonic development and in normal tissue homeostasis.
To obtain both mechanistic and in vivo information, we study the DNA damage response using cultured human cells and zebrafish embryos. Because the zebrafish embryo develops externally, it provides an outstanding opportunity to observe the effects of modulating checkpoints in a maturing whole organism. Furthermore, zebrafish can be used for classical forward genetic screens more easily than other vertebrates. We are currently studying the function of several checkpoint genes that we discovered through a genetic screen in zebrafish, including one gene called TICRR. This gene is of particular interest because it is required for both checkpoint signaling and DNA replication initiation. TICRR is largely uncharacterized and not found outside of metazoans, so we anticipate that studying this gene will reveal new mechanistic insight into cell cycle control in vertebrates.
Sansam CL, Pezza RJ. Connecting by breaking and repairing: mechanisms of DNA strand exchange in meiotic recombination. FEBS J 2015. [Abstract] EPub
Sansam CG, Goins D, Siefert JC, Clowdus EA, Sansam CL. Cyclin-dependent kinase regulates the length of S phase through TICRR/TRESLIN phosphorylation. Genes Dev 29:555-566, 2015. [Abstract]
Sansam CL, Cruz NM, Danielian PS, Amsterdam A, Lau ML, Hopkins N, Lees JA. A vertebrate gene, ticrr, is an essential checkpoint and replication regulator. Genes Dev 24:183-194, 2010. [Abstract]
Feng Y, Sansam CL, Singh M, Emeson RB. Altered RNA editing in mice lacking ADAR2 autoregulation. Mol Cell Biol 26:480-488, 2006. [Abstract]
Dawson TR, Sansam CL, Emeson RB. Structure and sequence determinants required for the RNA editing of ADAR2 substrates. J Biol Chem 279:4941-4951, 2004. [Abstract]
Sansam CL, Wells KS, Emeson RB. Modulation of RNA editing by functional nucleolar sequestration of ADAR2. Proc Natl Acad Sci U S A 100:14018-14023, 2003. [Abstract]
Cell Cycle & Cancer Biology Research Program, MS 48
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7677
Fax: (405) 271-3045