Yolanda Sanchez, Ph.D.
Associate Professor of Pharmacology & Toxicology
Associate Director for Basic Sciences, Norris Cotton Cancer Center
Pharmacology & Toxicology
Ph.D. Graduate School of Biomedical Sciences Houston, TX. Postdoctoral training Baylor College of Medicine
Heart and Vascular Research Center
Neuroscience Center at Dartmouth
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine
Dartmouth Medical School, HB 7650
Hanover NH 03755
Office: Vail 501
Dr. Sanchez's laboratory studies the pathways that protect genomic integrity and in particular the study of the Chk1 protein, a target of inhibitors currently in clinical trials for cancer. Her laboratory uses different model systems (yeast, insect and mammalian cells) to reconstitute spatial temporal signaling from stalled replication forks and DNA damage in order to dissect the mechanism by which mitosis is regulated by localized activation of enzyme complexes following DNA damage and to dissect the signal transduction pathways originating at a stalled replication fork, which orchestrate the DNA damage and S phase checkpoints.
DNA damage has been found to be an early event in pre-malignant lesions and can be caused by deregulation of cancer driving genes called oncogenes. This finding led the Sanchez laboratory to investigate the role that checkpoint pathways play in the early stages of cancer development. Dr. Sanchez's laboratory uses mouse models to study the role that Chk1 plays in the early stages of cancer development.
Dr. Sanchez laboratory also works on building genetic platforms for the identification of drugs and drug targets for the treatment of cancer.
Rotations and Thesis Projects:
1. The role of checkpoints in embryonic development
2. Optimization of model organisms for high-throughput drug discovery
3. The interplay of Oncogenes and Checkpoints during the early stages of cancer development.
4. Regulation of mitosis by localized activation of enzyme complexes.
5. Dissection of signal transduction pathways originating at a stalled replication fork.
NIH NCI RO1 CA84463
NINDS/NIH R21 NS060940
Samuel Waxman Cancer Research Foundation
PEMM Core Course
Goudelock DM, Jiang K, Pereira E, Russell B, Sanchez Y. Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex. J Biol Chem. 2003 Aug 8;278(32):29940-7. Epub 2003 May 19. (view details on MedLine)
Searle JS, Schollaert KL, Wilkins BJ, Sanchez Y. The DNA damage checkpoint and PKA pathways converge on APC substrates and Cdc20 to regulate mitotic progression. Nat Cell Biol. 2004 Feb;6(2):138-45. Epub 2004 Jan 25 (view details on MedLine)
Schollaert KL, Poisson JM, Searle JS, Schwanekamp JA, Tomlinson CR, Sanchez Y. A role for Saccharomyces cerevisiae Chk1p in the response to replication blocks. Mol Biol Cell. 2004 Sep;15(9):4051-63. Epub 2004 Jun 30. (view details on MedLine)
Chen Y, Sanchez Y. Chk1 in the DNA damage response: conserved roles from yeasts to mammals. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1025-32. Review. (view details on MedLine)
Searle JS, Sanchez Y. . Dissecting layers of mitotic regulation essential for maintaining genomic stability. Yeast as a tool in cancer research. Heitman, J., and Nitiss, J. L ed. Springer, 2007
Chen Y, Pereira E, Sanchez Y. Chk1. AfCS-Nature Molecule Pages (2007). (doi:10.1038/mp.a000642.01)
Caldwell JM, Chen Y, Schollaert KL, Theis JF, Babcock GF, Newlon CS, Sanchez Y. Orchestration of the S-phase and DNA damage checkpoint pathways by replication forks from early origins. J Cell Biol. 2008 Mar 24;180(6):1073-86. Epub 2008 Mar 17. (view details on MedLine)
Chen Y, Caldwell JM, Pereira E, Baker RW, Sanchez Y. ATRMec1 phosphorylation-independent activation of Chk1 in vivo. J Biol Chem. 2009 Jan 2;284(1):182-90. Epub 2008 Nov 4. (view details on MedLine)
Pereira E, Chen Y, Sanchez Y. Conserved ATRMec1 phosphorylation-independent activation of Chk1 by single amino acid substitution in the GD domain. Cell Cycle. 2009 Jun 1;8(11):1788-93. Epub 2009 Jun 15. (view details on MedLine)
Wood MD, Sanchez Y. Deregulated Ras signaling compromises DNA damage checkpoint recovery in S. cerevisiae. Cell Cycle. 2010 Aug 15;9(16):3353-63. Epub 2010 Aug 17. (view details on MedLine)