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Yolanda Sanchez, Ph.D.

Title(s):
Associate Professor of Pharmacology & Toxicology
Associate Director for Basic Sciences, Norris Cotton Cancer Center

Department(s):
Pharmacology & Toxicology

Education:
Ph.D. Graduate School of Biomedical Sciences Houston, TX. Postdoctoral training Baylor College of Medicine

Programs:
Heart and Vascular Research Center
Neuroscience Center at Dartmouth
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine
SYNERGY

Websites:
http://www.dartmouth.edu/~sanchezlab/

Contact Information:

Dartmouth Medical School, HB 7650
Hanover NH 03755

Office: Vail 501
Phone: 603-650-1669
Fax: 603-650-1129
Email: yolanda.sanchez@dartmouth.edu


Professional Interests:

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.

Grant Information:

NIH NCI RO1 CA84463
NINDS/NIH R21 NS060940
Samuel Waxman Cancer Research Foundation
Nancy P. Shea Trust

Courses Taught:

PEMM Core Course
Graduate Toxicology
Medical Pharmacology

Biography:

Dr. Sanchez is a geneticist trained in both mammalian and yeast models. Her laboratory uses yeast and mouse models to study the interplay between oncogenes and checkpoint pathways in the early stages of cancer development. As a postdoctoral fellow in Dr. Stephen Elledge’s laboratory Dr. Sanchez focused on using yeast and mammalian cells to dissect the signaling pathways that regulate S phase and Mitosis following DNA damage, where she cloned the mammalian and yeast checkpoint kinase 1 genes. The human Chk1 kinase is an oncology target in Phase I clinical trials. Her laboratory also builds genetic platforms that are used in synthetic lethal chemical screens for the identification of drugs and drug targets for the treatment of cancer including pancreatic cancer and numerous types of aggressive neurological cancers.

Dr. Sanchez serves on the steering committee for the Early Phase Trial Clinical Oncology Group and is a member of the Neuro-oncology program of the Norris Cotton Cancer Center. She co-directs the SYNERGY Pilot program in Methodology and Technology Innovation for Translational Research (MITRA) with Drs. Anna Tosteson and Richard Enelow. Dr Sanchez was a member of the NIH Molecular Genetics C study section and has served on numerous NIH panels. She is co-inventor on three patents and two provisional patent applications.

Mentoring Information:

Jennifer Searle Ph.D. (2006)
Julie Caldwell Ph.D. (2007)
Matthew Wood M.D. Ph.D. (Ph.D. 2010)
Robert Allaway (Ph.D. Candidate 2012-current)
Xianpei Jia - 2013-current
Stephanie Bouley - 2014-current


Selected Publications:

 

  • 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;278:29940-7. (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;6:138-45. (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;15:4051-63. (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;3:1025-32. Review. (view details on MedLine)

  • 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;180:1073-86. (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;284:182-90. (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;8:1788-93. (view details on MedLine)

  • Wood MD, Sanchez Y. Deregulated Ras signaling compromises DNA damage checkpoint recovery in S. cerevisiae. Cell Cycle. 2010 Aug;9:3353-63. (view details on MedLine)

  • Searle JS, Wood MD, Kaur M, Tobin DV, Sanchez Y. Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage. PLoS Genet. 2011 Jul;7:e1002176. (view details on MedLine)

  • Wood M, Rawe M, Johansson G, Pang S, Soderquist RS, Patel AV, Nelson S, Seibel W, Ratner N, Sanchez Y. Discovery of a small molecule targeting IRA2 deletion in budding yeast and neurofibromin loss in malignant peripheral nerve sheath tumor cells. Mol Cancer Ther. 2011 Sep;10:1740-50 (view details on MedLine)