Photo of Rosalie C. Sears, Ph.D.

Rosalie C. Sears Ph.D.

    • Professor of Molecular and Medical Genetics School of Medicine
    • Co-Director Brenden-Colson Center for Pancreatic Care School of Medicine
    • Krista L. Lake Chair in Cancer Research
    • Molecular and Medical Genetics Graduate Program School of Medicine
    • Cancer Biology Graduate Program School of Medicine
    • Program in Molecular and Cellular Biosciences School of Medicine

Dr. Sears received her Bachelor’s degree in Biology from Reed College (1986), Portland Oregon. She received her Ph.D. in Cell Biology from Vanderbilt University (1993), Nashville Tennessee, and conducted her post-doctoral studies at Duke University in the Genetics Department. Dr. Sears is a full professor in the Department of Molecular and Medical Genetics at Oregon Health & Science University. She is Co-Director of the Brenden-Colson Center for Pancreatic Care and a senior member in the Knight Cancer Institute. Dr. Sears has received funding from the National Institutes of Health, the Department of Defense, the Susan G. Komen Foundation, the Leukemia and Lymphoma Foundation, as well as several other private foundations. She has received both research and business innovation awards in the areas of cancer biology, therapeutics, and technology advancement.

The Sears lab studies cellular signaling pathways that control tumor cell behavior, with a focus on their convergence on the c-Myc oncoprotein and how this impacts Myc’s expression, activity, and its regulation of cell fate. Myc is constitutively overexpressed in the majority of human tumors and studies have demonstrated that this affects both tumor cell state (proliferation, differentiation, metabolism) as well as cross-talk with the tumor microenvironment affecting immune surveillance and vasculature. Dr. Sears’ work has identified a complex signaling pathway that coordinately post-translationally regulates c-Myc’s DNA binding and transcriptional activity with its turnover via ubiquitin-mediated proteolysis and she has demonstrated that c-Myc is post-translationally stabilized with increased activity in the majority of human tumors. The Sears lab has modeled post-translational activation of c-Myc in genetically engineered mice, where they have developed accurate mouse models of human breast and pancreatic cancer. Dr. Sears’ lab is pursuing new therapeutic strategies to target Myc by reversing its post-translational activation. This work has lead to the development of a new small molecule activator of the tumor suppressor phosphatase PP2A. This drug is orally available and has demonstrated dramatic inhibition of tumor growth and significant extension of survival in mouse breast and pancreas cancer models. 

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Areas of interest

  • Cancer genetics
  • Proteolysis and cell cycle control
  • Apoptosis
  • Mouse models of cancer
  • Genomics
  • Signal transduction

Education

  • B.S., Reed College, Portland Oregon United States 1986
  • Ph.D., Vanderbilt University, Nashville Tennessee United States 1993

Memberships and associations

  • American Association for Cancer Research

Publications

  • "MYC degradation" Cold Spring Harbor perspectives in medicine  2014
  • "Inhibition of 5-lipoxygenase selectively triggers disruption of c-Myc signaling in prostate cancer cells" Journal of Biological Chemistry February 20 2015
  • "The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc" Proceedings of the National Academy of Sciences of the United States of America March 24 2015
  • "The life cycle of c-Myc" Cell Cycle September 2004
  • "Ribosomal protein L11 recruits miR-24/miRISC to repress c-Myc expression in response to ribosomal stress" Molecular and Cellular Biology October 2011
  • "Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors and overcomes drug resistance in myeloid leukemia" Clinical Cancer Research April 15 2014
  • "Global rank-invariant set normalization (GRSN) to reduce systematic distortions in microarray data" BMC Bioinformatics December 4 2008
  • "Pin1 Regulates the Dynamics of c-Myc DNA Binding To Facilitate Target Gene Regulation and Oncogenesis" Molecular and Cellular Biology August 2013
  • "Direct interaction between the inhibitor 2 and ceramide via sphingolipid-protein binding is involved in the regulation of protein phosphatase 2A activity and signaling" FASEB Journal March 2009
  • "CIP2A Inhibits PP2A in Human Malignancies" Cell July 13 2007
  • "Diminished WNT → β-catenin → c-MYC signaling is a barrier for malignant progression of BRAFV600E-induced lung tumors" Genes and Development March 15 2014
  • "Protein phosphatase 2A regulatory subunit B56α associates with c-Myc and negatively regulates c-Myc accumulation" Molecular and Cellular Biology April 2006
  • "Phosphorylation regulates c-Myc's oncogenic activity in the mammary gland" Journal of Cancer Research February 1 2011
  • "Identification of a novel E2F3 product suggests a mechanism for determining specificity of repression by Rb proteins" Molecular and Cellular Biology May 2000
  • "Inhibition of c-Myc activity by ribosomal protein L11" EMBO Journal July 25 2007
  • "Identification of a Potent Inhibitor of CREB-Mediated Gene Transcription with Efficacious in Vivo Anticancer Activity" Journal of Medicinal Chemistry June 25 2015
  • "Detection of c-Myc protein-protein interactions and phosphorylation status by immunoprecipitation"   2013
  • "Serine 62-phosphorylated MYC Associates with nuclear lamins and its regulation by CIP2A is essential for regenerative proliferation" Cell Reports  2015
  • "Focal Adhesion Kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling" Developmental Cell August 2010
  • "Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability" Genes and Development October 1 2000
  • "Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals" Molecular and Cellular Biology September 1997
  • "Studying c-Myc serine 62 phosphorylation in leukemia cells" Blood June 5 2012
  • "A conserved pathway that controls c-Myc protein stability through opposing phosphorylation events occurs in yeast" Journal of Biological Chemistry February 23 2007
  • "Myc requires distinct E2F activities to induce S phase and apoptosis" Molecular Cell  2001
  • "Targeting inhibitors of the tumor suppressor PP2A for the treatment of pancreatic cancer" Molecular Cancer Research  2014
  • "Changes in the migratory properties of neural crest and early crest-derived cells in vivo following treatment with a phorbol ester drug" Developmental Biology  1988
  • "N terminus of ASPP2 binds to Ras and enhances Ras/Raf/MEK/ERK activation to promote oncogene-induced senescence" Proceedings of the National Academy of Sciences of the United States of America January 2 2013
  • "Erratum" Nature  1997
  • "Feedback regulation of c-Myc by ribosomal protein L11" Cell Cycle November 15 2007
  • "Mechanistic insight into Myc stabilization in breast cancer involving aberrant Axin1 expression" Proceedings of the National Academy of Sciences of the United States of America February 21 2012

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