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.Read more
Areas of interest
- Cancer genetics
- Proteolysis and cell cycle control
- Mouse models of cancer
- Signal transduction
- 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
- "Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer." Nature Communications In: , Vol. 9, No. 1, 3815, 01.12.2018.
- "Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals." Genes & development In: , Vol. 32, No. 21-22, 01.11.2018, p. 1398-1419.
- "Serum biomarker signature-based liquid biopsy for diagnosis of early-stage pancreatic cancer." Journal of Clinical Oncology In: , Vol. 36, No. 28, 01.10.2018, p. 2887-2894.
- "Small-molecule activators of protein phosphatas 2A for the treatment of castration-resistant prostate cancer." Cancer Research In: , Vol. 78, No. 8, 15.04.2018, p. 2065-2080.
- "ZEB1-repressed microRNAs inhibit autocrine signaling that promotes vascular mimicry of breast cancer cells." Oncogene In: , Vol. 37, No. 8, 22.02.2018, p. 1005-1019.
- "The ubiquitin-specific protease USP36 is a conserved histone H2B deubiquitinase." Biochemical and Biophysical Research Communications In: , Vol. 495, No. 3, 15.01.2018, p. 2363-2368.
- "MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance." Nature Communications In: , Vol. 8, No. 1, 1728, 01.12.2017.
- "The tumor suppressor phosphatase PP2A-B56α regulates stemness and promotes the initiation of malignancies in a novel murine model." PLoS One In: , Vol. 12, No. 11, e0188910, 01.11.2017.
- "Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth." Journal of Clinical Investigation In: , Vol. 127, No. 6, 01.06.2017, p. 2081-2090.
- "Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation : Implications for the oncoprotein c-MYC." American Journal of Physiology - Cell Physiology In: , Vol. 312, No. 2, 08.02.2017, p. C176-C189.
- "Epigenomic inactivation of RasGAPs activates RAS signaling in a subset of luminal B breast cancers." Cancer Discovery In: , Vol. 7, No. 2, 01.02.2017, p. 131-133.
- "ΔN-ASPP2, a novel isoform of the ASPP2 tumor suppressor, promotes cellular survival." Biochemical and Biophysical Research Communications In: , Vol. 482, No. 4, 22.01.2017, p. 1271-1277.
- "A model of phenotypic state dynamics initiates a promising approach to control heterogeneous malignant cell populations." 2016 IEEE 55th Conference on Decision and Control, CDC 2016. Institute of Electrical and Electronics Engineers Inc., 2016. p. 2481-2487 7798634.
- "Combined targeting of SET and tyrosine kinases provides an effective therapeutic approach in human T-cell acute lymphoblastic leukemia." Oncotarget In: , Vol. 7, No. 51, 2016, p. 84214-84227.
- "Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity." Structure In: , Vol. 23, No. 12, 01.12.2015, p. 2267-2279.
- "Identification of a Potent Inhibitor of CREB-Mediated Gene Transcription with Efficacious in Vivo Anticancer Activity." Journal of Medicinal Chemistry In: , Vol. 58, No. 12, 25.06.2015, p. 5075-5087.
- "The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 112, No. 12, 24.03.2015, p. 3734-3739.
- "Inhibition of 5-lipoxygenase selectively triggers disruption of c-Myc signaling in prostate cancer cells." Journal of Biological Chemistry In: , Vol. 290, No. 8, 20.02.2015, p. 4994-5006.
- "Deubiquitinating c-Myc : USP36 steps up in the nucleolus." Cell Cycle In: , Vol. 14, No. 24, 01.01.2015, p. 3786-3793.
- "Serine 62-phosphorylated MYC Associates with nuclear lamins and its regulation by CIP2A is essential for regenerative proliferation." Cell Reports In: , Vol. 12, No. 6, 2015, p. 1019-1031.
- "Targeting c-MYC by antagonizing PP2A inhibitors in breast cancer." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 111, No. 25, 24.06.2014, p. 9157-9162.
- "Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors and overcomes drug resistance in myeloid leukemia." Clinical Cancer Research In: , Vol. 20, No. 8, 15.04.2014, p. 2092-2103.
- "Diminished WNT → β-catenin → c-MYC signaling is a barrier for malignant progression of BRAFV600E-induced lung tumors." Genes and Development In: , Vol. 28, No. 6, 15.03.2014, p. 561-575.
- "MYC degradation." Cold Spring Harbor perspectives in medicine In: , Vol. 4, No. 3, a014365, 2014.
- "Targeting inhibitors of the tumor suppressor PP2A for the treatment of pancreatic cancer." Molecular Cancer Research In: , Vol. 12, No. 6, 2014, p. 924-939.
- "Pin1 Regulates the Dynamics of c-Myc DNA Binding To Facilitate Target Gene Regulation and Oncogenesis." Molecular and Cellular Biology In: , Vol. 33, No. 15, 08.2013, p. 2930-2949.
- "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 In: , Vol. 110, No. 1, 02.01.2013, p. 312-317.
- "Detection of c-Myc protein-protein interactions and phosphorylation status by immunoprecipitation." Methods in Molecular Biology. Vol. 1012 Humana Press Inc., 2013. p. 65-76 (Methods in Molecular Biology; Vol. 1012).
- "Detection of c-Myc protein-protein interactions and phosphorylation status by immunoprecipitation." Methods in Molecular Biology. Vol. 1012 2013. p. 65-76.
- "A critical role for Mnt in Myc-driven T-cell proliferation and oncogenesis." Proceedings of the National Academy of Sciences of the United States of America In: , Vol. 109, No. 48, 27.11.2012, p. 19685-19690.