1992 B.S. in Chemistry, University of Oklahoma
1994 M.S. in Biochemistry, University of Oklahoma
1997 Ph.D. in Biochemistry, University of Oklahoma (Advisor: Dr. Bruce A. Roe)
1997-2001 Postdoctoral Fellow, National Human Genome Research Institute, National Institutes of Health (Advisor: Dr. Francis S. Collins)
Dr. Crabtree’s research focuses on neuroendocrine and hormone-dependent oncogenesis:
Neuroendocrine tumors (NETs) encompass a broad spectrum of malignancies all derived from neuroendocrine cell lineage, affecting many different organs including the gastrointestinal (GI) tract, the endocrine pancreas, the thyroid, the skin and the respiratory tract. These tumors as a group are very heterogeneous, with varying characteristics attributed to each tissue of origin and tumor subtype, thus the Crabtree lab focuses on pancreatic neuroendocrine tumors, gut carcinoids and Merkel Cell carcinoma of the skin. The pathogenesis of the different subtypes of NETs is not fully understood, but recent studies suggest the Notch signaling pathway may be dysregulated in these tumors either by under or overexpression of Notch receptors and/or ligands, or by disruption of pathway functionality through other means. Cancer stem cells are present in these tumors and may be responsible for the high rate of chemotherapy resistance, recurrence and metastasis.
Retinoblastoma binding protein 2 (RBP2) is also involved in neuroendocrine tumorigenesis and interfaces with the Notch signaling pathway by serving as a key component of the Notch CSL repressor complex. Further, RBP2 is overexpressed in more than 80% of clinical neuroendocrine tumors and metastases from these primary tumors. The Crabtree lab is exploring the regulation and function of this protein as a causative mechanism using in vitro cell-based and in vivo models of tumorigenesis and metastasis.
E.C. Maggi and J.S. Crabtree. Novel Targets in the Treatment of Neuroendocrine Tumors: RBP2. International J. Endocrine Oncology 4(1):31-41 (2017)
J.S. Crabtree and L. Miele. Neuroendocrine tumors: current therapies, Notch signaling and cancer stem cells. J. Cancer Metastasis and Treatment 2:279-93 (2016).
E. Maggi, J. Trillo-Tinoco, A. Parker-Struckhoff, J. Vijayaraghavan, L. Del Valle and J.S. Crabtree. Retinoblastoma Binding Protein 2 (RBP2) is Frequently Expressed in Neuroendocrine Tumors and Promotes the Neoplastic Phenotype. Oncogenesis 5:e257 (2016). PMID: 27548814.
J. Vijayaraghavan, E.C. Maggi and J.S. Crabtree. miR-24 Regulates Menin in the Endocrine Pancreas. American Journal of Physiology - Endocrinology and Metabolism 307: E84-E92 (2014). doi:10.1152/ajpendo.00542.2013.
A.S. McCampbell, H.A. Harris, J.S. Crabtree, R.C. Winneker, C.L. Walker and R.R. Broaddus. Loss of inhibitory IRS-1 phosphorylation is an early event in mTOR-dependent growth of endometrial hyperplasia. Cancer Prevention Research3(3): 290-300 (2010).
J.S. Crabtree, B.J. Peano, X. Zhang, B.S. Komm, R.C. Winneker and H.A. Harris. Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary gland. Molecular and Cellular Endocrinology 287(1-2): 40-46 (2008).
J.S. Crabtree, X. Zhang, B.J. Peano, Z. Zhang, R.C. Winneker, H.A. Harris. Development of a Mouse Model of Mammary Gland versus Uterine Tissue Selectivity Using Estrogen- and Progesterone-Regulated Gene Markers. Journal of Steroid Biochemistry and Molecular Biology 101(1): 11-21 (2006).
J.S. Crabtree, P.C. Scacheri, J.M. Ward, S.R. McNally, G.P. Swain, J.H. Hager, D. Hanahan, H. Edlund, M.A. Magnuson, L. Garrett-Beal, A.L. Burns, S.C. Chandrasekharappa, S.J. Marx, A.M. Spiegel and F.S. Collins. Of Mice and MEN1: Insulinomas in a conditional mouse knockout. Molecular and Cellular Biology 23(17): 6075-6085 (2003).
S.K. Libutti, J.S. Crabtree, D. Lorang, A.L. Burns, C. Mazzanti, S. Hewitt, J.M. Ward, M. Emmert-Buck, A. Remaley, M. Miller, E. Turner, H.R. Alexander, A. Arnold, S.J. Marx, F.S. Collins and A.M. Spiegel. Parathyroid gland-specific deletion of the mouse Men1 gene results in parathyroid neoplasia and hypercalcemic hyperparathyroidism. Cancer Research 63(22):8022-8028 (2003).
J.S. Crabtree, P.C. Scacheri, J.M. Ward, L. Garrett-Beal, M.R. Emmert-Buck, K.A. Edgemon, D. Lorang, S.K. Libutti, S.C. Chandrasekharappa, S.J. Marx, A.M. Spiegel, and F.S. Collins. A mouse model of multiple endocrine neoplasia, type 1 develops multiple endocrine tumors. Proc. Natl. Acad. Sci, USA 98(3):1118-1123 (2001).
The Genome International Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409(6822), 860-921 (2001). (See web site supplemental information for complete author listing).
I. Dunham, N. Shimizu, B.A. Roe, S. Chissoe, et al. The DNA Sequence of Human Chromosome 22. Nature 402(6761):489-495 (1999).
S.C. Chandrasekharappa, S.C. Guru, P. Manickam, S.E. Olufemi, F.S. Collins, M.R. Emmert-Buck, L.V. Debelenko, Z. Zhuang, I.A. Lubensky, L.A. Liotta, J.S. Crabtree, Y. Wang, B.A. Roe, J. Weismann, M.S. Boguski, S.K. Agarwal, M.B. Kester, Y.S. Kim, C. Heppner, Q. Dong, A.M. Spiegel, A.L. Burns, S.J. Marx. Positional cloning of the gene for multiple endocrine neoplasia, type 1. Science 276(5311):404-407 (1997).