David S. Rickman   Assistant Professor of Pathology and Laboratory Medicine

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The focus of my lab is to elucidate the role of key oncogenic transcription factors in the biology of prostate cancer. One project focuses on the role of the commonly prostate-specific rearranged ETS family members in gene regulation, chromatin 3D architecture and response to taxanes. The other focus of the Rickman Lab is to understand the role and therapeutic potential of N-Myc in driving neuroendocrine prostate cancer (NEPC). NEPC does not respond to hormonal intervention; they frequently metastasize to visceral organs, and carry a poor prognosis with an average survival of less than one year.We discovered significant over-expression and gene amplification of AURKA (encoding Aurora-A) and MYCN in NEPC. More recently, the Rickman Lab lab has generated novel pre-clinical models of N-Myc driven prostate cancer including genetically engineered mice that molecularly and histologically mimic clinical NEPC and that elucidated a novel transcription regulating complex between N-Myc and (Enhancer of Zeste Homolog 2) EZH2 in driving the NEPC phenotype.

Selected References

1.   Pflueger, D., Terry, S., Sboner, A., Habegger, L., Esgueva, R., Lin, P.C., Svensson, M.A., Kitabayashi, N., Moss, B.J., MacDonald, T.Y., Cao, X., Barrette, T., Tewari, A.K., Chee, M.S., Chinnaiyan, A.M., Rickman, D.S., Demichelis, F., Gerstein, M.B., and Rubin, M.A., Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing. Genome Res, 2011. 21(1): p. 56-67.

2.   Beltran, H., Rickman, D.S., Park, K., Sboner, A., MacDonald, T.Y., Wang, Y., Chae, S.S., Sheikh, K., Terry, S., Tagawa, S.T., Dhir, R., Nelson, J., de la Taille, A., Allory, Y., Gerstein, M., Perner, S., Pienta, K., Chinnaiyan, A.M., Wang, Y., Collins, C., Gleave, M., Demichelis, F., Nanus, D.M., and Rubin, M.A., Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets. Cancer Discovery, 2011. 1(6): p. 487-495.

3.   Rickman, D.S., Soong, T.D., Moss, B., Mosquera, J.M., Dlabal, J., Terry, S., Macdonald, T.Y., Tripodi, J., Bunting, K., Najfeld, V., Demichelis, F., Melnick, A.M., Elemento, O., and Rubin, M.A., Oncogene-mediated alterations in chromatin conformation. Proc Natl Acad Sci U S A, 2012. 109(23): p. 9083-8.

4.   Elemento, O., Rubin, M.A., and Rickman, D.S., Oncogenic transcription factors as master regulators of chromatin topology: A new role for ERG in prostate cancer. Cell Cycle, 2012. 11(18).

5.  Galletti G, Beltran H, Matov A, Fontugne J, Mosquera JM, Cheung, C, MacDonald TY, Sung M, O’Toole S, Kench JG,  Sung Suk Chae SS, Kimovski D, Tagawa ST, Nanus DN, M, Rubin MA, Horvath, LG, Giannakakou, P and Rickman DS. ERG Induces Taxane Resistance in Castration-Resistant Prostate Cancer. Nature Communications. 2014 Nov 25;5:5548.

6. Beltran H, Eng K, Mosquera JM, Sigaras A, Romanel A, Rennert H, Kossai M, Pauli C, Faltas B, Fontugne J, Park K, Banfelder J, Prandi D, Madhukar N, Zhang T, Padilla J, Greco N, McNary TJ, Herrscher E, Wilkes D, MacDonald TY, Xue H, Vacic V, Emde AK, Oschwald D, Tan AY, Chen Z, Collins C, Gleave ME, Wang Y, Chakravarty D, Schiffman M, Kim R, Campagne F, Robinson BD, Nanus DM, Tagawa ST, Xiang JZ, Smogorzewska A, Demichelis F, Rickman DS, Sboner A, Elemento O, Rubin MA. Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response. JAMA Oncol. 2015 Jul;1(4):466-74. doi: 10.1001/jamaoncol.2015.1313. PMID: 26181256.

7.  Gayvert, K., Dardenne, E., Cheung, C., Boland, M.R., Lorberbaum, T., Wanjala, J., Chen, Y., Rubin, M.A., Tatonetti, N., Rickman, D.S. & Elemento, O. (2016). A Computational Drug Repositioning Approach for Targeting Oncogenic Transcription Factors. Cell Reports, 2016 Jun 14;15(11):2348-56. doi: 10.1016/j.celrep.2016.05.037.  Co-senior author

8.  Dardenne E, Beltran H, Benelli M, Gayvert K, Berger A, Puca L, Cyrta J, Sboner A, Noorzad Z, MacDonald TY, Cheung C, Yuen KS, Gao D, Chen Y, Eilers M, Mosquera JM, Robinson B, Elemento O, Rubin MA, Demichelis F and Rickman DS. N-Myc Induces an EZH2-mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer. Cancer Cell, 2016 Oct 10;30(4):563-577. doi: 10.1016/j.ccell.2016.09.005. PMID: 27728805

Lab Website

https://rickmanlab.squarespace.com


Lab Members

  1. Etienne Dardenne (postdoctoral fellow)
  2. Adeline Berger (postdoctoral fellow)
  3. Dylan Murphy (research technician)
  4. Elena Koumis (research technician)

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Primary Email

  • dsr2005@med.cornell.edu

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