Richard G. Pestell, MD, PhD, FACP, FRACP, MBA
President, Pennsylvania Cancer and Regenerative Medicine Center, Distinguished Professor, Translational Medical Research
Email: Richard.pestell@bblumberg.org
Website: http://www.pcarmrc.org
Laboratory: Lankenau Institute for Medical Research
100 E Lancaster Ave.
Wynnewood PA, 19096
Training:
New York University: M.B.A.
Harvard: Post Doctoral Fellowship
Massachusetts General Hospital: Post Doctoral Fellowship
Melbourne University: M.D.
Melbourne University: Ph.D.
University of Western Australia: M.B., B.S.
Appointment at the Blumberg: President Pennsylvania Cancer and Regenerative Medicine Center
Other appointments:
Royal College of Physicians (2022), Lee Kong Chian School of Medicine, Nantang Technological University
University of Melbourne
Research Overview
Research interest: Cancer and Regenerative Medicine
Research staff: Faculty
- Dr. Gabriele DiSante, Assistant Professor
- Dr. Agnese DiRocco, Assistant Professor
- Dr. Xuanmao Jiao, Associate Professor
- Dr. Zouren Yu, Visiting Professor
- Dr. Kongming Wu, Visiting Professor
Research Summary
The current studies examine the molecular mechanisms linking the drivers of mitophagy and autophagy with the mechanisms governing the symmetry of cell division and stem cell expansion. It is proposed that the symmetry of cell division is a determinant of stem cell expansion and that it is the cancer stem cells that give rise to therapy resistance. We are examining the role of key pathways in this biological interface using inducible deletion mice for cyclins, NFKB and Akt1.
We examine cell fate determination and its role in tumorigenesis using Dachshund transgenics. Dachshund plays a key role in specifying organismal development and the generation of tissues including the brain, yet appears to play a key role in tumorigenesis.
The role of cyclins in several types of tumors are being assessed assessing the non canonical functions. The non canonical functions contribute to miRNA maturation and expression, stem cell function and heterotypic signals.
Previous Publications
PubMed Link
Fan, S., Wang, J., Yuan, R., Ma, Y., Meng, Q., Erdos, M.R., Pestell, R.G., Yuan, F., Auborn, K.J., Goldberg, I.D., and Rosen, E.M., BRCA1 inhibition of estrogen receptor signaling in transfected cells. Science. 1999 May 21; 284(5418): p. 1354-6.
Bromberg, J.F., Wrzeszczynska, M.H., Devgan, G., Zhao, Y., Pestell, R.G., Albanese, C., and Darnell, J.E., Jr., Stat3 as an oncogene. Cell. 1999 Aug 6; 98(3): p. 295-303.
Tanaka, H., Matsumura, I., Ezoe, S., Satoh, Y., Sakamaki, T., Albanese, C., Machii, T., Pestell, R.G., and Kanakura, Y., E2F1 and c-Myc potentiate apoptosis through inhibition of NF-κB activity that facilitates MnSOD-mediated ROS elimination. Mol Cell. 2002 May; 9(5): p. 1017-29.
Genander, M., Halford, M.M., Xu, N.J., Eriksson, M., Yu, Z., Qiu, Z., Martling, A., Greicius, G., Thakar, S., Catchpole, T., Chumley, M.J., Zdunek, S., Wang, C., Holm, T., Goff, S.P., Pettersson, S., Pestell, R.G., Henkemeyer, M., and Frisen, J., Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression. Cell. 2009 Nov 13; 139(4): p. 679-92.
Casimiro MC, Crosariol M, Loro E, Ertel A, Yu Z, Dampier W, Saria E, Papanikolaou A, Li Z, Wang C, Fortina P, Addya A, Tozeren A, Knudsen ES, Arnold A, Pestell RG. ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice. J Clin Invest. 2012 Mar 1;122(3):833-43. doi: 10.1172/JCI60256. Epub 2012 Feb 6.
Yu Z, Wang L, Wang C, Ju X, Wang M, Chen K, Loro E, Wu K, Casimiro MC, Gormley M, Ertel A, Fortina P, Tozeren A, Liu Z, Chen Y, Pestell RG. Cyclin D1 Induction of Dicer Governs MicroRNA Processing and Expression in Breast Cancer. Nat Commun. 2013 Nov 29;4:2812. doi: 10.1038/ncomms3812.
Zhang J, Wang C, Chen X, Takada M, Fan C, Zheng X, Wen H, Liu Y, Pestell RG, Aird KM, Kaelin Jr W, Liu XS, Zhang Q. EgIN2 Associates, with the NRF1-PGC1 Complex and Controls Mitochondrial Function in Breast Cancer. EMBO J 2015 Oct 22. pii: e201591437
Recent Publications:
Sicoli D, Jiao X, Ju X, Velasco-Velazquez M, Ertel A, Addya S, Li Z, Ando S, Fatatis A, Paudyal B, Cristofanilli M, Thakur ML, Lisanti MP, Pestell RG. CCR5 receptor antagonists block metastasis to bone of Src-oncogene-transformed metastatic prostate cancer cell lines. Cancer Res. 2014 Dec 1;74(23):7103-14
Di Sante G, Pestell TG, Casimiro MC, Bisetto S, Powell MJ, Lisanti MP, Cordon-Cardo C, Castillo-Martin M, Bonal DM, Debattisti V, Chen K, Wang L, He X, McBurney MW, Pestell RG. Loss of sirt1 promotes prostatic intraepithelial neoplasia, reduces mitophagy, and delays park2 translocation to mitochondria. Am J Pathol. 2015 Jan;185(1):266-79. doi: 10.1016/j.ajpath.2014.09.014.
Di Sante G, Wang L, Wang C, Jiao X, Casimiro MC, Chen K, Pestell TG, Yaman I, Di Rocco A, Sun X, Horio Y, Powell MJ, He X, McBurney MW, Pestell RG. Sirt1 deficient mice have hypogonadotropic hypogonadism due to defective GnRH neuronal migration. Mol Endocrinol. 2014 Dec 29:me20141228. [Epub ahead of print]
Di Sante G, Wang L, Wang C, Jiao X, Casimiro MC, Chen K, Horio Y, Powell MJ, McBurney MW, Pestell RG. Sirt1 determines GnRH neuronal migration via FGF/FGFR1 and hypogonadotropic hypogonadism in mice. Mol Endocrinol. 2014, Dec 29, 20141228.
Chen K, Wu K, Wang L, Jiao X, Ju X, Li Z, Ertel A, Addya S, McCue P, Lisanti MP, Wang C, Davis RJ, Mardon G, Pestell RG. The endogenous Cell-Fate Factor Dachshund restrains prostate epithelial cell migration via repression of cytokine secretion via a CXCL Signaling Module. Cancer Research. 2015 Mar 13.
Casimiro MC, Di Sante G, Ju X, Chen K, Crosariol M, Yaman I, Gormley M, Meng H, Lisanti MP, Pestell RG. Cyclin D1 promotes androgen-dependent DNA damage repair in prostate cancer cells. Cancer Res. 2016 Jan 15;76(2):329-38.
Zhang Q. EgIN2 Associates, with the NRF1-PGC1 Complex and Controls Mitochondrial Function in Breast Cancer. EMBO J. 2015 Oct 22. pii: e201591437
Ozcan L,Ghorpade D,Cristina de Sozua J,Chen K, Bessler M,Bagloo M,Schrope B, Pestell RG, Tabas. Hepatocyte DACH1 is Increased in Obesity Via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance. Cell Rep. 2016 May 26. un 7;15(10):2214-25
Ju X, Jiao X, Ertel A, Lisanti MP, Disante G, Ly Xu DC, Casimiro M, Xu C, Ando S, Pestell RG. Oncogenic Src oncogene induces Trop2 proteolytic activation via cyclin D1. Cancer Research. 2016 September 15
Meng, L., Liu, C., Lü, J., Zhao, Q., Deng., S., Wang, G., Qiao. J., Zhang, C., Zhen, L., Lu,Y., Li, W., Yuzhen Zhang, Y., Pestell, RG, Fan, H., Chen, Y-h., , Liu., Z., and Yu, Z. Small RNA zippers: lock miRNA molecules and block miRNA function in mammalian cells. Nature Communications In Press. 2016.
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