Karen E. Knudsen, Ph.D.


Deputy Director for Basic Science, KCC
Professor

Professor
Cancer Biology

Telephone
215-503-8574

Office Address
1008A BLSB
233 South 10th Street, Philadelphia, PA 19107

Email Address
karen.knudsen@kimmelcancercenter.org

Further Information
Jefferson Faculty Interest Page

 

RESEARCH INTERESTS

Prostate cancer is the most commonly diagnosed malignancy in the Unites States and the second leading cause of cancer death in men. Early prostate cancers require androgen to survive and proliferate; this dependence is exploited in treatment for disseminated disease. Wherein androgen ablation in the first line of therapeutic intervention. Although these regimens are initially effective, tumors ultimately recur due to reactivation of androgen receptor (AR) signaling, causing treatment failure and patient morbidity.

Despite the importance of understanding androgen action in the prostate, little is understood about the mechanisms underlying androgen dependence, and the means by which the androgen requirement is bypassed in relapsed tumors. My lab is dedicated to delineating the molecular mechanisms that govern these events. We currently have four main projects in the lab:

1. Regulation of AR dependent gene expression and cellular proliferation by cell cycle crosstalk in prostate cancer

2. Impact of SWI/SNF chromatin remodeling factors on AR function and prostate tumorigenesis

3. Impact of cell cycle deregulation on therapeutic efficacy

4. Role of endocrine disrupting compounds in circumventing the androgen requirement.

Keywords: Cancer, Prostate, androgen receptor
 

PubMed Link For Knudsen KE


Selected Recent Publications

Flores O, Wang Z, Knudsen KE, Burnstein KL. Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition. Endocrinology. 151(3):896-908, 2010. ( Abstract )

Knudsen KE, Penning TM. Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer. Trends Endocrinol Metab. 21(5):315-24, 2010. ( Abstract )

Paronetto MP, Cappellari M, Busà R, Pedrotti S, Vitali R, Comstock C, Hyslop T, Knudsen KE, Sette C. Alternative splicing of the cyclin D1 proto-oncogene is regulated by the RNA-binding protein Sam68. Cancer Res. 70(1):229-39, 2010. ( Abstract )

Weissman B, Knudsen KE. Hijacking the chromatin remodeling machinery: impact of SWI/SNF perturbations in cancer. Cancer Res. 69(21):8223-30, 2009. ( Abstract )

Miao J, Fang S, Lee J, Comstock C, Knudsen KE, Kemper JK. Functional specificities of Brm and Brg-1 Swi/Snf ATPases in the feedback regulation of hepatic bile acid biosynthesis. Mol Cell Biol. 29(23):6170-81, 2009. ( Abstract )

Comstock CE, Augello MA, Benito RP, Karch J, Tran TH, Utama FE, Tindall EA, Wang Y, Burd CJ, Groh EM, Hoang HN, Giles GG, Severi G, Hayes VM, Henderson BE, Le Marchand L, Kolonel LN, Haiman CA, Baffa R, Gomella LG, Knudsen ES, Rui H, Henshall SM, Sutherland RL, Knudsen KE. Cyclin D1 splice variants: polymorphism, risk, and isoform-specific regulation in prostate cancer. Clin Cancer Res. 15(17):5338-49, 2009. ( Abstract )

Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res. 15(15):4792-8, 2009. ( Abstract )

Gan L, Liu P, Lu H, Chen S, Yang J, McCarthy JB, Knudsen KE, Huang H. Cyclin D1 promotes anchorage-independent cell survival by inhibiting FOXO-mediated anoikis. Cell Death Differ. 16(10):1408-17, 2009. ( Abstract )

Millar EK, Dean JL, McNeil CM, O'Toole SA, Henshall SM, Tran T, Lin J, Quong A, Comstock CE, Witkiewicz A, Musgrove EA, Rui H, Lemarchand L, Setiawan VW, Haiman CA, Knudsen KE, Sutherland RL, Knudsen ES. Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome. Oncogene. 28(15):1812-20, 2009. ( Abstract )

Knudsen ES, Knudsen KE. Tailoring to RB: tumour suppressor status and therapeutic response. Nat Rev Cancer. 8(9):714-24, 2008. ( Abstract )

Schiewer MJ, Morey LM, Burd CJ, Liu Y, Merry DE, Ho SM, Knudsen KE. Cyclin D1 repressor domain mediates proliferation and survival in prostate cancer. Oncogene. 28(7):1016-27, 2009. ( Abstract )

Shen H, Powers N, Saini N, Comstock CE, Sharma A, Weaver K, Revelo MP, Gerald W, Williams E, Jessen WJ, Aronow BJ, Rosson G, Weissman B, Muchardt C, Yaniv M, Knudsen KE. The SWI/SNF ATPase Brm is a gatekeeper of proliferative control in prostate cancer. Cancer Res. 68(24):10154-62, 2008. ( Abstract )

Shah S, Hess-Wilson JK, Webb S, Daly H, Godoy-Tundidor S, Kim J, Boldison J, Daaka Y, Knudsen KE. 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene stimulates androgen independence in prostate cancer cells through combinatorial activation of mutant androgen receptor and mitogen-activated protein kinase pathways. Mol Cancer Res. 6(9):1507-20, 2008. ( Abstract )

Knudsen ES, Knudsen KE. Tailoring to RB: tumour suppressor status and therapeutic response. Nat Rev Cancer. 2008 Aug 7; [Epub ahead of print]. ( Abstract )

Wang Y, Dean JL, Millar EK, Tran TH, McNeil CM, Burd CJ, Henshall SM, Utama FE, Witkiewicz A, Rui H, Sutherland RL, Knudsen KE, Knudsen ES. Cyclin D1b is aberrantly regulated in response to therapeutic challenge and promotes resistance to estrogen antagonists. Cancer Res. 68(14):5628-38, 2008. ( Abstract )

Link KA, Balasubramaniam S, Sharma A, Comstock CE, Godoy-Tundidor S, Powers N, Cao KH, Haelens A, Claessens F, Revelo MP, Knudsen KE. Targeting the BAF57 SWI/SNF subunit in prostate cancer: a novel platform to control androgen receptor activity. Cancer Res. 68(12):4551-8, 2008. ( Abstract )

Balk SP, Knudsen KE. AR, the cell cycle, and prostate cancer. Nucl Recept Signal. 6:e001, 2008. ( Abstract )

Olshavsky NA, Groh EM, Comstock CE, Morey LM, Wang Y, Revelo MP, Burd C, Meller J, Knudsen KE. Cyclin D3 action in androgen receptor regulation and prostate cancer. Oncogene. 27(22):3111-21, 2008. ( Abstract )

Hess-Wilson JK, Webb SL, Daly HK, Leung YK, Boldison J, Comstock CE, Sartor MA, Ho SM, Knudsen KE. Unique bisphenol A transcriptome in prostate cancer: novel effects on ERbeta expression that correspond to androgen receptor mutation status. Environ Health Perspect. 115(11):1646-53, 2007. ( Abstract )

Sharma A, Comstock CE, Knudsen ES, Cao KH, Hess-Wilson JK, Morey LM, Barrera J, Knudsen KE. Retinoblastoma tumor suppressor status is a critical determinant of therapeutic response in prostate cancer cells. Cancer Res. 67(13):6192-203, 2007. ( Abstract )

Comstock CE, Knudsen KE. The complex role of AR signaling after cytotoxic insult: implications for cell-cycle-based chemotherapeutics. Cell Cycle. 6(11):1307-13, 2007. ( Abstract )

Comstock CE, Revelo MP, Buncher CR, Knudsen KE. Impact of differential cyclin D1 expression and localisation in prostate cancer. Br J Cancer. 96(6):970-9, 2007. ( Abstract )

Hess-Wilson JK, Daly HK, Zagorski WA, Montville CP, Knudsen KE. Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult. Cancer Res. 66(24):11998-2008, 2006. ( Abstract )

Wetherill YB, Hess-Wilson JK, Comstock CE, Shah SA, Buncher CR, Sallans L, Limbach PA, Schwemberger S, Babcock GF, Knudsen KE. Bisphenol A facilitates bypass of androgen ablation therapy in prostate cancer. Mol Cancer Ther. 5(12):3181-90, 2006. ( Abstract )

Bosco EE, Wang Y, Xu H, Zilfou JT, Knudsen KE, Aronow BJ, Lowe SW, Knudsen ES. The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J Clin Invest. 117(1):218-28, 2007. ( Abstract )

Burd CJ, Morey LM, Knudsen KE. Androgen receptor corepressors and prostate cancer. Endocr Relat Cancer. 13(4):979-94, 2006. ( Abstract )

Knudsen KE. The cyclin D1b splice variant: an old oncogene learns new tricks. Cell Div. 1:15, 2006. ( Abstract )

Knudsen ES, Knudsen KE. Retinoblastoma tumor suppressor: where cancer meets the cell cycle. Exp Biol Med (Maywood). 231(7):1271-81, 2006. ( Abstract )

Knudsen KE, Diehl JA, Haiman CA, Knudsen ES. Cyclin D1: polymorphism, aberrant splicing and cancer risk. Oncogene. 25(11):1620-8, 2006. ( Abstract )
 

Web page revised: March 19, 2013.
URL: http://www.kimmelcancercenter.org/kcc/kccnew/staff/staffdefault.php


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