Ayesha Shajahan

Research Assistant Professor of Oncology

Co-Director, Tumor Biology Masters Program

Scientific coordinator, Breast Cancer Advocacy Committee
 
    I am interested in the role of Caveolin-1 (CAV1), a regulator of tumorigenesis, in the basic sub-cellular mechanisms that regulate cell death and survival in breast cancer. CAV1 is expressed as two distinct variants (a and b) in breast cancer cells and their expression/function is dependent on tumorigenicity and drug exposure. My objectives are: (1) to determine the distinct roles played by CAV1 variants in response to therapy in breast cancer cells, and (2) to determine factors that regulate CAV1 expression and function in the mammary gland
 
    Another area of research that I am involved is the mechanism of Unfolded Protein Response (UPR) in endocrine resistance in breast cancer. As an adaptive signaling pathway, the UPR promotes autophagy to allow the cells to survive the accumulation of unfolded proteins in the endoplasmic reticulum lumen in response to stress. Depending on the nature and duration of the stress, autophagy can be either pro-death or pro-survival. Currently, we are investigating the underlying signaling pathway that regulates UPR-mediated cell survival in endocrine resistance.
 

Selected Publications

1. Glucose-Regulated Protein 78 Controls Cross-talk between Apoptosis and Autophagy to Determine Antiestrogen Responsiveness.
Cook KL, Shajahan AN, Wärri A, Jin L, Hilakivi-Clarke LA, Clarke R.
Cancer Res. 2012 Jul 1;72(13):3337-49.
PMID: 22752300 [PubMed - in process]
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2. Tyrosine-phosphorylated caveolin-1 (Tyr-14) increases sensitivity to paclitaxel by inhibiting BCL2 and BCLxL proteins via c-Jun N-terminal kinase (JNK).
Shajahan AN, Dobbin ZC, Hickman FE, Dakshanamurthy S, Clarke R.
J Biol Chem. 2012 May 18;287(21):17682-92. Epub 2012 Mar 20.
PMID: 22433870 [PubMed - indexed for MEDLINE]
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3. Endoplasmic reticulum stress, the unfolded protein response, autophagy, and the integrated regulation of breast cancer cell fate.
Clarke R, Cook KL, Hu R, Facey CO, Tavassoly I, Schwartz JL, Baumann WT, Tyson JJ, Xuan J, Wang Y, Wärri A, Shajahan AN.
Cancer Res. 2012 Mar 15;72(6):1321-31. Review.
PMID: 22422988 [PubMed - indexed for MEDLINE]
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4. Nitric oxide-dependent Src activation and resultant caveolin-1 phosphorylation promote eNOS/caveolin-1 binding and eNOS inhibition.
Chen Z, Bakhshi FR, Shajahan AN, Sharma T, Mao M, Trane A, Bernatchez P, van Nieuw Amerongen GP, Bonini MG, Skidgel RA, Malik AB, Minshall RD.
Mol Biol Cell. 2012 Apr;23(7):1388-98. Epub 2012 Feb 9.
PMID: 22323292 [PubMed - in process] Free PMC Article
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5. The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer.
Schwartz JL, Shajahan AN, Clarke R.
Int J Breast Cancer. 2011;2011:912102. Epub 2011 Jul 3.
PMID: 22295238 [PubMed - in process] Free PMC Article
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6. Vitamin E succinate inhibits survivin and induces apoptosis in pancreatic cancer cells.
Patacsil D, Osayi S, Tran AT, Saenz F, Yimer L, Shajahan AN, Gokhale PC, Verma M, Clarke R, Chauhan SC, Kumar D.
Genes Nutr. 2012 Jan;7(1):83-9. Epub 2011 Aug 13.
PMID: 21842182 [PubMed - in process] Free PMC Article
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7. Autophagy and endocrine resistance in breast cancer.
Cook KL, Shajahan AN, Clarke R.
Expert Rev Anticancer Ther. 2011 Aug;11(8):1283-94. Review.
PMID: 21916582 [PubMed - indexed for MEDLINE]
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8. Co-inhibition of BCL-W and BCL2 restores antiestrogen sensitivity through BECN1 and promotes an autophagy-associated necrosis.
Crawford AC, Riggins RB, Shajahan AN, Zwart A, Clarke R.
PLoS One. 2010 Jan 6;5(1):e8604.
PMID: 20062536 [PubMed - indexed for MEDLINE] Free PMC Article
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9. BCL2 and CASP8 regulation by NF-kappaB differentially affect mitochondrial function and cell fate in antiestrogen-sensitive and -resistant breast cancer cells.
Nehra R, Riggins RB, Shajahan AN, Zwart A, Crawford AC, Clarke R.
FASEB J. 2010 Jun;24(6):2040-55. Epub 2010 Feb 12.
PMID: 20154269 [PubMed - indexed for MEDLINE] Free PMC Article
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10. Gene network signaling in hormone responsiveness modifies apoptosis and autophagy in breast cancer cells.
Clarke R, Shajahan AN, Riggins RB, Cho Y, Crawford A, Xuan J, Wang Y, Zwart A, Nehra R, Liu MC.
J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):8-20.
PMID: 19444933 [PubMed - indexed for MEDLINE] Free PMC Article
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11. Tyrosine phosphorylation-dependence of caveolae-mediated endocytosis.
Sverdlov M, Shajahan AN, Minshall RD.
J Cell Mol Med. 2007 Nov-Dec;11(6):1239-50. Review.
PMID: 18205698 [PubMed - indexed for MEDLINE]
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12. Human X-box binding protein-1 confers both estrogen independence and antiestrogen resistance in breast cancer cell lines.
Gomez BP, Riggins RB, Shajahan AN, Klimach U, Wang A, Crawford AC, Zhu Y, Zwart A, Wang M, Clarke R.
FASEB J. 2007 Dec;21(14):4013-27. Epub 2007 Jul 27.
PMID: 17660348 [PubMed - indexed for MEDLINE] Free Article
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13. Caveolin-1 tyrosine phosphorylation enhances paclitaxel-mediated cytotoxicity.
Shajahan AN, Wang A, Decker M, Minshall RD, Liu MC, Clarke R.
J Biol Chem. 2007 Feb 23;282(8):5934-43. Epub 2006 Dec 26.
PMID: 17190831 [PubMed - indexed for MEDLINE] Free Article
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14. Novel mechanism of endothelial nitric oxide synthase activation mediated by caveolae internalization in endothelial cells.
Maniatis NA, Brovkovych V, Allen SE, John TA, Shajahan AN, Tiruppathi C, Vogel SM, Skidgel RA, Malik AB, Minshall RD.
Circ Res. 2006 Oct 13;99(8):870-7. Epub 2006 Sep 14.
PMID: 16973909 [PubMed - indexed for MEDLINE] Free Article
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15. Differentiation of mammary gland as a mechanism to reduce breast cancer risk.
Hilakivi-Clarke L, Shajahan A, Yu B, de Assis S.
J Nutr. 2006 Oct;136(10):2697S-9S. No abstract available.
PMID: 16988155 [PubMed - indexed for MEDLINE] Free Article
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16. Isoflurane, but not sevoflurane, increases transendothelial albumin permeability in the isolated rat lung: role for enhanced phosphorylation of caveolin-1.
Hu G, Schwartz DE, Shajahan AN, Visintine DJ, Salem MR, Crystal GJ, Albrecht RF, Vogel SM, Minshall RD.
Anesthesiology. 2006 Apr;104(4):777-85.
PMID: 16571974 [PubMed - indexed for MEDLINE] Free Article
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17. Mechanisms mediating the effects of prepubertal (n-3) polyunsaturated fatty acid diet on breast cancer risk in rats.
Hilakivi-Clarke L, Olivo SE, Shajahan A, Khan G, Zhu Y, Zwart A, Cho E, Clarke R.
J Nutr. 2005 Dec;135(12 Suppl):2946S-2952S. Review.
PMID: 16317153 [PubMed - indexed for MEDLINE] Free Article
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18. Gbetagamma activation of Src induces caveolae-mediated endocytosis in endothelial cells.
Shajahan AN, Tiruppathi C, Smrcka AV, Malik AB, Minshall RD.
J Biol Chem. 2004 Nov 12;279(46):48055-62. Epub 2004 Sep 2.
PMID: 15345719 [PubMed - indexed for MEDLINE] Free Article
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19. Role of Src-induced dynamin-2 phosphorylation in caveolae-mediated endocytosis in endothelial cells.
Shajahan AN, Timblin BK, Sandoval R, Tiruppathi C, Malik AB, Minshall RD.
J Biol Chem. 2004 May 7;279(19):20392-400. Epub 2004 Mar 8.
PMID: 15007081 [PubMed - indexed for MEDLINE] Free Article
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