Khandan Keyomarsi, Ph.D.
Department of Experimental Radiation Oncology, Division of Radiation Oncology
Present Title & Affiliation
Primary Appointment
Professor, Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Professor with Commendation, Graduate School of Biomedical Sciences, The University of Texas, Houston, TX
Hubert L. and Olive Stringer Professorship in Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Education & Training
Degree-Granting Education
| 1993 | Harvard Medical School, Boston, MA, USA, Post-doc, BCMP |
| 1989 | University of Southern California, Los Angeles, CA, USA, PHD, Biochemistry |
| 1983 | University of California at Santa Barbara, Santa Barbara, CA, USA, BA, Pharmacology |
Postgraduate Training
| 1989-1993 | Postdoctoral Fellow, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA |
Experience & Service
Academic Appointments
Professor, Graduate School in Biomedical Sciences, The University of Texas, Houston, TX, 2005 - 2009
Honors & Awards
| 2009 | Hubert L. and Olive Stringer Professorship in Medical Oncology |
| 2002 | Faculty Scholar Award, MD Anderson Cancer Center |
Selected Publications
Peer-Reviewed Articles
- Nanos-Webb A, Jabbour NA, Multani AS, Wingate H, Oumata N, Galons H, Joseph B, Meijer L, Hunt KK, Keyomarsi K. Targeting low molecular weight cyclin E (LMW-E) in breast cancer. Breast Cancer Res Treat 132(2):575-88, 2012. e-Pub 2011. PMID: 21695458.
- Akli S, Zhang XQ, Bondaruk J, Tucker SL, Czerniak PB, Benedict WF, Keyomarsi K. Low molecular weight cyclin E is associated with p27-resistant, high-grade, high-stage and invasive bladder cancer. Cell Cycle 11(7):1468-76, 2012. e-Pub 2012. PMID: 22441703.
- Duong MT, Akli S, Wei C, Wingate HF, Liu W, Lu Y, Yi M, Mills GB, Hunt KK, Keyomarsi K. LMW-E/CDK2 deregulates acinar morphogenesis, induces tumorigenesis, and associates with the activated b-Raf-ERK1/2-mTOR pathway in breast cancer patients. (Comment - Loeb KR, ChenX, Too much cleavage of cyclin E promotes breast tumorigenesis, PloS Genet.8(3)1002623 Mar 2012). PLoS Genet 8(3):e1002538, 2012. e-Pub 2012. PMID: 22479189.
- Valero V, Wingate H, Chada S, Liu Y, Palalon F, Mills G, Keyomarsi K, Hunt KK. MDA-7 results in downregulation of AKT concomitant with apoptosis and cell cycle arrest in breast cancer cells. Cancer Gene Ther 18(7):510-9, 2011. e-Pub 2011. PMID: 21546925.
- Akli S, Van Pelt CS, Bui T, Meijer L, Keyomarsi K. Cdk2 is required for breast cancer mediated by the low molecular weight isoform of cyclin E. Cancer Res 71(9):3377-86, 2011. e-Pub 2011. PMID: 21385896.
- Keyomarsi K, Efuet ET, Bui TN. Semi-high throughput method of measuring proteasome inhibition in vitro and in cultured cells. Cell Biol Toxicol 27(2):123-31, 2011. e-Pub 2010. PMID: 20853140.
- Caruso JA, Hunt KK, Keyomarsi K. The Neutrophil Elastase Inhibitor Elafin Triggers Rb-Mediated Growth Arrest and Caspase-Dependent Apoptosis in Breast Cancer. Cancer Res 70(18):7125-36, 2010. e-Pub 2010. PMID: 20823156.
- Mittendorf EA, Liu Y, Tucker SL, McKenzie T, Qiao N, Akli S, Biernacka A, Liu Y, Meijer L, Keyomarsi K, Hunt KK. A novel interaction between HER2/neu and cyclin E in breast cancer. Oncogene 29(27):3896-907, 2010. e-Pub 2010. PMID: 20453888.
- Bagheri-Yarmand R, Biernacka A, Hunt KK, Keyomarsi K. Low molecular weight cyclin E overexpression shortens mitosis, leading to chromosome missegregation and centrosome amplification. Cancer Res 70(12):5074-84, 2010. e-Pub 2010. PMID: 20530685.
- Bagheri-Yarmand R, Nanos-Webb A, Biernacka A, Bui T, Keyomarsi K. Cyclin E deregulation impairs mitotic progression through premature activation of Cdc25C. Cancer Res 70(12):5085-95, 2010. e-Pub 2010. PMID: 20530684.
- Akli S, Bui T, Wingate H, Biernacka A, Moulder S, Tucker SL, Hunt KK, Keyomarsi K. Low-molecular-weight cyclin E can bypass letrozole-induced G1 arrest in human breast cancer cells and tumors. Clin Cancer Res 16(4):1179-90, 2010. e-Pub 2010. PMID: 20145171.
- Mull BB, Cox J, Bui T, Keyomarsi K. Post-translational modification and stability of low molecular weight cyclin E. Oncogene 28(35):3167-76, 2009. e-Pub 2009. PMID: 19561641.
- Shaye A, Sahin A, Hao Q, Hunt K, Keyomarsi K, Bedrosian I. Cyclin E deregulation is an early event in the development of breast cancer. Breast Cancer Res Treat 115(3):651-9, 2009. e-Pub 2008. PMID: 19107593.
- Agarwal R, Gonzalez-Angulo AM, Myhre S, Carey M, Lee JS, Overgaard J, Alsner J, Stemke-Hale K, Lluch A, Neve RM, Kuo WL, Sorlie T, Sahin A, Valero V, Keyomarsi K, Gray JW, Borresen-Dale AL, Mills GB, Hennessy BT. Integrative analysis of cyclin protein levels identifies cyclin B1 as a classifier and predictor of outcomes in breast cancer. Clin Cancer Res 15(11):3654-62, 2009. e-Pub 2009. PMID: 19470724.
- Lott ST, Chen N, Chandler DS, Yang Q, Wang L, Rodriguez M, Xie H, Balasenthil S, Buchholz TA, Sahin AA, Chaung K, Zhang B, Olufemi SE, Chen J, Adams H, Band V, El-Naggar AK, Frazier ML, Keyomarsi K, Hunt KK, Sen S, Haffty B, Hewitt SM, Krahe R, Killary AM. DEAR1 is a dominant regulator of acinar morphogenesis and an independent predictor of local recurrence-free survival in early onset breast cancer. PLoS Med 6(5):e1000068, 2009. e-Pub 2009. PMID: 19536326.
- Wingate H, Puskas A, Duong M, Bui T, Richardson D, Liu Y, Tucker SL, Van Pelt C, Meijer L, Hunt K, Keyomarsi K. Low molecular weight cyclin E is specific in breast cancer and is associated with mechanisms of tumor progression. Cell Cycle 8(7):1062-8, 2009. e-Pub 2009. PMID: 19305161.
- Delk NA, Hunt KK, Keyomarsi K. Altered subcellular localization of tumor-specific cyclin E isoforms affects cyclin-dependent kinase 2 complex formation and proteasomal regulation. Cancer Res 69(7):2817-25, 2009. e-Pub 2009. PMID: 19318554.
- Keyomarsi K. A novel MCM-2 fragment with potential biological function in senescence. Cell Cycle 7(22):3480, 2008. e-Pub 2008. PMID: 19001846.
- Lambert LA, Qiao N, Hunt KK, Lambert DH, Mills GB, Meijer L, Keyomarsi K. Autophagy: a novel mechanism of synergistic cytotoxicity between doxorubicin and roscovitine in a sarcoma model. Cancer Res 68(19):7966-74, 2008. PMID: 18829554.
- Javanmoghadam-Kamrani S, Keyomarsi K. Synchronization of the cell cycle using lovastatin. Cell Cycle 7(15):2434-40, 2008. e-Pub 2008. PMID: 18677105.
- Yokota T, Bui T, Liu Y, Yi M, Hunt KK, Keyomarsi K. Differential regulation of elafin in normal and tumor-derived mammary epithelial cells is mediated by CCAAT/enhancer binding protein beta. Cancer Res 67(23):11272-83, 2007. PMID: 18056453.
- von Holzen U, Pataer A, Raju U, Bocangel D, Vorburger SA, Liu Y, Lu X, Roth JA, Aggarwal BB, Barber GN, Keyomarsi K, Hunt KK, Swisher SG. The double-stranded RNA-activated protein kinase mediates radiation resistance in mouse embryo fibroblasts through nuclear factor kappaB and Akt activation. Clin Cancer Res 13(20):6032-9, 2007. PMID: 17947465.
- Akli S, Van Pelt CS, Bui T, Multani AS, Chang S, Johnson D, Tucker S, Keyomarsi K. Overexpression of the low molecular weight cyclin E in transgenic mice induces metastatic mammary carcinomas through the disruption of the ARF-p53 pathway. Cancer Res 67(15):7212-22, 2007. PMID: 17671189.
- Bedrosian I, Lee C, Tucker SL, Palla SL, Lu K, Keyomarsi K. Cyclin E-associated kinase activity predicts response to platinum-based chemotherapy. Clin Cancer Res 13(16):4800-6, 2007. PMID: 17699858.
- Lambert L, Keyomarsi K. Cell cycle deregulation in breast cancer: insurmountable chemoresistance or Achilles' heel?. Adv Exp Med Biol 608:52-69, 2007. PMID: 17993232.
- Barton MC, Akli S, Keyomarsi K. Deregulation of cyclin E meets dysfunction in p53: closing the escape hatch on breast cancer. J Cell Physiol 209(3):686-94, 2006. PMID: 17001684.
- McGahren-Murray M, Terry NH, Keyomarsi K. The Differential Staurosporine-Mediated G1 Arrest in Normal versus Tumor Cells Is Dependent on the Retinoblastoma Protein. Cancer Res 66(19):9744-53, 2006. PMID: 17018634.
- Le XF, Bedrosian I, Mao W, Murray M, Lu Z, Keyomarsi K, Lee MH, Zhao J, Bast RC, Jr. Anti-HER2 Antibody Trastuzumab Inhibits CDK2-Mediated NPAT and Histone H4 Expression via the PI3K Pathway. Cell Cycle 5(15):1654-61, 2006. PMID: 16861913.
- Efuet ET, Keyomarsi K. Farnesyl and geranylgeranyl transferase inhibitors induce G1 arrest by targeting the proteasome. Cancer Res 66(2):1040-51, 2006. PMID: 16424040.
- Eder AM, Sui X, Rosen DG, Nolden LK, Cheng KW, Lahad JP, Kango-Singh M, Lu KH, Warneke CL, Atkinson EN, Bedrosian I, Keyomarsi K, Kuo WL, Gray JW, Yin JC, Liu J, Halder G, Mills GB. Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci U S A 102(35):12519-24, 2005. PMID: 16116079.
- Wingate H, Zhang N, McGarhen MJ, Bedrosian I, Harper JW, Keyomarsi K. The tumor-specific hyperactive forms of cyclin E are resistant to inhibition by p21 and p27. J Biol Chem 280(15):15148-57, 2005. PMID: 15708847.
- Bales E, Mills L, Milam N, McGahren-Murray M, Bandyopadhyay D, Chen D, Reed JA, Timchenko N, van den Oord JJ, Bar-Eli M, Keyomarsi K, Medrano EE. The low molecular weight cyclin E isoforms augment angiogenesis and metastasis of human melanoma cells in vivo. Cancer Res 65(3):692-7, 2005. PMID: 15705861.
- Keyomarsi K, Moran RG. Folinic acid augmentation of the effects of fluoropyrimidines on murine and human leukemic cells. Cancer Res 46(10):5229-35, 1986. PMID: 2944577.
- Benjamin Mull, John Andrew Livingston, Nalini Patel, Tuyen Bui, Kelly Hunt, and Khandan Keyomarsi. Specific, reversible G1 arrest by UCN-01 in vivo provides cytostatic protection of normal cells against cytotoxic chemotherapy in breast cancer. British Journal of Cancer.
- Karakas C, Francis AM, Ha MJ, Wingate HF, Meena RA, Yi M, Rasaputra KS, Barrera AMG, Arun B, Do KA, Sahin A, Keyomarsi K, Hunt KK. Cytoplasmic Cyclin E Expression Predicts for Response to Neoadjuvant Chemotherapy in Breast Cancer. Ann Surg. e-Pub 2019. PMID: 31436549.
- Sun B, Wingate H, Swisher SG, Keyomarsi K, Hunt KK. Absence of pRb facilitates E2F1-induced apoptosis in breast cancer cells. Cell Cycle 9(6). e-Pub 2010. PMID: 20237430.
Grant & Contract Support
| Title: | Cyclin E as a Novel and Powerful Prognosticator for Breast Cancer |
| Funding Source: | NIH/NCI |
| Role: | Project 2 SPORE Principal Investigator |
| Title: | Proteolytic Processing of Cyclin E in Breast Cancer |
| Funding Source: | NIH/NCI |
| Role: | Principal Investigator |
| Title: | LMW-E, A Novel Indicator of Letrozole Resistance in Breast Cancer |
| Funding Source: | Susan G. Komen Breast Cancer Foundation |
| Role: | Principal Investigator |
| Title: | Targeting the cell cycle in triple negative breast cancer |
| Funding Source: | NIH/NCI |
| Role: | Principal Investigator |
| Title: | The Future of Cancer Research: Training Program for Basic and Translational Scientists |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Principal Investigator |
| Title: | PHD training for predoctoral fellows in the area of Clinical and Translational Science |
| Funding Source: | NIH |
| Role: | Collaborator |
| Title: | Cancer Center Support (Core) Grant - Breast Cancer Program |
| Funding Source: | DHHS - NIH-NCI |
| Role: | Co-Principal Investigator |
| Title: | Lonestar Oncology Network for Epigenetics, Therapy and Research: Breast Cancer Cell Resource Core Facility C:1 Tissue Culture |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Core Leader |
| Title: | CDK2 is a Novel Target for Triple Negative Breast Cancer |
| Funding Source: | Susan G. Komen Breast Cancer Foundation |
| Role: | Co-Investigator |
| Title: | Multidisciplinary Subspecialty Pathology Research Fellowship Program |
| Funding Source: | NIH/NCI |
| Role: | Multi-Investigator |
| Title: | Evaluating pharmacological inhibition of neutrophil elastase as an anti-tumor strategy against breast cancer |
| Funding Source: | Dainippon Sumitomo Pharma Co., Ltd |
| Role: | Principal Investigator-MDACC |
| Title: | Ekem Efuet, Novel Mechanism of interaction of statins with the proteasome: implications in breast cancer |
| Funding Source: | NIH/NCI |
| Role: | Mentor of PI |
| Title: | Sonia Kamrani, Cell cycle regulation of ER alpha in breast cancer, US Department of Defense |
| Funding Source: | Department of Defense (DOD) |
| Role: | Mentor of PI |
| Title: | Benjamin Mull, Specific reversible cytostatic protection of normal cells against chemotherapeutics in breast cancer therapy, US Department of Defense |
| Funding Source: | Department of Defense (DOD) |
| Role: | Mentor of PI |
| Title: | Tomoya Yokota, Mechanism of elafin downregulation in breast cancer cells |
| Funding Source: | MDACC Odyssey Fellowship |
| Role: | Mentor of PI |
| Title: | Elizabeth Mittendorf, Her2 regulation of low molecular weight cyclin E isoforms in breast cancer, American Association for Cancer Researach-Genentech BioOncology Fellowship for Cancer Research on the Her Family Pathway |
| Funding Source: | American Association for Cancer Research (AACR) |
| Role: | Mentor of PI |
| Title: | Elizabeth Mittendorf, Cyclin E: Implications for targeted therapy in Her2-overexpressing breast cancer |
| Funding Source: | NIH/NCI |
| Role: | Mentor of PI |
| Title: | Nikki Delk, Mechanistic regulation of the tumor specific forms of cyclin E in breast cancer |
| Funding Source: | NIH/NCI |
| Role: | Mentor of PI |
| Title: | MyLinh Duong, Cell cycle deregulation by LMW cyclin E and p53 disrupts mammary acinar morphogenesis. Department of Defense |
| Funding Source: | Department of Defense (DOD) |
| Role: | Mentor of PI |
| Title: | Joseph A. Caruso, Isaiah J. Fidler Graduate Fellowship in Cancer Metastasis, UT MD Anderson Cancer Center, Graduate Program in Cancer Metastasis Research: From Bench to Bedside |
| Funding Source: | UT MD Anderson Cancer Center |
| Role: | Mentor of PI |
| Title: | Kimberly Szymanski, Department of Defense Breast Cancer Research Program |
| Funding Source: | Department of Defense (DOD) |
| Role: | Mentor of PI |
| Title: | Anna Biernacka, Susan G. Komen for the Cure, HER2 and Cyclin E: Novel interaction and opportunities for therapy |
| Funding Source: | Susan G. Komen Breast Cancer Foundation |
| Role: | Mentor of PI |
| Title: | Natalie Jabbour, Autophagy as a therapeutic target against triple negative breast cancer |
| Funding Source: | NIH CCTS T32 Fellowship (UT Health Science Center Houston) |
| Role: | Mentor of GSBS student and PI |
| Title: | NBCF Prog Mark Ghanian Breast |
| Funding Source: | UTMDACC |
| Role: | Principal Investigator |
| Title: | Novel Preclinical Therapeutic approached for Triple Negative Breast cancer Targeting the PARP Pathway |
| Funding Source: | Tesaro Inc |
| Role: | Principal Investigator |
| Title: | Targeting the RB-pathway in sarcoma: Utility of CDK4/6 inhibitors |
| Funding Source: | Sarcoma Foundation of America (SFA) |
| Role: | Principal Investigator |
| Title: | Targeting CDK4 for the treatment of soft tissue sarcoma |
| Funding Source: | The Alan B, Slifka Foundation |
| Role: | Principal Investigator |
| Title: | LIN28 and RNA Uridylation in Breast Cancer: Mouse Models and Molecular Analyses |
| Funding Source: | NIH/NCI |
| Role: | Co-Investigator |
| Title: | Cytoplasmic cyclin E is an early event for progression to invasive breast cancer |
| Funding Source: | NIH/NCI |
| Role: | Principal Investigator |
| Title: | Rational Combination Treatment Options to Reverse Resistance in Hormone Receptor- Positive Breast Cancer Refractory to Standard Therapy |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Co-Leader of the Administrative Core |