Khandan Keyomarsi, Ph.D. 1989, University of Southern California UT M. D. Anderson Cancer Center Experimental Radiation Oncology Contact Information

Research Interests: Breast cancer; cell cycle control; molecular targeting; drug targeting; estrogen receptor; statins; experimental therapeutics

The research in my laboratory is focused on the development of novel strategies for treatment and prognosis of breast cancer by combining experimental therapeutics with cell biology while targeting the cell cycle. To this end, the laboratory is currently involved in 5 areas of research, which fall into translational and basic research categories:

• Investigation of the low-molecular-weight (LMW) forms of cyclin E as prognostic markers in breast cancer for routine use in the clinic.
• Delineation of how the alteration of cyclin E, a G 1 cyclin, could lead to the tumorigenic phenotype and determination of the oncogenic potential of the altered forms of cyclin E in breast cancer.
• Inhibition of LMW forms of cyclin E as a therapeutic target.
• Examination of the in vivo and subsequent clinical feasibility of a novel treatment strategy (i.e., a protection strategy) designed to protect normal proliferating cells against the toxic effects of chemotherapeutic agents.
• Determination of whether the proteasome is the target of G 1 arrest/growth inhibition mediated by farnasyl-transferase inhibitors and structurally related compounds.

A tutorial in my laboratory will provide experience with cell biology of breast cancer cells including culturing normal and tumor-derived breast cell, transfection and immunohistochemistry. Experience with molecular biology techniques (cloning, RNA and genomic DNA analysis), protein chemistry (purification of proteins interacting with cyclin E in normal and tumor cells), and experimental therapeutics (treatment of normal and tumor cells with novel agents targeting the cell cycle) will also be gained. The tutorial will also help the student gain an understanding on how research can be translated from the bench to the clinic.

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Keyomarsi K, Tucker SL, Buchholz TA, Lawrence C, Ding Y, Hortobagyi GN, Knickerbucker C, Toyofuku W, Lowe M, Herliczek TW and Bacus SS (2002) Cyclin E, a powerful predictor of survival in breast cancer. N Engl J Med 347:1566-1575.

Keyomarsi K, Tucker SL, Bedrosian I (2003) Cyclin E is a more powerful predictor of breast cancer outcome than proliferation. Nature Med 9:152.

Wingate H, Bedrosian I, Akli S and Keyomarsi K (2003) The Low Molecular Forms of Cyclin E Deregulate the Cell Cycle of Mammary Epithelial Cells. Cell Cycle 2(5):461-6.

Harwell, RM, Mull B, Porter DC, and Keyomarsi K (2004) Activation of CDK2 by full length and low molecular weight forms of cyclin E in breast cancer cells. J Biol Chem 279 (13):12695-705.

Bedrosian I, Lu KH, Verschraegen C and Keyomarsi K (2004) Ovarian cancer cells circumvent G1 arrest through deregulation of cyclin E. Oncogene 23:2648-57.

Akli S, Zheng P-J, Multani AS, Wingate H, Pathak S, Zhang N, Tucker SL, Chang S and Keyomarsi K (2004) The Tumor Specific Low Molecular Weight Forms of Cyclin E Induce Genomic Instability and Resistance to p21, p27, and Anit-estrogens in Breast Cancer. Cancer Res 64:3198-3208.

Wingate H, Zhang N, McGarhen MJ, Bedrosian I, Harper JW, Keyomarsi K (2005) The tumor specific hyperactive forms of cyclin E are resistant to inhibition by p21 and p27. J Biol Chem 280:15148-15157.

Efuet ET, Keyomarsi, K (2006) Farnesyl and geranylgeranyl transferase inhibitors induce G1 arrest by targeting the proteasome. Cancer Res 66(2):1040-51.

McGahren-Murray M, Terry NHA, Keyomarsi K. The Differential Staurosporine Mediated G 1 Arrest in Normal Versus Tumor Cells Is Dependent on the Retinoblastoma Protein. In press, Cancer Res.

Program Affiliations:
Program in Cancer Biology
Program in Cell and Regulatory Biology