CMRC Children's Memorial Research Center
Zhila Khalkhali-Ellis

Zhila Khalkhali-Ellis

Children's Plaza, Box 222
Room 475
Chicago, IL 60614
Phone: (773) 755-6353
Fax: (773) 755-6594

Year Degree Institution
Ph.D. London University, UK

Work Experience
Period Description Organization
2004 - Present Research Professor, Dept. of Pediatrics, Children's Memorial Research Center
1999 - 2004 Associate Research Scientist, Holden Comprehensive Cancer Center member Dept. of Anatomy and Cell Biology, The University of Iowa
1994 - 1997 Research Scientist, Dept of Internal Medicine, Division of Rheumatology Dept. of Pediatrics, St. Louis University
1992 - 1994 Research Associate, Dept. of Biology Washington University, St. Louis

Research Interests
Mammary glands undergo structural remodeling and biochemical changes from embryogenesis through aging in females. This process is tightly regulated by hormones and involves a complex cooperation of a variety of genes participating in cell division, proliferation, matrix degradation and remodeling. Like mammary epithelial cells breast cancer tumors require estrogen for continued growth. Anti-estrogen therapy alone or in combination with other drugs, has long been a common procedure for breast cancer treatment and prophylaxis. The clinical efficacy of an anti-estrogen tamoxifen (TAM) has been attributed to growth arrest and induction of apoptosis in breast cancer cells, but the ability of TAM as a potential modulator of tumor suppressor genes has never been reported.
Maspin, a serine protease inhibitor (serpin), is highly expressed in normal mammary and reproductive organs, and is believed to play a critical role in mammary gland development. Maspin is present in high concentrations in normal mammary epithelial (and myoepithelial) cells, but its expression is down-regulated in primary breast cancer and lost in metastatic cells. Maspin promoter contains hormone response element and AP1 sites and maspin induction following androgen ablation and/or radical prostectomy in prostate cancer have been reported. Thus, we hypothesized that that tamoxifenís anti-tumor action could also be mediated, at least in part, through its ability to induce the tumor suppressor gene maspin. We are currently studying the effect of TAM (over various time period) on maspin expression in normal mammary epithelial cells and breast cancer cell lines and verifying our observations in patients tissue.
Recent studies have also indicated the importance of sex hormones and gender in autoimmune disorders such as rheumatoid arthritis. Regulation of immune response, matrix metalloproteinases and cytokine system by hormones could have a direct effect on cartilage and synovial tissue. Thus, we hypothesized that sex hormones could exert direct and indirect effects on cartilage synthesis and degradation and thus modulate the course of the disease. Studies in our lab are directed to answer such questions.

Research Funding
Title Funding Source Period Amount Duties
Biological function(s) of maspin R01 NIH/National Cancer Institute 2004 - 2009 $1,278.000 Co-PI
Role of secreted maspin Eisenberg Scholarship, CMRC 2004 - 2005 $6,000 PI
Tamoxifen regulation of tumor suppressor gene maspin Breast Cancer SPORE, R.H. Lurie Comprehensive Cancer Center, Northwestern University 2003 - 2004 $50,000 PI
Nitric oxide regulation of maspin in mammary epithelium under normal and neoplastic conditions American Cancer Society Institutional Research Grant, University of Iowa 2000 - 2001 $20,000 PI
Role of sex hormones in cartilage degradation associated with rheumatoid arthritis Howard Hughes Medical Institute Pilot Grant 2000 - 2001 $50,000 PI
Gender specific regulation of synoviocytes function by sex hormones. University of Iowa College of Medicine Pilot Grant 2000 - 2001 $15,000 PI

Lab Affiliations
Mary J.C. Hendrix Research Laboratory
Recent Publications
Khalkhali-Ellis Z, Christian AL, Kirschmann DA, Edwards EM, Rezaie-Thompson, M, Vasef, MA, Gruman, LM, Seftor, REB, Norwood, LE, Hendrix MJC. (January, 2004). Regulating the tumor suppressor gene maspin expression in normal mammary epithelia and breast cancer cells: a potential mechanism for tamoxifenís anti-tumor properties.. Clinical Cancer Research: 10:449-454.

Khalkhali-Ellis Z, and Hendrix MJC. (May, 2003). Nitric oxide regulation of maspin in normal mammary epithelial and breast carcinoma.. American J. of Pathology: 162:1411-1418.

Odero V, Khalkhali-Ellis Z, Chunthapong J, Amir, S, Seftor EA, and Hendrix MJC. (2003). Maspin regulates different signalling pathways for motility and adhesion in breast cancer cells. Cancer Biology and Therapy: 2:67-72.

Odero V, Khalkhali-Ellis Z, Schneider GB, Seftor EA, Seftor REB, Koland JG and Hendrix MJC. (2002). Maspin phosphorylation is involved in the regulation of human breast cancer cell motility. Biochem Biophys Res. Communications: 295:800-805.

Khalkhali-Ellis Z, Handa RJ, Price Jr. RH and Hendrix MJC (2002). Androgen receptors in synoviocytes: androgen regulation of IL-1 induced IL-6 production.. J. Rheumatology: 29:1843-1845.

Tobacmann J, Khalkhali-Ellis Z (2001). Steroid sulfatase expression in mammary myoepithelial cells and its regulation by steroid hormones. J. Steroid Biochem. Mol. Biol: 81:65-68.

Khalkhali-Ellis Z, Seftor EA, Handa RJ, Price Jr. RH, Nieva DRC, Kirschmann DA, Baragi VM, Sharma, RV, Bhalla RC, Moore TL and Hendrix MJC. (2000). Estrogen and progesterone regulation of human fibroblast-like synoviocytes in vitro: implications in rheumatoid arthritis. J Rheumatology: 27:1622-1631.

Khalkhali-Ellis Z, Bulla GA, Schlesinger L , Kirschmann DA, Moore TL and Hendrix MJC (1999). C1q containing immune complexes purified from sera of juvenile rheumatoid arthritis patients mediate IL-8 production by human synoviocytes. J Immunology: 163:4612-4620.

2004 - Eisenberg Scholar, Childrenís Memorial Research Institute , ďRole of secreted maspin"

2000 - Howard Hughes Investigator Research Award

2000 - University of Iowa Florence Lindsay Young Investigator Award

Professional Service
2001 - Present Grant Review services: Department of Defense Study Section on Prostate Cancer, Department of Defense Study Section on breast Cancer, NIH/NCI Special Emphasis Panel on Cancer Metastasis to Bone
1997 - Present Journal Reviewer (Intermittent), Cancer Research, American Journal of Pathology, Journal of Clinical Cancer Research, Clinical and Experimental Metastasis, Arthritis and Rheumatism, Journal of Rheumatology, Journal of Cellular Biology, Oncogene
2002 - 2002 Grant review (Ad hoc), British Research Council

Last Updated: Sep 8 2004 2:13PM

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