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Jennifer Sims-Mourtada, Ph.D.

Senior Clinical Scientist, Center for Translational Cancer Research, Helen F. Graham Cancer Center, Affiliated Faculty, Department of Biological Sciences, University of Delaware, Newark, DE.

(302) 623-4648

jsimsmourtada@christianacare.org

Center for Translational Cancer Research, Helen F. Graham Cancer Center,

Newark, DE

2004 - Ph.D. in Biomedical Sciences, Department of Immunology, The University of Texas Graduate School of Biomedical Sciences. Houston, Texas. Doctoral Dissertation: Studies on Gene Expression within Germinal Centers Advisor: Hector Martinez-Valdez, M.D., Ph.D., The University of Texas M.D. Anderson Cancer Center. 1995 - Bachelor of Arts in Psychology. The University of Texas at Austin, Austin, Texas. Post-Doctoral Training 2004-2006: Post-doctoral Fellow, Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Cancer stem cell signatures in hereditary and aggressive breast cancers Approximately 85% of women with germ-line mutations in the BRCA1 gene will eventually develop breast cancer. For these women, the only current preventative measure is bilateral mastectomy or oophorectomy The goal of this project is to find less invasive measures to prevent and treat cancer in this patient population. BRCA1 plays a role in differentiation of mammary stem cells as well as DNA repair. Loss of BRCA1 is thought to result in the accumulation of genetically unstable stem cells, leading to further carcinogenic events and the generation of cancer stem cells (CSC). Intrinsic features of CSC include the capacity for self-renewal, increased resistance to radiation and chemotherapy and the ability to induce tissue vascularization and invasion. These attributes suggest that CSC may be the principal driving force behind tumor growth, metastases and recurrence. Several developmental pathways have been shown to regulate self-renewal and differentiation of mammary stem cells. These pathways, such as Hedgehog, WNT and Notch have been linked to tumorigenesis and are often activated in aggressive tumors. Inhibitors to these pathways are currently under clinical development by several major pharmaceutical companies. This project will identify stem cell pathways that are activated in tumor specimens from patients with BRCA1 mutations and examine the effects of targeted inhibition of these pathways on the growth and survival of breast cancer cell lines harboring BRCA1 mutations. Radiation induced expansion of cancer stem cells Increased activation of the hedgehog pathway has been observed in cancer stem cells. Increased mRNA levels of SHH, Gli and the receptor PTCH-1 have been reported in CD44+CD24-/low/lin- breast cancer cells isolated from human tumors, compared to the bulk of tumor cells. Our group has identified a higher expression of the PTCH receptor on the surface of breast cancer stem-like cells than the total cellular population in several breast cancer cell lines. Additionally, we have shown that breast cancer cells cultured in stem cell promoting conditions secrete higher levels of SHH. Previous studies by our group and others have suggested that there is an increase in cancer stem cells after exposure to radiation and chemotherapy. The goal of this project is to determine if hedgehog signaling contributes to the survival and proliferation of cancer stem cells after radiation treatment and how hedgehog interacts with other stem cell pathways that are activated under these conditions.

1.Smith, D.L., Breeman, WAP, Sims-Mourtada, J. The untapped potential of 68-Gallium-PET: the next wave of 68-gallium agents. Journal of Applied Radiation and Isotopes, 2012, 2012 Oct 29 <a>(12)00537-4</a>. 2. Sims-Mourtada,J. Yang,D., Tworowka, I, Larson, R, Smith, D, Tsao, N, Opdenaker, L., Mourtada, F. Woodward, W. Detection of canonical hedgehog signaling in breast cancer by 131-Iodine-labeled derivatives of the sonic hedgehog protein. Journal of Biomedicine and Biotechnology, 2012, Article ID 639562. 3. Delpassand,E., Samarghandi,,A., Sims Mourtada,J, Zamanian,S ., Espanan,G., Sharif,R., MacKenzie,S., Kosari,K., Barakat, B., Naqvi,S.,Seng,JE., Lowell Anthony,L. Long-term survival and toxicity profile of patients with progressive neuroendocrine tumors following Peptide Receptor Radionuclide Therapy with high activity 111In pentetreotide Theranostics,2012, in press. 4. McKeller MR, Herrera-Rodriquez S, Ma W, Ortiz-Quintero, b, Rangel R, Cande C, Sims-Mourtada, J, Melinikova, V, Kashi C, Phan LM, Chen Z Huang P, Dunner K, Kroemer G,Singh KK, Martinez-Valdez, H. Vital function of PRELI and essential requirement of its LEA motif. Cell Death and Disease, 2010 (1) 113. 5. Delpassand,E.S., Sims-Mourtada, J., Saso, H, Azhdarinia, A; Ashoori, F, Torabi, F., Espenan, G., Moore, W.H, Woltering, E. and Anthony, A. Safety and efficacy of radionuclide therapy with multiple 500 mCi doses of In-111 Pentetreotide in patients with progressive neuroendocrine tumors. Cancer Biotherapy and Radiopharmaceuticals, 2008, 23(3): 292-300. 6. Sims-Mourtada, J., Azhdarinia, A., Yang, D.J.., Mourtada, F. Regulatory Requirements for PET Radiopharmaceuticals Production: Is Automation an Answer? Current Molecular Imaging Reviews: 2008, 4(1): 28-33. 7. Yang, D.Y., Chandra, M., Sims-Mourtada, J., Azhdarinia, A., Oh,C.S., Kim, E. Challenges and Opportunities in Molecular Imaging. Current Molecular Imaging Reviews: 2008 4(1) 46-50 . 8. Izzo, JG., Luthra, R., Sims-Mourtada, J, Chao, KSC, Lee, JH, Wu, TT, Correa, AM, Luthra, M, Aggarwal, B, Hung, MC, Ajani, A. Emerging Molecular Targets in Esophageal Cancer. GastroIntestinal Cancer Research: 2007 1(4) S3-S6. 9. Chen, Y.J., Sims-Mourtada, J., Izzo, J.G., Chao, KSC. Targeting the Hedgehog Pathway to mitigate treatment resistance. Cell Cycle: 2007, 6(15):1826-30. 10. Sims-Mourtada,J., Izzo, J.G., Ajani, J.A., Chao, K.S.C. Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport, Oncogene. 2007 Aug 16;26(38):5674-9. 11. Sims-Mourtada, J, Izzo, J.G., Apisarnthanarax,S., Wu, TT, Malhotra, U, Luthra,R., Liao, Z, Komaki, R., van der Kogel, A., Ajani, J, Chao, K.S.C. Hedgehog: an attribute to tumor regrowth after chemoradiotherapy and a target to improve radiation response. Clinical Cancer Research. 2006. Nov 1;12(21):6565-72. 12. Sims-Mourtada, JC, Guzman-Rojas, L. Rangel, R, McKellar,M, Gordon, J, Popescu, N., Lopez, C., Bruce, S., Wilkinson, M. and Martinez-Valdez, H. The human AKNA gene maps to chromosome 9q32.1, expresses alternatively spliced transcripts and translates into overlapping protein isoforms . DNA Cell Biol. 24(5):325-38, (2005). 13. Rangel, R, McKeller MR, Sims-Mourtada JC, Kashi C, Cain K, Wieder ED, Moldrem, JJ, Phan LV, Ford RJ, Yotnda, P, Guret C., Frances V, Martinez-Valdez H. Assemble of the k PreB receptor requires the Vk- like protein encoded by germline transcripts. J Biol Chem. 280(18):17807-14. (2005). 14. Sims-Mourtada JC, Guzman-Rojas L, Rangel R, Nghiem DX, Ullrich SE, Guret C, Cain K, Martinez-Valdez H. In vivo expression of interleukin-8, and RANTES by human germinal centre B lymphocytes. Immunology. 110(3):296-303 (2003). 15. Guzman-Rojas, L. Sims-Mourtada, JC, Rangel, R and Martinez-Valdez, H. Life and death within germinal centers: a double-edged sword. Immunology. 107:167-175. (2002). 16. Siddiqa, A. Sims-Mourtada, J., Guzman-Rojas, L., Rangel, R., Guret, C., Madrid-Marina, V, Sun, Y. and Martinez-Valdez, H. Regulation of CD40 and CD40 ligand by the AT-hook transcription factor AKNA. Nature 41: 383-387, (2001). Co-first author 17. Guzman-Rojas L, Sims JC, Rangel R, Guret C, Sun Y, Alcocer JM, & Martinez-Valdez H. PRELI, the human homologue of the avian px19, is expressed by germinal center B lymphocytes. Int Immunol.12:607-12.(2000).

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