Cancer Stem Cells, Therapy Resistance and Metastasis; Individualized Cancer Treatments and Functional Ex Vivo Drug Testing.
Dr. Diana Azzam earned her PhD in Biochemistry & Molecular Biology from the University of Miami in 2012. Her research has focused on the identification, functional characterization and targeting of therapy resistant and metastatic cancer stem cells in the most lethal forms of breast and ovarian cancers. Based on her work and publications, she received the 2014 Women in Cancer Research scholar award from the American Association for Cancer Research. During her postdoctoral training at the Center for Therapeutic Innovation, Dr. Azzam implemented a patient-specific ex vivo high-throughput drug screening platform for personalized cancer therapy. This novel iterative functional/genomics approach was a multidisciplinary collaborative project with oncologists that enabled clinical application of individualized treatments for refractory patients with no alternative options. Significantly higher response rates were observed in patients whose treatment was based on drug screening and mutation profiling compared to non-guided therapy. In addition, Dr. Azzam optimized a high-throughput screening approach to identify novel drugs that target therapy-resistant cancer stem cell subsets in a tumor. Her research efforts led to the identification of new cancer stem-cell specific functions of histone methyltransferases (HMT) and histone deacetylases (HDAC) in breast and ovarian cancer.
Dr. Azzam joined the Department of Environmental Health Sciences at the Florida International University in April 2018. She is a grant recipient of the Florida Department of Health first-ever Live Like Bella Pediatric Cancer Research Initiative (http://www.floridahealth.gov/newsroom/2018/03/030818-live-like-bella-2018.html) that funds an ongoing multi-center clinical trial, in collaboration with Nicklaus Children’s hospital, on individualized treatments in children with advanced cancers. The study enrolls children with relapsed and/or refractory leukemias and solid tumors to implement ex vivo drug sensitivity in combination with genomic profiling to guide clinical decision making and provide novel therapeutic options for children (https://conta.cc/2oGjblc).
The Azzam lab investigates metastatic and therapy-resistant cancer stem cells and how they result from chronic environmental exposures, such as heavy metals. In addition, a major focus of the lab is to continue to clinically validate and implement functional ex vivo high-throughput drug testing in patients with advanced cancers and no alternative options.
- PhD, 2007-2012, University of Miami, Biochemistry & Molecular Biology
- MS, 2003-2006, American University of Beirut, Lebanon. (Biochemistry)
- BS, 2000-2003, Lebanese University, Lebanon. (Chemistry)
For complete list of published work: https://scholar.google.com/citations?hl=en&user=v42J5dMAAAAJ&view_op=list_works&sortby=pubdate
Selected List of Publications:
- Loth M., Guariglia S., Re D., Perez J., Nunez De Paiva V., Dziedzic J., Chambers J., Azzam DJ and Guilarte TR. A Novel Interaction of Translocator Protein 18 kDa (TSPO) with NADPH Oxidase in Microglia. Mol Neurobiol. Aug 2. Online ahead of print (2020)
- Lohse I.*, Azzam DJ.*, Al-Ali H., Volmar CH., Brothers SP., Ince TA., Wahlestedt C. Ovarian Cancer Treatment Stratification Using Ex Vivo Drug Sensitivity Testing. Anticancer Res. Aug;39(8):4023-4030 (2019) *Co-first authors; equal contributions to paper
- Simpkins F., Jang K., Yoon H., Hew K., Kim M., Azzam DJ., Sun J., Zhao D., Ince T., Lui W., Guo W., Wei Z., Zhang., Mills G., Slingerland JM. Dual Src and MEK inhibition decreases ovarian cancer growth and targets tumor initiating stem-like cells. Cli Can Res. Oct 1;24(19):4874-4886 (2018).
- Swords R.*, Azzam D.*, Al-Ali H.*, Ines L.*, Volmar CH. , Watts J., Perez A., Rodriguez A., Vargas F., Elias R., Zelent A., Abassi T., Rangwala S., Deutsch Y., Drusbosky L., Cogle C., and Wahlestedt C. Ex-vivo Sensitivity Profiling to Guide Clinical Decision Making in Acute Myeloid Leukemia. Leuk Res. Nov 11;64:34-41 (2017). *Co-first authors; equal contributions to paper
- Ariazi E., Taylor J., Black M., Nicolas E., Slifker M., Azzam D. and Boyd J. A New Role for ERα: Silencing via DNA methylation of Basal, Stem Cell, and EMT Genes. Mol Cancer Res. 15(2):152-164 (2017).
- Witt A., Lee C., Lee T., Azzam DJ., Grosso J., Cohick E., Wang B., Gropper A., Merritt M., Petrocca F., Richardson A., Young R., Wahlestedt C. and Ince TA., Identification of a Cancer Stem Cell-Specific Function for the Histone Deacetylases in Breast and Ovarian Cancer. Oncogene, Mar 23;36(12):1707-1720 (2017).
- Picon-Ruiz M., Pan C., Drews-Elger K., Jang K., Besser AH., Zhao D., Morata-Tarifa C., Kim M., Ince TA., Azzam DJ., Wander SA., Wang B., Ergonul B., Datar RH., Cote RJ., Howard GA., El-Ashry D., Torné-Poyatos P., Marchal JA., Slingerland JM., Interactions between Adipocytes and Breast Cancer Cells Stimulate Cytokine Production and Drive Src/Sox2/miR-302b-Mediated Malignant Progression. Cancer Res, 76 (2):491-504 (2016).
- Zhao D., Pan C., Sun J., Gilbert C., Drews-Elger K., Azzam DJ., Picon-Ruiz M., Kim M.,Ullmer W., El-Ashry D., Creighton CJ. and Slingerland JM. VEGF drives cancer-initiating stem cells through VEGFR-2/Stat3 signaling to upregulate Myc and Sox2. Oncogene, 11;34(24):3107-19 (2015).
- Azzam DJ., Volmar CH., Al-Ali H., Perez A., Watts J., Vargas F., Elias R., Rodriguez A., Zelent A., Cogle C., Swords R. and Wahlestedt C. A Patient-Specific Ex Vivo Screening Platform for Personalized Acute Myeloid Leukemia (AML) Therapy. Blood, 126 (23): 1352 (2015).
- Boelens M, Wu T, Nabet B, Xu B, Qui Y, Yoon T, Azzam DJ, Twyman-Saint Victor C, Wiemann B, Ishwaran H, Brugge P, Jonkers J, Slingerland J and Minn A. Exosome Transfer from Stromal to Breast Cancer Cells Regulates Therapy Resistance Pathways. Cell, 159 (3), 499-513 (2014).
- Elger KD, Brinkman J, Miiler P, Shah S, Harrell J, Da Silva T, Ao Z, Schlater A, Azzam D, Diehl K, Thomas D, Slingerland JM, Perou C, Lippmann M, El-Ashry D. Primary breast tumor-derived cellular models: characterization of tumorigenic, metastatic, and cancer-associated fibroblasts in dissociated tumor (DT) cultures. Breast Cancer Res Treat. 144 (3):503-17 (2014).
- Azzam, D. J., Zhao, D., Sun, J., Minn, A. J., Ranganathan, P., Drews-Elger, K., Han, X., Picon-Ruiz, M., Gilbert, C. A., Wander, S. A., Capobianco, A. J., El-Ashry, D. and Slingerland, J. Triple negative breast cancer initiating cell subsets differ in functional and molecular characteristics and in γ-secretase inhibitor drug responses. EMBO Mol Med. 5: 1502–1522 (2013).
- Simpkins F, Paez P, Sun J, Ullmer W, Gilbert C, Da Silva T, Pedram A, Levin E, Reis I, Rabinovich B, Azzam D, Xu X, Ince TA, Yang J, Verhak R, Lu Y, Mills G, Slingerland JM. Src inhibition with Saracatinib reverses fulvestrant resistance in ER-positive ovarian cancer models in vitro and in vivo, Clin Cancer Res. 1;18(21):5911-23 (2012).
- Chen Y, Alvarez EA, Azzam D, Wander, SA, Guggisberg N, Jorda M, Ju Z, Hennessy BT, Slingerland JM. Combined Src and ER blockade impairs human breast cancer proliferation in vitro and in vivo without increasing tumor-initiating cells. Breast Cancer Res Treat. 128(1):69-78 (2011).
- Azzam DJ, Usta JA, Mouneinme Y, El Hokayem JA, Mikati MA. High-performance liquid chromatographic method for quantifying sphingomyelin in rat brain. J Chromatogr B Analyt Technol Biomed Life Sci, 1; 859(1):131-6 (2007).