NON-COMMUNICABLE DISEASES / Cancer
Regulation of gene expression by transcription factors, role of receptor tyrosine kinases in cancer malignancies, aberrant gene expression in carcinogenesis, alterations in signal transduction pathways and gene translocations.
Description of Research
The overall goals of the Group are to utilize genomics and proteomics tools and signal transduction resources to accelerate comparative analysis of aberrant gene expression in carcinogenesis and to study alterations in signal transduction pathways during development of cancers.
Cancer Cell Survival and Apoptosis
We recently identified the two members of the GADD45 family as key players in apoptosis induction of cancer cells and inhibition of tumor formation. We demonstrated that GADD45α and GADD45γ repression plays an unambiguous and universal role in the ability of tumors to escape programmed cell death. Analysis of in vivo interacting proteins using a mass spectrometry approach identified the cdk11 p58 and a DCND1 (defective in cullin neddylation 1) as partners of the GADD45 family members.
Transcription factors and cancer
A number of transcription factors are overactive in most human cancer cells, making these good targets for the development of anticancer drugs. The epithelium-specific Ets transcription factor, PDEF, plays a role in prostate and breast cancer, although its precise function has not been established. Our studies also focus on determining the biological relevance of PDEF in prostate cancer. Current efforts are focused on understanding how the PDEF transcription factor is regulated and, more importantly, degraded.
The Role of tyrosine kinase receptors in cancer development
Our Group also focused on identification of potential therapeutic targets that are upregulated in cancer with particular emphasis on cell surface receptors. We identified several tyrosine kinase receptors whose expression was specifically increased in cancer when compared to control or other subtypes. AXL is most consistently upregulated tyrosine kinase receptor in several cancer types. Our hypothesis is that targeting the AXL tyrosine kinase will inhibit cancer growth and thus lead to a novel therapeutic entry point for cancer.
Genetics of Prostate Cancer in African men
Researchers have been investigating factors that govern the aggressive prostate cancer phenotype which is commonly found in black populations. Considering the low socioeconomic status of most African patients, a novel non-invasive and affordable marker specifically tailored towards early diagnosis and treatment monitoring is most desirable. We will perform large scale genomics and proteomics research in order to identify genes and biomarkers involved in the development of aggressive stage of the disease that is more prevalent in men with African descent.
Semreen MH, Alniss H, El-Awady R, Cacciatore S, Mousa M, Almehdi AH, El-Huneidi W, Zerbini LF, Soares NC. GC-MS based comparative metabolomic analysis of MCF7 and MDA-MB-231 cancer cells treated with Tamoxifen and/or Paclitaxel. Journal of Proteomics. In Press. 2020
Temilola DO, Wuim M , Coulidiati TH, Adeola HA, Carbone GM, Catapano CV andZerbini LF.The Prospect and Challenges to the Flow of Liquid Biopsy in Africa. Cells 8:862. 2019
Paccez JP, Duncan K, Sekar D, Correa RG, Wang Y, Gu X, Bhasin M, Chibale K, Libermann TL, Zerbini LF. Dihydroartemisinin inhibits prostate cancer via JARID2/miR-7/miR-34a-dependent downregulation of Axl. Oncogenesis8:14. 2019
Omar R, Cooper A, Maranyane HM, Zerbini LF, Prince S. The T-box transcription factor TBX3 activates expression of COL1A2 to impact migration of fibrosarcoma and chondrosarcoma cells. Cancer Letters 459:227-239 2019
Colizzi V, Daniele Mezzana D, Ovseiko PV, Caiati G, Colonnello C, Declich A, Montesano C, Edmunds L, Buzan E, Djilianov D, Zerbini LF, Schmidt EK, Bielawski KP, Elster D, Salvato1 M, Alcantara LC, Minutolo A, Potesta M, Moyankova D, Rusanov K, Wium M, Raszczyk I, Gwizdala JP, Konieczny I, Sledzik K, Barendziak T, Birkholz J, Muller N, Warrelmann J, Meyer U, Filser J, Barreto FK, Milano MJ; Henderson LR, Kiparoglou V, Friesen P, Sheehan M, Bachiddu E, Buchan AM. Structural Transformation to Attain Responsible BIOSciences (STARBIOS2): Protocol for a Horizon 2020 funded European multi-centre project to promote Responsible Research and Innovation (RRI), a learning process on RRI-oriented structural change, and an RRI model for biosciences. JMIR Research Protocols Vol 8 No 3. 2019
Wium M; PaccezJD; Zerbini LF. The dual role of TAM receptors in autoimmune diseases and cancer: an overview. Cells 7: pii: E166. 2018