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.
Tamura R.E., Paccez J.D., Duncan K.C., Morale M.G., Simabuco F., Dillon S., Correa R.G., Gu X., Libermann T.A., Zerbini L.F. 2016. GADD45α and g interaction with CDK11p58 regulates SPDEF protein stability and SPDEF-mediated effects on cancer cell migration. In Press. Oncotarget.
Adeola H.A., Smith M., Kaestner L., Blackburn J.M., Zerbini L.F. 2016. Novel potential serological prostate cancer biomarkers using CT100+ cancer antigen microarray platform in a multi-cultural South African cohort. In Press. Oncotarget.
Adeola H.A., Calder B., Soares N.C., Kaestner L., Blackburn J.M., Zerbini LF. 2016. In-Silico Verification and PRM Prevalidation of Potential Prostate Cancer Biomarkers.Future Oncology. 12:43-57.
Paccez J.D., Duncan K., Correa R.G., Parker M.I. and Zerbini L.F. 2015. Inactivation of GSK3β and activation of NF-κB pathway via Axl represents an important mediator of tumorigenesis in Esophageal Squamous Cell Carcinoma. Molecular Biology of the Cell. 1:821-31.
Adeola H.A., Soares N.C., Paccez P.D., Kaestner L., Blackburn J.M., Zerbini L.F. 2015. Discovery of novel candidate urinary protein biomarkers for prostate cancer in a multi-ethnic cohort of South African patients via label-free mass spectrometry. Proteomics Clinical Applications. 9:597-609.
Vasconcellos JF, Laranjeira A.A, Leal P.C, Bhasin M.K, Zenatti P.P, Nunes R.J, Yunes R.A, Nowill A.E, Libermann TL, Zerbini L.F, Yunes J.A.2 015. SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1. Plos One. 10:e0134783.