B.S., Biochemistry and Molecular Biology, Gettysburg College (Graduated May of 2009)
Master’s Program in Biochemistry (Graduating January of 2015)
Dr. Lindsay Farrer Lab
Chen Khuan Wong
B.S. Biotechnology, Indiana University Bloomington (2012)
Graduate Program in Genetics and Genomics, BUSM (2012-Present)
Dr. Sam Thiagalingam Lab
Dissecting the Smad4 Metastasis Suppressor Complex to Identify Novel Therapeutic Targets & Prognostic Markers in Colon Cancer
Despite early detection through routine screening with colonoscopy, colon cancer remains the second leading cause of cancer mortality in men and women combined in the United States, mostly attributed to metastasis. Hence, it is essential to elucidate the molecular mechanisms underlying metastasis, identify novel druggable targets, and develop prognostic markers that can predict disease progression and stratify patients for therapy based on these markers. In advanced colon cancer, there is frequent loss of heterozygosity (LOH) at chromosome 18q21; interestingly, SMAD4, a tumor suppressor that plays a central role in the canonical TGF-beta anti-growth signaling pathway, is localized to this region. Previously, we have shown that SMAD4 can inhibit hypoxia-inducible factor 1 alpha (HIF1-alpha) to suppress various malignant phenotypes, whereas inactivation of SMAD4 in colon cancer enhances cell migration, increases the expression of VEGF, GLUT1, and MMP9, and promotes resistance to 5’-fluorouracil. Based on this study, we hypothesized that SMAD4 interacts with transcription factors and cofactors to form a complex that negatively regulates metastasis. We have generated Flag- and HA-tagged SMAD4 proteins and plan to identify co-immunoprecipitated proteins using mass spectrometry. The functional roles of these proteins in regulating metastasis will be characterized in experimental models of cancer progression and their contribution to human colon cancer assessed through in silico analysis of gene expression profiles and examination of clinical specimens at different stages of disease progression. We suggest that the genes corresponding to the proteins in this complex may be potentially useful in predicting disease progression, and the gene products may eventually serve as therapeutic targets to treat metastatic colon cancer.
Wong CK, Lambert AW, Ozturk S, Papageorgis P, Abdolmaleky HM, and Thiagalingam S. 2014. Dissecting the Smad4 metastasis suppressor complex to identify novel therapeutic targets and prognostic markers in colon cancer. The 20th Annual Henry I Russek Student Achievement Day, Boston University School of Medicine.
Wong CK, Lambert AW, Ozturk S, Papageorgis P, Abdolmaleky HM, and Thiagalingam S. 2013. Dissecting the Smad4 metastasis suppressor complex to identify novel therapeutic targets and prognostic markers in colon cancer. Genome Science Institute Fifth Annual Research Symposium, Boston University School of Medicine.