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.
Postdoctoral Associate, Biomedical Genetics, BUSM
2010-2014, Ph.D., Tufts University, USA
2008-2010, Master of Science, Tufts University, USA
2005-2008, Master of Medicine, Fudan University, China
2000-2005, MD., Fudan University, China
I have research experience in the fields of gene-by-environment interactions, epigenetics, genetic epidemiology, nutritional genetics & genomics, biostatistics/statistics, and public health. I have particular research interest in the interactions between genetics, epigenetics, and environmental factors. I have found that epigenetics, especially DNA methylation, is regulated by the haplotypes of genetic variants on a genome-wide scale. My researches further suggested that DNA methylation contribute partially to the observed gene-by-environment interactions. For example, at the APOE locus, I found that one promoter single nucleotide polymorphism (SNP) interacted with the age to modulate APOE methylation. Also, I have shown that the DNA methylation mechanism may, in part, explain the observed interactions between omega-3 polyunsaturated fatty acids and genetic variants to modulate blood lipids and inflammation markers.
I do believe that most diseases are contributed by both genetics and epigenetics. Genetics determines whether an individual is susceptible to the disease while epigenetics controls when and how the individual will develop the disease. Currently, I am testing this hypothesis in Alzheimer disease (AD), one of the major diseases showing extremely intimate relationships with both genetics and epigenetics.
- 1. Ma Y., Tucker KL., Smith CE., Lee YC., Huang T., Richardson K., Parnell LD., Lai CQ., Young KL., Justice AE., Shao Y., North KE., Ordovas JM. Lipoprotein lipase variants interact with polyunsaturated fatty acids for obesity traits in women: replication in two populations. Nutrition, Metabolism & Cardiovascular Disease., 2014, PubMed PMID: 25156894.
- 2. Ma Y., Smith CE., Lai CQ., Irvin MR., Parnell LD., Lee YC., Pham L., Aslibekyan S., Claas SA., Tsai M., Borecki IB., Kabagambe EK., Berciano S., Ordovas JM. and Absher D. and Arnett DK. Genetic variants modulate the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study. Aging Cell, 2014. PubMed PMID: 25476875.
- 3. Ma Y., Guo H. Determination of deoxynivalenol in grains and beans by capillary gas chromatography. Chinese J. Health Lab. Tech., May. 2007; 5(17): 789-790.
- 4. Ma Y., Guo H. Mini-review of studies on the carcinogenicity of deoxynivalenol. Environ. Toxicol. Pharmacol. 2008 Jan. PubMed PMID: 21783829.
- 5. Zheng JS, Arnett DK, Parnell LD, Lee YC, Ma Y, Smith CE, Richardson K, Li D, Borecki IB, Ordovas JM, Tucker KL, Lai CQ. Genetic Variants at PSMD3 Interact with Dietary Fat and Carbohydrate to Modulate Insulin Resistance. J. Nutr. 2013 Jan. PubMed PMID: 23303871.
- 6. Zheng JS, Arnett DK, Parnell LD, Lee YC, Ma Y, Smith CE, Richardson K, Li D, Borecki IB, Tucker KL, Ordovas JM, Lai CQ. Polyunsaturated fatty acids modulate the association between PIK3CA-KCNMB3 genetic variants and insulin resistance. Plos One, 2013 Jun. PubMed PMID: 23826284.
- 7. Parnell LD, Blokker BA, Dashti HS, Nesbeth PD, Cooper BE, Ma Y, Lee YC, Hou R, Lai CQ, Richardson K, Ordovas JM, CardioG×E, a catalog of gene-environment interactions for cardiometabolic traits. BioData Mining, 2014. PubMed PMID: 25368670.
- 8. Smith CE, Follis JL, Nettleton JA, Foy M, Wu JHY, Ma Y, et al., Dietary fatty acids interactions with genetic variants for plasma and erythrocyte fatty acids: meta-analysis of 9 studies in the CHARGE consortium. 2014. Molecular Nutrition and Food Research. 2015 Jan. PubMed PMID: 25626431.
- 1. Ma Y., Smith CE., Lee YC., Parnell LD., Lai CQ., Ordovas JM. Haplotypes of CpG-related SNPs and associations with DNA methylation patterns. Book: Genome-Wide Association Studies: From Polymorphism to Personalized Medicine, Chapter 27., 2015. Cambridge University Press.
- 2. Lai CQ., Ma Y., Parnell LD., Genetics and gene-environment interactions on longevity and lifespan. Book: Gene-Environment Interactions and its Role in Human Health and Disease, 2015. Nova Science Publishers.