Bio

Professional Education


  • Bachelor of Science, Hong Kong University Of Science & Technology (2009)
  • Doctor of Philosophy, Purdue University (2014)

Stanford Advisors


Publications

All Publications


  • SIRT6: Novel Mechanisms and Links to Aging and Disease. Trends in endocrinology and metabolism Tasselli, L., Zheng, W., Chua, K. F. 2017; 28 (3): 168-185

    Abstract

    SIRT6, a member of the Sirtuin family of NAD(+)-dependent enzymes, has established roles in chromatin signaling and genome maintenance. Through these functions, SIRT6 protects against aging-associated pathologies including metabolic disease and cancer, and can promote longevity in mice. Research from the past few years revealed that SIRT6 is a complex enzyme with multiple substrates and catalytic activities, and uncovered novel SIRT6 functions in the maintenance of organismal health span. Here, we review these new discoveries and models of SIRT6 biology in four areas: heterochromatin stabilization and silencing; stem cell biology; cancer initiation and progression; and regulation of metabolic homeostasis. We discuss the possible implications of these findings for therapeutic interventions in aging and aging-related disease processes.

    View details for DOI 10.1016/j.tem.2016.10.002

    View details for PubMedID 27836583

    View details for PubMedCentralID PMC5326594

  • SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence NATURE STRUCTURAL & MOLECULAR BIOLOGY Tasselli, L., Xi, Y., Zheng, W., Tennen, R. I., Odrowaz, Z., Simeoni, F., Li, W., Chua, K. F. 2016; 23 (5): 434-440

    Abstract

    Pericentric heterochromatin silencing at mammalian centromeres is essential for mitotic fidelity and genomic stability. Defective pericentric silencing has been observed in senescent cells, aging tissues, and mammalian tumors, but the underlying mechanisms and functional consequences of these defects are unclear. Here, we uncover an essential role of the human SIRT6 enzyme in pericentric transcriptional silencing, and we show that this function protects against mitotic defects, genomic instability, and cellular senescence. At pericentric heterochromatin, SIRT6 promotes deacetylation of a new substrate, residue K18 of histone H3 (H3K18), and inactivation of SIRT6 in cells leads to H3K18 hyperacetylation and aberrant accumulation of pericentric transcripts. Strikingly, depletion of these transcripts through RNA interference rescues the mitotic and senescence phenotypes of SIRT6-deficient cells. Together, our findings reveal a new function for SIRT6 and regulation of acetylated H3K18 at heterochromatin, and demonstrate the pathogenic role of deregulated pericentric transcription in aging- and cancer-related cellular dysfunction.

    View details for DOI 10.1038/nsmb.3202

    View details for Web of Science ID 000375633100015

    View details for PubMedID 27043296

  • Altered Glucose Metabolism in Harvey-ras Transformed MCF10A Cells MOLECULAR CARCINOGENESIS Zheng, W., Tayyari, F., Gowda, G. A., Raftery, D., McLamore, E. S., Porterfield, D. M., Donkin, S. S., Bequette, B., Teegarden, D. 2015; 54 (2): 111-120

    Abstract

    Metabolic reprogramming that alters the utilization of glucose including the "Warburg effect" is critical in the development of a tumorigenic phenotype. However, the effects of the Harvey-ras (H-ras) oncogene on cellular energy metabolism during mammary carcinogenesis are not known. The purpose of this study was to determine the effect of H-ras transformation on glucose metabolism using the untransformed MCF10A and H-ras oncogene transfected (MCF10A-ras) human breast epithelial cells, a model for early breast cancer progression. We measured the metabolite fluxes at the cell membrane by a selective micro-biosensor, [(13)C6 ]glucose flux by (13)C-mass isotopomer distribution analysis of media metabolites, intracellular metabolite levels by NMR, and gene expression of glucose metabolism enzymes by quantitative PCR. Results from these studies indicated that MCF10A-ras cells exhibited enhanced glycolytic activity and lactate production, decreased glucose flux through the tricarboxylic acid (TCA) cycle, as well as an increase in the utilization of glucose in the pentose phosphate pathway (PPP). These results provide evidence for a role of H-ras oncogene in the metabolic reprogramming of MCF10A cells during early mammary carcinogenesis.

    View details for DOI 10.1002/mc.22079

    View details for Web of Science ID 000347279800004

    View details for PubMedID 24000146

  • Maternal exercise during pregnancy reduces risk of mammary tumorigenesis in rat offspring EUROPEAN JOURNAL OF CANCER PREVENTION Camarillo, I. G., Clah, L., Zheng, W., Zhou, X., Larrick, B., Blaize, N., Breslin, E., Patel, N., Johnson, D., Teegarden, D., Donkin, S. S., Gavin, T. P., Newcomer, S. 2014; 23 (6): 502-505

    Abstract

    Breast cancer is the most common cancer among women. Emerging research indicates that modifying lifestyle factors during pregnancy may convey long-term health benefits to offspring. This study was designed to determine whether maternal exercise during pregnancy leads to reduced mammary tumorigenesis in female offspring. Pregnant rats were randomly assigned to exercised and sedentary groups, with the exercised group having free access to a running wheel and the sedentary group housed with a locked wheel during pregnancy. Female pups from exercised or sedentary dams were weaned at 21 days of age and fed a high fat diet without access to a running wheel. At 6 weeks, all pups were injected with the carcinogen N-methyl-N-nitrosourea. Mammary tumor development in all pups was monitored for 15 weeks. Pups from exercised dams had a substantially lower tumor incidence (42.9%) compared with pups from sedentary dams (100%). Neither tumor latency nor histological grade differed between the two groups. These data are the first to demonstrate that exercise during pregnancy potentiates reduced tumorigenesis in offspring. This study provides an important foundation towards developing more effective modes of behavior modification for cancer prevention.

    View details for DOI 10.1097/CEJ.0000000000000029

    View details for Web of Science ID 000342896600002

    View details for PubMedID 24950432

  • 1,25-Dihydroxyvitamin D regulation of glucose metabolism in Harvey-ras transformed MCF10A human breast epithelial cells JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY Zheng, W., Tayyari, F., Gowda, G. A., Raftery, D., McLamore, E. S., Shi, J., Porterfield, D. M., Donkin, S. S., Bequette, B., Teegarden, D. 2013; 138: 79-89
  • 1 alpha, 25-Dihydroxyvitamin D regulates hypoxia-inducible factor-1 alpha in untransformed and Harvey-ras transfected breast epithelial cells CANCER LETTERS Jiang, Y., Zheng, W., Teegarden, D. 2010; 298 (2): 159-166

    Abstract

    The purpose of this study was to determine the mechanism by which 1?, 25-dihydroxyvitamin D (1,25(OH)(2)D) alters hypoxia-inducible factor-1? (HIF-1?) protein in untransformed and Harvey-ras (H-ras) oncogene transfected MCF10A breast epithelial cells. Treatment with 1,25(OH)(2)D (10nM) increased both mRNA (2.550.6-fold vs. vehicle, p=0.03) and protein levels (2.370.3-fold vs. vehicle, p<0.0001) of HIF-1? in MCF10A cells in 12h, which remained elevated at 24h. However, in H-ras transfected MCF10A cells, 1,25(OH)(2)D treatment increased HIF-1? protein level (2.080.38-fold vs. vehicle, p=0.05) at 12h, with no change in mRNA level and HIF-1? protein level returned to baseline after 24h. A transcription inhibitor prevented the 1,25(OH)(2)D induction of HIF-1? protein and mRNA levels in MCF10A cells, but failed to alter the induction of HIF-1? protein level in H-ras transfected MCF10A cells. On the other hand, inhibition of proteasomal degradation prevented the 1,25(OH)(2)D-induced HIF-1? protein level in H-ras transfected MCF10A but not in MCF10A cells. These results support that 1,25(OH)(2)D regulates HIF-1? protein level via transcriptional regulation in MCF10A cells in contrast to through proteosomal degradation with the presence of H-ras oncogene in MCF10A cells.

    View details for DOI 10.1016/j.canlet.2010.06.014

    View details for Web of Science ID 000284300000003

    View details for PubMedID 20655141

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