Nam Yong Lee

Interests

No activities entered.

Courses

Scholarly Contributions

Journals/Publications

• Ahmed, T., Cruz-Flores, P., Pan, C. C., Ortiz, H. R., Lee, Y. S., Langlais, P. R., Mythreye, K., & Lee, N. Y. (2022). EPDR1 is a noncanonical effector of insulin-mediated angiogenesis regulated by an endothelial-specific TGF-β receptor complex.. Journal of Biological Chemistry.
• Kwak, E. A., Pan, C. C., Ramonett, A., Kumar, S., Cruz-Flores, P., Ahmed, T., Ortiz, H. R., Lochhead, J. L., Ellis, N., Mouneimne, G., Lee, Y. S., Vanderah, T. W., Milnes, T. M., Mohler, P. J., Hund, T. J., Langlais, P. R., Mythreye, K., & Lee, N. Y. (2022). BIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling. Nature Communications.
• Lee, N. Y., Mythreye, K., Langlais, P. R., Hund, T. J., Mohler, P. J., Milnes, T. M., Vanderah, T. W., Lee, Y. S., Mouneimne, G., Ellis, N., Lochhead, J. L., Ortiz, H. R., Ahmed, T., Cruz-Flores, P., Kumar, S., Ramonett, A., Pan, C. C., & Kwak, E. A. (2021). BIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling. Nature Communications.
• Lee, N. Y., Mythreye, K., Langlais, P. R., Kashatus, D. F., Milnes, T. M., Vanderah, T. W., Lee, Y. S., Ortiz, H. R., Flores, P. C., Ahmed, T., Kwak, E. A., & Ramonett, A. (2022). Regulation of mitochondrial fission by GIPC-mediated Drp1 retrograde transport. Molecular biology of the cell, 33(1), ar4.
  More info

  Dynamin-related protein 1 (Drp1) is a key regulator of mitochondrial fission, a large cytoplasmic GTPase recruited to the mitochondrial surface via transmembrane adaptors to initiate scission. While Brownian motion likely accounts for the local interactions between Drp1 and the mitochondrial adaptors, how this essential enzyme is targeted from more distal regions like the cell periphery remains unknown. Based on proteomic interactome screening and cell-based studies, we report that GAIP/RGS19-interacting protein (GIPC) mediates the actin-based retrograde transport of Drp1 toward the perinuclear mitochondria to enhance fission. Drp1 interacts with GIPC through its atypical C-terminal PDZ-binding motif. Loss of this interaction abrogates Drp1 retrograde transport resulting in cytoplasmic mislocalization and reduced fission despite retaining normal intrinsic GTPase activity. Functionally, we demonstrate that GIPC potentiates the Drp1-driven proliferative and migratory capacity in cancer cells. Together, these findings establish a direct molecular link between altered GIPC expression and Drp1 function in cancer progression and metabolic disorders.
• Long, V. P., Bonilla, I. M., Baine, S., Glynn, P., Kumar, S., Schober, K., Mowrey, K., Weiss, R., Lee, N. Y., Mohler, P. J., Györke, S., Hund, T. J., Fedorov, V. V., & Carnes, C. A. (2020). Chronic heart failure increases negative chronotropic effects of adenosine in canine sinoatrial cells via A1R stimulation and GIRK-mediated I. Life sciences, 240, 117068.
  More info

  Bradycardia contributes to tachy-brady arrhythmias or sinus arrest during heart failure (HF). Sinoatrial node (SAN) adenosine A1 receptors (ADO A1Rs) are upregulated in HF, and adenosine is known to exert negative chronotropic effects on the SAN. Here, we investigated the role of A1R signaling at physiologically relevant ADO concentrations on HF SAN pacemaker cells.
• Kim, Y. S., Gupta Vallur, P., Jones, V. M., Worley, B. L., Shimko, S., Shin, D. H., Crawford, L. C., Chen, C. W., Aird, K. M., Abraham, T., Shepherd, T. G., Warrick, J. I., Lee, N. Y., Phaeton, R., Mythreye, K., & Hempel, N. (2019). Context-dependent activation of SIRT3 is necessary for anchorage-independent survival and metastasis of ovarian cancer cells. Oncogene.
  More info

  Tumor cells must alter their antioxidant capacity for maximal metastatic potential. Yet the antioxidant adaptations required for ovarian cancer transcoelomic metastasis, which is the passive dissemination of cells in the peritoneal cavity, remain largely unexplored. Somewhat contradicting the need for oxidant scavenging are previous observations that expression of SIRT3, a nutrient stress sensor and regulator of mitochondrial antioxidant defenses, is often suppressed in many primary tumors. We have discovered that this mitochondrial deacetylase is specifically upregulated in a context-dependent manner in cancer cells. SIRT3 activity and expression transiently increased following ovarian cancer cell detachment and in tumor cells derived from malignant ascites of high-grade serous adenocarcinoma patients. Mechanistically, SIRT3 prevents mitochondrial superoxide surges in detached cells by regulating the manganese superoxide dismutase (SOD2). This mitochondrial stress response is under dual regulation by SIRT3. SIRT3 rapidly increases SOD2 activity as an early adaptation to cellular detachment, which is followed by SIRT3-dependent increases in SOD2 mRNA during sustained anchorage-independence. In addition, SIRT3 inhibits glycolytic capacity in anchorage-independent cells thereby contributing to metabolic changes in response to detachment. While manipulation of SIRT3 expression has few deleterious effects on cancer cells in attached conditions, SIRT3 upregulation and SIRT3-mediated oxidant scavenging are required for anoikis resistance in vitro following matrix detachment, and both SIRT3 and SOD2 are necessary for colonization of the peritoneal cavity in vivo. Our results highlight the novel context-specific, pro-metastatic role of SIRT3 in ovarian cancer.
• Mukhopadhyay, H., & Lee, N. Y. (2019). Multifaceted roles of TAK1 signaling in cancer. Oncogene.
  More info

  Context-specific signaling is a prevalent theme in cancer biology wherein individual molecules and pathways can have multiple or even opposite effects depending on the tumor type. TAK1 represents a particularly notable example of such signaling diversity in cancer progression. Originally discovered as a TGF-β-activated kinase, over the years it has been shown to respond to numerous other stimuli to phosphorylate a wide range of downstream targets and elicit distinct cellular responses across cell and tissue types. Here we present a comprehensive review of TAK1 signaling and provide important therapeutic perspectives related to its function in different cancers.
• Parker, S. S., Krantz, J., Kwak, E. A., Barker, N. K., Deer, C. G., Lee, N. Y., Mouneimne, G., & Langlais, P. R. (2019). Insulin Induces Microtubule Stabilization and Regulates the Microtubule Plus-end Tracking Protein Network in Adipocytes. Molecular & cellular proteomics : MCP, 18(7), 1363-1381.
  More info

  Insulin-stimulated glucose uptake is known to involve microtubules, although the function of microtubules and the microtubule-regulating proteins involved in insulin action are poorly understood. CLASP2, a plus-end tracking microtubule-associated protein (+TIP) that controls microtubule dynamics, was recently implicated as the first +TIP associated with insulin-regulated glucose uptake. Here, using protein-specific targeted quantitative phosphoproteomics within 3T3-L1 adipocytes, we discovered that insulin regulates phosphorylation of the CLASP2 network members G2L1, MARK2, CLIP2, AGAP3, and CKAP5 as well as EB1, revealing the existence of a previously unknown microtubule-associated protein system that responds to insulin. To further investigate, G2L1 interactome studies within 3T3-L1 adipocytes revealed that G2L1 coimmunoprecipitates CLASP2 and CLIP2 as well as the master integrators of +TIP assembly, the end binding (EB) proteins. Live-cell total internal reflection fluorescence microscopy in adipocytes revealed G2L1 and CLASP2 colocalize on microtubule plus-ends. We found that although insulin increases the number of CLASP2-containing plus-ends, insulin treatment simultaneously decreases CLASP2-containing plus-end velocity. In addition, we discovered that insulin stimulates redistribution of CLASP2 and G2L1 from exclusive plus-end tracking to "trailing" behind the growing tip of the microtubule. Insulin treatment increases α-tubulin Lysine 40 acetylation, a mechanism that was observed to be regulated by a counterbalance between GSK3 and mTOR, and led to microtubule stabilization. Our studies introduce insulin-stimulated microtubule stabilization and plus-end trailing of +TIPs as new modes of insulin action and reveal the likelihood that a network of microtubule-associated proteins synergize to coordinate insulin-regulated microtubule dynamics.
• Kwak, E. A., & Lee, N. Y. (2018). Synergetic roles of TGF-β signaling in tissue engineering. Cytokine, 115, 60-63.
  More info

  Recent advances in tissue engineering highlight biomaterial designs with context-specific growth factors, cytokines and various small molecules to better mimic the natural extracellular matrix (ECM) microenvironments. These efforts have led to direct improvements in cell-cell and cell-ECM interactions while mitigating undesirable cellular and immunogenic responses. In this short review, we focus on the crucial roles and regulation of transforming growth factor β (TGF-β) signaling in biomaterial applications during tissue repair and regeneration.
• Lee, N. Y. (2018). GPx3 supports ovarian cancer progression by manipulating the extracellular redox environment. Redox Biology.
• Lee, N. Y. (2018). Mediator of kinase CDK8/CDK19 drives YAP1 dependent BMP4 induced EMT in cancer. Oncogene.
• Lee, N. Y. (2018). Regulation of Microtubule Acetylation and Intracellular Transport by TGF-beta Activated Kinase 1 (TAK1). Nature Communications.
• Lee, N. Y. (2018). Tumor-derived Inhibin is a new paracrine factor of angiogenesis. Cancer Research.
• Pan, C. C., Shah, N., Kumar, S., Wheeler, S. E., Cinti, J., Hoyt, D. G., Beattie, C. E., An, M., Mythreye, K., Rakotondraibe, L. H., & Lee, N. Y. (2017). Angiostatic actions of capsicodendrin through selective inhibition of VEGFR2-mediated AKT signaling and disregulated autophagy. Oncotarget, 8(8), 12675-12685.
• Varadaraj, A., Jenkins, L. M., Singh, P., Chanda, A., Snider, J., Lee, N. Y., Amsalem-Zafran, A. R., Ehrlich, M., Henis, Y. I., & Mythreye, K. (2017). TGF-β triggers rapid fibrillogenesis via a novel TβRII-dependent fibronectin-trafficking mechanism. Molecular biology of the cell, 28(9), 1195-1207.
• Wheeler, S. E., & Lee, N. Y. (2017). Emerging Roles of Transforming Growth Factor β Signaling in Diabetic Retinopathy. Journal of cellular physiology, 232(3), 486-489.

Poster Presentations

• Langlais, P. R., Parker, S. S., Krantz, J., Kwak, E., Barker, N. K., Deer, C. G., Lee, N. Y., & Mouneimne, G. (2019, June/Summer). What’s on the Tube? Microtubule-Associated Proteins, Microtubule Stabilization, and Insulin Action.. Federation of American Societies For Experimental Biology - The Regulation of Glucose Metabolism Conference.