Hui-Wen Lo Laboratory

My research interests are primarily in molecular and cell biology that underlies tumor growth, tumor progression and response to cancer therapy. We have been focused on two cancer types, namely, breast cancer and glioblastoma, the most common and deadliest brain malignancy in adults. More recently, we are exploring prostate cancer biology and experimental therapeutics.

Aberrant cell signaling is a major hallmark of almost all types of cancer. Thus, the majority of targeted therapies have been directed against tyrosine and Ser/Thr kinases that mediate cancer cell signaling pathways. In this regard, my laboratory has been investigating several of these pathways, including those mediated by EGFR and HER2, as well as, the effectors downstream of both kinases, such as STAT3 and Akt. Our work has led to the discovery of several novel signaling axes within the EGFR/HER2 pathways and their contributions to tumor cell growth, patient prognosis and resistance to anti-cancer therapy.

Another major direction of my laboratory is to investigate a novel transcription factor within the sonic hedgehog pathway. We discovered the existence of truncated glioma-associated oncogene homolog (tGLI1) in 2009 and the evidence to date indicates that tGLI1 behaves as a gain-of-function GLI1 transcription factor that plays an important role in promoting tumor progression and angiogenesis. Our results also suggest that tGLI1 may be expressed in a tumor-specific fashion. Building on these observations, ongoing projects in my laboratory aim at gaining a deeper understanding of tGLI1 functionality in human cancers and also the molecular events leading to tGLI1 synthesis in tumor cells.

Selected Peer-Reviewed Publications (from 48) 

1. Wang, S-C., Lien, H-C., Xia, W., Chen, I-F., Lo, H.-W., Wang, Z., Ali-Seyed, M., Bartholomeusz, G., Ou-Yang, F., Giri, D.K. and Hung, M.-C. Binding at and transactivation of COX-2 promoter by nuclear tyrosine kinase receptor ErbB2. Cancer Cell 6:251-261, 2004.

2.   Lo, H.-W., Hsu, S.-C., Ali-Seyed, M. Gunduz, M., Xia, W., Wei, Y., Bartholomeusz, G., Shih, J.-Y. and Hung, M.-C. Nuclear interaction of EGFR and STAT3 in the activation of iNOS/NO pathway. Cancer Cell 6:575-589, 2005.

3.   Lo, H.-W., Xia, W., Wei, Y., Ali-Seyed, M., Huang, S.-F. and Hung, M.-C. Novel prognostic value of nuclear EGF receptor in breast cancer. Cancer Research 65:338-348, 2005. 

4.   Lo, H.-W., Day, C.-P., Hung, M.-C. Cancer-specific Gene Therapy. Advances in Genetics 54:235-255, 2005.

5.   Hanada, N., Lo, H.-W. (co-first author), Day, C.-P., Pan, Y., Nakajima, Y. and Hung, M-C. Co-regulation of B-Myb expression by E2F1 and EGF receptor. Molecular Carcinogenesis 45:10-17, 2006.

6.   Lo, H.-W. and Hung, M.-C. Nuclear EGFR signaling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival. British Journal of Cancer 94:184-188, 2006.

7.  Lo, H.-W., Ali-Seyed M., Wu, Y., Bartholomeusz, G., Hsu, Sheng-Chieh, and Hung, M.-C. Nuclear-cytoplasmic transport of EGFR involves receptor endocytosis, importin b1 and CRM1. Journal of Cellular Biochemistry 98:1570-1583, 2006.

8.   Lo, H.-W., Hsu, S.-C., and Hung, M.-C. EGFR signaling pathway in breast cancers: from traditional signal transduction to direct nuclear translocalization. Breast Cancer Research and Treatment 95:211-218, 2006.

9.   Lo, H.-W., Hsu, S-C., Xia, W., Cao, X., Shih, J.-Y., Wei, Y., Abbruzzese, J. L., Hortobagyi, G. N. and Hung, M.-C. Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Research 67:9066-9076, 2007.

10. Lo, H.-W. (corresponding author), et al. Constitutively activated STAT3 frequently co-expresses with EGFR in high-grade gliomas and targeting STAT3 sensitizes them to Iressa and alkylators. Clinical Cancer Research 14:6042-6054, 2008. 

11. Lo, H.-W. (corresponding author), et al. A novel splice variant of GLI1 that promotes glioblastoma cell migration and invasion. Cancer Research 17:6790-6798, 2009. 

12.   Lo, H.-W. EGFR-targeted therapy in malignant glioma: Novel aspects and mechanisms of drug resistance. (invited review) Current Molecular Pharmacology 3:37-52, 2010. 

13.   Lo, H.-W. (corresponding author), et al. COX-2 is a novel transcriptional target of the nuclear EGFR-STAT3 and EGFRvIII-STAT3 signaling axes. (Selected as Journal Highlight; the most cited article published in 2010 in Molecular Cancer Research) Molecular Cancer Research 8:232-245, 2010.

14.   Zhu, H., Cao, X., Ali-Osman, F., Keir, S. and Lo, H.-W. EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity. Cancer Letters 294:101-110, 2010.

15.   Zhu, H. and Lo, H.-W. The human glioma-associated oncogene Homolog 1 (GLI1) family of transcription factors in gene regulation and diseases. (invited review) Current Genomics 11:238-245, 2010. 

16.   Lo, H.-W. Nuclear Mode of the EGFR Signaling Network: Biology, Prognostic Value, and Therapeutic Implications. (invited review) Discovery Medicine 10:44-51, 2010. 

17.   Lo, H.-W. Emerging therapeutic targets and agents for glioblastoma therapy. (invited editorial) Anti-Cancer Agents in Medicinal Chemistry Part I. 10(6):437, 2010 and Part II. 10(7):511. 2010. 

18.   Lo, H.-W. Targeting Ras-RAF-ERK and its interactive pathways as a novel therapy for malignant gliomas. (invited review) Current Cancer Drug Targets 10:840-848, 2010. 

19.   Lo, H.-W. EGFR-targeted Cancer Therapy: Promise, Problems and Potential Solutions. Translational Medicine 1:105e. doi:10.4172/2161-1025.1000105e, 2011.

20.   Cao, X., Zhu, H., Ali-Osman, F. and Lo, H.-W. EGFR and EGFRvIII undergo stress- and EGFR kinase inhibitor-induced mitochondrial translocalization: A novel mechanism of EGFR-driven antagonism of apoptosis. Molecular Cancer 10:26, 2011. 

21.   Zhong, P., Xing, F., Huang, X., Zhu, H., Lo, H.-W., Zhong, X., Pruitt, S. and Robertson, C. HIFU as a Neoadjuvant Therapy in Cancer Treatment. 10TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND (ISTU 2010) 1359:289-294, 2011. 

22.   Cao, X., Geradts, J., Dewhirst, M. and Lo, H.-W. Upregulation of VEGF-A and CD24 gene expression by the tGLI1 transcription factor contributes to the aggressive behavior of breast cancer cells. Oncogene 31:104-115, 2012. 

23.   Carpenter, RL. and Lo, H.-W. Hedgehog Pathway and GLI1 Isoforms in Human Cancer. (invited review) Discovery Medicine 13:105-113, 2012. 

24.   Han, W. and Lo, H.-W. Landscape of EGFR Signaling Network in Human Cancers: Biology and Therapeutic Response in Relation to Receptor Subcellular Locations. (invited review) Cancer Letters 318:124-134, 2012. 

25.   Huang, X., Yuan, F., Liang, M., Lo*, H.-W. (co-corresponding author), Shinohara*, M. L., Robertson, C., Zhong*, P. M-HIFU inhibits tumor growth via suppressing STAT3 activity and enhancing tumor specific immunity in a transplant tumor model of prostate cancer. PLoS ONE 7: e41632, 2012. *Co-corresponding Authors

26.   Carpenter, R. L. and Lo, H.-W. Identification, Functional Characterization and Pathobiological Significance of GLI1 Isoforms in Human Cancers. In Vitamins & Hormones-HEDGEHOG SIGNALING. Ed: Gerald Litwack. Elsevier Inc., Volume 88, pp. 115-140, 2012.

27.   Carpenter, RL. and Lo, H.-W. Dacomitinib, an Emerging HER-Targeted Therapy for Non-Small Cell Lung Cancer. Journal of Thoracic Disease, 4:639-642, 2012.

28.   Lo, H.-W. Akt destabilizes p57Kip2: Akt at the converging crossroad? (Invited News & Views) Cell Cycle 12(6):870-871, 2013. 

29.   Han, W., Carpenter, RL, and Lo, H.-W. TGLI1 upregulates expression of VEGFR2 and VEGF-A, leading to a robust VEGF-VEGFR2 autocrine loop and cancer cell growth. doi:10.1166/ch.2013.1006. Cancer Hallmarks 1: 28-37, 2013.

30.   Carpenter, R. L and Lo, H.-W. Regulation of Apoptosis by HER2 in Breast Cancer. Journal of Carcinogenesis & Mutagenesis S7:300, 2013.

31.   Carpenter, R. L, Han, W., Paw, I. and Lo, H.-W. HER2 phosphorylates and destabilizes proapoptotic PUMA, leading to antagonized apoptosis in cancer cells. PLoS ONE 8(11):e78836, 2013.

32.   Han, W., Carpenter, R. L., Cao, X. and Lo, H.-W. STAT1 gene expression is enhanced by nuclear EGFR and HER2 via cooperation with STAT3. Molecular Carcinogenesis 52(12):959-969, 2013.

33.   Zhu, H., Carpenter, R. L, Han, W., and Lo, H.-W. The GLI1 splice variant TGLI1 is a novel mediator of glioblastoma angiogenesis and growth. Cancer Letters 343(1):51-61. 2014.

34.   Carpenter, R. L. and Lo, H.-W. STAT3-regulated Genes Relevant to Human Cancers. In Special Issue: STAT3 Signalling in Cancer: Friend or Foe. Cancers 6:897-925, 2014. 

35.   Carpenter, R. L., Paw, I, Dewhirst, M. W., Lo, H.-W. Akt phosphorylates and activates HSF-1 independent of heat shock, leading to Slug overexpression and epithelial-mesenchymal transition (EMT) of HER2-overexpressing breast cancer cells. Oncogene, Published ahead of print, Jan 27, 2014. PMC4112182, 2014

 

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