Dr. Hui-Wen Lo is a tenured professor and the Director of the Metastatic Brain Tumor Research Program. She is a basic and translational cancer biologist with more than 30 years of experience in conducting cancer-related studies. She has published more than 100 peer-reviewed publications, and her innovative research and scientific discoveries have led to two patents and one clinical trial. As a nationally and internationally recognized cancer scientist, Dr. Lo has been invited to speak and participate in many grant review panels for the NIH, DoD and agencies worldwide and to serve on several journal editorial boards.
Over the past 16 years, her laboratory has been continuously funded by NIH and DoD grants, as well as funding from private foundations.
Throughout her academic career, Dr. Lo has had many leadership roles at the departmental and institutional levels. In addition to being a seasoned cancer researcher and a leader, Dr. Lo is committed to mentoring the next generation of scientists – including graduate students, medical students, physician scientists, and junior faculty.
Dr. Lo received her PhD in Biochemistry and Molecular Biology from McGovern Medical School at UTHealth Houston. Her PhD dissertation was titled “Signaling pathways in the transcriptional and post-translational regulation of the human glutathione S-transferase P1 gene in human glioblastoma.”
Prior to her PhD studies, Dr. Lo obtained a master of arts degree in Nutritional Sciences from the University of Texas at Austin, and a master of science degree in Biomedical Sciences from UTHealth Houston. Her MS thesis was focused on molecular cloning and structural characterization of hGSTP1*C, an allelic human pi class glutathione S-transferase gene variant from human glioblastoma. Dr. Lo conducted her NCI- and ACS-funded postdoctoral fellowship followed by an Instructor position at the University of Texas MD Anderson Cancer Center where she investigated the impact of novel EGFR signaling on breast cancer.
Dr. Lo started her independent academic career at Duke University School of Medicine and NCI-designated Duke University Comprehensive Cancer Center in 2006 as a tenure-track assistant professor. While at Duke, Dr. Lo excelled not only in publications but also in her extramural funding from the NCI, DoD, and private foundations, with more than $3 million dollars of funding. She was promoted to a tenure-track associate professor in 2000 and continued to make breakthrough discoveries. In 2014, Dr. Lo was recruited to Wake Forest School of Medicine and NCI-designated Wake Forest Comprehensive Cancer Center as a tenured associate professor. Four years later in 2018, she was promoted to professor with tenure. At Wake Forest, Dr. Lo demonstrated herself as an outstanding educator, mentor, researcher, and leader. She has trained many graduate students, postdoctoral fellows, and physician scientists. Some of these individuals successfully obtained NIH funding, faculty positions, and industry positions.
In addition to her roles as a mentor and principal investigator, she served as an executive leader in the NCI-designated Wake Forest Comprehensive Cancer Center. As the Associate Director for Shared Resources Management and Associate Director for Basic Sciences, Dr. Lo helped to bolster the research programs and obtain successful renewal of the NCI Cancer Center Support Grant (CCSG) for the Wake Forest Comprehensive Cancer Center.
In 2022, Dr. Lo joined the Vivian L. Smith Department of Neurosurgery in the McGovern Medical School at UTHealth Houston as a tenured professor. She leads the Metastatic Brain Tumor Research Program as the inaugural director. At UTHealth Houston, Dr. Lo expands her research program in primary and metastatic CNS malignancies, as well as metastatic breast cancer. Her research program continues to be highly collaborative and multi-dimensional with a high potential for clinical translation.
- Postdoctoral Fellowship
- University of Texas MD Anderson Cancer Center
- PhD, MS
- UTHealth Houston
- University of Texas at Austin
Areas of Interest
Dr. Lo research interests are primarily in molecular and cell biology that underlies tumor growth, tumor progression/metastasis and response to cancer therapy. Dr. Lo has focused her research program on three cancer types, namely, brain/bone-metastatic breast cancer, and glioblastoma (GBM) the most common and deadliest brain malignancy in adults.
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 AKT, HSF1, and STAT3. Dr. Lo’s 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 Dr. Lo’s laboratory is to investigate a novel transcription factor within the sonic hedgehog pathway. Dr. Lo’s team discovered the existence of truncated glioma-associated oncogene homolog 1 (tGLI1) in 2009 and the evidence to date indicates that tGLI1 behaves as a gain-of-function GLI1 transcription factor that may play a role in tumor progression and angiogenesis. The results suggested that tGLI1 may be expressed in a tumor-specific fashion. Based on these observations, there are projects ongoing in Dr. Lo’s laboratory to gain a deeper understanding of tGLI1 functionality in human cancers, and to explore means to target tGLI1. The results indicated that tGLI1 promotes cancer stem cells, glioblastoma progressing and breast cancer brain metastasis. Dr. Lo’s laboratory recently identified tGLI1 promotes breast cancer metastasis to the brain by activating cancer stem cells and astrocytes in the brain metastatic niche by secreting miR-1290-containing extracellular vesicles. Most recently, Dr. Lo’s laboratory identified FDA-approved antifungal ketoconazole inhibits the ability of tGLI1 to bind to DNA and thereby suppresses tGLI1-mediated breast cancer brain metastasis.
In addition to breast cancer, Dr. Lo’s laboratory is actively investigating GBM, the most common & most malignant brain tumor in adults. We are working to understand the role of a novel tumor suppressor TUSC2 in GBM. We are also actively testing novel combination therapies for GBM.
Visit the PubMed profile page
- Representative publications are listed below (>100 peer-reviewed publications).
Daniel Doheny, Sara Manore, Sherona R. Sirkisoon, Dongqin Zhu, Noah R. Aguayo, Alexandria Harrison, Mariana Najjar, Marlyn Anguelov, Anderson O’Brien Cox, Cristina Furdui, Kounosuke Watabe, Thomas Hollis, Alexandra Thomas, Roy Strowd, Hui-Wen Lo. FDA-approved antifungal, ketoconazole, and its novel derivative suppress tGLI1-mediated breast cancer brain metastasis by inhibiting the DNA-binding activity of brain metastasis-promoting transcription factor tGLI1. Cancers 14(17), 4256, 2022.
- Grace Wong, Sara Manore, Daniel L. Doheny, Hui-Wen Lo. STAT Family of Transcription Factors in Breast Cancer: Pathogenesis and Therapeutic Opportunities and Challenges, Seminars in Cancer Biology S1044-579X(22)00183-3, 2022.
- Tadas K. Rimkus, Austin Arrigo, Dongqin Zhu, Richard L. Carpenter, Sherona Sirkisoon, Daniel Doheny, Angelina T. Regua1, Yang Yu, Grace L. Wong, Sara Manore, Calvin Wagner, Hui-Kuan Lin, Guangxu Jin, Jimmy Ruiz, Michael Chan, Waldemar Debinski, Hui-Wen Lo. NEDD4 degrades TUSC2 to promote glioblastoma progression. Cancer Letters 531:124-135, 2022.
- Sherona R. Sirkisoon, Grace L. Wong1, Noah R. Aguayo, Daniel L. Doheny, Dongqin Zhu, Angelina T. Regua, Austin Arrigo, Sara G. Manore1, Calvin J. Wagner, Yang Yu, Alexandra Thomas, Ravi Singh, Fei Xing, Guangxu Jin, Kounosuke Watabe, and Hui-Wen Lo. Breast cancer-derived exosomal miR-1290 activates astrocytes in the brain-metastatic microenvironment through the miR-1290-FOXA2-CNTF signaling axis to promote progression of brain metastases. Cancer Letters 540:21572, 2022.
- Angelina Tobias Regua, Noah Reeve Aguayo, Sara Abu Jalboush, Daniel Doheny, Sara Manore, Dongqin Zhu, Grace Wong, Austin Arrigo, Calvin Wagner, Yang Yu, Alexandra Thomas, Jimmy Ruiz, Guangxu Jin, Roy Strowd, Peiqing Sun, Jiayuh Lin, and Hui-Wen Lo. TrkA interacts with and phosphorylates STAT3 to enhance gene transcription and promote breast cancer stem cells in triple-negative and HER2-enriched breast cancers. Cancers. 13(10):2340, 2021.
- Wang G, Wang J, Chang A, Cheng D, Huang S, Wu D, Sirkisoon S, Yang S, Lin HK, Lo HW, Xiang R, Sun P. Her2 promotes early dissemination of breast cancer by suppressing the p38 pathway through Skp2-mediated proteasomal degradation of Tpl2. Oncogene Sep 28. doi: 10.1038/s41388-020-01481-y. Online ahead of print. PMID: 32989258. 2020.
- Doheny D, Sirkisoon S, Carpenter RL, Aguayo NR, Regua AT, Anguelov M, Manore SG, Arrigo A, Jalboush SA, Wong GL, Yu Y, Wagner CJ, Chan M, Ruiz J, Thomas A, Strowd R, Lin J, Lo HW. Combined inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 pathways synergistically suppresses breast cancer stem cells, tumor growth, and metastasis. PMID: 32929154. PMCID: PMC7572897. Oncogene 39(42):6589-6605, 2020.
- Sirkisoon SR, Carpenter RL, Rimkus T, Doheny D, Zhu D, Aguayo NR, Xing F, Chan M, Ruiz J, Metheny-Barlow LJ, Strowd R, Lin J, Regua AT, Arrigo A, Anguelov M, Pasche B, Debinski W, Watabe K, Lo HW. TGLI1 transcription factor mediates breast cancer brain metastasis via activating metastasis-initiating cancer stem cells and astrocytes in the tumor microenvironment. PMID: 31462709. Oncogene 39(1):64-78, 2020.
- Rimkus TK, Carpenter RL, Sirkisoon SR, Zhu D, Pasche B, Chan MD, Lesser GJ, Tatter SB, Watabe K, Debinski W, Lo HW. Truncated glioma-associated oncogene homolog 1 (tGLI1) mediates mesenchymal glioblastoma via transcriptional activation of CD44. PMID:29463580. PMCID: PMC5955849 Cancer Research 78(10):2589-2600, 2018.
- Sirkisoon, SR., Carpenter, RL., Rimkus T., Anderson, A., Harrison, A., Lange, AM., Jin, G., Watabe, W., & Lo, H.W. Interaction between STAT3 and GLI1/tGLI1 oncogenic transcription factors promotes the aggressiveness of Triple-negative and HER2-enriched breast cancers. PMID:29449694. PMCID: PMC5948110 Oncogene 37(19):2502-2514, 2018.
- Carpenter RL, Sirkisoon S., Zhu D., Tadas Rimkus, Harrison A., Anderson A., Paw I., Qasem, S., Xing F., Liu Y., Chan M., Metheny-Barlow, L., Pasche, B., Debinski, D., Watabe, K., Lo, H-W. Combined inhibition of AKT and HSF1 suppresses breast cancer stem cells and tumor growth. PMID: 29088759 PMCID: PMC5650314 OncoTarget 8(43):73947-73963, 2017.
- Carpenter, R. L, Paw, I., Zhu, H., Sirkisoon, S., Xing, F., Watabe, K., Debinski, W., and Lo, H.-W. The gain-of-function GLI1 transcription factor TGLI1 enhances expression of VEGF-C and TEM7 to promote glioblastoma angiogenesis. OncoTarget 6:22653-65, 2015
- Carpenter, R. L., Paw, I, Dewhirst, M. W. and 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 34:546–557, 2015. (selected as featured original article)
- 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.
- Han, W., Carpenter, RL., 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.
- 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.
- 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.
- Zhu, H., Cao, X., 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.
- 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.
- Lo, H.-W. (corresponding author), Zhu, H., Cao, X., Ali-Osman, F. A novel splice variant of GLI1 that promotes glioblastoma cell migration and invasion. Cancer Research 17:6790-6798, 2009.
- Lo, H.-W. (corresponding author), Cao, X., Zhu, H., Ali-Osman, F. 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.
- 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.
- 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.