Biography
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.
Education
- Postdoctoral Fellowship
- University of Texas MD Anderson Cancer Center
- PhD, MS
- UTHealth Houston
- MA
- University of Texas at Austin
Areas of Interest
Research Interests
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.
Publications
Visit the PubMed profile page
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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)
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.