Division of Surgical Research Michael E. DeBakey Department of Surgery

Division of Surgical Research
Michael E. DeBakey Department of Surgery
The Division of Surgical Research is a new division in the Michael E. DeBakey Department of
Surgery established to meet the challenges posed by an increasingly competitive and rapidly advancing
research environment. The division brings together department researchers to “compare notes,” share
ideas, benefit from each other’s knowledge and experience, and lend support in grant and publication
efforts. At the same time, the division aims to create a critical mass of well-recognized researchers
with whom other investigators at BCM and elsewhere can readily collaborate. The mission of the
division is to promote the development and growth of highly successful research and training programs
by providing a supportive environment for investigators and trainees. Division members strive to
achieve two major goals to meet their overall mission.
1). To enhance communication and collaboration among investigators inside and outside of the
division:
--- Establish an effective administrative structure and a strategic plan for the growth of the division
--- Promote a spirit of teamwork and collaboration among investigators and staff
--- Strengthen collaborations between laboratory investigators and clinical partners inside and
outside of the department
--- Provide research infrastructure and support systems to all investigators
2). To increase the quality and impact of our research and training programs:
--- Optimize research areas or topics by considering clinical significance, high innovation, new
technologies, and the existing strengths of investigators and resources
--- Increase research productivity including grants, publications, and presentations
--- Translate discoveries from laboratory research to clinical practice
--- Provide mentoring and training opportunities to junior faculty, surgical residents, fellows, and
students
--- Enhance the department’s national and international reputation for excellence in surgical
research
Faculty members
Primary faculty (12):
Changyi (Johnny) Chen, MD, PhD, Professor of Surgery
Xinhua Feng, PhD, Professor of Surgery
Qizhi (Cathy) Yao, MD, PhD, Professor of Surgery
Austin J. Cooney, PhD, Associate Professor of Surgery
Kaiyi (Kelly) Li, PhD, Associate Professor of Surgery
Xia Lin, PhD, Associate Professor of Surgery
Megumi Mathison, MD, PhD, Associate Professor of Surgery
Narasimhaswamy Belaguli, PhD, Assistant Professor of Surgery
Lidong Liu, PhD, Assistant Professor of Surgery
Jian-Ming Lu, PhD, Assistant Professor of Surgery
Hu Ying Shen, MD, PhD, Assistant Professor of Surgery
Yulong Liang, PhD, Instructor in Surgery
Joint faculty (14):
William E. Fisher, MD, Professor of Surgery
Ronald H. Kerman, PhD, Professor of Surgery
Scott A. LeMaire, MD, Professor of Surgery
George P. Noon, MD, Professor of Surgery
Jed G. Nuchtern, MD, Professor of Surgery
Oluyinka Olutoye, MBChB, PhD, Professor of Surgery
Todd K. Rosengart, MD, Professor of Surgery
Charles T. Van Buren, MD, Professor of Surgery
John M. Vierling, MD, Professor of Surgery
Eugene Kim, MD, Assistant Professor of Surgery
Sanjeev Vasudevan, MD, Assistant Professor of Surgery
Lalita Wadhwa, PhD, Assistant Professor of Surgery
Pawel Kolodziejski, MD, PhD, Instructor of Surgery
Xiaoying Shang, PhD, Instructor in Surgery
Changyi (Johnny) Chen, MD, PhD
Professor
Michael E. DeBakey Department of Surgery
Department of Molecular and Cellular Biology
Molecular Surgery Endowed Chair
Chief of Division of Surgical Research
Director, Molecular Surgeon Research Center
Education
MD: Southeast University School of Medicine, Nanjing, China
PhD: Georgia Institute of Technology, Atlanta
Clinical residency training: Southeast University School of
Medicine, Nanjing, China
Postdoctoral training: Emory University, Atlanta
Research Interests
My laboratory is actively conducting several basic science and translational research projects that
are highly relevant to clinical cardiovascular disease and pancreatic cancer.
Cardiovascular risk factors and their molecular mechanisms in cardiovascular disease
We are investigating the effects and the molecular mechanisms of several cardiovascular risk
factors, including HIV protease inhibitors, the adipokine resistin, soluble CD40L, and uric acid,
on biochemical pathways associated with endothelial cell functions. Some of the biochemical
pathways under investigation are the endothelial nitric oxide synthase system, the oxidative
stress system, and signal transduction pathways. We are carrying on these investigations using
several experimental models, such as myographies, organ cultures, mouse models, human tissue
samples, and different types of endothelial cells. Based on the molecular mechanisms we
uncover, we develop effective therapeutic strategies to treat endothelial dysfunction and
atherosclerosis.
Endothelial cell differentiation and angiogenesis
We are studying the role played by and the molecular mechanisms of hemodynamic factors and
several novel molecules on endothelial cells differentiated from embryonic stem cells and from
bone marrow-derived stem cells. We are identifying key regulatory genes that trigger endothelial
cell differentiation and promote stable angiogenesis. These findings can potentially be applied to
the design of novel therapeutic strategies to treat ischemic tissues using genetically engineered
endothelial cells. In addition, these studies may provide useful information to genetically
engineer novel tissues for vascular grafts.
Pancreatic cancer
We have been heavily involved in pancreatic cancer research programs for many years. We have
several projects focusing on the role and on the mechanisms of several genes, such as microRNA
196a (miR-196a), X-inactive specific transcript (XIST), and Jude-2 in pancreatic cancer. Our
comprehensive studies analyze human cancer specimens, clinical outcomes, established cell
lines, a nude mouse model, and a genetically engineered mouse model of pancreatic cancer
called the KPC model. We are developing PLGA [poly(lactic-co-glycolic acid)]-based
nanotechnology for molecular imaging and for specific drug and gene delivery, which has great
potential clinical applications, such as molecular diagnostics and targeted therapies.
Contact Information
Baylor College of Medicine
One Baylor Plaza, BCM 391
Houston, TX 77030
Phone: 713-798-4401
Fax: 713-798-6633
E-mail: [email protected]
Selected Publications
1. Chen C, Ochoa LN, Kagan A, Chai H, Liang Z, Peter Lin PH, Yao Q. (2012),
Lysophosphatidic acid causes endothelial dysfunction in porcine coronary arteries and human
coronary artery endothelial cells. Atherosclerosis, 222(1):74-83.
2. Chen C, Jiang J, Lü J, Chai H, Wang X, Lin PH, Yao Q. (2010), Resistin decreases
expression of endothelial nitric oxide synthase through oxidative stress in human coronary
artery endothelial cells. Am J Physiol Heart Circ Physiol, 299(1):H193-201.
3. Liao D, Wang X, Li M, Lin PH, Yao Q, Chen C. (2009), Human protein S inhibits the
uptake of AcLDL and expression of SR-A through Mer receptor tyrosine kinase in human
macrophages. Blood, 113(1):165-74.
4. Chen C, Jamaluddin MS, Yan S, Sheikh-Hamad D, Yao Q. (2008), Human stanniocalcin-1
blocks TNF-α-induced monolayer permeability in human coronary artery endothelial cells.
Arterioscler Thromb Vasc Biol, 28(5):906-912.
5. Chen C, Chai H, Wang X, Jiang J, Jamaluddin MS, Liao D, Zhang Y, Wang H, Bharadwaj
U, Zhang S, Li M, Lin P, Yao Q. (2008), Soluble CD40 ligand induces endothelial
dysfunction in human and porcine coronary artery endothelial cells. Blood, 112(8):32053216.
6. Mu H, Wang X, Lin PH, Yao Q, Chen C. (2008), Nitrotyrosine promotes human aortic
smooth muscle cell migration through oxidative stress and ERK1/2 activation. Biochim
Biophys Acta - Molecular Cell Research, 1783(9):1576-1584.
7. Li M, Zhang Y, Liu Z, Bharadwaj U, Wang H, Wang X, Zhang S, Liuzzi JP, Chang SM,
Cousins RJ, Fisher WE, Brunicardi FC, Logsdon CD, Chen C, Yao Q. (2007), Aberrant
expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic
cancer pathogenesis and progression. Proc Natl Acad Sci USA, 104(47):18636-18641.
8. Wang X, Mu H, Chai H, Liao D, Yao Q, Chen C. (2007), Human immunodeficiency virus
protease inhibitor ritonavir inhibits cholesterol efflux from human macrophage-derived foam
cells. Am J Pathol, 171(1):304-314.
9. Wang H, Riha GM, Yan S, Li M, Chai H, Yang H, Yao Q, Chen C. (2005), Shear stress
induces endothelial differentiation from a murine embryonic mesenchymal progenitor cell
line. Arterioscler Thromb Vasc Biol, 25(9):1817-1823.
10. Chen C, Mattar SG, Hughes JD, Pierce GF, Cook JE, Ku DN, Hanson SR, Lumsden AB.
(1996), Recombinant mitotoxin basic fibroblast growth factor-saporin reduces venous
anastomotic intimal hyperplasia in the arteriovenous graft. Circulation, 94(8):1989-1995.
Key words (disease and expertise):
• Angiogenesis
• Atherosclerosis
• Cardiovascular disease
• Endothelial dysfunction
• Endothelial nitric oxide synthase
• Hemodynamics
• Oxidative stress and antioxidant
• Pancreatic cancer
• PLGA-based nanotechnology
• Vascular tissue engineering
Xin-Hua Feng, PhD
Professor
Michael E. DeBakey Department of Surgery
Department of Molecular & Cellular Biology
Education
PhD: University of Maryland, College Park
Postdoctoral training: University of California, San Francisco
Research interests
Protein modifications and signaling networks in cell growth control, tumorigenesis, and
development
My research aims to elucidate the underlying mechanisms and interplays among protein
modifications, signaling pathways, and gene transcription as well as understanding their roles in
cell proliferation, tissue differentiation, and pathogenesis of human diseases.
My current research projects include:
Phosphatome: genome-wide investigation of protein dephosphorylation
Signal transduction pathways are often regulated by the dynamic interplay between protein
kinases and phosphatases. Using all the human protein serine/threonine phosphatases available,
we systematically investigate the effect of dephosphorylation on key proteins involved in cell
signaling and cell functions. We are currently genetically disrupting individual phosphatases to
elucidate their in vivo functions during development.
SUMO, ubiquitin, and control of protein turnover and functions
We examine the effect of post-translational modifications, particularly ubiquitination and
SUMOylation of transcription factors, in normal and cancer cells. We attempt to understand the
molecular mechanisms by which environmental and developmental cues regulate the
ubiquitination/proteasome and SUMOylation systems. Our studies will provide insights into the
relationships between protein deregulation and human cancers or abnormal development.
TGF-ß/BMP signal transduction
SMADs are evolutionarily conserved signal transducers and transcription factors controlling
TGF-ß/BMP functions. A large number of mutations that inactivate SMADs have been linked to
human cancers and genetic diseases. We address the molecular interactions, requirements, and
functionality of SMADs in TGF-ß/BMP responses using cellular, genomic, and proteomic
approaches. We investigate how SMADs mediate transcription and how their actions are
terminated. We also use in vitro and in vivo model systems to study how SMADs as tumor
suppressors interplay with oncogenic pathways, in particular with those involved in lymphoma
and in pancreatic and breast cancer.
Genetic screens, BMP/TGF-ß signaling, and ES cells
We are conducting genome-wide studies (e.g. genetic screens using lentiviral RNAi library) to
identify novel TGF-ß signal modifiers or regulators involved in stem cell differentiation. Novel
molecules that control TGF-ß/BMP signaling or participate in human ES cell self-renewal and
differentiation will be further studied and in model organisms to define the molecules’
physiological roles in tissue differentiation and organ development.
Immune suppression by TGF-ß
TGF-ß is a major inflammatory and immune-regulatory cytokine, but the mechanisms by which
TGF-ß exerts its actions are unclear. We are interested in investigating the signaling interactions
between the TGF-ß pathway and other cytokine pathways (such as TNF-alpha, IL-1, and IL-6
pathways) in immune responses. This area of research may lead to the discovery of drugs to treat
cancer and inflammatory diseases.
Contact information
Baylor College of Medicine
One Baylor Plaza, Room R712
Houston, TX 77030
Phone: 713-798-4756
E-mail: [email protected]
Selected publications
1.
Dai F, Lin X, Chang C, Feng XH. (2009), Nuclear export of Smad2 and Smad3 by
RanBP3 facilitates termination of TGF-ß signaling. Dev Cell, 16(3):345-357.
2.
Wrighton K, Lin X, Feng XH. (2008), Critical regulation of TGF-β signaling by HSP90.
Proc Natl Acad Sci USA, 105(27): 9244-9249.
3.
Wang D*, Long J*, Dai F, Liang M, Feng XH, Lin X. (2008), BCL6 represses Smad
signaling in transforming growth factor-beta resistance. Cancer Res, 68(3): 783-789.
4.
Dai F, Chang C, Lin X, Dai G, Mei L, Feng XH. (2007), Erbin inhibits transforming
growth factor beta signaling through a novel Smad-interacting domain. Mol Cell Biol,
27(17): 6183-6194.
5.
Wrighton KH, Willis D, Long J, Liu F, Lin X, Feng XH. (2006), Small C-terminal domain
phosphatases dephosphorylate the regulatory linker regions of Smad2 and Smad3 to
enhance transforming growth factor beta signaling. J Biol Chem, 281(50): 38365–38375.
6.
Lin X*, Duan X*, Liang YY*, Su Y*, Wrighton K, Long J, Hu M, Davis C, Wang J,
Brunicardi FC, Shi Y, Chen YG, Meng A, Feng XH. (2006), PPM1A functions a Smad
phosphatase to terminate TGF-ß signaling. Cell, 125(5): 915-928.
7.
Feng XH, Derynck R. (2005), Specificity and versatility of TGF-ß signaling through
Smads. Annu Rev Cell Dev Biol, 21: 659-693.
8.
Liang M, Liang YY, Wrighton K, Ungermannova D, Wang X, Brunicardi FC, Liu X, Feng
XH, Lin X. (2004), Ubiquitination and proteolysis of cancer-derived Smad4 mutants by
SCFSkp2. Mol Cell Biol, 24(17): 7524-7537.
9.
Lin X, Sun B, Liang M, Liang YY, Gast A, Hildebrand J, Brunicardi FC, Melchior F, Feng
XH. (2003), Opposed regulation of corepressor CtBP function by SUMOylation and PDZ
binding. Mol Cell, 11(5):1389-1396.
10.
Feng XH, Liang YY, Liang M, Zhai W, Lin X. (2002), Direct interaction of c-Myc with
Smad2 and Smad3 to inhibit TGF-ß-mediated induction of the CDK inhibitor p15 (Ink4B).
Mol Cell, 9(1):133-143.
Keywords (disease and expertise):
• Embryonic stem cells
• Serine/threonine phosphatases available
• SMADs
• SUMOylation
• TGF-ß/BMP
• Ubiquitination
Qizhi Cathy Yao, MD, PhD
Professor
Michael E. DeBakey Department of Surgery
Department of Molecular Virology and Microbiology
Department of Pathology and Immunology
Education
MD: Southeast University School of Medicine, China
PhD: Emory University School of Medicine, Atlanta, GA
Postdoctoral training: Emory University School of Medicine,
Atlanta, GA
Research Interests
My research programs include HIV vaccine development, pancreatic cancer pathogenesis, and
therapy. Specifically:
•
•
•
•
•
•
Developing chimeric virus-like particle HIV vaccines
Understanding the functional roles of mesothelin in pancreatic cancer pathogenesis
Understanding the functional roles of miR-198 in pancreatic cancer pathogenesis
Understanding the functional roles of axon guidance gene Semaphorin 3E in pancreatic
cancer pathogenesis
Developing targeted nanoparticle therapy in pancreatic cancer
Developing immunotherapy for pancreatic cancer
HIV Vaccines
My lab is interested in developing non-infectious HIV virus-like particles (VLPs) as candidate
HIV mucosal vaccines for both preventive and therapeutic purposes. In preclinical studies, VLPs
formed by structural proteins are highly immunogenic and capable of inducing protective
immunity against various viral infections. We have modified vaccine immunogens into chimeric
HIV VLPs which contain influenza viral surface glycoprotein HA or other immunologically
functional molecules. We have shown that the chimeric HIV VLPs can induce enhanced humoral
and cellular immune responses against HIV in a mouse model.
We have also studied the basic mechanisms of VLP-induced humoral and cellular immune
responses, and other factors that affect these responses. For example, we found that VLP
vaccines activate conventional B2 cells and promote B cell differentiation to IgG2a producing
plasma cells; that VLP vaccines travel to the lymph nodes upon immunization and can be
directly visualized by optical imaging techniques; and that intradermal immunization generates
improved responses and might be a preferable delivery route for viral and cancer
immunotherapeutic studies involving VLPs.
1
Since dendritic cells (DCs) have long been known to be pivotal in initiating immune responses,
we are also interested in how VLPs modulate DC functions and will evaluate the efficacy of
VLP-pulsed DC vaccines. In addition, we are interested in testing the efficacy of modified
chimeric VLP oral-mucosal immunization in non-human primates.
Pancreatic cancer pathogenesis and therapy
Pancreatic cancer has one of the highest mortality rates and ranks as the fourth leading cause of
cancer death in North America. Survival is poor because there are no reliable tests for early
diagnosis and no effective therapies to treat metastatic disease. There is a need to better
understand the molecular mechanisms of pancreatic cancer tumorigenesis and to develop
effective treatments. My lab currently focuses on the study of key molecules in pancreatic
cancer, including mesothelin (MSLN), trop2, and semaphorin 3E, and in their mechanisms of
regulation. I am also interested in the involvement of microRNAs (miR-198) in pancreatic
cancer, and how their dysregulation leads to pathogenesis. We are also currently exploring
tumor-associated molecule targeted therapies and RNA interference delivery by liposomes and
PLGA nanoparticles in vivo. Our group has shown that vaccinating mice with chimeric viruslike particles containing MSLN significantly inhibited tumor progression, suggesting a new
therapeutic vaccine strategy whereby MSLN is targeted to attempt to control pancreatic cancer
progression. We are also employing a K-ras mutation spontaneous pancreatic cancer mouse
model to study prevention and the potential of our therapeutic regimens.
Contact Information
Baylor College of Medicine
One Baylor Plaza, BCM 391
Houston, TX 77030
Phone: 713-798-1765
Fax: 713-798-6633
[email protected]
Selected Publications
1. Zhang, S, Li, F, Younes, M, Liu, H, Chen, C, Yao Q. (2013), Reduced selenium-binding
protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative
effects of selenium. PLoS One, 8(5):e63702.
2. Zhang, S, Yong, L, Li D, Cubas, R, Chen, C, Yao, Q. (2013), Mesothelin virus-like particle
immunization controls pancreatic cancer growth through CD8+ T cell induction and
reduction in the frequency of CD4+foxp3+ICOS-regulatory T cells. PLoS One, 8(7):e68303.
3. Marin-Muller C, Rios A, Anderson D, Siwak E, Yao Q. (2013), Complete and repeatable
inactivation of HIV-1 viral particles in suspension using a photo-labeled non-nucleoside
reverse transcriptase inhibitor. J Virol Methods, 189(1):125-128.
2
4. Bharadwaj U, Marin-Muller C, Li M, Chen C, Yao Q. (2011), Mesothelin confers pancreatic
cancer cell resistance to TNF-α-induced apoptosis through Akt/PI3K/NF-κB activation and
IL-6/Mcl-1 overexpression. Mol Cancer, 10:106.
5. Bharadwaj U, Marin-Muller C, Zhang Y, Li M, Chen C, Yao Q. (2011), Mesothelin
overexpression promotes autocrine IL-6/sIL-6R trans-signaling to stimulate pancreatic cancer
cell proliferation. Carcinogenesis, 32(7):1013-1024.
6. Cubas R, Zhang S, Li M, Chen C, Yao Q. (2011), Chimeric Trop2 virus-like particles: a
potential immunotherapeutic approach against pancreatic cancer. J Immunother, 34(3):251263.
7. Cubas R, Zhang S, Li M, Chen C, Yao Q. (2010). Trop2 expression contributes to tumor
pathogenesis by activating the ERK MAPK pathway. Mol Cancer, 9:253.
8. Zhang R, Zhang S, Li M, Chen C, Yao Q. (2010), Incorporation of CD40 ligand into SHIV
virus-like particles (VLP) enhances SHIV-VLP-induced dendritic cell activation and boosts
immune responses against HIV. Vaccine, 28(31):5114-5127.
9. Zhang S, Cubas R, Li M, Chen C, Yao Q. (2009), Virus-like particle vaccine activates
conventional B2 cells and promotes B cell differentiation to IgG2a producing plasma cells.
Mol Immunol, 46(10):1988-2001.
Key words (disease and expertise):
• Breast cancer
• HIV
• Immunotherapy
• Mesothelin
• MicroRNA
• Nanoparticle targeted delivery
• Pancreatic cancer
• Vaccine
3
Austin J. Cooney, PhD
Associate Professor
Michael E. DeBakey Department of Surgery
Department of Molecular and Cellular Biology
Education
PhD: National University of Ireland, Galway
Postdoctoral training: Baylor College of Medicine
Research Interests
My laboratory is actively conducting several basic science and translational research projects that
are highly relevant to clinical cardiovascular disease and regenerative medicine. The focus of my
research group over the last decade and a half has been the transcriptional regulation of the
pluripotent state in embryonic stem (ES) cells and their differentiation. Coming from a nuclear
receptor, background I naturally focused on this family of ligand-activated transcription factors,
which I found to play key roles in regulating ES cell differentiation. My research group has four
broad focuses: (1) the maintenance of pluripotency through the nuclear receptor liver receptor
homolog-1 (LRH-1), which interacts with Wnt/βCatenin signaling; (2) silencing of pluripotency
gene expression via the nuclear receptor germ cell nuclear factor (GCNF); (3) generation of
induced pluripotent stem (iPS) cells focusing on nuclear receptors (NRs); and (4) ES cell
differentiation into cardiomyocytes.
Differentiation of ES and iPS cells into cardiomyocytes
In terms of differentiation into cardiomyocytes, we have several projects in progress. For the
purpose of modeling regenerative medicine, we generated mouse iPS cells and efficiently
differentiated them into functional cardiomyocytes to study the regulation of this process. With
Robert Schwartz we collaborate on defining the roles of early lineage determinants in cardiac
development. We have focused on the transcription factor Mesp1 and on Wnt signaling.
However, it is our work with LRH-1 in ES cells that has pushed us further into understanding
cardiac differentiation. We made the novel observation that over-expression of LRH-1 in ES
cells leads to a dramatic increase in the number of beating colonies after differentiation. We
have shown that the nodal coreceptor Cripto is an LRH-1 target gene. Cripto is highly expressed
in ES cells, is rapidly down-regulated upon differentiation, and its expression is specific to the
cardiac crescent. Using various Cre drivers developed in the Schwartz lab for early cardiac
development, we will study the yin-yang roles of LRH-1 and GCNF in cardiac development
using Cre/Lox approaches. In parallel with these genetic approaches, we will test the effects of
LRH-1 and GCNF ligands on improving iPS generation and cardiomyocyte differentiation. Our
goal is to translate these novel findings to human ES and iPS cells.
In vitro and in vivo cardiac regeneration
In collaboration with Dr. Todd K. Rosengart, we are developing virus-based strategies to treat
cardiovascular diseases, such as infarction in situ. The goal is using viral vectors to induce
transdifferentiation of cardiac fibroblasts and myofibroblasts into functional cardiomycytes in
situ in a patient’s heart. We are modeling and developing the processes in rats, pigs, and in
human cardiac fibroblasts.
Silencing of pluripotency gene transcription
Lrh-1 and GCNF, which are orphan members of the steroid receptor gene family of ligandactivated transcription factors, play yin/yang roles in regulating pluripotent gene expression. We
showed that Lrh-1 maintains pluripotent gene expression in response to canonical Wnt signaling
through βCatenin. GCNF is the major transcriptional repressor of pluripotency gene expression
during the exit from this distinct phase in development, which is initiated by differentiation or
gastrulation. GCNF silences pluripotency gene expression by the recruitment of the DNA
methylation machinery. We have established GCNF knockout (KO) ES cells as a genetic model.
We use proteomic and genomic strategies to dissect the role of GCNF in the regulation of DNA
methylation, which is of fundamental importance. We are also testing GCNF ligands, which act
as antagonists on ES cell differentiation.
Generation of patient-specific iPS cell lines
We are using genetic and pharmaceutical approaches to study the roles of Lrh-1 and GCNF
during iPS formation. Using Cre/lox approaches, we will analyze the roles of LRH-1 and GCNF
in iPS formation to generate KO fibroblasts for each factor. We will also test the ligands for
LRH-1 and GCNF to determine if they promote iPS formation and quality.
Contact Information
Baylor College of Medicine
One Baylor Plaza, BCM 391
Houston, TX 77030
Phone: 713-798-6250
Fax: 713-790-1275
E-mail: [email protected]
Selected Publications
1. Wang Q, Wagner RT, Cooney AJ. (2013), Regulatable in vivo biotinylation expression
system in mouse embryonic stem cells. PLoS One, 8(5):e63532.
2. Wang H, Wang X, Xu X, Zwaka TP, Cooney AJ. (2013), Epigenetic re-programming of the
germ cell nuclear factor gene is required for proper differentiation of induced pluripotent
cells. Stem Cells, Mar 14. doi: 10.1002/stem.1367. [Epub ahead of print].
3. Li Y, Yu W, Cooney AJ, Schwartz RJ, Liu Y. (2013), Oct4 and canonical Wnt signaling
regulate the cardiac lineage factor Mesp1 through a Tcf/Lef-Oct4 composite element. Stem
Cells, 31(6):1213-1217.
4. Gu P, Xu X, Le Menuet D, Chung AC, Cooney AJ. (2011), Differential recruitment of
methyl CpG-binding domain factors and DNA methyltransferases by the orphan receptor
germ cell nuclear factor initiates the repression and silencing of Oct4. Stem Cells,
29(7):1041-1051.
5. Wagner RT, Xu X, Yi F, Merrill BJ, Cooney AJ. (2010), Canonical Wnt/β--catenin
regulation of liver receptor homolog-1 mediates pluripotency gene expression. Stem Cells,
28(10):1794-1804.
6. Gu P, LeMenuet D, Chung A CK, Mancini M, Wheeler D, Cooney AJ. (2005), Orphan
nuclear receptor GCNF is required for the repression of pluripotency genes during retinoic
acid-induced embryonic stem cell differentiation. Mol Cell Biol, 25(19):8507-8519.
7. Gu P, Goodwin B, Chung A C-, Xu X, Wheeler DA, Price RR, Galardi C, Peng L, Latour
AM, Koller BH, Gossen J, Kliewer SA, Cooney AJ. (2005), Orphan nuclear receptor LRH-1
is required to maintain Oct4 expression at the epiblast stage of embryonic development. Mol
Cell Biol, 25(9): 3492-3505.
8. Lan ZJ, Gu P, Xu X, Jackson K, DeMayo FJ, O’Malley BW, Cooney AJ. (2003), GCNFdependent repression of BMP-15 and GDF-9 expression mediates gamete regulation of
female fertility. EMBO J, 22(16):4070-4081.
9. Lan ZJ, Gu P, Xu X, Cooney AJ. (2003) Expression of the orphan nuclear receptor, germ
cell nuclear factor, in mouse gonads and preimplantation embryos, Biol Reprod, 68(1): 282289.
10. Fuhrmann G, Chung ACK, Jackson KJ, Hummelke G, Baniahmad A, Sutter J, Sylvester I,
Schöler HR, Cooney AJ. (2001) Mouse Germline Restriction of Oct4 Expression by Germ
Cell Nuclear Factor. Dev Cell 1(3):377-387. Review: Donovan PJ (2001) High Oct-ane fuel
powers the stem cell. Nat Genet, 29(3):246-247. PMID: 11702949.
Key words (disease and expertise):
• Cardiac differentiation
• Embryonic stem cells
• Gene regulation
• Generation of iPS cells
• Hemodynamics
• Nuclear receptors
• Oxidative stress and antioxidant
• Pluripotent stem cells
• TGA-based nanotechnology
• Vascular tissue engineering
Kaiyi (Kelly) Li, PhD
Associate Professor
Michael E. DeBakey Department of Surgery
Department of Pathology and Immunology
Education
PhD: The University of Texas M.D. Anderson Cancer Center,
Houston
Postdoctoral training: Baylor College of Medicine, Houston
Research Interests
My research goal is to develop novel cancer therapies by identifying new key pathways for
cancer development and progression.
There are three major areas of investigation in my laboratory:
Characterization of the function of DNA-repair proteins in tumor suppression using both
knockout mouse models and clinical specimens
BRIT1/MCPH1 knockout mice have been generated in the lab and BRIT1’s role in the
suppression of breast, liver, and pancreatic cancer is studied extensively using the unique
knockout mouse model, as well as clinical specimens.
Development of cancer-specific therapies by targeting DNA repair deficiency in cancer
We use a synthetic lethality approach and combination therapy to develop more effective
treatments for breast and liver cancer.
Identification of novel genes that drive breast and liver cancer development
Using a bio-informatics approach, we select candidate genes analyzing The Cancer Genome
Atlas (TCGA) data and we characterize the genuine functions of these candidate genes in vitro
and in animal models.
Contact Information
Baylor College of Medicine
One Baylor Plaza, Rm. ABBR-R417
Mail Stop: BCM 391
Houston, TX 77030
Phone: 713-798-1323
E-mail: [email protected]
Selected Publications
1. Pan MR, Hsieh HJ, Dai H, Hung WC, Li K, Peng G, Lin SY. (2012), Chromodomain
helicase DNA-binding protein 4 (CHD4) regulates homologous recombination DNA repair,
and its deficiency sensitizes cells to poly(ADP-ribose) polymerase (PARP) inhibitor
treatment. J Biol Chem, 287(9): 6764-6772.
2. Liang Y, Gao H, Lin SY, Goss JA, Brunicardi FC, Li K. (2010), siRNA-based targeting of
cyclin E overexpression inhibits breast cancer cell growth and suppresses tumor development
in breast cancer mouse model. PLoS One, 5(9):e12860.
3. Liang Y, Gao H, Lin SY, Peng G, Zhang P, Huang X, Goss JA, Brunicardi FC, Multani AS,
Chang S, and Li K. (2010), BRIT1/MCPH1 is essential for mitotic and meiotic
recombination DNA repair and maintaining genomic stability in mice. PLoS Genet, 6(1):
e1000826.
4. Peng G, Yim EK, Dai H, Jackson AP, van der Burgt I, Pan MR, Hu R, Li K, Lin SY. (2009),
BRIT1/MCPH1 links chromatin remodeling to DNA damage response. Nat Cell
Biol,11(7):865-872.
5. Wood JL, Liang Y, Li* K, Chen* J. (2008), Microcephalin/MCPH1 associates with the
Condensin II complex to function in homologous recombination repair. J Biol Chem,
283(43): 29586-29592. (*share corresponding authors).
6. Rai R, Dai H, Multani AS, Li K, Chin K, Gray J, Lahad JP, Liang J, Mills GB, MericBernstam F, Lin SY. (2006), BRIT1 regulates early DNA damage response, chromosomal
integrity, and cancer. Cancer Cell, 10(2):145-157.
7. Lin SY, Li K, Stewart GS, Elledge SJ. (2004), Human Claspin works with BRCA1 to both
positively and negatively regulate cell proliferation. Proc Natl Acad Sci USA,
101(17):6484-6489.
8. Li K, Lin, SY, Brunicardi FC, Seu P. (2003), Use of RNA interference to target cyclin Eoverexpressing hepatocellular carcinoma. Cancer Res, 63(13):3593-3597.
9. Li K, Ramírez M, Rose E, and Beaudet AL. (2002), A gene fusion method to screen for
regulatory effects on gene expression: application to the LDL receptor. Hum. Mol. Genet,
11(26): 3257-3265.
10. Li K, Shao R, Hung MC. (1999), Collagen-homology domain deletion mutant of Shc
suppresses the transformation mediated by neu through a MAPK-independent pathway.
Oncogene, 18(16): 2617- 2626.
Key words (disease and expertise):
• Breast cancer
• DNA damage response pathways
• DNA repair
• Knockout mouse model
• Liver cancer
• Pancreatic cancer
• Synthetic lethality
• Targeted cancer therapy
• Tumor Suppressor
Xia Lin, PhD
Associate Professor
Department of Surgery
Education
PhD: University of Maryland at College Park, College Park,
MD
Postdoctoral training: University of California at San
Francisco, San Francisco, CA
Research Interests
My research focuses on the molecular mechanisms of cancer initiation and progression and in the
identification of potential targets for cancer therapy.
My specific research interests include:
Physiological functions of TGF-β signaling in normal and cancer cells
Regulation of TGF-β signaling by other molecules and signaling pathways
Chromosome aneuploidy as a potential target for cancer therapy
Contact Information
Baylor College of Medicine
One Baylor Plaza, BCM 391
Houston, TX 77030
Phone: 713-798-4899
Fax: 713-798-4093
E-mail: [email protected]
Selected Publications
1. Qin J, Wu S, Creighton CJ, Dai FY, Xie X, Cheng C, Frolov A, Ayala G, Lin X, Feng X,
Ittmann M, Tsai S, Tsai M, and Tsai S. (2013), XOUP-TFII inhibits TGF-β-induced growth
barrier to promote prostate tumorigenesis. Nature, 493(7431):236-240.
2. Lin X, Yang X, Li, Q, Cui S, He D, Lin X, Scharwtz RJ and Chang J. (2012), Protein tyrosine
phosphatase-like A regulates myoblast proliferation and differentiation through MyoG and cell
cycling signaling pathway. Mol Cell Biol, 32(2):297-308.
3. Liang, YY, Brunicardi FC, and Lin X. (2009), Smad3 mediates early induction of Id1 by
TGF‐β. Cell Res, 19(1):140‐148.
4. Wrighton KH, Liang M, Bryan B, Luo K, Liu M, Feng XH, Lin X. (2007), Transforming
growth factor-beta-independent regulation of myogenesis by SnoN sumoylation. J Biol Chem,
282(9): 6517–6524.
5. Han G, Li AG, Liang YY, Owens P, He W, Lu S, Yoshimatsu Y, Wang D, Ten Dijke P, Lin
X, Wang XJ. (2006), Smad7-induced β-catenin degradation alters epidermal stem appendage
development. Dev Cell, 11(3):301-312.
6. Lin X, Duan X, Liang YY, Su Y, Wrighton KH, Long J, Hu M, Davis CM, Wang J, Brunicardi
FC, Shi Y, Chen YG, Meng A, Feng XH. (2006), PPM1A functions as a Smad phosphatase to
terminate TGF-β signaling. Cell, 125(5): 915-928.
7. Lin X, Sun B, Liang M, Liang YY, Gast A, Hildebrand J, Brunicardi FC, Melchior F, Feng
XH. (2003), Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding. Mol
Cell, 11: 1389-1396.
8. Lin X, Liang M, Feng XH. (2000), Smurf2 is a ubiquitin E3 ligase mediating proteasomedependent degradation of Smad2 in transforming growth factor-beta signaling. J Biol Chem,
275(47): 36818-36822.
9. Lin X, Sikkink RA, Rusnak F, Barber DL. (1999), Inhibition of calcineurin phosphatase
activity by a calcineurin B homologous protein. J Biol Chem, 274(51): 36125-36131.
10. Lin X, Barber DL. (1996), A calcineurin homologous protein inhibits GTPase-stimulated NaH exchange. Proc Nat Acad Sc. USA, 93(22): 12631-12636.
Key words (disease and expertise):
• Cancer
• Cell cycle regulation
• Diabetes
• Mouse development
• TGF-b signaling
Megumi Mathison, MD, PhD
Associate Professor
Michael E. DeBakey Department of Surgery
Education
MD: Tokyo Medical and Dental University, Tokyo, Japan
PhD: University of Tokyo, Tokyo, Japan
Clinical residency training:
University of Tokyo School of Medicine, Tokyo, Japan
Research Interests
In situ cardiac regeneration
Dr. D. Srivastava and his colleagues reported that the combination of three transcription factors,
Gata4, Mef2c, and Tbx5, reprogrammed postnatal murine cardiac fibroblasts directly into
differentiated cardiomyocyte-like cells in vitro.
Furthermore, Dr. Srivastava and others, including us, recently reported that resident cardiac
fibroblasts were reprogrammed into cardiomyocyte-like cells in the murine heart by direct
injection of Gata4, Mef2c, and Tbx5 into the myocardium after coronary ligation. These results
raise the possibility that we can generate new cardiomyocytes from scar tissue after myocardial
infarction in humans.
Contact Information
Baylor College of Medicine
One Baylor Plaza, BCM 390
Houston, TX 77030
Phone: 713-798-3259
Fax: 713-798-8258
E-mail: [email protected]
Selected Publications
1. Mathison M, Gersch RP, Nasser A, Lilo S, Korman M, Fourman M, Hackett N, Shroyer K,
Yang J, Ma Y, Crystal RG, Rosengart TK. (2012), In vivo cardiac cellular reprogramming
efficacy is enhanced by angiogenic preconditioning of the infarcted myocardium with
vascular endothelial growth factor, J Am Heart Assoc,1(6):e005652.
2. Cui J, Mathison M ,Tondato F, Mulkey SP, Micko C, Chronos NA, Robinson KA. (2005), A
clinically relevant large-animal model for evaluation of tissue-engineered cardiac patch
materials. Cardiovasc Revasc Med, 6(3):113-120.
3. Robinson KA, Mathison M, Redkar A, Cui J, Chronos NA, Matheny RG, Badylak SF.
(2005), Extracellular matrix scaffold for cardiac repair. Circulation, 112:I35-43.
4. Mathison M, Becker GJ, Katzen BT, Benenati JF, Zemel G, Powell A, Lima MM. (2003),
Implications of problematic access in transluminal endografting of abdominal aortic
aneurysm. J Vasc Interv Radiol, 14(1): 33-39, 2003.
5. Becker GJ, Kovacs M, Mathison M. (2002), Transluminal repair of abdominal aortic
aneurysm: a call for selective use, careful surveillance, new device design, and systematic
study of transrenal fixation. J Vasc Surg, 35(3):611- 615.
6. Mathison M. (2002), Experience of coronary artery bypass grafting on the beating heart with
right heart bypass. (Invited commentary) Japanese Journal of Thoracic Surgery (Kyobu
Geka), 55:5-7.
7. Mathison M, Becker GJ, Katzen BT, Benenati JF, Zemel G, Powell A, Kovacs ME, Lima
MM. (2001),The influence of female gender on the outcome of endovascular abdominal
aortic aneurysm repair. J Vasc Interv Radiol, 12(9):1047-1051.
8. Dewey TM, Magee MJ, Edgerton JR, Mathison M, Tennison D, Mack MJ.(2001), Off-pump
bypass grafting is safe in patients with left main coronary disease. Ann Thorac Surg, 72(3):
788-791.
9. Mathison M, Edgerton JR, Horswell JL, Akin JJ, Mack MJ. (2000), Analysis of
hemodynamic changes during beating heart surgical procedures. Ann Thorac Surg,
70(4):1355-1361.
10. Mathison M, Buffolo E, Jatene AD, Jatene FB, Reichenspurner H, Matheny RG, Shennib H,
Akin JJ, Mack MJ. (2000), Right heart circulatory support facilitates coronary artery bypass
without cardiopulmonary bypass. Ann Thorac Surg, 70(3):1083-1085.
Key words (disease and expertise):
• Cardiovascular disease
• Cardiac regeneration
Narasimhaswamy S. Belaguli, PhD
Assistant Professor
Michael E. DeBakey Department of Surgery
Michael E. DeBakey Veterans Affairs Medical Center
Education
BVSc: Bangalore Veterinary College, Karnataka, India
MVSc: Bangalore Veterinary College, Karnataka, India
PhD: Memorial University, Newfoundland, Canada
Post-doctoral training: Baylor College of Medicine, Houston,
Texas
Research Interests
My lab is interested in understanding the transcriptional regulatory mechanisms involved in the
induction and maintenance of differentiation programs in various cell types such as myogenic
cells, pancreatic beta cells, gastrointestinal epithelial cells, and colorectal cancer cells.
Myogenic cells
In depth studies over the last three decades have helped understand the mechanisms by which
cells commit to a particular cell lineage, undergo differentiation, and maintain the differentiated
phenotype. The differentiation program unique to a cell type can be switched and cells are made
to assume an alternate differentiation program without transitioning through an intermediate
pluripotential “stem cell” phase by a process called “transdifferentiation.” Previously, I have
determined that fibroblasts can be transdifferentiated into vascular smooth muscle cells by
overexpressing three transcriptional regulators, SRF, GATA6, and CRP2, which are highly
enriched in vascular smooth muscle cells. More recent studies from several labs have shown that
fibroblasts can also be transdifferentiated into cardiac muscle cells by overexpressing a defined
set of cardiac muscle-enriched transcriptional regulators. The mechanisms and signaling events
involved in transdifferentiation of fibroblasts in to cardiac myocytes is an area of active research
in my laboratory.
Pancreatic beta cells
Pancreatic beta cells secrete insulin, a vital hormone that regulates blood glucose levels. Insulin
deficiency and/or inefficient utilization of insulin cause diabetes. We have identified serum
response factor (SRF) as a beta cell-enriched transcriptional regulator of insulin gene expression.
My lab has been using genetically modified mice, genomic, transcriptomic, and biochemical
approaches to investigate the mechanisms by which SRF and co-accessory factors regulate beta
cell gene expression and glucose homeostasis.
Gastrointestinal epithelial cells
The mammalian intestine is one of the organs in which the epithelium is rapidly and perpetually
turned over. Several growth factors, signaling molecules, and transcriptional regulators are
involved in maintaining intestinal epithelial homeostasis. GATA factors are zinc-dependent
transcriptional regulators important for proliferation and differentiation of intestinal epithelial
cells. To identify proteins that cooperate with GATA factors to regulate intestinal gene
expression I have employed yeast-two-hybrid screens, proteomics, and biochemical approaches.
Colorectal cancer
Colorectal cancer is the third most commonly diagnosed cancer. Development and metastasis of
colorectal cancer is associated with increased expression of GATA6. I have been using
transcriptional profiling of colorectal cancer cells, human cancer tissue arrays, and biochemical
approaches to examine the mechanisms by which GATA6 and GATA6-interacting factors
promote colorectal cancer development and metastasis.
Contact Information
Baylor College of Medicine
One Baylor Plaza, BCM 391
Houston, TX 77030
Phone: 713-798-3528
Fax: 713-798-6633
E-mail: [email protected]
Selected Publications
1. Belaguli** NS, Zhang M, Brunicardi FC, Berger DH. (2012), Forkhead box protein A2
(FOXA2) protein stability and activity are regulated by sumoylation. PLoS ONE,
7(10):e48019.
2. Belaguli** NS, Zhang M, Garcia AH, Berger DH. (2012), PIAS1 is a GATA4 SUMO ligase
that regulates GATA4-dependent intestinal promoters independent of SUMO ligase activity
and GATA4 sumoylation. PLoS ONE, 7(4):e35717.
3. Sarkar A, Zhang M, Liu SH, Sarkar S, Brunicardi FC, Berger DH, Belaguli NS. (2011),
Serum response factor expression is enriched in pancreatic β cells and regulates insulin gene
expression. FASEB J, 25(8):2592-2603.
4. Belaguli** NS, Aftab M, Rigi M, Zhang M, Albo D, Berger DH. (2010), GATA6 promotes
colon cancer cell invasion by regulating urokinase plasminogen activator gene expression.
Neoplasia, 12(1):856-865.
5. Feanny MA, Fagan SP, Ballian N, Liu SH, Li Z, Wang X, Fisher W, Brunicardi FC, Belaguli
NS. (2008), PDX-1 expression is associated with islet proliferation in vitro and in vivo. J
Surg Res, 144(1):8-16.
6. **Belaguli NS, Zhang M, Rigi M, Aftab M, Berger DH. (2007), Cooperation between
GATA4 and TGF-beta regulates intestinal epithelial gene expression. Am J Physiol
Gastrointest Liver Physiol, 292(6):G1520-1533.
7. Chang DF, Belaguli NS, Chang J, Schwartz RJ. (2007), LIM-only protein, CRP2, switched
on smooth muscle gene activity in adult cardiac myocytes. Proc Natl Acad Sci USA,
104(1):157-162.
8. Niu Z, Yu W, Zhang SX, Barron M, Belaguli NS, Schneider MD, Parmacek M, Nordheim
A, Schwartz RJ. (2005), Conditional mutagenesis of the murine serum response factor gene
blocks cardiogenesis and the transcription of downstream gene targets. J Biol Chem,
280(37):32531-32538.
9. Barron MR*, Belaguli NS*, Zhang SX, Trinh M, Iyer D, Merlo X, Lough JW, Parmacek
MS, Bruneau BG, Schwartz RJ. (2005), Serum response factor, an enriched cardiac
mesoderm obligatory factor, is a downstream gene target for TBX genes. J Biol Chem,
280(12):11816-11828.
10. Chang* DF, Belaguli* NS, Iyer D, Roberts WB, Wu SP, Dong XR, Marx JG, Moore MS,
Beckerle MC, Majesky MW, Schwartz RJ. (2003), Cysteine-rich LIM-only proteins CRP1
and CRP2 are potent smooth muscle differentiation factors. Dev Cell, 4(1):107-118.
*First coauthors; ** Corresponding author
Keywords (disease and expertise):
• Colorectal cancer
• Gastrointestinal epithelial cells
• GATA6
• Myogenic cells,
• Pancreatic beta cells
• Serum response factor (SRF)
• Transdifferentiation
Lidong Liu, PhD
Assistant Professor
Michael E. DeBakey Department of Surgery
Education
BS and MS: Wuhan University, China
PhD: Kyoto University, Japan
Postdoctoral training:
Biomolecular Engineering Research Institute, Japan
University of Washington, Seattle
Research Interests
I am interested in understanding the signaling transduction mechanisms that regulate cancer
initiation, progression, and metastasis.
My current research is focused on two areas:
TGF-β signaling in cancer
I am investigating the molecular mechanisms of TGF-β signaling involved in cancer progression
and metastasis, with special emphasis on the roles Smads play as regulators and mediators of
TGF-β signaling via cross-talk with other signaling pathways
EMT in cancer
I am studying the molecular basis of epithelial-mesenchymal transition (EMT) and the roles of
EMT and stem-like cells generated by EMT in cancer invasion and metastasis. The ultimate goal
of my research is to reveal the molecular basis of malignancy and discover targets for cancer
treatment.
Contact Information
Baylor college of Medicine
One Baylor Plaza, ABBR, R731E
Houston, TX 77030
Phone: 713-798-4994
E-mail: [email protected]
Selected Publications
1. Liu L, Cundiff P, Abel G, Wang Y, Faigle F, Sakagami H, Xu M, and Xia Z (2006),
Extracellular signal-regulated kinase (ERK) 5 is necessary and sufficient to specify cortical
neuronal fate. Proc Natl Acad Sci USA, 103 (25): 9697- 9702.
2. Liu L, Cavanaugh JE, Wang Y, Sakagami H, Mao Z, and Xia Z (2003), ERK5 activation of
MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of
developing but not mature cortical neurons. Proc Natl Acad Sci USA, 100(14): 8532-8537.
3. Takahashi N, Kakinuma H, Liu L, Nishi Y, and Fujii I. (2001), In vitro abzyme evolution to
optimize antibody recognition for catalysis. Nat Biotechnol, 19(6): 563-567.
Key words (disease and expertise):
• Cancer stem cell
• Epithelial-mesenchymal transition (EMT)
• Prostate cancer
• TGF-β
Jian-Ming Lü, PhD
Assistant Professor
Michael E. DeBakey Department of Surgery
Education
PhD: Lanzhou University, Lanzhou, China
Postdoctoral training:
University of Texas, Health Science Center at Houston
University of Houston
Leipzig University
Research Interests
My research is focused on several basic science and translational research projects that are highly
relevant to clinical diseases and pancreatic cancer. I have a strong background and research
experience in organic chemistry, medicinal and synthetic chemistry, and biochemistry, including
enzyme activities and mechanisms.
In recent years, I have been studying the fields of translational medicine and medicinal
chemistry, working with cell-free, well-established in vitro as well as in vivo models. The
primary goal of my projects is to develop new, safe, and effective therapies using natural or
naturally-derived substances. For example, I have been developing medicines for hyperuricemiarelated diseases, such as gout, using natural substances and by modifying their structure to
enhance their effects. Currently, I am also screening naturally-derived substances for inhibitors
of enzymes such as myeloperoxidase, HIV protease, and arginase, key enzymes in the
development of diseases.
Another focus of my research is the delivery of nanoparticle gene/drug complexes targeted to
cancer cells as well as to vascular cells by using antibodies or other specific proteins conjugated
to PLGA (poly(lactic-co-glycolic acid)-based nanoparticles. I am developing a new PLGA-based
material for molecular imaging and specific drug and gene delivery, which has great potential
clinical applications such as molecular diagnostics and targeted therapies.
Contact Information
Baylor College of Medicine
One Baylor Plaza, BCM 391
Houston, TX 77030
Phone: 713-798-1035
Fax: 713-798-6633
E-mail: [email protected]
Selected Publications
1. Lü JM, Weakley SM, Yang Z, Hu M, Yao Q, Chen C. (2012), Ginsenoside Rb1 directly
scavenges hydroxyl radical and hypochlorous acid, Curr Pharm Des, 18(38):6339-6347.
2. Lü JM, Yan S, Jamaluddin S, Weakley SM, Liang Z, Siwak EB, Yao Q, Chen C. (2012),
Ginkgolic acid inhibits HIV protease activity and HIV infection in vitro. Med Sci Monit,
18(8):BR293-298.
3. Lü JM, Rogge CE, Wu G, Kulmacz RJ, van der Donk WA, Tsai AL. (2011),
Cyclooxygenase reaction mechanism of PGHS — evidence for a reversible transition
between a pentadienyl radical and a new tyrosyl radical by nitric oxide trapping, J Inorg
Biochem, 2011, 105 (3), 356-365.
4. Lü JM, Nurko J, Jiang J, Weakley SM, Lin PH, Yao Q, Chen C. (2011),
Nordihydroguaiaretic acid (NDGA) inhibits ritonavir-induced endothelial dysfunction in
porcine pulmonary arteries. Med Sci Monit, 17(11):BR312-318.
5. Wu G, Lü JM, van der Donk WA, Kulmacz RJ, Tsai AL. (2011), Cyclooxygenase reaction
mechanism of prostaglandin H synthase from deuterium kinetic isotope effects, J Inorg
Biochem, 105 (3), 382-390.
6. Lü JM, Lin PH, Yao Q, Chen, C. (2010), Chemical and molecular mechanisms of
antioxidants: experimental approaches and model systems. J Cell Mol Med, 14(4):840-60.
7. Lü JM, Nurko J, Weakley SM, Jiang J, Kougias P, Lin PH, Yao Q, Chen C. (2010),
Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and
its derivatives: an update. Med Sci Monit, 16(5):RA93-100.
8. Lü JM, Wang X, Marin-Muller C, Wang, H, Lin PH, Yao Q, Chen C. (2009), Current
advances in research and clinical applications of PLGA-based nanotechnology. Expert Rev
Mol Diagn, 9(4):325-41.
9. Lü JM, Yao Q, Chen C. (2009), Ginseng compounds: an update on their molecular
mechanisms and medical applications. Curr Vasc Pharmacol, 7(3):293-302.
10. Lü JM, Rosokha SV, Neretin IS, Kochi JK. (2006), Quinones as electron acceptors. X-ray
structures, spectral (EPR, UV-vis) characteristics and electron-transfer reactivities of their
reduced anion radicals as separated vs contact ion pairs. J Am Chem Soc, 128(51), 1670816719
Key words (disease and expertise):
• Cardiovascular disease
• Drug discovery and development
• Enzyme inhibitors, mechanisms
• Gout and hyperuricemia
• Natural substances and structure modification
• Organic synthesis, characterization
• Oxidative stress, free radicals, and antioxidants
• Pancreatic cancer
• Polymer nanoparticle drug/gene delivery
• Xanthine oxidase, HIV protease, cyclooxygenase, arginase
Ying H. Shen, MD, PhD
Assistant Professor
Michael E. DeBakey Department of Surgery
Director of Cardiothoracic Surgery Research Laboratory
Education
MD: Beijing Medical College, Beijing, China
PhD: University of New South Wales, Sydney, Australia
Research Interests
My broad research interest is on vascular diseases. One of my main interests is to study the
molecular mechanisms of aortic aneurysms and dissections, highly lethal but poorly understood
conditions. During the past few years, we have established mouse models of aortic aneurysms
and dissections and developed various techniques to evaluate the aortic structure and functions.
We have also developed several projects to study the regulation of aortic inflammation and
destruction, as well as aortic repair and remodeling.
Contact Information
Cardiothoracic Surgery Research Laboratory
Michael E. DeBakey Department of Surgery
Mail: BCM 390, One Baylor Plaza, Houston, TX 77030
Lab: C-1095, Texas Heart Institute, 6770 Bertner Ave., Houston, TX 77030
Tel.: (832) 355-9952, Fax: (832) 355-9951
Email: [email protected]
Selected Publications
1. Shen YH, Zhang L, Ren P, Nguyen MT, Zou S, Wu D, Wang XL, Coselli J, LeMaire SA. (2013),
AKT2 confers protection against aortic aneurysms and dissections. Circ Res, 112(4): 618-632.
2. Ren P, Zhang L, Xu G, Palmero LC, Albini PT, Coselli JS, Shen YH, LeMaire SA. (2013), ADAMTS1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections. Ann Thorac Surg,
95(2): 570-577.
3. Zou S, Ren P, Nguyen MT, Coselli JS, Shen YH, LeMaire SA. (2012), Notch signaling in descending
thoracic aortic aneurysm and dissection. PLoS One, 7(12):e52833.
4. Shen YH, Hu X, Zou S, Wu D, Coselli JS, LeMaire SA. (2012), Stem cells in thoracic aortic
aneurysms and dissections: potential contributors to aortic repair. Ann Thorac Surg, 93(5):1524-1533.
5. Li XN, Song J, Zhang L, LeMaire SA, Hou X, Zhang C, Coselli JS, Chen L, Wang XL, Zhang Y, Shen
YH. (2009), Activation of the AMPK-FOXO3 pathway reduces fatty acid-induced increase in
intracellular reactive oxygen species by upregulating thioredoxin. Diabetes, 58(10):2246-2257.
6. Wang XL, Zhang L, Youker K, Zhang MX, Wang J, LeMaire SA, Coselli JS, Shen YH. (2006), Free
fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through
upregulating PTEN or inhibiting Akt kinase. Diabetes, 55(8):2301-2310.
7. Shen YH, Zhang L, Gan Y, Wang X, Wang J, LeMaire SA, Coselli JS, Wang XL. (2006), Upregulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) mediates p38 MAPK
stress signal-induced inhibition of insulin signaling A cross-talk between stress signaling and insulin
signaling in resistin-treated human endothelial cells. J Biol Chem, 281(12): 7727-7736.
8. Shen YH, Zhang L, Utama B, Wang J, Gan Y, Wang X, Wang J, Chen L, Vercellotti GM, Coselli JS,
Mehta JL, Wang XL. (2006), Human cytomegalovirus inhibits Akt-mediated eNOS activation through
upregulating PTEN (phosphatase and tensin homolog deleted on chromosome 10). Cardiovasc Res,
69(2):502-511.
9. Shen YH, Utama B, Wang J, Raveendran M, Senthil D, Waldman WJ, Belcher JD, Vercellotti G,
Martin D, Mitchelle BM, Wang XL. (2004), Human cytomegalovirus causes endothelial injury through
the ataxia telangiectasia mutant and p53 DNA damage signaling pathways. Circ Res, 94(10):1310-1317.
10. Shen YH, Godlewski J, Zhu J, Sathyanarayana P, Leaner V, Birrer MJ, Rana A, Tzivion G. (2003),
Cross-talk between JNK/SAPK and ERK/MAPK pathways: sustained activation of JNK blocks ERK
activation by mitogenic factors. J Biol Chem, 278(29): 26715-26721.
Key words (disease and expertise):
• Aortic aneurysms and dissections
• Diabetic vascular diseases
• Vascular biology and diseases
Yulong Liang, PhD
Instructor
Michael E. DeBakey Department of Surgery
Education
PhD: Fudan University Shanghai Medical College, China
Postdoctoral training: Baylor College of Medicine, Houston
Research Interests
My research focuses on elucidating the roles and the underlying mechanisms of DNA damage
and repair pathways in tumor development, progression, and metastasis, as well as developing
novel therapeutic methods to target cancer cells.
DNA damage response and genomic instability in cancer
DNA repair deficiency and genomic instability are important hallmarks of cancer. By
elucidating the roles of BRIT1/MCPH1, an important protein involved in DNA damage and
repair pathways, I will provide insights into the relationship of DNA repair deficiency with
genomic instability, cancer initiation, progression, and/or metastasis.
Translational research and treatment of cancer
In this area, I will investigate how to target cancer cells with genomic instability, which may
eventually lead to the discovery of drugs for cancer treatment.
Contact Information
ABBR Building, R431, MS-BCM391
One Baylor Plaza
Houston, TX 77030
713-798-1035
Selected Publications
1. Liang Y, Gao H, Lin SY, Peng G, Huang X, Zhang P, Goss JA, Brunicardi FC, Multani AS,
Chang S, Li K. (2010), BRIT1/MCPH1 Is essential for mitotic and meiotic recombination
DNA repair and maintaining genomic stability in mice. PLoS Genet, 6(1): e1000826.
2. Liang Y, Gao H, Lin SY, Goss JA, Brunicardi FC, Li K. (2010), siRNA-based targeting of
cyclin E overexpression inhibits breast cancer cell growth and suppresses tumor development
in breast cancer mouse model. PLoS ONE, 5(9): e12860.
3. Liang Y, Lin SY, Li K. (2010), MCPH1 (microcephalin 1). Atlas Genet Cytogenet Oncol
Haematol, 14(3): 243-245.
4. Lin SY, Liang Y, Li K. (2010), Multiple roles of BRIT1/MCPH1 in DNA damage response,
DNA repair, and cancer suppression. Yonsei Med J, 51(3):295-301.
5. Liang Y, Lin SY, Brunicardi FC, Goss J, Li K. (2009), DNA damage response pathways in
tumor suppression and cancer treatment. World J Surg, 33(4): 661-666.
6. Zhao H, Liang Y, Xu Z, Wang L, Zhou F, Li Z, Jin J, Yang Y, Fang Z, Hu Y, Zhang L, Su J,
Zha X. (2008), N-glycosylation affects the adhesive function of E-Cadherin through
modifying the composition of adherens junctions (AJs) in human breast carcinoma cell line
MDA-MB-435. J Cell Biochem, 104(1): 162-175.
7. Wood JL, Liang Y, Li K, Chen J. (2008), Microcephalin/MCPH1 associates with the
Condensin II complex to function in homologous recombination repair. J Biol Chem,
283(43): 29586-29592.
8. Wang L, Liang Y, Li Z, Cai X, Zhang W, Wu G, Jin J, Fang Z, Yang Y, Zha X. (2007),
Increase in beta1-6 GlcNAc branching caused by N-acetylglucosaminyltransferase V directs
integrin beta1 stability in human hepatocellular carcinoma cell line SMMC-7721. J Cell
Biochem, 100(1): 230-241.
9. Fang Z, Fu Y, Liang Y*, Li Z, Zhang W, Jin J, Yang Y, Zha X*. (2007), Increased
expression of integrin beta1 subunit enhances p21WAF1/Cip1 transcription through the Sp1
sites and p300-mediated histone acetylation in human hepatocellular carcinoma cells. J Cell
Biochem, 101(3): 654-664. (* Co-Corresponding Author)
10.Wu N, Zhang W, Yang Y, Liang Y, Wang LY, Jin JW, Cai XM, Zha XL. (2006), Profilin 1
obtained by proteomic analysis in all-trans retinoic acid-treated hepatocarcinoma cell lines is
involved in inhibition of cell proliferation and migration. Proteomics, 6(22): 6095-6106.
Key words (disease and expertise):
• Breast cancer
• DNA damage response
• Double-strand breaks
• Genomic instability
• Homologous recombination
• Liver cancer
• Synthetic lethality model
• Targeting therapy of cancer
• Tumorigenesis
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