Reactive nitrogen and oxygen species, Nitrosylation, Estrogens, Hormones, Growth factors, Angiogenesis, Placenta, Corpus luteum, Ovary, Uterus, Menopause, Pregnancy, Maternal adaptation, Preeclampsia, Perinatal vascular biology, Obstetrics and Gynecology.
• Pfizer Award, SGI, 2013
• External Expert Panel, NMRC, Singapore, 2012-2014
• Pfizer Award, SGI, 2012
• Regular Member, NIH/NICHD CHHDB Study Section, 07/2011-06/2014
• Pfizer Award, SGI, 2011
• USDA NRI Merit Award (Mentor), SSR 2011
• Elected to Council, Perinatal Research Society, 2010-2012.
• Member, Vascular Wall Biology Basic Science 3 Committee,, AHA, 2010-
• Pfizer Award, SGI, 2010
• Member, NIH Pregnancy & Neonatology Study Section, 02/2007, 01/2008
• President’s Presenter Award (Mentor), SGI 2005
• NIH Young Investigator Award, Perinatal Research Society, 1999
• Lalor Postdoctoral Fellowship, Lalor Foundation, 1998
• Lalor Postdoctoral Fellowship, Lalor Foundation, 1997
07/2013 – Present: Professor, Dept of Ob/Gyn, UC Irvine
04/2010 – Present: Associate Professor Jointly Appointed, Dept of Experimental Pathology, UC Irvine
06/2008 – 07/2013: Associate Professor and Director, Perinatal Research Laboratories, Dept of Ob/Gyn, UC Irvine
07/2007 - 05/2008: Associate Professor with Tenure, Dept of Reproductive Medicine, UC San Diego
07/2005 - 06/2007: Assistant Professor on Tenure-Track, Dept of Reproductive Medicine, UC San Diego
07/2003 - 06/2005: Assistant Adjunct Professor, Dept of Reproductive Medicine, UC San Diego
10/2001 - 07/2003: Specialist/Assistant Scientist, Dept of Reproductive Medicine, UC San Diego
06/2000 - 10/2000: Consultant, Genetics Computer Group (GCG)
01/1999 - 10/2001: Research Assistant Professor/Assistant Scientist, Perinatal Research Laboratories, Dept of Ob/Gyn, University of Wisconsin - Madison, WI
05/1995 - 05/1999: Postdoctoral Fellow/Research Associate, The Women’s Research Institute, Dept of Ob/Gyn, University of Kansas School of Medicine - Wichita, KS
07/1993 - 05/1995; Postdoctoral Fellow, Dept of Ob/Gyn, Baylor College of Medicine, Houston, TX
We are currently investigating the cellular and molecular mechanisms underlying hormone and growth factor regulation of vasodilatation and angiogenesis at the maternal, fetal and placental interface with focus on reactive nitrogen and oxygen species as well as reactive sulfides.
1. Lei JZ, Nie Q, Chen DB (2018) A single-cell epigenetic model for parental psychological stress-induced transgenerational reprogramming in offspring. Biol Reprod. Published on 28 February 2018 (https://doi.org/10.1093/biolre/ioy050)
2. Chen DB, Feng L, Hodges JK, Lechuga TJ, Zhang H. Human trophoblast-derived hydrogen sulfide stimulates placental artery endothelial cell angiogenesis. Biol Reprod. 2017; 97(3):478-489.
3. Zhang HH, Chen JC, Sheibani L, Lechuga TJ, Chen DB. Pregnancy Augments VEGF-Stimulated In Vitro Angiogenesis and Vasodilator (NO and H2S) Production in Human Uterine Artery Endothelial Cells. J Clin Endocrinol Metab. 2017; 102(7):2382-2393.
4. Sheibani L, Lechuga TJ, Zhang H, Hameed A, Wing DA, Kumar S, Rosenfeld CR, Chen DB. Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation. Biol Reprod. 2017; 96(3):664-672.
5. Zhang HH, Lechuga TJ, Chen Y, Yang Y, Huang L, Chen DB. Quantitative Proteomics Analysis of VEGF-Responsive Endothelial Protein S-Nitrosylation Using Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and LC-MS/MS. Biol Reprod. 2016; 94(5):114.
6. Tan K, An L, Miao K, Ren LK, Hou ZC, Tao L, Zhang ZN, Wang XD, Xia W, Liu JH, Wang ZQ, Xi GY, Gao S, Sui LL, Zhu DS, Wang SM, Wu ZH, Bach I, Chen DB, Tian JH. Impaired imprinted X-chromosome inactivation is responsible for the skewed sex ratio following in vitro fertilization. Proc Natl Acad Sci USA. 2016; 113(12):3197-202.
7. Wu L, Lu Y, Jiao Y, Chen DB, Chen XJ, Li XY. Paternal psychological stress reprograms hepatic gluconeogenesis in offspring. 2016. Cell Metabolism 23: 735–743
8. Lechuga TJ, Zhang HH, Sheibani L, Karim M, Jia J, Magness RR, Rosenfeld CR, Chen DB. Estrogen Replacement Therapy in Ovariectomized Nonpregnant Ewes Stimulates Uterine Artery Hydrogen Sulfide Biosynthesis by Selectively Up-Regulating Cystathionine ß-Synthase Expression. Endocrinology. 2015 156(6):2288-98
9. Zhang HH, Lechuga TJ, Tith T, Wang W, Wing DA, Chen DB. S-nitrosylation of cofilin-1 mediates estradiol-17ß-stimulated endothelial cytoskeleton remodeling. Mol Endocrinol. 2015 29(3):434-44.
10. Satohisa S, Zhang HH, Feng L, Yang YY, Huang L, Chen DB. Endogenous NO upon estradiol- 17ß stimulation and NO donor differentially regulate mitochondrial S-nitrosylation in endothelial cells. Endocrinology. 2014; 155(8):3005-16.
11. Zhang HH, Wang W, Feng L, Yang Y, Zheng J, Huang L, Chen DB. S-nitrosylation of Cofilin-1 serves as a Novel Pathway for VEGF-stimulated Endothelial Cell Migration. J Cell Physiol. 2015; 230(2): 406–417.
12. Chen DB, Wang W. Human placental microRNAs and preeclampsia. Biol Reprod. 2013;88(5):130.
13. Feng L, Zhang HH, Wang W, Zheng J, Chen DB. Compartmentalizing proximal FGFR1 signaling in ovine placental artery endothelial cell caveolae. Biol Reprod. 2012 Aug 23;87(2):40. Cover page story
14. Wang W, Feng L, Zhang H, Hachy S, Satohisa S, Laurent LC, Parast M, Zheng J, Chen DB. Preeclampsia up-regulates angiogenesis-associated microRNA (i.e., miR-17, -20a, and -20b) that target ephrin-B2 and EPHB4 in human placenta. J Clin Endocrinol Metab. 2012;97(6): E1051-9.
http://f1000.com/prime/14265965#eval15778071 Highlighted in Faculty of 1000, 18 Apr 2012.
15. Smith A, Contreras C, Ko KH, Chow J, Dong X, Tuo B, Zhang HH, Chen DB, Dong H. Gender- specific protection of estrogen against gastric acid-induced duodenal injury: stimulation of duodenal mucosal bicarbonate secretion. Endocrinology. 2008;149(9):4554-66.
16. Ramadoss J, Liao WX, Morschauser TJ, Lopez GE, Patankar MS, Chen DB, Magness RR. Endothelial caveolar hub regulation of adenosine triphosphate-induced endothelial nitric oxide synthase subcellular partitioning and domain-specific phosphorylation. Hypertension. 2012;59(5):1052-9.
17. Liao WX, Feng L, Zheng J, Chen DB. Deciphering mechanisms controlling placental artery endothelial cell migration stimulated by vascular endothelial growth factor. Endocrinology. 2010;151(7):3432-44. Cover page story
18. Zhang HH, Feng L, Livnat I, Hoh JK, Shim JY, Liao WX, Chen DB. Estradiol-17beta stimulates specific receptor and endogenous nitric oxide-dependent dynamic endothelial protein S-nitrosylation: analysis of endothelial nitrosyl-proteome. Endocrinology. 2010;151(8):3874-87.
19. Li SM, Zeng LW, Feng L, Chen DB. Rac1-dependent intracellular superoxide formation mediates vascular endothelial growth factor-induced placental angiogenesis in vitro. Endocrinology. 2010;151(11):5315-25.
20. Mata-Greenwood E, Liao WX, Wang W, Zheng J, Chen DB. Activation of AP-1 transcription factors differentiates FGF2 and vascular endothelial growth factor regulation of endothelial nitric- oxide synthase expression in placental artery endothelial cells. J Biol Chem. 2010; 285(23):17348-58.
21. Liao WX, Feng L, Zhang H, Zheng J, Moore TR, Chen DB. Compartmentalizing VEGF-induced ERK2/1 signaling in placental artery endothelial cell caveolae: a paradoxical role of caveolin-1 in placental angiogenesis in vitro. Mol Endocrinol. 2009; 23(9):1428-44.
22. Byers MJ, Zangl A, Phernetton TM, Lopez G, Chen DB, Magness RR. Endothelial vasodilator production by ovine uterine and systemic arteries: ovarian steroid and pregnancy control of ERalpha and ERbeta levels. J Physiol. 2005;565(Pt 1):85-99.
23. Magness RR, Phernetton TM, Gibson TC, Chen DB. Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17beta-treated, intact follicular and pregnant sheep. J Physiol. 2005; 565(Pt 1):71-83.
24. Chen DB, Bird IM, Zheng J, Magness RR. Membrane estrogen receptor-dependent extracellular signal-regulated kinase pathway mediates acute activation of endothelial nitric oxide synthase by estrogen in uterine artery endothelial cells. Endocrinology. 2004; 145(1):113-25.
25. Chen DB, Westfall SD, Fong HW, Roberson MS, Davis JS. Prostaglandin F2alpha stimulates the Raf/MEK1/mitogen-activated protein kinase signaling cascade in bovine luteal cells. Endocrinology. 1998;139(9):3876-85.
26. Chen DB, Hilsenrath R, Yang ZM, Le SP, Kim SR, Chuong CJ, Poindexter AN 3rd, Harper MJ. Leukaemia inhibitory factor in human endometrium during the menstrual cycle: cellular origin and action on production of glandular epithelial cell prostaglandin in vitro. Hum Reprod. 1995;10(4):911-8.
NIH 1 R01 AR073172-01.
Vascular Pathogenesis of Port Wine Stain. Direct Cost: $250,000/yr, total=$386, 250/yr).
Duration: 04/01/2018- 03/31/2023.
Role on the Project: Co-Investigator.
Goals: to establish the role of lesional endothelial exosomes in the vascular phenotypes in the pathogenesis of PWS.
Development of Endothelial Optical Exosomes for the Treatment of Port Wine Stains.
Direct Cost: $200,000 Total = $308,999).
Duration: 04/01/2018- 03/31/2020.
Role on the Project: Co-Investigator.
Goals: to characterize the novel molecular mechanism of co-expression of EphB1 and EfnB2 in CM EPCs underlying progressive dilation of CM vasculatures and determine whether fNETs can be
novel therapeutic agents for specific targeting of CM EPCs.
NIH RO1 HL70562-09.
Estrogen actions in uterine artery endothelium.
Direct Cost: $250,000/yr Total = 386, 250/yr).
Duration: 04/01/2015- 04/30/2020.
Role on the Project: Principal Investigator.
Goals: to investigate a hypothesis that endogenous H2S production by enhanced CBS expression in UA endothelium and smooth muscle functions as a novel vasodilator for mediating estrogen actions on uterine endothelium via interactions with endothelial eNOS-NO.
Function as PI
NIH 1 R03 HD084972
Quantitative Proteomics Analysis of Endothelial nitroso-Proteome using SILAC
Direct Cost: $50,000/yr (Total $154,500)
Goals: to development a quantitative proteomics approach for analyzing protein S-nitrosylation in endothelial cells.
Estrogen and endothelial protein nitrosylation
Direct Cost: $175,000/yr (Total $ 427,000)
Duration: 05/01/2010 to 04/30/2013
This grant is to test the effects of estrogen on protein nitrosylation in endothelial cells and to profile estrogen-induced endothelial nitrosyl-proteome.
NIH RO1 HL70562-05
Estrogen actions in uterine artery endothelium
Direct Cost: $250,000/yr (Total $1,427,625)
Duration: 07/01/2006- 06/30/2011 (no cost extension to 6/30/2013)
Goals: to investigate the cross-talk between membrane estrogen receptor (ERa and ERß) initiated estrogen signaling and nuclear ER signaling to reciprocally regulate eNOS and caveolin-1 expression by estrogen.
NIH RO1 HL74947
Caveolin-1, caveolae, and placental angiogenesis
Direct Cost: $200,000/yr (Total $1,322,902)
Goals: The purpose of this project is to investigate a role of caveolin-1/caveolae in regulating VEGF/VEGFR signaling in relation to placental artery endothelial cell proliferation and differentiation, i.e., in vitro angiogenesis.
NIH RO1 HL70562-01
Estrogen actions in uterine artery endothelium
Direct Cost: $200,000/yr (Total $786,330)
Duration: 09/25/2001- 06/30/2005
Goals: This grant investigated acute and chronic estrogen signaling that regulates eNOS activation and NO production in uterine artery endothelium.
• Society for the Study of Reproduction, 1995 -
• Society for Gynecological Investigation, 1999 -
• Perinatal Research Society, 2003 -
• Endocrine Society, 2007 -
• Society for Free Radical Biology and Medicine, 2006 -
• Sigma X, 2009 -
• North American Vascular Biology Organization, 2010-
• American Physiological Society, 2011-
• American Heart Association, 2011-
Cellular and Molecular Biosciences
Obstetrics and Gynecology