The research activities in my laboratory have two major focuses. The one is to investigate the cellular and molecular mechanisms underlying the uterine vascular adaptation to pregnancy and chronic hypoxia. These studies are to test the hypothesis that chronic hypoxia during gestation causes maladaptation of steroid hormone receptor gene expression patterns in the uterine artery through enhanced promoter methylation resulting in heightened myogenic response of the uterine artery in pregnancy. The other area of research interests is to study fetal epigenetic programming of gene expression patterns caused by adverse intrauterine environments, which is essential in explaining many fundamental biological processes by which a variety of cardiovascular dysfunctions and disease emerge and evolve. We are interested in the assessments of molecular mechanisms of DNA methylation in epigenetic programming of gene expression patterns in the developing heart, and the role of sex and sex-defining steroids in determining an “ischemia-sensitive” phenotype in the heart.
1. Tong W, Zhang L. Hypoxia and fetal programming of matrix metalloproteinases. Drug Discovery Today invited keynote review, 17: 124-134, 2012.
2. Shi L, Mao C, Zeng F, Zhang L, Xu Z. Central angiotensin I increases fetal swallowing activity and oxytocin release in near-term ovine fetus. Neuroendocrinology 95: 248-256, 2012.
3. Patterson AJ, Xiao D, Xiong F, Dixon B, Zhang L. Hypoxia-derived oxidative stress mediates epigenetic repression of PKCε gene in foetal rat hearts. Cardiovas Res 93: 302-310, 2012.
4. Xiong F, Xiao D, Zhang L. Norepinephrine causes epigenetic repression of PKCε gene in rodent hearts by activating Nox1-dependent reactive oxygen species production. FASEB J 26: 2753-2763, 2012.
5. Hu X, Zhang L. Function and regulation of large conductance Ca2+-activated K+ channel in vascular smooth muscle Cells. Drug Discovery Today invited keynote review, 17: 974-987, 2012.
6. Li Y, Gonzalez P, Zhang L. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions. Progress in Neurobiology 98: 145-165, 2012.
7. Dasgupta C, Xiao D, Xu Z, Yang S, Zhang L. Developmental nicotine exposure results in programming of alveolar simplification and interstitial pulmonary fibrosis in adult male rats. Reproduc Toxicol 34: 370– 377, 2012.
8. Hu X, Xiao D, Zhu R, Huang X, Yang S, Wilson S, Zhang L. Chronic hypoxia suppresses pregnancy-induced upregulation of large conductance Ca2+-activated K+ channel activity in uterine arteries. Hypertension 60: 214-222, 2012.
9. Li Y, Xiao D, Dasgupta C, Xiong F, Tong W, Yang S, Zhang L. Perinatal nicotine exposure increases vulnerability of hypoxic-ischemic brain injury in neonatal rats: role of angiotensin II receptors. Stroke 43: 2483-2490, 2012.
10. Dasgupta C, Chen M, Zhang H, Yang S, Zhang L. Chronic hypoxia during gestation causes epigenetic repression of ERa gene in ovine uterine arteries via heightened promoter methylation. Hypertension 60: 697-704, 2012.
11. Xiao D, Huang X, Zhang L. Chronic hypoxia differentially up-regulates PKC-mediated ovine uterine arterial contraction via actin polymerization signaling in pregnancy. Biol Reproduc 87(6):142, 1–9, 2012.
12. Paradis A, Zhang L. Role of endothelin in uteroplacental circulation and fetal vascular function. Curr Vascu Pharmacol 11: 594-605, 2013.
13. Zhu R, Xiao D, Zhang L. Potassium channels and uterine vascular adaptation to pregnancy and chronic hypoxia. Curr Vascu Pharmacol 11: 737-747, 2013.
14. Zhang L. Uteroplacental circulation and fetal vascular development and function. Editorial, Curr Vascu Pharmacol 11: 543, 2013.
15. Xiong F, Zhang L. Role of hypothalamic-pituitary-adrenal axis in developmental programming of health and disease. Frontiers in Neuroendocrinology 34: 27-46, 2013
16. Chen M, Xiong F, Zhang L. Promoter methylation of Egr-1 site contributes to fetal hypoxia-mediated PKCε gene repression in the developing heart. Am J Physiol Regul Integr Comp Physiol 304: R683-R689, 2013.
17. Tong W, Xiong F, Li Y, Zhang L. Hypoxia inhibits cardiomyocyte proliferation in fetal rat hearts via upregulating TIMP-4. Am J Physiol Regul Integr Comp Physiol 304: R613-R620, 2013.
18. Xiao D, Huang X, Yang S, Zhang L. Estrogen Normalizes Perinatal Nicotine-Induced Hypertensive Responses in Adult Female Rat Offspring. Hypertension 61: 1246-1254, 2013.
19. González P, Tong W, Xue Q, Hu S, Zhang L. Fetal hypoxia results in programming of aberrant angiotensin II receptor expression patterns and kidney development. Int J Med Sci 10: 532-538, 2013.
20. Zhu R, Hu XQ, Xiao D, Yang S, Wilson SM, Longo LD, Zhang L. Chronic hypoxia inhibits pregnancy-induced upregulation of SKCa channel expression and function in uterine arteries. Hypertension 62: 367-374, 2013.
21. Mao C, Liu R, Li S, Bo L, Chen N, Xia S, Chen J, Li D, Zhang L, Xu Z. High salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system. J Endocrinol 218: 61-73, 2013.
22. Zhou J, Xiao D, Hu Y, Wang J, Paradis A, MataGreenwood E, Zhang L. Gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 signaling in pregnant rats. Hypertension 62: 599-607, 2013.
23. Li Y, Xiao D, Yang S, Zhang L. Promoter methylation suppresses AT2R gene and increases brain hypoxic-ischemic injury in neonatal rats. Neurobiol Dis 60: 32-38, 2013.
24. Xiao D, Hu XQ, Huang X, Wilson S, Yang S, Zhang L. Chronic hypoxia during gestation enhances uterine arterial myogenic tone via heightened oxidative stress. PLoS One 8: e73731, 2013.
25. González P, Xiong F, Li Y, Zhang L. Fetal hypoxia increases vulnerability of hypoxic-ischemic brain injury in neonatal rats: role of glucocorticoid receptors. Neurobiol Dis 65: 172-179, 2014.
26. Paradis AN, Gay MS, Zhang L. Binucleation of cardiomyocytes: the transition from a proliferative to a terminally differentiated state. Drug Discovery Today, 19: 602-609, 2014.
27. Xiao D, Dasgupta C, Chen M, Zhang K, Buchholz J, Xu Z, Zhang L. DNA demethylation reverses norepinephrine-induced cardiac hypertrophy and failure. Cardiovasc Res 101: 373-382, 2014.
28. Goyal R, Zhang L, Blood A, Baylink DJ, Longo LD, Oshiro B, Mata-Greenwood E. Characterization of an animal model of pregnancy-1 induced vitamin D deficiency due to metabolic gene dysregulation. Am J Physiol Endo 306: E256-E266, 2014.
29. Paradis AN, Xiao D, Zhou J, Zhang L. Endothelin-1 promotes cardiomyocyte terminal differentiation in the developing heart via heightened DNA methylation. Int J Med Sci 11: 373-380, 2014.
30. Xia S, Lv J, Gao Q, Li L, Chen N, Wei X, Xiao J, Chen J, Tao J, Sun M, Mao C, Zhang L, Xu Z. Prenatal exposure to hypoxia induced Beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses. Reprod Sci 2014 May 28. pii: 1933719114536474. [Epub ahead of print].
31. Xiao D, Huang X, Xue Q, Zhang L. Antenatal hypoxia induces programming of reduced arterial blood pressure response in female rat offspring: role of ovarian function. PLoS One 9: e98743, 2014.
32. Zhu R, Huang X, Hu X, Xiao D, Zhang L. Gestational hypoxia increases ROS and inhibits steroid hormone-mediated upregulation of Ca2+-activated K+ channel function in uterine arteries. Hypertension 64: 415-422, 2014.
33. Chen M, Dasgupta C, Xiong F, Zhang L. Epigenetic upregulation of large-conductance Ca2+-activated K+ channel expression in uterine vascular adaptation to pregnancy. Hypertension 64: 610-618 2014.
34. Xiao D, Zhu R, Zhang L. Gestational hypoxia inhibits calcium-activated potassium channels in ovine uterine arteries. Int J Med Sci 11: 886-892, 2014.
35. Xiao D, Dasgupta C, Li Y, Huang X, Zhang L. Perinatal nicotine exposure increases angiotensin II receptor-mediated vascular contractility in adult offspring. PLoS One 9: e108161, 2014.
36. Xue Q, Patterson AJ, Xiao D, Zhang L. Glucocorticoid modulates angiotensin II receptor expression patterns and protects the heart from ischemia and reperfusion injury. PLoS One 9: e106827, 2014.
37. Zhang L, Ducsay CA. Ed. Advances in fetal and neonatal physiology. Springer New York, July 2014.
38. Zhang L, Longo LD. Ed. Stress and developmental programming of health and disease: Beyond phenomenology. Nova Science Publishers, Inc. New York, September 2014.
39. Ma Q, Zhang L. Epigenetic programming of brain developmental plasticity. Progress in Neurobiology accepted for publication.
40. Song M, Paradis AN, Gay MS, Shin J, Zhang L. Differential expression of microRNAs in ischemic heart disease. Drug Discovery Today accepted for publication.
41. Ma Q, Xiong F, Zhang L. Gestational hypoxia and epigenetic programming of brain development disorders. Drug Discovery Today accepted for publication.
42. González P, Li Y, Martinez F., Zhang L. Dexamethasone protects against hypoxic-ischemic brain injury in neonatal rats via activation of LPGDS-dependent PGD2-DP1-pERK signaling pathway. PLoS One minor revision.
43. Paradis AN, Gay M, Wilson CG, Zhang L. Newborn hypoxia/anoxia decreases cardiomyocyte proliferation and endowment in the developing heart: role of endothelin-1. PLoS One revision.
44. Xue Q, Patterson AJ, Xiao D, Zhang L. Estrogen regulates angiotensin II receptor expression patterns and protects the heart from ischemic injury in female rats. Am J Physiol Heart Circ Physiol minor revision.