Cardiovascular and pulmonary diseases (CVPDs) are the top leading causes of death in China and worldwide. The morbidity and mortality of such diseases has been linked to environmental pollution. The central focuses of our research are to decipher the mechanisms by which environmental pollutants damage the cardiovascular and pulmonary systems and exacerbate the risk of CVPDs with the goal of developing new preventive and therapeutic approaches for CVPDs.

Project 1: Energy metabolism and cardiopulmonary vasculature injury.

Energy metabolism is a fundamental survival mechanism for all mammals. Metabolic alterations have been implicated in the development of many CVPDs. We aim to investigate the crucial roles of metabolic pathways and metabolites in regulating environmental biohazards e.g., heavy metals, pesticides, and nanomaterials induced damages in the cardiovascular and pulmonary systems.

Project 2: Redox stresses and cardiopulmonary vasculature dysfunctions.

Cellular redox homeostasis is finely tuned by antioxidants (antioxidant enzymes and nonenzymatic antioxidants) and pro-oxidants (reactive oxygen/nitrogen species; ROS/RNS). Imbalance between these two arms leads to redox stresses including oxidative stress and reductive stress, both of which are detrimental to biological processes. We aim to elucidate how environmental pollutants perturb cellular redox balance leading to cardiopulmonary vasculature dysfunctions.

1. US NIH R01 Project: L-2-hydroxyglutarate and metabolic remodeling in hypoxia. Researcher; 2020-2022

2. US NIH NIH R37 Project：GPx-3 and peroxide flux in the endothelial cell. Researcher; 2015-2017

3. US NIEHS Iowa Superfund Project：Semi-volatile PCB exposure and oxidative stress in mammalian cells. Researcher; 2010-2014

1. He H, Mulhern RM, Oldham WM, Xiao W, Lin Y, Liao R, Loscalzo J. L-2-hydroxyglutarate protects against cardiac injury via metabolic remodeling. Circulation Research. 2022, 131: 562-579.

2. Xiao W, Oldham WM, Priolo C, Pandey AK, Loscalzo J. Immunometabolic endothelial phenotypes: integrating inflammation and glucose metabolism. Circulation Research. 2021, 129: 9-29.

3. Xiao W and Loscalzo J. Metabolic response to reductive stress. Antioxidants & Redox Signaling. 2020, 32: 1330-1347.

4. Xiao W, Wang RS, Handy DE, Loscalzo J. NAD(H) and NADP(H) redox couples and cellular energy metabolism. Antioxidants & Redox Signaling. 2018, 28: 251-272.

5. Xiao W, Sarsour EH, Wagner BA, Doskey CM., Buettner GR, Domann FE, Goswami PC. Succinate dehydrogenase activity regulates PCB3-quinone induced metabolic oxidative stress and toxicity in HaCaT human keratinocytes. Archives of Toxicology. 2016, 90: 319-332.

6. Xiao W, Vorrink SU, Domann FE, Goswami PC. Ligand-independent activation of aryl hydrocarbon receptor signaling in PCB3-quinone treated HaCaT human keratinocytes. Toxicology Letters. 2015, 233: 258-266.

7. Xiao W and Goswami PC. Down-regulation of peroxisome proliferator activated receptor γ coactivator 1α induces oxidative stress and toxicity of 1-(4-Chlorophenyl)-benzo-2,5-quinone in HaCaT human keratinocytes. Toxicology In Vitro. 2015, 29: 1332-1338.

8. Xiao W, Zhu Y, Sarsour EH, Kalen AL, Aykin-Burns N, Spitz DR, Goswami PC. Selenoprotein P regulates 1-(4-Chlorophenyl)-benzo-2,5-quinone induced oxidative stress and toxicity in human keratinocytes. Free Radical Biology and Medicine. 2013, 65: 70-77.

9. Xiao W, Zhang J, Liang J, Zhu H, Zhou Z, Wu Q. Adverse effects of neonatal exposure 3,3',4,4',5,5'-hexachlorobiphenyl on hormone levels and testicular function in male Sprague-Dawley rats. Environmental Toxicology. 2011, 26: 657-668.

10. Xiao W, Li K, Wu Q, Nishimura N, Chang X, Zhou Z. Influence of persistent thyroxine reduction on spermatogenesis in rats neonatally exposed to 2,2',4,4',5,5'-hexachlorobiphenyl. Birth Defects Research. 2010, 89: 18-25.