Xiaowen Bai, MD, PhD

My research interests are centered on the application of stem cells on disease modeling and tissue regeneration. The current major focus of the laboratory is to utilize gain- and loss-of-function approaches to examine the novel molecular mechanisms underlying the roles of non-coding RNAs, mitochondria, and genetic factors in neurodegeneration and cardiotoxicity in mice, and translate the findings to humans using stem cell-derived brain cells, heart cells, three-dimensional mini brains, and heart organoids.

Research Area 1: Non-coding RNAs, mitochondria, and cell stress-related genes in neurodegeneration:
Neurological disorders have emerged as a predominant healthcare concern in recent years due to their severe consequences on quality of life and prevalence throughout the world. Understanding the underlying mechanisms of these diseases and the interactions between different brain cell types is essential for the development of new therapeutics. Many drugs (e.g., anesthetics), environmental factors (e.g., alcohol), diseases, and genetic risks are related to neurodegeneration. We examine the novel molecular mechanisms underlying the roles of microRNAs, long non-coding RNAs, mitochondria, immediate early and other cell stress-related genes in neurodegeneration using both mouse, and human stem cell-derived brain cell and three-dimensional mini brain models

Human induced pluripotent stem cell-derived mini brain (left) and the neurons in mini brain (middle). Alcohol-induced neuroapoptosis (red) in neonatal mouse brain (right).

Research Area 2: Stem cell-mediated myocardial regeneration
Myocardial infarction is one of the major causes of death throughout the world. Currently, there is not a highly effective approach for treatment. Stem cells hold promise in repairing injured cardiac tissue. Our lab is involved in studying the effect of the transplantation of adipose tissue-derived stem cells and induced pluripotent stem cell-derived cardiomyocytes on myocardial regeneration following ischemia injury. A molecular imaging method has been developed to investigate the molecular mechanisms controlling homing, engraftment, and survival of injected cells in vivo.

Research Area 3: The mechanisms of impaired cardioprotection under diabetic conditions
Hyperglycemia has been shown to be particularly detrimental to the cardioprotective effects, with the underlying mechanisms remaining largely unknown. We have developed and validated a clinically relevant model of functional human cardiomyocytes derived from both normal induced pluripotent stem cells (iPSCs) and diabetes mellitus iPSCs. This in vitro model of human disease will enable developmental and comparative studies of normal and diabetic cardiomyocytes to address genetic and environmental mechanisms responsible for attenuation of cardioprotection signaling in diabetics.

Functional contracting human cardiomyocytes generated from induced pluripotent stem cells

Mitochondrial dynamics (movement, fusion and fission) in human neurons generated from embryonic stem cells. Green signals represent mitochondria. Red and yellow colors highlight mitochondria in process of fusion.