Dr. Xiucui Ma joined the Department of Medicine in the Cardiovascular Division as an assistant professor in February 2023. Dr. Ma received her PhD in 2006 from Zhejiang University through a joint program with Washington University School of Medicine, where she trained in molecular biology and gene therapy. After graduation, she pursued postdoctoral research training in gene therapy for disorders such as mucopolysaccharidoses (MPS), which are lysosomal storage disorders, in Dr. Katherine Ponder’s lab in the Department of Medicine at Washington University School of Medicine. During this phase, she gained valuable experience and acquired skills in cell biology, molecular biology, virology, immunology, and biochemistry, in both the in-vitro and in-vivo model systems. Subsequently, she transitioned to the role of a staff scientist under the supervision of Dr. Samuel L. Stanley, the former Vice-chancellor for Research at Washington University, in the Infectious Diseases division of the Departments of Medicine and Molecular Microbiology.
She studied the biological mechanisms by which cells respond to infectious agents such as amoebae, and the molecular underpinnings of the inflammatory response. Fascinated by the role of inflammation in cardiovascular disease, she transferred to Dr. Abhinav Diwan’s lab as a staff scientist in 2009 and grew in the ranks to lead a senior scientist in 2014-2022 in his program. During this period, she studied the role of lysosomal pathways in cellular homeostasis and under stress in cardiac pathophysiology. Together with Dr. Diwan, she led a talented team that uncovered evidence for dysregulation of the lysosome machinery as a major contributor in myocardial ischemia-reperfusion injury and described intermittent fasting as a strategy to stimulate lysosome function in vivo. She further demonstrated the intermittent fasting stimulates activation of transcription factor EB, a master regulator of the lysosome biogenesis program, to rescue advanced cardiomyopathy triggered by genetic mutations that cause protein aggregate pathology and desminopathies.
She also discovered the role of an innate immunity effector, TRAF2, which functions as an E3 ubiquitin ligase to drive mitophagy and prevent inflammation to maintain cardiac myocyte homeostasis. Her collaborative efforts helped uncover evidence for acquired lysosome dysfunction in various CNS cell types in Alzheimer’s disease; whereby enhancing flux through the autophagy-lysosomal pathway (ALP) is an attractive therapeutic option to attenuate amyloid plaque pathology. Drawing upon her comprehensive knowledge and experience in both basic sciences and biomedical research, she is interested in mechanistically probing lysosome biology and developing targeted strategies to harness lysosome function to treat diseases, in her role as a Research Assistant Professor, in Dr. Abhinav Diwan’s research program. Dr. Ma’s primary research interest is in defining the molecular and cellular mechanisms of cardiomyopathy and heart failure, and in development of novel therapeutic approaches targeting lysosome function to treat cardiac and metabolic diseases.