Research Focus
Cells communicate with each other and their environments in a variety of ways, including using chemical signals to send messages. Traditionally, biomedical research has been dominated by the study of these chemical signals and how they influence cell growth and fate. Yet nearly all cells also experience mechanical stimuli—cells are pushed, pressured, and sheared constantly. Many diseases, including deafness, osteoporosis, and hypertension, are caused by a cell’s inability to sense mechanical stimuli properly.
Our group uses an interdisciplinary approach to understand how cells sense and process mechanical stimuli in health and disease. We hope to identify novel “mechanosensing” pathways as promising drug targets for different diseases.
Research Projects
Immune Cell Mechanotransduction
The Role of Mechanotransduction in Blood Disorders
Mechanosensing in Human Biology
Immune Cell Mechanotransduction
Chemical signaling pathways have been extensively studied in immune cells. Despite the fact that these cells also experience physical forces, how mechanical forces influence immune cells at the molecular level is largely unknown. Additionally, the impact of immune cell mechanotransduction at the organismal level in physiological settings or in response to disease states remains elusive. We are establishing in vitro and in vivo models to answer these questions.
The Role of Mechanotransduction in Blood Disorders
Rare mutations in PIEZO1 mechanically activated ion channels cause hereditary xerocytosis, a disorder characterized by red blood cell dehydration. Recently, comprehensive medical exams of xerocytosis patients identified other perplexing syndromes associated with PIEZO1 variants. We hypothesize that PIEZO1-dependent mechanotransduction could play important roles in various blood cell lineages, beyond its normal functions in erythrocytes. We use humanized mouse models to uncover the molecular basis of these disorders.
Mechanosensing in Human Biology
Rapid developments in precision medicine and computational science have provided us with a growing number of genome and metabolome databases to explore. Our lab is using these data to explore uncharted territories of human biology by creating exciting hypotheses to test. Already we have found new mutations in genes encoding mechanosensitive proteins associated with surprising phenotypic traits from a half million individuals. We will investigate more novel areas of human biology where mechanotransduction plays unrecognized roles.
About Dr. Ma
Shang Ma, Ph.D., received his bachelor’s degree from University of British Columbia in Vancouver, Canada, with a major in genetics. He earned his Ph.D. in cellular and molecular biology from University of Wisconsin in Madison, where he focused on chemical signaling pathways that mediate mammalian brain development. In 2015, Dr. Ma joined Dr. Ardem Patapoutian’s group at Scripps Research to study how cells sense mechanical forces during pathogenesis. During this postdoc training, he discovered that overactive PIEZO mechanosensitive ion channels play important roles in various human disorders.
In 2022, Dr. Ma joined the faculty of Children’s Medical Center Research Institute at UT Southwestern as an Assistant Professor. He holds a secondary appointment in the Department of Pediatrics.
Selected Publications
Ma, S., Dubin, A.E., Romero, L.O., Loud, M., Salazar, A., Wang, Y., Chesler, A.T., Wilkinson, K., Vásquez, V., Marshall, K.L., et al. (2022). Excessive Mechanotransduction in Sensory Neurons Causes Joint Contractures in a Mouse Model of Arthrogryprosis. Science, 2022 (in press). (bioRxiv)
Ma, S., Dubin, A.E., Zhang, Y., Mousavi, S.A.R., Wang, Y., Coombs, A.M., Loud, M., Andolfo, I., and Patapoutian, A. (2021). A role of PIEZO1 in iron metabolism in mice and humans. Cell 184, 969-982.e13. (PubMed)
Ma, S., Cahalan, S., LaMonte, G., Grubaugh, N.D., Zeng, W., Murthy, S.E., Paytas, E., Gamini, R., Lukacs, V., Whitwam, T., et al. (2018). Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates Plasmodium Infection. Cell 173, 443-455.e12. (PubMed)
