Dr. Xin Tang earns trio of federal grants

MAE professor Xin Tang won three significant awards selected nationwide this past year, receiving grant money from the National Institute of Health (NIH), the National Science Foundation (NSF), and the Air Force Office of Scientific Research (AFOSR).

The NIH granted Tang a prestigious Maximizing Investigators’ Research Award (MIRA R35), which essentially has the goal of increasing scientific productivity of early-career investigators by giving investigators stability and flexibility. This has the intended effect of encouraging more efficient use of funding to promote the career development of young investigators provided by the NIH’s National Institute of General Medical Sciences. Tang’s project for this grant aims to establish a solid theoretical foundation of mechanobiology and promote the innovationdevelopment of new therapeutic strategies that leverage these mechanobiological theories. 

All cells in our bodies are affected by mechanical forces, which heavily influence the cells’ intracellular biochemical signaling and gene expression. The process by which cells sense and transduce mechanical stimuli from their microenvironment into intracellular signaling and gene expression is called mechanotransduction, and the failure to properly regulate mechanotransduction is a key factor of various pathologies. 

“Currently, a major knowledge gap in the biomechanics field is that how mechanotransduction takes place in cells is not understood,” Tang said. “In this MIRA R35 project, we will create a multidisciplinary research pipeline to systematically elucidate the mechanotransduction process and to establish a theoretical foundation to bridge the knowledge gap.”

He explained that the research pipeline will focus particularly on decoding the mechanically regulated biochemical waves and chaos in human tissue cells, since these biochemical waves link the extracellular mechanical forces with intracellular biochemical signaling, thereby serving as a functional nexus. 

“The success of this project will enable tackling a variety of critical and challenging scientific questions regarding the interplay between mechanical forces and cell signaling,” Tang said.

For the NSF grant, his project will aim to create a novel experimental-computational framework that will enable optical interrogation of mechano-electrical dynamics of neurons in a mechanobiologically guided, multiscale, and non-invasive manner. Essentially, Tang’s team hopes to develop a new mechanobiology-guided, all-optical, and machine-learning-powered system to measure multi-scale neural dynamics in mechanical microenvironments at an unprecedented speed. Dr. Kejun Huang of the Computer and Information Science and Engineering (CISE) Department will serve as a co-primary investigator (co-PI) with Tang on this project.

The dynamics of electrical signals are an essential phenotype of many cell types (especially neurons), serving as both a functional regulator to mediate neural behavior and as a physiological indicator of the cellular states of neurons in health or disease. Therefore, quantitative recording and manipulation of electrical dynamics in neurons could provide insights that would advance the current understanding of the function and behavior of nervous systems.

Like most living cells, neurons sense their surrounding biomechanical and biochemical microenvironments, and they respond to mechanical signals by adapting and changing their cellular states.

“However, past neurobiology research, in particular in vitro studies, has mostly studied neurons cultured in rigid petri dishes, which have dramatically different mechanical microenvironments compared to those in soft brains and peripheral tissues,” Tang said. “As such, the physiological relevance of recorded membrane voltage dynamics in labs and neural behavior in nature remain unknown.”

For the AFOSR project, Tang will research how the brains of vertebrates compute signals received by the eyes, and how they make corresponding cognitive decisions.

“We are all living in a dynamic world and need to make different decisions all the time, such as deciding which food to eat or which hotel to live in,” Tang said. “A long-standing puzzle in neuroscience is how the brain senses and computes the eye-received signals to generate cognition and behavior. A deep understanding of this process will provide important insights of how our brain mechanistically functions and interprets our surrounding world.”

For the project that includes Prof. Jose Principe as co-PI from the Department of Electrical and Computer Engineering (ECE), Tang plans to develop a synergistic experimental-computational platform to capture the electrical dynamics in a zebrafish’s brain while the fish is sensing and computing visual signals. The zebrafish was chosen as the study sample because the species’s brains are structurally and functionally similar to human brains.

“The success of this project will bridge the current technology gaps and provide important answers to the critical knowledge gaps in understanding cognitive behaviors,” Tang said.