Session: 20-17-01: Rising Stars of Mechanical Engineering

Paper Number: 173422

Studying Mechano-Immunology on Earth and in Space 

Mechanical forces profoundly influence immune function, yet their role in driving immune dysfunction in extreme macroenvironments or pathological microenvironments remains poorly understood. My lab investigates how mechanical stressors—whether from tumor growth, tissue damage, or hostile environments—shape immune cell behavior, survival, and therapeutic responsiveness. Supported by three early career awards from the National Institutes of Health (K22, R35) and the Air Force Office of Scientific Research (YIP), our research spans both fundamental and translational axes of mechano-immunology.

 

With the support of these awards, we are addressing three major gaps in this nascent field. First, we are establishing the first comprehensive immune mechanome, a multiscale study (in vitro, ex vivo, in vivo) of how innate and adaptive immune cells respond to mechanical forces across diverse organ systems. This effort combines tissue-level mechanical perturbations with multi-omics (e.g., single-cell/spatial transcriptomics, epigenomics, proteomics, metabolomics), dynamic intravital imaging through transparent windows in mice, and machine learning-based cell state analysis.

 

Second, in glioblastoma models on Earth and in space, we are uncovering a mechanopathological feedback loop between tumor-driven solid mechanical forces and tumor-supporting myeloid cells. These interactions promote immune suppression, vascular collapse, and resistance to immunotherapy. Our models suggest that targeting this reciprocal mechanical-immune axis may reprogram the tumor microenvironment and enhance response to immune checkpoint blockade. These investigations now include cancer-immune organoids grown in the permanent microgravity environment of the International Space Station, revealing unique mechanobiological phenomena of cancer-immune dynamics.

 

Third, using spheroids/organoids as health avatars, we are modeling the effects of compounded warfighter stressors—including mechanical loading, environmental extremes, and altered gravity—on immune cell function. These avatars simulate key features of immune compromise seen in operational settings and serve as a testbed for identifying pharmacological and engineering-based countermeasures for the Air Force and Space Force.

 

I will share exciting results from all three projects, including: i) how macrophages alone can exert measurable mechanical forces on their surrounding microenvironments; ii) the morphological, transcriptional, metabolic, and functional changes macrophages undergo in response to chronic mechanical compression; iii) the superior growth and development of cancer-immune organoids in the permanent microgravity of space compared to organoids grown under Earth’s gravity; and iv) novel methods to simulate both microgravity and warfighter immunity in terrestrial laboratories.

 

Together, these projects form a unified framework to understand and therapeutically target immune dysregulation under mechanical and environmental stress—on Earth and in space. This integrative approach aims to reveal new fundamental knowledge of mechano-immunology and to inform biomedical health and treatment approaches for humans on Earth and in space. 

Presenting Author: Meenal Datta University of Notre Dame

Presenting Author Biography: Meenal Datta is an assistant professor in the Department of Aerospace and Mechanical Engineering at the University of Notre Dame, with a concurrent appointment in the Department of Chemical and Biomolecular Engineering. Prof. Datta received her Ph.D. in chemical and biological engineering from Tufts University in 2018, after which she completed a postdoctoral fellowship at Harvard Medical School and Massachusetts General Hospital, before starting her faculty position in 2021. Her research focuses on deciphering the atypical tumor microenvironment that drives disease progression and treatment resistance in incurable cancers. By understanding and overcoming the biological, chemical, electrical, and mechanical abnormalities found in solid tumors, new therapeutic approaches can be discovered.

Prof. Datta specializes in multidisciplinary and mechanism-based preclinical research that has the potential to be rapidly translated to improve treatment approaches in the clinic. She has spent her time as a researcher deciphering and reprogramming abnormal tissue microenvironments that are present in a variety of diseases ranging from virulent tuberculosis to benign schwannoma to deadly glioblastoma that, surprisingly, share unifying features: abnormal blood vessels, abundant extracellular matrix, immunosuppression, and mechanopathologies. During her Ph.D., Dr. Datta normalized the aberrant blood vasculature found in pulmonary tuberculosis granulomas to improve drug delivery. In her postdoctoral training, Dr. Datta re-engineered the immunosuppressive brain tumor microenvironment to improve glioblastoma response to immunotherapy.

As the director of the Tumor Immune Microenvironment & Mechanics (TIME) Lab at Notre Dame (https://timelab.nd.edu), Prof. Datta’s research group applies engineering fundamentals and problem-solving approaches to explore immunomechanics and mechano-immunology in health and disease and to discover novel biophysical mechanisms that can be targeted therapeutically to enhance treatment outcomes in cancer and other conditions. Prof. Datta’s lab also conducts science-in-space experiments on the International Space Station (ISS) to test novel modeling and treatment approaches on cancer avatars in microgravity.

Prof. Datta has received numerous awards in support of her research including a National Heart, Lung, and Blood Institute F31 predoctoral fellowship (2016), a postdoctoral fellowship from the American Association of Cancer Research (2019), a National Cancer Institute K22 career transition award (2021), a junior faculty award from the Oak Ridge Associated Universities (2022), a National Institute of General Medical Sciences R35 award for early-stage investigators (2023), and an AFOSR Young Investigator Program award (2025). Dr. Datta’s in-space research on the ISS is supported by grants from NSF/CASIS Tissue Engineering and Mechanobiology (2024) and AFOSR Space Biosciences (2024). In 2024, Prof. Datta was awarded the Young Innovator Award in Cellular and Molecular Bioengineering from the Biomedical Engineering Society.

Authors:

Meenal Datta University of Notre Dame