Going Deeper

We develop technologies to image and control the function of cells deep inside the body. These technologies take advantage of biomolecules with unusual physical properties allowing them to interact with sound waves and magnetic fields. We apply these tools to problems in synthetic biology, neuroscience, cancer, immunology and the mammalian microbiome.

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Imaging and controlling cellular function with ultrasound.
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New molecules and mechanisms for MR imaging and magnetic actuation.
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Biophysics of cellular interactions with sound waves, temperature and magnetic fields.
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Spatially, molecularly and temporally precise control of neural circuits.
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Magnetically-enhanced GI colonization

Congratulations to Marjorie, Pradeep and colleagues on their new paper in Advanced Materials describing the use of magnetic fields to help probiotic agents localize and colonize within the mammalian gastrointestinal tract. This technology can help bacterial therapies find and establish themselves in their niche without disruptive antibiotics.

Buss MT#, Ramesh P#, English MA, Lee-Gosselin A, Shapiro MG*. Spatial control of probiotic bacteria in the gastrointestinal tract assisted by magnetic particles. Advanced Materials 33, 2007473 (2021).

Ultrasound-actuated bacterial immunotherapy

Congratulations to Mohamad, Michael and colleagues on their new study describing the development of ultrasound-controlled bacterial immunotherapy for solid tumors. This work increases the specificity and safety of an important class of emerging therapeutics by combining gene circuit engineering with ultrasound physics.

Abedi MH#, Yao M#, Mittelstein DR, Bar-Zion A, Swift MB, Lee-Gosselin A, Shapiro MG*. Acoustic remote control of bacterial immunotherapy. bioRxiv preprint

Ultrasonic brain-machine interfaces

Congratulations to Sumner, David, Vasileios and colleagues on their new paper describing the use of functional ultrasound imaging to decode movement intentions. This work represents a critical first step towards minimally invasive, ultrasound-based brain-machine interfaces. Thanks to wonderful collaborators Richard Andersen and Mickaël Tanter.

Norman SL#, Maresca D#, Christopoulos VN#, Griggs WS, Demene C, Tanter M, Shapiro MG*, Andersen RA*. Single-trial decoding of movement intentions using functional ultrasound neuroimaging. Neuron 109, 1554-1566 (2021). article | press

Imaging the function of liver macrophages

Congratulations to Bill, Justin, David, Audrey, Dina and Margaret on their new study using systemically injected gas vesicles to non-invasively quantify both phagocytosis and lysosomal function in liver disease. This work represents the first diagnostic application of biomolecular ultrasound.

Ling B, Lee J, Maresca D, Lee-Gosselin A, Malounda D, Swift MB, Shapiro MG*. Biomolecular ultrasound imaging of phagolysosomal function. ACS Nano 14, 12210-12221 (2020). article

Acoustic biosensors of enzyme activity

Congratulations to Anu, Zhiyang, Suchita and colleagues on their new paper in Nature Chemical Biology describing the first acoustic biosensors. These biosensors turn on nonlinear ultrasound contrast in response to protease activity. This allows the action of enzymes such as TEV, Calpain and ClpXP to be visualized in cells deep inside the body.

Lakshmanan A#, Jin Z#, Nety SP, Sawyer DP, Lee-Gosselin A, Malounda D, Swift MB, Maresca D, Shapiro MG*. Acoustic biosensors for ultrasound imaging of enzyme activity. Nature Chemical Biology 16, 988-986 (2020).
article | readcube | behind the paper | press

Thermal control of engineered T-cells

Congratulations to Mohamad, Justin and Dan on their new paper in ACS Synthetic Biology describing genetic circuits allowing engineered T-cell immunotherapies to be controlled with temperature. Their work creates the possibility of controlling T-cells inside the body with brief pulses of heat delivered by focused ultrasound, magnetic hyperthermia or infrared light.

Abedi MH, Lee J, Piraner DI, Shapiro MG*. Thermal control of engineered T-cells. ACS Synthetic Biology 9, 1941-50 (2020). article | bioRxiv preprint

Shapiro Lab holiday party 2019

Thanks to everyone who joined us to celebrate the holiday season, toast to an exciting and fulfilling 2020 and squeeze into a selfe!

Ultrasound imaging of gene expression in mammalian cells

Congratulations to Arash, Gabrielle, Danny and Ray on their new paper in Science describing the mammalian expression of gas vesicles. For the first time, ultrasound can be used to image gene expression in mammalian cells.

Farhadi A, Ho GH, Sawyer DP, Bourdeau RW, Shapiro MG*. Ultrasound imaging of gene expression in mammalian cells. Science 365, 1469 (2019). article | perspective | news

Thermal control of protein association

Congratulations to Dan and Echo on their publication describing modular protein domains with sharp, tunable, temperature-dependent heterodimerization. Fusing these domains with other proteins provides control over their association and localization using temperature, which can be delivered globally and locally using methods such as focused ultrasound and magnetic hyperthermia.

Piraner DI, Wu Y, Shapiro MG*. Modular thermal control of protein dimerization. ACS Synthetic Biology 8, 2256-2262 (2019). article

Shapiro Lab summer retreat 2019

Thanks to all the lab members, alumni and friends who joined us for the Shapiro Lab summer retreat in Temecula, CA.