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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  • Welcome to the Shapiro Lab at the California Institute of Technology.

    Welcome to the Shapiro Lab at the California Institute of Technology.

  • Pasadena, California, USA.

    Pasadena, California, USA.

BIOACOUSTICS

BIOACOUSTICS

Imaging and controlling cellular function with ultrasound.
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BIOMAGNETISM

BIOMAGNETISM

New molecules and mechanisms for MR imaging and magnetic actuation.
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BIOPHYSICS

BIOPHYSICS

Biophysics of neuromodulation with ultrasound and other forms of energy.
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BIOCHEMISTRY

BIOCHEMISTRY

Spatially, molecularly and temporally precise control of neural circuits.
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Acoustic window to the human brain

Can we image and decode brain activity with ultrasound noninvasively in adult humans? Yes, by installing a permanent customized acoustic window. Congratulations to Claire, Sumner, Whitney and our collaborators at Caltech (Richard Andersen) and USC (Charles Liu, Vasileios Christopoulos et al.) on this advance in human brain imaging. This is also the product of our long collaboration with Mickael Tanter and colleagues in Paris.

Rabut C#, Norman S#*, Griggs W#, Russin JJ, Jann K, Christopoulos V, Liu C*, Andersen RA*, Shapiro MG*. Functional ultrasound imaging of human brain activity through an acoustically transparent cranial window. Science Translational Medicine 16, eadj3143 (2024). article | press

Making cells dance to ultrasound

Can we use ultrasound to remote-control the location and motion of specific cells? Yes! We show that gas vesicles are exceptionally good “acoustic antennae”, experiencing strong acoustic forces relative to their nm size. In ultrasound gradients, GVs and cells expressing them get pushed more strongly – and in the opposite direction – from other biological materials. As a result, we can selectively push them, trap them, pattern them and sort them selectively under acoustic remote control. Congratulations to Di and colleagues on this foundational advance in acoustic actuation and sonogenetics.

Wu D, Baresch D, Cook C, Duan M, Malounda D, Maresca D, Abundo MP, Lee J, Shivaei S, Mittelstein DR, Qiu T, Fischer P, Shapiro MG*. Biomolecular actuators for genetically selective acoustic manipulation of cells. Science Advances 9, eadd9186 (2023). article | press | video

Acoustic Reporter Genes 2.0

The first generation of acoustic reporter genes provided a key proof of concept but were insensitive, burdensome and impossible to image continuously. Welcome ARG 2.0! These new reporter genes provide much greater sensitivity, nonlinear ultrasound contrast, and ease-of-use for expression in a variety of cell types. Congrats to Rob, Marjorie, Tom and colleagues on this major advance! Constructs for mammalian cells and bacteria available on Addgene.

Hurt RC#, Buss MT#, Duan M#, Wong K, You MY, Sawyer DP, Swift MB, Dutka P, Barturen-Larrea P, Mittelstein DR, Jin Z, Abedi MH, Farhadi A, Dephande R, Shapiro MG*. Genomically mined acoustic reporter genes for real-time in vivo monitoring of tumors and tumor-homing bacteria. Nature Biotechnology 41, 919 (2023). article

ISBUS

Delighted to host the first International Symposium on Biomolecular Ultrasound and Sonogenetics. Thanks to the researchers from 10 countries who joined us for this inaugural event and to all the Shapiro Lab members who participated, helped organize, and hosted live demos.

Fun in the sun 2022

Thanks to all the lab members, collaborators and friends who joined us for the annual Shapiro Lab beach party in Oceanside, CA! Extra fun to be joined by Moore Scholar Mickael Tanter.

CryoEM Structure of Gas Vesicles

How do you make a protein that self-assembles, fills with air, excludes water and withstands several atmospheres of pressure? A century-old mystery for Gas Vesicles. Congratulations to Przemek and colleagues in the Shapiro and Jensen labs on figuring this out with a beautiful CryoET structure.

Dutka P, Metskas LA, Hurt RA, Salahshoor H, Wang TY, Malounda D, Lu GJ, Chou TS, Shapiro MG*, Jensen GJ*. Structure of Anabaena flos-aquae gas vesicles revealed by cryo-ET. Structure (2023). article

Lab excursion to Catalina Island

Thanks to the intrepid explorers who joined the Shapiro Lab expedition to Catalina Island!

Ultrasound-controlled probiotic therapy

Can we activate the production of immunotherapy drugs specifically inside solid tumors? Yes, by engineering gene circuits in tumor-homing bacteria to take commands from thermal focused ultrasound. Congratulations to Mohamad, Michael and collaborators on this new paper demonstrating the local delivery of checkpoint inhibitors inside solid by ultrasound-controlled probiotic agents.

Abedi MH#, Yao M#, Mittelstein DR, Bar-Zion A, Swift MB, Lee-Gosselin A, Barturen-Larrea P, Buss MT, Shapiro MG*. Ultrasound-controllable engineered bacteria for cancer immunotherapyNature Communications 13, 1585 (2022). article | press

How does ultrasound excite neurons?

Focused ultrasound excites cortical neurons by opening specific mechanosensitive ion channels, leading to gradual calcium accumulation, activation of calcium-gated channels, depolarization and spiking. Congratulations to Sangjin and collaborators on this detailed biophysical study.

Yoo S, Mittelstein DR, Hurt RC, Lacroix JJ, Shapiro MG*. Focused ultrasound excites cortical neurons via mechanosensitive calcium accumulation and ion channel amplification. Nature Communications 13, 493 (2022). article

Joining HHMI!

HHMI Logo & Guidelines | HHMI Thank you to the Howard Hughes Medical Institute for welcoming our group and supporting our vision of biomolecular ultrasound as an emerging technology for basic biology and medicine. press