Laboratory for Synthetic and Spatial Tissue Dynamics
Our team seeks to understand how molecular & cellular signaling dynamics are spatially controlled in tissue, and how they can be therapeutically manipulated to treat disease.
We focus on inflammation and cancer, and combine an interdisciplinary toolset to shed light on multicellular regulation within disease microenvironments. New nanomaterial and synthetic biology technologies enable our studies using in vivo imaging and network-level computation.
Our interdisciplinary approach benefits from close collaboration — including with other groups in CSB — to successfully marry computational analyses with appropriate experimental measurements and models of disease. We acknowledge funding from the NIH Common Fund, the NIH National Cancer Institute, the Department of Defense, the American Thyroid Association and the Thyroid Cancer Survivors’ Association, Inc., among others.
We are actively growing our team in all project areas and are considering applications on a rolling basis. For enquiries, please send CVs to email@example.com.
Ng TSC, Gunda V, Li R, Prytyskach M, Iwamoto Y, Kohler RH, Parangi S, Weissleder R, Miller MA Detecting Immune Response to Therapies Targeting PDL1 and BRAF by Using Ferumoxytol MRI and Macrin in Anaplastic Thyroid Cancer. Radiology. 2021;298(1):123-132 - PMID: 33107799 - PMCID: PMC7771993 - DOI: 10.1148/radiol.2020201791
Gerosa L, Chidley C, Fröhlich F, Sanchez G, Lim SK, Muhlich J, Chen JY, Vallabhaneni S, Baker GJ, Schapiro D, Atanasova MI, Chylek LA, Shi T, Yi L, Nicora CD, Claas A, Ng TSC, Kohler RH, Lauffenburger DA, Weissleder R, Miller MA, Qian WJ, Wiley HS, Sorger PK Receptor-Driven ERK Pulses Reconfigure MAPK Signaling and Enable Persistence of Drug-Adapted BRAF-Mutant Melanoma Cells. Cell Syst. 2020;11(5):478-494.e9 - PMID: 33113355 - DOI: 10.1016/j.cels.2020.10.002
Luthria G, Li R, Wang S, Prytyskach M, Kohler RH, Lauffenburger DA, Mitchison TJ, Weissleder R, Miller MA In vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells. Nat Commun. 2020;11:3521 - PMID: 32665556 - PMCID: PMC7360550 - DOI: 10.1038/s41467-020-17147-y
Baskaran JP, Weldy A, Guarin J, Munoz G, Shpilker PH, Kotlik M, Subbiah N, Wishart A, Peng Y, Miller MA, Cowen L, Oudin MJ Cell shape, and not 2D migration, predicts extracellular matrix-driven 3D cell invasion in breast cancer. APL Bioeng. 2020;4(2):026105 - PMID: 32455252 - PMCID: PMC7202897 - DOI: 10.1063/1.5143779
Wang SJ, Li R, Ng TSC, Luthria G, Oudin MJ, Prytyskach M, Kohler RH, Weissleder R, Lauffenburger DA, Miller MA Efficient blockade of locally reciprocated tumor-macrophage signaling using a TAM-avid nanotherapy. Sci Adv. 2020;6(21):ePub - PMID: 32937338 - PMCID: PMC7244320 - DOI: 10.1126/sciadv.aaz8521
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Image-guided cellular reprogramming in cancer
A growing and largely descriptive single-cell atlas of tissues has begun providing insight into the spatial organization of microenvironments, yet it remains a challenge to understand cause-and-eﬀect relationships from such data. How does the signaling state of one cell aﬀect that of its neighbors? We aim to address this question by leveraging advances in in vivo imaging, nanotechnology, and synthetic biology to generate a framework for image-guided manipulation, real-time monitoring, and systems-level analysis of signal propagation. Although this project will yield fundamental insights into signaling propagation, we also aim to extend image-guided genetic reprogramming to therapeutic applications.
Nanomaterials for localized therapy
Thousands of biomaterials and nanoparticles have been developed for drug and nucleic acid delivery, but molecular and cellular-level mechanisms of their action in tissue are often poorly understood. Our group expands on novel in vivo imaging techniques to analyze the combined distribution and action of biomaterials and nanoformulations at a multi-scale level. This project pursues a systematic, molecular-level understanding of drug action, with the goal of informing improved therapeutic and biomaterial designs.
Multi-scale dissection of tumor microenvironment dynamics
Through new technologies, including single-cell RNA sequencing (scRNAseq) and multiplexed tissue imaging (MTI), tissues can now be visualized with incredible molecular and cellular detail. However, such rich maps of tissue structure are typically static snapshots from a fixed sample, and lack important information about how the tissue actually functions — how cells, fluids, and biomolecules dynamically interact to govern multicellular behaviors. This project aims to overcome this limitation by building an integrated computational and experimental platform for quantitatively linking functional dynamics within tissue to a map of its molecular and cellular composition.