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 firstname.lastname@example.org.
Quintana JM, Arboleda D, Hu H, Scott E, Luthria G, Pai S, Parangi S, Weissleder R, Miller MA Radiation Cleaved Drug-Conjugate Linkers Enable Local Payload Release. Bioconjug Chem. 2022;33(8):1474-1484 - PMID: 35833631 - PMCID: PMC9390333 - DOI: 10.1021/acs.bioconjchem.2c00174
Villalba JA, Hilburn CF, Garlin MA, Elliott GA, Li Y, Kunitoki K, Poli S, Alba GA, Madrigal E, Taso M, Price MC, Aviles AJ, Araujo-Medina M, Bonanno L, Boyraz B, Champion SN, Harris CK, Helland TL, Hutchison B, Jobbagy S, Marshall MS, Shepherd DJ, Barth JL, Hung YP, Ly A, Hariri LP, Turbett SE, Pierce VM, Branda JA, Rosenberg ES, Mendez-Pena J, Chebib I, Rosales IA, Smith RN, Miller MA, Rosas IO, Hardin CC, Baden LR, Medoff BD, Colvin RB, Little BP, Stone JR, Mino-Kenudson M, Shih AR Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and ARDS. Am J Respir Crit Care Med. 2022;206(7):857-873 - PMID: 35671465 - DOI: 10.1164/rccm.202109-2150OC
Giacomini KM, Yee SW, Koleske ML, Zou L, Matsson P, Chen E, Kroetz DL, Miller MA, Gozalpour E, Chu X New and emerging research on solute carrier (SLC) and ABC transporters in drug discovery and development: Outlook from the International Transporter Consortium. Clin Pharmacol Ther. 2022;112(3):540-561 - PMID: 35488474 - PMCID: PMC9398938 - DOI: 10.1002/cpt.2627
Ng TSC, Hu H, Kronister S, Lee C, Li R, Gerosa L, Stopka SA, Burgenske DM, Khurana I, Regan MS, Vallabhaneni S, Putta N, Scott E, Matvey D, Giobbie-Hurder A, Kohler RH, Sarkaria JN, Parangi S, Sorger PK, Agar NYR, Jacene HA, Sullivan RJ, Buchbinder E, Mikula H, Weissleder R, Miller MA Overcoming differential tumor penetration of BRAF inhibitors using computationally guided combination therapy. Sci Adv. 2022;8(17):eabl6339 - PMID: 35486732 - PMCID: PMC9054019 - DOI: 10.1126/sciadv.abl6339
Hu H, Quintana J, Weissleder R, Parangi S, Miller M Deciphering albumin-directed drug delivery by imaging. Adv Drug Deliv Rev. 2022;185:114237 - PMID: 35364124 - PMCID: PMC9117484 - DOI: 10.1016/j.addr.2022.114237
- More publications ...
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.