Our Projects

Selected research highlights are presented. Additional ongoing work is not shown.

Breaking Physical Barriers to Tumor Immunity

Effective anti-tumor immunity requires immune cells to find, navigate, and infiltrate tumors before they can eliminate cancer cells. We investigate how the physical and biochemical properties of the tumor microenvironment, including ECM architecture, confinement, adhesion, mechanics, and interstitial flow, govern T-cell trafficking and function. Using engineered 3D microenvironments and patient-relevant tumor models, we aim to uncover the barriers that restrict immune-cell access to tumors and identify strategies to improve cancer immunotherapy.

The exhausting journey of CAR T cells in the TME: In this journey, CAR T cells must be able to detect chemokines at the tumor site, effectively roll and adhere to the blood vessel wall, initiate transendothelial migration, and invade the tumor stroma. Here, the immune cells must overcome various biochemical and physical barriers to then encounter pro-tumor cells that suppress CAR T cell activity. Some CAR T cells may eventually make contact with target cancer cells that express abundant immune checkpoints, further reducing anti-tumor function. Adapted from Nguyen et. al. PMID: 35741103.

Engineering Tissue-Like Interstitial Networks to Guide 3D T-Cell Trafficking. The tissue interstitial network is interconnected and composed of a gel phase and a fluid phase. A gel phase is made up of collagen, elastin, and polysaccharides such as hyaluronan and glycosaminoglycans, whereas the fluid phase comprises interstitial fluid and soluble proteins. In solid tumors, ECM deposition and crosslinking disrupt the structure of the interstitial network. This leads to increased physical confinement and the formation of ECM-rich barriers that prevent T cell infiltration or trap them in the stroma. Thus, we aim to engineer this interstitial network to uncover the fundamental biophysical rules governing T-cell migration. A) Representative histological images showing the spatial distribution of CD8⁺ T cells within the tumor interstitial space. B) The interstitial network of a BioLLS μ-gels resembles that of tissue in A. C) The interstitial spaces between μ-gels offer pathways for cell migration. D) T cells navigate paths of least resistance to reach their target sites. Adapted from Nguyen et al. PMID: 37788737

Collaborative Research with Dr. Alfonso Pepe, PhD.

Collaborative Research with Colleagues at the University of Minnesota. PMID: 41528848.

Engineering the Tumor Microenvironment One Building Block at a Time. The tumor microenvironment is a complex ecosystem in which cells continuously interact with their physical and biochemical surroundings. A major component of this environment the extracellular matrix (ECM) varies widely across tissues in its composition, architecture, and physical properties. Yet, existing 3D models offer limited ability to independently control these features and reconstruct a microenvironment of choice. We address this challenge using bioconjugated microgels as discrete, independently tunable building blocks that can be assembled to engineer tissue-specific 3D microenvironments. Their packing also creates interconnected interstitial networks through which immune cells can migrate, allowing us to uncover how the physical organization of the tumor microenvironment governs T-cell trafficking. PMID: 41528848, PMID: 37788737.

Credit: We sincerely thank Dr. Diego I. Pedro, PhD, for his kind assistance with the 3D bioprinter.

Engineering Spatially Defined 3D Microenvironments to Decode Cancer and Immune Cell Migration. The tumor microenvironment is not spatially uniform. Cancer and immune cells encounter distinct regions of ECM organization, architecture, and composition that can profoundly influence where and how they migrate. Yet, recreating this spatial complexity in a controlled 3D system remains challenging. We combine embedded 3D bioprinting with our bioconjugated microgel platform to build defined tissue-mimetic microenvironments with near single-cell spatial resolution. This approach allows us to place cells and ECM components where we choose and engineer distinct microenvironmental zones within the same system. Using a dual-zone model, we find that cancer cells (yellow) persist and migrate along printed collagen fibers (white), while T cells (red) preferentially navigate the surrounding interstitial network along paths of least resistance, providing a platform to uncover how spatial organization of the ECM shapes cancer and immune-cell migration. Data generated as part of Harrison M. Haley’s Master’s thesis research.

Preserve, Perturb, Predict: Patient-Derived Models

Every patient’s tumor is unique. We develop bioengineered approaches to preserve the native cellular, extracellular, and spatial complexity of patient tumors while maintaining their viability and function outside the body. By enabling controlled perturbation and longitudinal monitoring of living tumor tissues, these models bridge laboratory discovery and patient biology, helping us understand disease mechanisms, evaluate therapeutic response, and advance precision cancer medicine.

We are grateful to Dr. Ryan Smolchek PhD. for the design of the injection-molded Darcy plates. PMID: 35326418.

Collaborative Research with Dr. Sawyer and His Team, with Contributions from Moffitt’s Department of Translational Pathology and AADL Laboratory in Spatial Multiplex Technologies. We also thank the Nikon Center of Excellence and its director, Dr. Jose Serrano-Velez, PhD for their valuable training and kind support.

collagen I stromal cells cell cytoskeleton nuclei

PDAC (Work in collaboration with Dr. W. Gregory Sawyer, PhD)

collagen I CD45+ immune cells epithelial cells nuclei

Endometrial (Work in collaboration with Dr. Erin George, PhD)

Decoding the Hidden Life of Cancer:

Survival, Adaptation & Reawakening

Cancer cells can survive extreme environmental and therapeutic stresses by entering adaptive states that remain largely hidden from conventional measurements. We impose controlled metabolic, mechanical, and therapeutic stresses to uncover how cancer cells survive, persist, and ultimately reawaken. By understanding these survival strategies, we aim to identify vulnerabilities that can prevent recurrence and overcome treatment resistance.

Decoding How Tissue Stiffness Shapes Cancer Cell Behavior. Cancer cells do not simply live within their surroundings, but they "sense" them. As tumors develop, the stiffness of the surrounding tissue can change dramatically, providing physical cues that influence how cancer cells move, grow, and adapt. We recreate these different mechanical environments in 3D to understand how cancer cells respond to changes in tissue stiffness while keeping other features of their surroundings consistent. By isolating stiffness as a single variable, we can uncover how the physical properties of the tumor microenvironment contribute to cancer progression. Atomic force microscopy (AFM) allows us to gently probe the mechanical properties of both the physical microenvironment and living cells at the microscale, revealing how soft or stiff cells and their surroundings are. Bottom-right video: AFM delicately probing the mechanical properties of a live T cell. Videos (left): Glioblastoma cells migrating within a mechanically tuned environment of ~2 kPa.

Tumor growth creates a fundamental challenge: as tumors expand, their demand for nutrients and oxygen can exceed what diffusion alone can provide. While angiogenesis helps sustain continued growth, cancer cells can still experience periods of severe and prolonged metabolic stress. How some cells survive these conditions, and later regain their ability to grow, remains an important question. We recreate these periods of metabolic stress to uncover the survival strategies that allow cancer cells to persist, adapt, and eventually reawaken.

Integrating Engineering Education with Cancer Research

Our partnership with the USF Department of Medical Engineering provides a meaningful bridge between engineering education and cancer research at Moffitt. The broader USF-Moffitt Partnership gives biomedical engineering students opportunities to apply classroom knowledge to authentic biomedical and clinical challenges while learning alongside scientists, engineers, and clinicians.

As part of this partnership, Dr. Duy T. Nguyen serves as a primary mentor for USF Biomedical Engineering Design I & II (BME 4882 and BME 4883C). Through year-long senior capstone projects, students bring their engineering training into the cancer research environment, where they learn to define real-world biomedical problems, develop and test solutions, and experience firsthand how engineering can contribute to cancer research and patient care.

Capstone Teams:
2026–2027: Ian Broadman, Sara Leonardis, Oscar Colin-Castruita, Huy (Bill) Dao
2025–2026: Adam Carr, Joseph Groom, Miguel Garcia, William Rosario
2024–2025: Gabriel Sortica Reichmann, Vitor Riekes Viana, Vanditha Akula

Team 2025-2026

Team 2024-2025

Note: This page highlights selected areas of our research and does not represent the full scope of our ongoing work.

Under Review, Revision, or In Press

[1] Sonal Srivastava, ... Duy T. Nguyen, Mitsuo Yamauchi, Jeffery West, Christine H. Chung, J. Silvio Gutkind5,, Antonio L. Amelio.”Collagen remodeling promotes a GPCR-mediated mechanosensory immune checkpoint in ADGRG1+ CD8+ T cells and serves as a spatial biomarker of response to immunotherapy”. Nature Communications. 2026. [Under Revision].

[2] Rachel V Jimenez,...Duy T. Nguyen, Jose R. Conejo-Garcia, Timothy I. Shaw, Paulo Cesar Rodriguez. ”Mitochondrial stress mediator LONP1 governs myeloid celldriven immunosuppression in tumors through IL-16 inhibition”. Immunity. 2026. [Under Revision].

[3] Acevedo-Acevedo, S.; Ackerman, H. D.; Rubio, V. Y.; Hackel, N.; Carr, C. L.; Miranda, K. A.; Baldwin, J. R.; Reiser, M.; Lockhart, J. H.; Lui, A.; Stewart, P. A.; Yu, X.; Wright, G. M.; Alontaga, A. Y.; Koomen, J. M.; Nguyen, D. T.; Sawyer, W. G.; DeNicola, G. M.; Boyle, T.; Cress, W. D.; Haura, E. B.; Flores, E. R. ”Ex Vivo Culture of Patient-Derived Primary, Metastatic, and Post-Mortem Lung Cancer Reveals Targetable States of EMT and Metabolic Plasticity”. June 18, 2026. https://doi.org/10.64898/2026.06.14.731898. [Under Revision].

[4] Laxmi Swetha Karanam, Yuxi Zhou, Jacob Torrez, Andres Valdivia, Praveen K Neeli, Marilena Tauro, Conor Lynch, Marcelo Bonini, Thordur Oskarsson, Erin George, Duy T. Nguyen.”Collagen I Sustains Persistent Survival of Quiescent Cancer Cells Under Progressive Metabolic Stress”. [Under Revision].

Published Peer-Reviewed Articles

[1] Roberto Alonso Matilla; Alfonso Pepe; Diego I. Pedro; Jose Serrano-Velez; Michael Dunne; Nguyen, Duy T; W. Gregory Sawyer; Paolo P. Provenzano; David J. Odde. ”Biophysical modeling identifies an optimal hybrid amoeboid-mesenchymal mechanism for maximal T cell migration speeds”. Cell Reports. 45(1), 116824. PMID: 41528848 https://doi.org/10.1016/j.celrep.2025.116824

[2] Nguyen, Duy T, Schaller, M.A., Terracina, K.P., Xu, X., Pedro, D.I., Pepe, A., Urue˜na, J.M., Dupee, Z., Diodati, N., Smolchek, R.A., Famiglietti, J.E., Nguyen, N.T.Y., Tushoski-AlemÅLan, G.W., Cheng, K., Chen, L., Linn, D., Vidimar, V., Fatima, A., Kwon, S.W., Sun, D., Chen, H., Xu, H., Long, B., Moy, L.Y., Howell, B.J., Addona, G.H., Sawyer, W.G., 2025. ”Patient-derived colorectal microtumors predict response to anti-PD-1 therapy.” Frontiers in Immunology. 16, 1640500. PMID:40873566. https://doi.org/10.3389/fimmu.2025.1640500

[3] Qdaisat, S., Wummer, B., Stover, B.D., Zhang, D., McGuiness, J., Weidert, F., Chardon-Robles, J., Grippin, A., DeVries, A., Zhao, C., Marconi, C., Karachi, A., Xie, C., Jobin, G., Liu, R., Michel, S., Ma, X., Moor, R.S.F., von Roemeling, C., Nguyen, Duy T, Elliott, L., Thomas, N., Barpujari, A., Geffrard, H., Campaneria, Y., Ogando-Rivas, E., Rabideau, C., Soni, D., Huang, J., Carrera-Justiz, S., Fredenburg, K., Silver, N.L., Sawyer, W.G., Rahman, M., Ligon, J.A., Flores, C.T., Lee, J.-H., Mitchell, D.A., Castillo, P., Mendez-Gomez, H.R., Sayour, E.J., 2025. ”Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading.” Nature Biomedical Engineering. PMID: 40681861. https://doi.org/10.1038/s41551-025-01380-1

[4] Tao, H., Chen, D., Yang, C., Nguyen, Duy T, Abboud, G., Liu, R., Liu, T., Chakraborty, A., Hou, A.Y., Petit, N.A., Abbas, M., Davis, R.W., Zhang, J., Von Roemeling, C., Gbadamosi, M.O., Jin, L., Gu, T., Lin, T., Wang, P., Pepe, A., Pedro, D.I., Mendez-Gomez, H.R., Xie, C., Karachi, A., Weidert, F., Jin, D., Wang, C., Long-James, K., Molchan, E.K., Castillo, P., Ligon, J.A., Ghiaseddin, A.P., Sayour, E.J., Rahman, M., Deleyrolle, L.P., Kim, B.Y., Mitchell, D.A., Sawyer, W.G., Huang, J., 2025. “Targeting immune checkpoint LAIR1 with antibody blockade or 3-in-1 CAR T cells enhances antitumor response.” Journal of Clinical Investigation. 135, e184043. PMID: 40591413. https://doi.org/10.1172/JCI184043

[5] Diodati, Nickolas G., Zadia E. Dupee, Felipe T. Lima, Jack Famiglietti, Ryan A. Smolchek, Ganlin Qu, Yana Goddard, Duy T. Nguyen, W. Gregory Sawyer, Edward A. Phelps, Borna Mehrad, and Matthew A. Schaller. 2024. “3D Culture Analysis of Cancer Cell Adherence to Ex Vivo Lung Microexplants.” Tissue Engineering. Part C. Methods 30(8):343–52. doi: 10.1089/ten.TEC.2024.0146

[6] Nguyen, Duy T, Ruixuan Liu, Elizabeth Ogando-rivas, Alfonso Pepe, Diego Pedro, Sadeem Qdasait, Changlin Yang, et. al. “Bioconjugated Liquid-Like Solid (LLS) Enhances Characterization of Solid Tumor - Chimeric Antigen Receptor T Cell Interactions.”Acta Biomaterialia. 2023. PMID: 37788737. https://doi.org/10.1016/j.actbio.2023.09.042

[7] Nguyen, Duy T, D. I. Pedro, A. Pepe, J. G. Rosa, J. I. Bowman, L. Trachsel, G. R. Golde, I. Suzuki,J. M. Lavrador, N.T.Y. Nguyen, M. A. Kis, R. A. Smolchek, N. Diodati, R. Liu, P. Castillo, E. l. Sayour, B. S. Sumerlin, W. G. Sawyer. “Bioconjugation of COL1 Protein on Liquid-like Solids Surfaces to Study Tumor Invasion Dynamics.” Biointerphases. 2023. PMID: 36898958. https://doi.org/10.1116/6.0002083.

[8] Nguyen, Duy T., Elizabeth Ogando-Rivas, Ruixuan Liu, Theodore Wang, Jacob Rubin, Linchun Jin, Haipeng Tao, William W. Sawyer, Hector R. Mendez-Gomez, Matthew Cascio, Duane A. Mitchell, Jianping Huang, W. Gregory Sawyer, Elias J. Sayour, and Paul Castillo. 2022. “CAR T Cell Locomotion in Solid Tumor Microenvironment.” Cells. 2022. PMID: 35741103. https://doi.org/10.3390/cells11121974

[9] Nguyen, Duy T., Jack E. Famiglietti, Ryan A. Smolchek, Zadia Dupee, Nickolas Diodati, Diego I. Pedro, Juan M. Urue˜na, Matthew A. Schaller, and W. Gregory Sawyer. 2022. “3D In Vitro Platform for Cell and Explant Culture in Liquid-like Solids.” Cells. 2022. PMID: 35326418. https://doi.org/10.3390/cells11060967 [14] Pedro, Diego I., Nguyen, Duy T, Lucca Trachsel, Jose G. Rosa, Britney Chu, Stephen Eikenberry, Brent S. Sumerlin, and W. Gregory Sawyer. 2021. “Superficial Modulus, Water-Content, and Mesh-Size at Hydrogel Surfaces.” Tribology Letters. 69 (4): 1–9. https://doi.org/10.1007/s11249-021-01538-3.

[10] Pedro, Diego I., Nguyen, Duy T, Lucca Trachsel, Jose G. Rosa, Britney Chu, Stephen Eikenberry, Brent S. Sumerlin, and W. Gregory Sawyer. 2021. “Superficial Modulus, Water-Content, and Mesh-Size at Hydrogel Surfaces.” Tribology Letters. 69 (4): 1–9. https://doi.org/10.1007/s11249-021-01538-3.

[11] Pedro, D. I., Nguyen, Duy T, J. G. Rosa, N. Diodati, J. Kim, J. I. Bowman, R. A. Olson, J. M. Urue˜na, B. S. Sumerlin, and W. G. Sawyer. 2021. “Gel-Forming Mucin Improves Lubricity Across Model Gemini Epithelial Cell Interfaces.” Tribology Letters. 69 (4): 1–9. https://doi.org/10.1007/s11249-021-01529-4.

[12] Schaller, Matthew A., Yamini Sharma, Zadia Dupee, Duy Nguyen, Juan Urue˜na, Ryan Smolchek, Julia C. Loeb, et al. 2021. “Ex Vivo SARS-CoV-2 Infection of Human Lung Reveals Heterogeneous Host Defense and Therapeutic Responses.” JCI Insight. 2021. PMID: 34357881 https://doi.org/10.1172/jci.insight.148003

Book Chapters & Conference Articles

[1] McGhee, A., D. Nguyen, and P. Ifju. “Surface Deformation with Simultaneous Contact Area Measurement for Soft Transparent Media Due to Spherical Contact.” SpringerLink. Springer International Publishing, January 1, 1970. https://link.springer.com/chapter/10.1007/978-3-319-63028-112.

[2] Haipeng Tao, Dongjiang Chen, Changlin Yang, Linchun Jin, Christina Von Roemeling, Hector Mendez-Gomez, Ruixuan Liu, Duy Nguyen, Alicia Y Hou, Alfonso Pepe, Frances Weidert, Ashley Ghiaseddin, Duane Mitchell, Loic Deleyrolle, Elias Sayour, W Sawyer, David Tran, Jianping Huang, “Identification of novel immune checkpoint molecule in glioma, LAIR1.” Volume 24, Issue Supplement 7, November 2022 https://doi.org/10.1093/neuonc/noac209.855

[3] Sawyer, W Gregory, Duy T. Nguyen, Ryan Smolchek, Jack Famiglietti, and Stephanie Warrington. “Immunotherapy in Three Dimensions: The Tumor Microenvironment, Immune Cells, and Tumor Invasion.” Journal for ImmunoTherapy of Cancer. BMJ Specialist Journals, November 1, 2022. https://jitc.bmj.com/content/10/Suppl2/A1274.

[4] Nguyen, Duy T, J Gabriel Rosa, Ryan A Smolchek, Jack E Famiglietti, Eric O Mcghee, Diego I Pedro, Juan M Urue˜na, Matthew A Schaller, W Gregory Sawyer, and Krista P Terracina. 2021. “Cancer Immunotherapy in Three Dimensions: In Situ Visualization of Tumor Explant-Immune Interactions.” 2021. P2.18. https://app.oxfordabstracts.com/events/1729/program-app/submission/279343

[5] Webber, Alexander R., Simon R. Phillpot, Duy T. Nguyen, Eric O. McGhee, W. Gregory Sawyer, and Paul Gader. “ACESO: A 3D Agent-Based Simulation of the Interaction between Immune and Tumor Cells: Proceedings of the 2022 ACM SIGSIM Conference on Principles of Advanced Discrete Simulation.” ACM Conferences, June 1, 2022. https://dlnext.acm.org/doi/fullHtml/10.1145/3518997.3534990.

Grateful for a Collaborative Community

Engineering and the physical sciences offer different ways of looking at cancer, but the greatest impact comes through integration with biology and medicine. We are tremendously grateful to Moffitt faculty, clinicians, surgeons, scientists, research cores, staff, and trainees who have welcomed our perspectives with openness, curiosity, and a shared commitment to improving cancer care.

We especially thank our colleagues and leadership in Tumor Microenvironment and Metastasis, Breast Oncology, Translational Pathology, and Immuno-Oncology for their warm welcome and collaborative spirit. We are equally grateful for our academic partnerships in Medical Engineering and Oncologic Sciences and for the broader USF community, whose dedicated faculty, outstanding programs, and wonderful students continually enrich our research, education, and training environment.

Page updated

Report abuse