About

David Odde is a professor in the Department of Biomedical Engineering at the University of Minnesota. His research focuses on understanding how the fundamental thermodynamics, kinetics, diffusive transport, and mechanics of the molecular components of the cell enable basic cellular functions such as migration, division, and polarization. He employs an integrated modeling-experimental approach, developing physics-based models that are predictive of cell behavior to identify potential therapeutic strategies through computer simulation constrained by live cell microscopy imaging. Dr. Odde's work includes developing a cell migration simulator in collaboration with other groups at UMN and Mayo Clinic, which is the focus of a Physical Sciences in Oncology Center that he directs. His research also involves creating a simulator for the interaction of microtubules and the protein tau, which plays an important role in the progression of Alzheimer's disease. His broader goal is to integrate biophysical modeling and simulation into preclinical studies and clinical trials to better stratify patients and de-risk new therapeutics. He holds degrees in Chemical Engineering from the University of Minnesota and Rutgers University, with his PhD completed at Rutgers University.

Research topics

• Internal medicine
• Biology
• Chemistry
• Medicine
• Engineering
• Physics
• Materials science
• Political Science
• Biophysics
• Cell biology
• Medical education
• Pediatrics
• Structural engineering
• Neuroscience
• Nanotechnology
• Molecular biology
• Engineering physics
• Virology
• Genetics
• Engineering ethics
• Oncology
• Composite material

Selected publications

• Biophysical modeling identifies an optimal hybrid amoeboid-mesenchymal mechanism for maximal T cell migration speeds

  Cell Reports · 2026-01-01

  articleOpen accessSenior author

  Despite recent advances in cell migration mechanics, the principles governing rapid T cell movement remain unclear. Efficient migration is critical for antitumoral T cells to locate and eliminate cancer cells. To investigate the upper limits of cell speed, we develop a hybrid stochastic-mean field model of bleb-based cell motility. Our model suggests that cell-matrix adhesion-free bleb migration is highly inefficient, challenging the feasibility of adhesion-independent migration as a primary fast mode. Instead, we show that T cells can achieve rapid migration by combining bleb formation with adhesion-based forces. Supporting our predictions, three-dimensional gel experiments confirm that T cells migrate significantly faster under adherent conditions than in adhesion-free environments. These findings highlight the mechanical constraints of T cell motility and suggest that controlled modulation of tissue adhesion could enhance immune cell infiltration into tumors. Our work provides insights into optimizing T cell-based immunotherapies and underscores that indiscriminate antifibrotic treatments may hinder infiltration.

  PublisherDOI

• Engineering “physically optimized” T cells for increased sampling of complex tumor microenvironments

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-01

  article

  Pancreatic ductal adenocarcinoma (PDA) remains highly lethal, in part, because its dense fibroinflammatory stroma restricts therapy distribution, including adoptive T cell immunotherapies where direct interactions between T and carcinoma cells are essential for effective therapy. While T cell function must be maintained once effector-target engagement occurs, without inducing co-localization subsequent cytotoxic function steps cannot be undertaken. We therefore developed a strategy to "physically optimize" T cells to more effectively sample complex tumor volumes. Informed by pharmacologic perturbations and mathematical modeling we shifted T cell phenotype through expression of constitutively activated RhoA to increase cortical contractility, activation, migration, and sampling in PDA, while showing decreases in exhaustion markers. In CAR T cells this results in more efficient targeting through decreased sampling time and increased engagement with carcinoma cells, consistent with modeling predictions. This significantly increases T cell infiltration and distribution in PDA, resulting in improved tumor control in vivo, suggesting that this is an effective strategy to overcome stromal constraints, improve tumor engagement, and enhance the therapeutic performance of engineered T cell therapies in solid tumors.

  PublisherDOI

• FLIM quality metric visualization as a means to validate consistency across large-area non-homogeneous FLIM datasets

  Methods and Applications in Fluorescence · 2026-03-06

  articleOpen access

  Robust and interpretable analysis of fluorescence lifetime imaging microscopy (FLIM) data requires careful assessment of data across biological samples. Due to limitations in sample availability, difference in protein expression, photobleaching, or acquisition time, FLIM datasets are often susceptible to signal variability. This is only exacerbated with large field-of-view FLIM data, such as examining metabolic fluxes across whole tissue slices due to morphology changes. We adapt the FLIM F-value (or figure-of-merit) within our analysis as a statistical metric to capture the confidence in lifetime by comparing variance across fitted parameters, analogous to typical image SNR. In this study, we apply pixelwise and regional analysis of F-values across large-area FLIM datasets to identify image regions with similar confidence levels. Visualization of F-value distribution enables detection of acquisition outliers or poor-quality regions within a large mosaic collection, which can be flagged for reacquisition or removal. This approach enhances the statistical power of downstream biological interpretation by ensuring that only data with quantifiable and stable lifetime information are retained. To our knowledge, this is the first application of F-value mapping as a dataset-wide quality control measure in FLIM.

  PublisherDOI

• Mechanistic modeling predicts efficacy of CISH knockout in tumor-infiltrating lymphocytes with synergistic gene editing

  Physical Biology · 2026-02-17

  articleOpen accessSenior author

  Abstract Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cell therapy, where the lymphocytes of a cancer patient’s tumor are harvested, expanded in vitro using IL-2 stimulation, and then infused back into the patient Rosenberg and Restifo (2015 Science 348 62–68), Bonini and Mondino (2015 Eur. J. Immunol. 45 2457–69). However, even with the use of TIL therapy, cancer cells can survive for various reasons, such as poor lymphocyte infiltration into tumors, chronic activation of the T cell receptor and the immunosuppressive tumor microenvironment Morgan et al (1976 Science 193 1007–8). Cytokine-inducible SH2-containing (CISH) protein is a negative regulator of T cell activation, and in a recent clinical trial was knocked out in TILs to improve TIL therapy efficacy Rosenberg et al (1985 J. Exp. Med. 161 1169–88). A mechanistic signaling pathway model was developed to theoretically evaluate the efficacy of CISH knockout ( CISH KO) in T cell activation and examine potential alternative target genes that can theoretically be targeted using multiplex gene-editing or drugs to further improve T cell activation and function Donohue et al (1984 J. Immunol. 132 2123–8). Based on the results, CISH knockout increases the transcription of activation biomarkers IL-2 and TNF- α , but also inhibitory biomarkers such as PD1 and FasL. Using global sensitivity analysis, we also found that GSK3B , which is responsible for the deactivation of NFAT, is also predicted to further increase T cell activation when knocked out. In addition, it was predicted that PDCD1, FAS and CTLA4 can be knocked out in combination with CISH to further enhance T cell activation and prevent exhaustion and apoptosis.

  PublisherDOI

• Physiomimetic culture bias durotaxis toward soft environments

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-26

  articleOpen access

  Directed cell migration underlies many biological phenomena, from embryonic development to tumor metastasis and organ fibrosis. Most cells typically migrate toward stiffer regions of their extracellular matrix -a behavior known as positive durotaxis. Here we show that culture on rigid plastic reinforces this response, whereas preconditioning in soft 3D physiomimetic environments reprograms migration towards softer environments, a phenomenon known as negative durotaxis. Fetal rat lung fibroblasts preconditioned in 3D physiomimetic hydrogels exhibited negative durotaxis and accumulated near ~5 kPa, corresponding to the physiological stiffness of the lung. In contrast, genetically identical cells maintained on conventional 2D plastic substrates migrated up stiffness gradients, toward stiffer regions. Although both populations displayed a biphasic force-stiffness relationship, they differed in force magnitude and cytoskeletal organization. Molecular-clutch modeling revealed that durotaxis reversal emerges from two distinct mechanical regimes: a mechanosensitive, high-motor-clutch state that stabilizes adhesions on stiff substrates and drives positive durotaxis, and a low-motor, weak-adhesion state in which clutch slippage on the stiff side causes negative durotaxis. Our results show that durotaxis direction is not an intrinsic cellular property. Rather, it emerges from the interplay between motor activity and adhesion dynamics and can be tuned by culture conditions.

  PublisherDOI

• BPS2025 - Optimization of therapeutic T cells through biophysical modeling

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• UNC-45A drives ATP-independent microtubule severing via defect recognition and repair inhibition, contributing to neurite dystrophy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-27

  preprintOpen access

  Abstract UNC-45A is the only known ATP-independent microtubule severing protein. Using in vitro reconstitution and TIRF microscopy, we show that, unlike canonical severing enzymes such as katanin, spastin, and fidgetin, which hydrolyze ATP to remove tubulin dimers and promote lattice repair, UNC-45A selectively binds to pre-existing microtubule defects and inhibits GTP-tubulin incorporation. This mechanism prevents the formation of stabilized hot spots that typically protect microtubules from disassembly, resulting in persistent lattice damage and net microtubule loss, even in the presence of physiological levels of free GTP-tubulin. We further demonstrate that UNC-45A localizes near amyloid deposits in both mouse models and human cases of Alzheimer’s disease (AD). In cultured neurons, UNC-45A accumulates in axonal swellings—regions of pronounced microtubule disruption and experimental surrogates for dystrophic neurites in AD—and exacerbates their size and number, particularly under conditions mimicking microtubule damage. Notably, this is the first report of a microtubule severing protein that both localizes near amyloid plaques in tissue and accumulates in neurite swellings in cultured neurons, where it modulates their pathology. Together, our findings establish the mechanism of ATP-independent, damage-responsive severing pathway that couple defects recognition to repair inhibition, defining a new paradigm in microtubule quality control with broad implications for cytoskeletal integrity and remodeling in health and disease.

  PublisherOA PDFDOI

• TMIC-23. Glioblastoma subtype influences overall survival and migration of glioblastoma cells and T cells in synegeneic mouse models and are modeled with a novel Brownian Dynamics Tumor Simulator (BDTS)

  Neuro-Oncology · 2025-11-01

  articleOpen accessSenior author

  Abstract Based on transcriptional expression, most studies divide glioblastoma roughly into proneural (PDGFRA), mesenchymal (NF1) and classical (EGFR) subtypes. We created genetically engineered, spontaneous glioblastoma-like tumors in mice by Sleeping Beauty (SB) transposable element. These genetically induced mouse models of different glioblastoma subtypes showed increased survival in the NRAS oncogene-driven mesenchymal-like subtype (median survival: 70.5 days) compared with the PDGFB-driven proneural-like subtype (median survival: 32 days). To investigate the difference in overall survival, the migration of glioblastoma cells and immune cell content was examined. The tumor cells in mesenchymal subtype of glioblastoma-like tumors were more infiltrative and migrated faster. The primary glioblastoma cells from mesenchymal-like mouse models and human patient-derived xenograft (PDX) lines with mesenchymal characteristics both showed significantly higher random motility coefficient (p<0.001) and cell area (p<0.001) compared with proneural-like mouse models and human patient-derived xenograft (PDX) lines (Shamsan et. al, 2022, BioRxiv). Based on these observations, we hypothesized that cytotoxic T lymphocytes (CTLs) contribute to the differential survival in mesenchymal and proneural subtypes of glioblastoma-like mice tumor models, and the difference can be computationally modeled. Endogenous CTL migration profiles were collected and the survival of adaptive immune system deficient mice with glioblastoma-like tumors of different subtypes is ongoing. It is expected that adaptive immune system deficient mice with mesenchymal glioblastoma-like tumors live shorter than wildtype mice. The Brownian Dynamics Tumor Simulator (BDTS) is a three-dimensional computation model for glioblastoma that incorporates a wide range of parameters involved in tumor growth. This computer-based simulator consists of tumor cells and T cells, in which both cell types migrate, proliferate, and undergo apoptosis. The migration profiles of cells under the microscope can help parameterize the simulator and make it more resemble in vivo tumor development. The BDTS successfully modeled tumor growth and predicted anti-migratory therapy responses in glioblastoma.

  PublisherOA PDFDOI

• BPS2025 - Optimization of therapeutic T cells through biophysical modeling

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Physical principles and mechanisms of cell migration

  npj Biological Physics and Mechanics. · 2025-01-16 · 29 citations

  reviewOpen accessSenior author

  Cell migration is critical in processes such as developmental biology, wound healing, immune response, and cancer invasion/metastasis. Understanding its regulation is essential for developing targeted therapies in regenerative medicine, cancer treatment and immune modulation. This review examines cell migration mechanisms, highlighting fundamental physical principles, key molecular components, and cellular behaviors, identifying existing gaps in current knowledge, and suggesting potential directions for future research.

  PublisherOA PDFDOI

Recent grants

• Modeling and microsystems approach to glioma invasion

  NIH · $2.3M · 2013–2019

• Molecular mechanisms and cellular implications of tau dysfunction

  NIH · $2.9M · 2016–2021

• NIH Grant RC1CA145044

  NIH · $1.0M · 2012

• CAREER: Microtubule Severing Mechanisms

  NSF · $266k · 2000–2004

• Education & Outreach Unit

  NIH · $19.9M · 2016–2023

Frequent coauthors

• Melissa K. Gardner

  University of Minnesota

  30 shared

• L. Prahl

  University of Pennsylvania

  27 shared

• Ghaidan A. Shamsan

  University of Minnesota

  26 shared

• Hrishikesh Belani

  Institute of Accelerating Systems and Applications

  25 shared

• Ken Cohen

  Optum (United States)

  21 shared

• Brian T. Castle

  University of Minnesota

  20 shared

• Mahya Hemmat

  Twin Cities Orthopedics

  20 shared

• Michael A. Puskarich

  Hennepin County Medical Center

  20 shared

Labs

• Tissue Mechanics LaboratoryPI

Awards & honors

• CSE awards
• Outstanding Achievement
• Distinguished Leadership
• Honorary Doctorate Degrees