About

Robert Austin is a Professor of Physics at Princeton University, affiliated with the Center for the Physics of Biological Function, an NSF Physics Frontier Center. His role involves research and academic responsibilities within the physics community, focusing on the intersection of physics and biological systems. Further details about his specific research focus, background, and key contributions are not provided on the page.

Research topics

• Computer Science
• Artificial Intelligence
• Engineering
• Data science
• Cancer research
• Nanotechnology
• Internal medicine
• Biochemical engineering
• Mathematics
• Biology
• Medicine
• Geophysics
• Physics
• Materials science

Selected publications

• Abstract B030: <i>In vitro</i> tumor hypoxia model enables induction and real-time detection of polyaneuploid cancer cells (PACCs) in prostate cancer

  Cancer Research · 2026-01-20

  articleSenior author

  Abstract Metastasis accounts for the majority of cancer-related deaths, yet only a rare subset of tumor cells can successfully complete this process. Among these, polyaneuploid cancer cells (PACCs), which arise via endoreplication in response to stressors such as hypoxia, have been implicated as stress-resistant drivers of metastasis. In prostate cancer, the presence of PACCs within primary tumors correlates with poor prognosis and reduced metastasis-free survival, and these cells are consistently detected in metastatic lesions from patients. However, identifying PACCs and reproducibly modeling their formation in vitro remain major challenges to understanding their metastatic potential. Here, we build upon our validated in vitro model of tumor hypoxia to develop a reliable system for PACC induction and detection within prostate cancer. This membrane-based culture system permits the self-generated development of hypoxia as prostate cancer cells consume a limited amount of oxygen, while a phosphorescent oxygen-sensing film enables real-time, spatially resolved mapping of oxygen distribution across the culture. Under these conditions, heterogeneous populations of PACC and non-PACC cells emerge along an oxygen gradient, with cells at the core of the system experiencing the most severe hypoxia, thus effectively recapitulating the tumor microenvironment. This approach represents a marked departure from traditional PACC models, which rely on high doses of chemotherapy or hypoxia-mimetic agents to artificially induce their formation. To validate PACC induction, we performed flow cytometric DNA content analysis following 16 hours of hypoxia and observed a nearly threefold increase in the proportion of cells exceeding 4N genomic content. These results suggest that the tumor model promotes the emergence of prostate cancer-derived PACCs. To enable live detection of PACCs without DNA-binding dyes that may interfere with replication and cause phototoxicity, we established a morphology-based criterion. Cells exceeding 1500 µm2 in area and demonstrating ≥3-fold growth over 16 hours corresponded to the polyaneuploid population identified by conventional nuclear area analysis following DNA dye staining. Preliminary single-cell tracking using this classification showed that PACCs exhibit greater net and total displacements than non-PACCs under hypoxia, which are behaviors consistent with successful invasion during metastasis. Altogether, this system provides a physiologically-relevant model for inducing and identifying prostate cancer-derived PACCs in vitro. Coupled with the robust criteria for real-time PACC detection, this model establishes a foundation for future work to investigate the mechanisms by which PACCs may promote metastatic progression in prostate cancer. Citation Format: Noreen Hosny, Shengkai Li, Sarah Amend, Robert Gatenby, Kenneth J. Pienta, Joel Brown, Junle Qu, Robert H. Austin. In vitro tumor hypoxia model enables induction and real-time detection of polyaneuploid cancer cells (PACCs) in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B030.

  PublisherDOI

• Informational Memory Shapes Collective Behavior in Intelligent Swarms

  Physical Review Letters · 2026-03-03

  preprintOpen access

  We present an experimental and theoretical study of 2-D swarms in which collective behavior emerges from both direct local mechanical coupling between agents and from the exchange and processing of information between agents. Each agent, an air-table drone endowed with internal memory and a binary decision variable, updates its state by integrating a time series of memories of local past collisions. This internal computation transforms the swarm into a dynamical information network in which history-dependent feedback drives spontaneous complete spin polarization, pitchfork bifurcated spin collectives, and chaotic switching between collective states. By tuning the depth of memory and the decision algorithm, we uncover a memory-induced phase transition that breaks spin symmetry at the population level. A minimal theoretical model maps these dynamics onto an effective potential landscape sculpted by informational feedback, revealing how temporally correlated computation can replace instantaneous forces as the driver of collective organization, informed by experiments. These results position physically interacting drone swarms as a model system for exploring the physics of informational drone ensembles whose emergent behavior arises from the interplay between physical interaction and information processing.

  PublisherOA PDFDOI

• Abstract 3473: Hypoxia reveals a polyaneuploid cancer cell phenotype with features implicated in tumor escape and early metastasis

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Ten million people die every year globally due to metastasis, as metastatic disease remains largely incurable with existing therapies. Polyaneuploid cancer cells (PACCs), which are large, endoreplicated cells that arise in response to environmental stressors, have recently been shown to possess an increased capacity for metastatic behavior. Prior studies have enriched for PACCs using high doses of chemotherapy and have demonstrated their altered nutrient-sensing capabilities, yet the dynamics of PACCs within a native, tumor-like hypoxic microenvironment remain poorly defined. In this study, we use our previously established in vitro membrane-based culture system that allows cancer cells to self-generate physiologically relevant oxygen gradients. Prostate cancer cells rest beneath an acrylic plug and consume the limited oxygen available directly beneath it, while oxygen diffuses inward from the plug periphery to generate a stable radial gradient. This is coupled with a phosphorescent oxygen-sensing film, whose signal increases in the absence of oxygen, enabling real-time spatial visualization and quantification of hypoxia. Prostate cancer-derived PACCs emerged in response to the hypoxic stress and were identified in real time using morphology-based criteria (≥1500 µm2 area and ≥3-fold growth over 16 hours). Similar to previous reports in normoxia, long-term single-cell tracking under hypoxia revealed that PACCs exhibited significantly greater net displacement than non-PACCs, suggesting a heightened capacity to invade surrounding tissue during metastatic progression. PACCs also demonstrated a stronger directional bias toward higher oxygen regions within the gradient. This aerotactic behavior suggests two possible roles in PACC dynamics: (1) escape from severely hypoxic tumor regions for survival, and (2) migration toward oxygen-rich vasculature for intravasation during metastasis. Preliminary work in ovarian cancer cells demonstrates similarly enhanced motility of PACCs, suggesting that this phenotype may extend beyond prostate cancer. Altogether, these findings suggest that hypoxia shapes a PACC phenotype with enhanced motility and oxygen-directed migration, which may confer increased metastatic potential. Future work will incorporate hanging-drop tumor spheroids in this system to enable 3D modeling of hypoxic PACC behavior and determine whether aerotaxis facilitates outward migration toward oxygen-rich regions. Citation Format: Noreen Hosny, Shengkai Li, Sarah R. Amend, Arwa Abdelshafy, Robert A. Gatenby, Kenneth J. Pienta, Joel Brown, Junle Qu, Robert H. Austin. Hypoxia reveals a polyaneuploid cancer cell phenotype with features implicated in tumor escape and early metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3473.

  PublisherDOI

• Gradient metapopulation microfluidic ecologies shape genetic and biofilm drivers of T4r phage resistance in E. coli

  npj Biofilms and Microbiomes · 2026-04-25

  articleOpen accessSenior author

  We use a gradient microfluidic metapopulation ecology which generates non-uniform phage concentration gradients and micro-ecological niches to reveal the importance of time, spatial population structure and collective population dynamics in the de novo evolution of T4r bacteriophage resistant motile E. coli. An insensitive bacterial population against T4r phage occurs within 20 hours in small interconnected population niches created by a gradient of phage virions, driven by evolution in transient biofilm patches. Sequencing of the resistant bacteria reveals mutations at the receptor site of bacteriophage T4r as expected but also in genes associated with biofilm formation and surface adhesion, supporting the hypothesis that evolution within transient biofilms drives de novo phage resistance.

  PublisherOA PDFDOI

• HIF-1α and RhoA Drive Enhanced Motility and Aerotaxis of Polyaneuploid Prostate Cancer Cells in Hypoxia

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-05

  preprintOpen accessSenior author

  ABSTRACT Most cancer deaths result from metastasis, yet only a rare subset of tumor cells can complete this process. Among these, polyaneuploid cancer cells (PACCs), which arise via endoreplication under stressors such as hypoxia, are implicated as metastatic drivers, but how they acquire this potential is poorly understood. Here, we show that prostate cancer-derived PACCs exhibit features predictive of invasion and intravasation. Time-lapse fluorescence microscopy and single-cell tracking under hypoxia revealed that PACCs migrated significantly farther than Non-PACCs, consistent with local invasion. PACC trajectories showed a strong tendency to migrate toward oxygen, consistent with aerotaxis and predictive of intravasation. siRNA-mediated knockdown demonstrated that the enhanced motility and aerotaxis of hypoxic PACCs require both HIF-1αand RhoA, with RhoA expression suppressed upon HIF-1α inhibition. Altogether, we propose a HIF-1α→ RhoA → motility/aerotaxis mechanism enabling PACCs to escape hypoxic cores, invade tissue, and access vasculature, highlighting them as a uniquely invasive subpopulation with implications for anti-metastatic therapies.

  PublisherOA PDFDOI

• Phosphorescence-based <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si1.gif"> <mml:mrow> <mml:msub> <mml:mi mathvariant="normal">O</mml:mi> <mml:mn>2</mml:mn> </mml:msub> </mml:mrow> </mml:math> sensing reveals size-dependent survival and motility of metastatic prostate cancer cells in self-generated hypoxia

  iScience · 2025-04-03 · 2 citations

  articleOpen accessSenior author

  consumption shifted cell distributions to larger sizes, whereas prolonged hypoxia induced apoptosis, producing cell populations of smaller areas post-hypoxia. Such resilience to hypoxia was absent for noncancerous fibroblasts. Our findings suggest that larger PC3 cells have enhanced metabolic fitness under hypoxia, identifying these cells as potential targets of cancer therapy.

  PublisherDOI

• Digitization can stall swarm transport: Commensurability locking in quantized-sensing chains

  Physica A Statistical Mechanics and its Applications · 2025-12-18

  articleOpen access
  PublisherOA PDFDOI

• Protocol to model tumor hypoxia in vitro using real-time phosphorescence-based sensing of O2 gradients generated by metastatic cancer cells

  STAR Protocols · 2025-10-28 · 1 citations

  articleOpen accessSenior authorCorresponding

  Tumor hypoxia plays a critical role in cancer progression and therapeutic resistance. Here, we present a protocol for the self-generation of hypoxia by metastatic cancer cells using phosphorescence-based O 2 sensing. We describe steps for phosphorescent film calibration, system assembly, and real-time imaging of hypoxia development. We then detail approaches to spatially map resulting O 2 gradients. This protocol supports applications for studying key behaviors linked to metastatic progression, including motility and aerotaxis, under physiologically relevant hypoxic conditions. For complete details on the use and execution of this protocol, please refer to Hosny et al. 1 • Steps for calibrating O 2 -sensing phosphorescent films for hypoxia visualization • Instructions for assembling a chamber enabling cancer-cell-mediated hypoxia generation • Guidance on time-lapse imaging to capture real-time hypoxia development • Steps for spatially mapping O 2 gradients under hypoxia Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Tumor hypoxia plays a critical role in cancer progression and therapeutic resistance. Here, we present a protocol for the self-generation of hypoxia by metastatic cancer cells using phosphorescence-based O 2 sensing. We describe steps for phosphorescent film calibration, system assembly, and real-time imaging of hypoxia development. We then detail approaches to spatially map resulting O 2 gradients. This protocol supports applications for studying key behaviors linked to metastatic progression, including motility and aerotaxis, under physiologically relevant hypoxic conditions.

  PublisherDOI

• Microfluidic Ecology Unravels the Genetic andEcological Drivers of T4r Bacteriophage Resistancein E. coli: Insights into Biofilm-Mediated Evolution

  Research Square · 2024-05-24 · 1 citations

  preprintOpen access1st authorCorresponding

  <title>Abstract</title> We use a microfluidic ecology which generates non-uniform phage concentration gradients and micro-ecological niches to reveal the importance of time, spatial population structure and collective population dynamics in the {\em de novo} evolution of T4r bacteriophage resistant motile {\em E. coli}. An insensitive bacterial population against T4r phage occurs within 20 hours in small interconnected population niches created by a gradient of phage virions, driven by evolution in transient biofilm patches. Sequencing of the resistant bacteria reveals mutations at the receptor site of bacteriophage T4r as expected but also in genes associated with biofilm formation and surface adhesion, supporting the hypothesis that evolution within transient biofilms drives {\em de novo} phage resistance.

  PublisherOA PDFDOI

• Review of: "Darwin, Gödel, Luria, Delbrück: Biomedical, Mathematical, and Metamathematical Perspectives on Attributes and Consequences of Random Somatic Mutations Subject to Selection"

  2024-01-21

  peer-reviewOpen access1st authorCorresponding
  PublisherOA PDFDOI

Recent grants

• Evolution Game Theory Modeling of Tumor Dormancy

  NSF · $300k · 2017–2020

• The Physics of Evolution and Adaptation in a Nanofabricated World

  NSF · $360k · 2008–2011

• NIH Grant R03RR008032

  NIH · $33k · 1994

• NIH Grant U54CA143803

  NIH · $5.6M · 2016

Frequent coauthors

• James C. Sturm

  Princeton University

  88 shared

• Kenneth J. Pienta

  55 shared

• Edward C. Cox

  52 shared

• Jonas O. Tegenfeldt

  Lund University

  52 shared

• Robert Riehn

  North Carolina State University

  40 shared

• Nicholas C. Darnton

  Amherst College

  38 shared

• Sarah R. Amend

  Johns Hopkins University

  36 shared

• Thomas Duke

  33 shared

Education

• PhD, Physics

  University of Illinois Urbana-Champaign

  1975

• MS, Physics

  University of Illinois Urbana-Champaign

  1970

• BA, Physics

  Hope College

  1968