About

Bumsoo Han is a Professor of Mechanical Science and Engineering and the Phil & Ann Sharp Scholar in Cancer Research at the University of Illinois Urbana-Champaign. His research centers on understanding and designing transport processes in living matter, with a particular focus on cancer and brain diseases. His work investigates how transport across cellular, tissue, and organ scales regulates disease progression and therapeutic response. Current efforts integrate systems-level transport modeling with engineered microphysiological platforms to study drug delivery in the tumor microenvironment, interstitial transport in stromal tissues, and neurovascular transport associated with inflammation and barrier dysfunction in the brain. In parallel, his laboratory develops advanced microfluidic and 3D biomanufacturing technologies to reconstruct physiologically relevant tissue architectures and quantitatively interrogate transport dynamics in complex biological systems. Through these approaches, his research seeks to establish engineering design principles for transport in living systems and to enable new strategies for drug discovery and therapeutic intervention.

Research topics

• Materials science
• Chemistry
• Cell biology
• Nanotechnology
• Biology

Selected publications

• A Systems Approach to Biomechanics, Mechanobiology, and Biotransport.

  UNC Libraries · 2026-04-18

  articleOpen access

  The human body represents a collection of interacting systems that range in scale from nanometers to meters. Investigations from a systems perspective focus on how the parts work together to enact changes across spatial scales, and further our understanding of how systems function and fail. Here, we highlight systems approaches presented at the 2022 Summer Biomechanics, Bio-engineering, and Biotransport Conference in the areas of solid mechanics; fluid mechanics; tissue and cellular engineering; biotransport; and design, dynamics, and rehabilitation; and biomechanics education. Systems approaches are yielding new insights into human biology by leveraging state-of-the-art tools, which could ultimately lead to more informed design of therapies and medical devices for preventing and treating disease as well as rehabilitating patients using strategies that are uniquely optimized for each patient. Educational approaches can also be designed to foster a foundation of systems-level thinking.

  PublisherDOI

• Depletion of Fibrinogen Suppresses Growth of Primary Tumors and Metastasis of Pancreatic Ductal Adenocarcinoma

  UNC Libraries · 2026-03-13

  articleOpen access
  PublisherDOI

• Interrogating functional connectivity of in vitro neural glia tissue model modulated through integrative control of matrix stiffness and a neurotrophic factor

  Biomaterials · 2025-09-14 · 1 citations

  article
  PublisherDOI

• Abstract B037: Validation and translation of therapeutic potential of thrombin-PAR1 signaling in suppressing fibrosis using microphysiological PDAC tumor models

  Cancer Research · 2025-09-28

  articleSenior author

  Abstract Pancreatic ductal adenocarcinoma (PDAC) creates complex tumor microenvironment (TME) hallmarked with a desmoplastic stroma that facilitates tumor growth/invasion, chemoresistance, and immunosuppression. It urgently needs the identification and evaluation of stromal components that can be targeted to reprogram the stroma to improve drug delivery and efficacy without making tumors more aggressive. Thus, we hypothesize that the coagulation system in the PDAC TME can be targeted to reprogram PDAC stroma to alleviate chemoresistance and drug delivery barriers. Specifically, the thrombin/protease-activated receptor 1 (PAR1) signaling axis can be targeted to suppress growth/invasion of pancreatic cancer cells (PCCs) and cancer associated fibroblast (CAF)-derived fibrosis. Our underlying rationale is based upon a leaky tumor vasculature in PDAC resulting in the release of circulating coagulation factors and subsequent activation of the coagulation system in the TME. Tissue factor expressed by PCCs initiates the conversion of prothrombin to the active serine protease thrombin, which then activates PAR1, whose signaling is thought to promote PCC growth/invasion and CAF-mediated fibrosis. We developed and employed novel microphysiological systems (MPS) of PDAC tumor-stroma, which were designed to reconstitute extravascular coagulation in the PDAC TME to specifically investigate the role of thrombin-PAR1 signaling events on PCC growth and CAF-mediated fibrosis. Our MPS was a microfluidic platform where PCC and CAF were co-cultured in the 3D extracellular matrix perfused with/without thrombin. In addition, PAR1 expression in murine and human PCCs and CAFs was genetically modified or pharmacologically inhibited. Our MPS enabled systematic and translational analyses on the therapeutic potential of blocking PAR1 signaling in PCCs, CAFs, or both. In murine MPS, genetic deletion of PAR1 drastically decreased thrombin-mediated PCC and CAF growth compared to that of MPS with wildtype cells. Human MPS with varying levels of PAR1 also suggest thrombin stimulates PCC-CAF crosstalk, including CAF growth, elevated expression of a-SMA and secreted collagen levels. Furthermore, pharmacological inhibition of PAR1 by vorapaxar decreases both PCC and CAFs in all human PCC/CAF pairs studied. Finally, we confirm the findings from our MPS using PDAC tumor-stroma xenograft models with both human PCC and CAF. A significant reduction in tumor size is observed with vorapaxar treatment, which attributes primarily to the reduction of CAFs. In summary, we validate and translate the therapeutic potential of thrombin-PAR1 signaling in reprogramming PDAC stroma using novel MPS of PDAC tumor-stroma model. Our study also demonstrates MPS as a promising system for target identification, validation, and streamlining preclinical studies for drug discovery. Citation Format: Sae Rome. Choi, Hye-ran Moon, Natalia Ospina Muñoz, Yun Chang, Xiaoping Bao, Bennett D. Elzey, Meliss L. Fishel, Matthew J. Flick, Bumsoo Han. Validation and translation of therapeutic potential of thrombin-PAR1 signaling in suppressing fibrosis using microphysiological PDAC tumor models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B037.

  PublisherDOI

• DNA Origami‐Cyanine Nanocomplex for Precision Imaging of KRAS‐Mutant Pancreatic Cancer Cells

  Advanced Science · 2025-02-14 · 3 citations

  articleOpen accessSenior authorCorresponding

  Selective delivery of imaging agents to pancreatic cancer cells (PCCs) within the highly desmoplastic tumors of pancreatic ductal adenocarcinoma (PDAC) represents a significant advancement. This approach allows for precise labeling of PCCs while excluding cancer-associated fibroblasts (CAFs), thereby enhancing both research and diagnostic capabilities. Additionally, it holds the potential to target and eliminate PCCs precisely without harming the surrounding stromal cells in the PDAC tumor microenvironment (TME). In this study, DNA origami-cyanine (Do-Cy) nanocomplexes are synthesized to image KRAS-mutant PCCs selectively in the PDAC TME. These Do-Cy nanocomplexes are hypothesized to be internalized preferentially to KRAS-mutant PCCs over CAFs via elevated macropinocytosis. Several designs of Do-Cy nanocomplexes are synthesized and characterized their cellular uptake using both engineered in vitro and xenograft pancreatic cancer models. The results are further discussed for the implication of precision delivery of therapeutic and imaging agents to KRAS-mutant cancers.

  PublisherDOI

• Abstract A120: Disrupting PAR-1-mediated protease signaling in the PDAC tumor and its microenvironment

  Cancer Research · 2025-09-28

  article

  Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, with a five-year survival rate of 13%. The desmoplastic tumor microenvironment (TME) that is characteristic of PDAC facilitates tumor growth and invasion and drug resistance. This dense TME is composed of extracellular matrix proteins and cancer-associated fibroblasts (CAFs) which directly contribute to tumor development. Modulating these components is a promising strategy to enhance the anti-tumor activities of existing drugs. As PDAC is a hypercoagulative disease, one component of interest is the coagulation system. To target this system without increasing bleeding risk, our group is investigating the specific roles of downstream signaling cascades including the protease-activated receptor 1 (PAR-1). Overproduction of tissue factor (TF) by PDAC cells promotes tumor growth, invasion, and metastasis through the PAR-1 signaling axis. Knockdown or knockout of PAR-1 in KPC2 cells dramatically reduced tumor growth in vivo and reduced the incidence and severity of lung metastases by a similar margin. These observations and the high expression of PAR-1 on PDAC cells posit PAR-1 as a viable therapeutic target for PDAC. The requirement of tumor cell PAR-1 for metastatic potential was investigated using the tail vein injection/experimental metastasis model. Time course analyses revealed that KPC2 control cells form high numbers of macroscopically evident pulmonary metastatic foci by 14 days post-injection whereas the number of pulmonary metastatic foci is significantly reduced with KPC2-PAR1KO cells. Injection of CFSE-labeled cells indicated PAR-1 is not required for the initial adherence or survival of metastatic tumor cells as the number of micrometastatic lesions were not different between KPC2 control and KPC2-PAR1KO cells 24 hours after injection. Metastasis experiments in NSG mice suggest tumor cell PAR-1 supports metastatic potential through mechanisms linked to and independent from evasion of anti-tumor immunity. Although the anti-tumor activity of immune cells within the PDAC microenvironment is limited, this compartment still offers significant promise for anti-cancer therapies. To potentiate the anti-tumor T cell response, chimeric antigen receptor T (CAR-T) cells targeting PAR-1, which is overexpressed on pancreatic tumor cells, were generated. Preliminary studies in vitro have demonstrated robust killing of PAR-1 expressing tumor cells. Additionally, single cell sequencing revealed that PAR-1 expression is significantly elevated in CAF populations within the TME, specifically myCAF subtype which shows significantly higher PAR-1 expression than iCAF (1.36-fold). Understanding the crosstalk between malignant cells and other populations within the PDAC TME is critical for the development of therapies that target the coagulation system through the PAR-1 signaling axis. Investigating these targets will enhance our understanding of the cancer-relevant mechanisms of various components of the coagulation cascade in PDAC and facilitate clinical management of this disease. Citation Format: Jessica A. Occhiuto, Claire E. Reist, Jacqueline Peil, Malak Khalifeh, Huda Salman, Ateeq M. Khaliq, Ashiq Masood, Bumsoo Han, Matthew J. Flick, Melissa Fishel. Disrupting PAR-1-mediated protease signaling in the PDAC tumor and its microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A120.

  PublisherDOI

• Quantifying cellular autonomy in multi-cue environments.

  PubMed · 2025-06-25

  preprintOpen access

  A cell routinely responds to one of many competing environmental cues. A fundamental question is whether the cell follows the cue prioritized by its internal signaling network or the cue that carries the most external information. We introduce a theoretical framework to answer this question. We derive information limits for four types of directional cues: external and self-generated chemical gradients, fluid flow, and contact inhibition of locomotion. When the cues compete as pairs, these limits predict which cue a cell should follow if its decision is based on environmental information alone. We compare these predicted decision boundaries with data from our and others' cell migration experiments, finding cases where the boundary is obeyed and cases where it is violated by orders of magnitude. Both outcomes are informative, and we find that they rationalize known properties, or predict putative properties, of cells' internal signaling networks. Our work introduces a physical framework to quantify the degree to which a cell acts like an autonomous agent, rather than a passive detector, favoring a cue even when it is less informative.

  PublisherOA PDF

• DNA Origami‐Cyanine Nanocomplex for Precision Imaging of KRAS‐Mutant Pancreatic Cancer Cells (Adv. Sci. 19/2025)

  Advanced Science · 2025-05-01

  articleOpen accessSenior author

  DNA OrigAmi-CyANiNe NANOCOmplexThe internalization of DNA origami-cyanine nanocomplex via micropinocytosis, characterized by membrane ruffling and vesicle formation, is significantly enhanced in pancreatic cancer cells with KRAS mutation.In article number 2410278 by Jong Hyun Choi, Bumsoo Han, and co-workers, a new molecular imaging method is proposed based on this finding to selectively visualize pancreatic cancer cells in desmoplastic tumors.

  PublisherOA PDFDOI

• Statin-dye conjugates for selective targeting of <i>KRAS</i> mutant cancer cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-06

  preprintOpen access

  ABSTRACT Over 90% of pancreatic ductal adenocarcinoma (PDAC) patients involve KRAS mutations ( KRAS MUT ), for which current treatment options are limited. Statins, commonly used to lower cholesterol, have demonstrated certain selective toxicity towards KRAS -transformed cells, prompting the question of whether statins could achieve selective uptake specifically in KRAS MUT cells. To investigate this, we synthesized statin-dye conjugates by attaching a fluorescent dye (Cy5.5) to two statins: simvastatin and pravastatin, aiming to assess whether selective uptake indeed occurs. Our findings revealed that these conjugates exhibited markedly enhanced uptake in KRAS MUT cells compared to KRAS wild-type ( KRAS WT ) cells. Given the magnitude of the selective uptake, we realized that the uptake of these conjugates itself is of considerable intrinsic interests. We evaluated the uptake of these conjugates in both KRAS MUT and KRAS WT cells and examined their potential to selectively target KRAS MUT pancreatic cancer cells (PCCs) using an engineered PDAC tumor model co-cultured with PCCs and cancer-associated fibroblasts (CAFs). Our findings indicate that KRAS MUT cancer cells exhibited higher uptake of statin-Cy5.5 conjugates via enhanced macropinocytosis compared to KRAS WT cancer cells and CAFs. We also found enhanced uptake of the statin-Cy5.5 conjugate in MCF10A cells with PTEN deficiency, a condition known to elevate macropinocytosis, compared to control MCF10A cells with wild-type PTEN . Notably, in the PCC and CAF co-culture model, the pravastatin-Cy5.5 conjugate selectively killed KRAS MUT PCCs without affecting the KRAS WT CAFs. These findings highlight the potential of stain-drug conjugates as targeted delivery vehicles for KRAS MUT cancer therapy.

  PublisherOA PDFDOI

• Biomechanical 3D tumor models on a micro-milled high-throughput force sensor array

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-24

  preprintOpen access

  ABSTRACT The tumor microenvironment plays a critical role in drug resistance, with extracellular matrix (ECM) mechanics, cell-cell crosstalk, and transport barriers contributing to poor therapeutic outcomes. Traditional two-dimensional (2D) cultures fail to capture these features, and drug efficacy in 2D often does not translate to three-dimensional (3D) models or in vivo tumors. Here, we introduce a 3D tumor model integrated with a high- throughput biomechanical sensor array that enables simultaneous measurement of cellular forces, matrix remodeling, and molecular transport. Fabricated using a scalable and cost-effective micro-milling approach, the platform allows parallel generation of multiple tumor constructs within a single dish. Using patient-derived pancreatic ductal adenocarcinoma (PDA) cells and stromal fibroblasts, we show that responses to gemcitabine and all-trans retinoic acid (ATRA) in 3D differ markedly from 2D cultures, consistent with clinical observations. By integrating biochemical and biomechanical readouts, this technology provides a more physiologically relevant tumor model and a powerful tool for preclinical drug testing and personalized medicine.

  PublisherOA PDFDOI

Recent grants

• CAREER: Multi-scale cell-fluid-matrix interactions during freezing/thawing of biological tissues

  NSF · $405k · 2008–2009

• CAREER: Multi-scale cell-fluid-matrix interactions during freezing/thawing of biological tissues

  NSF · $294k · 2009–2013

• Reprogramming PDAC Stroma by Targeting Coagulation in the Tumor Microenvironment

  NIH · $3.7M · 2022–2027

• NIH Grant R01EB008388

  NIH · $1.2M · 2013

• Targeting the Plasminogen Activation System to Limit Pancreatic Cancer Progression and Associated Thrombosis

  NIH · $4.2M · 2018–2025

Frequent coauthors

• Hye‐ran Moon

  Purdue University West Lafayette

  44 shared

• Andrew Mugler

  University of Pittsburgh

  39 shared

• Altuğ Özçelikkale

  Middle East Technical University

  34 shared

• J. C. Dutton

  University of Illinois Urbana-Champaign

  20 shared

• John C. Bischof

  University of Minnesota

  20 shared

• Melissa L. Fishel

  17 shared

• Silpa Gampala

  Indiana University – Purdue University Indianapolis

  17 shared

• Ka Yaw Teo

  16 shared

Education

• Ph.D., Mechanical Engineering

  University of Minnesota Twin Cities

  2001

• M.S., Mechanical Engineering

  Seoul National University

  1996

• B.S., Mechanical Engineering

  Seoul National University

  1993

Awards & honors

• Biohub Investigator, Chan Zuckerberg Biohub Chicago, 2024
• Fellow, American Society of Mechanical Engineers (ASME), 202…
• US AFOSR Summer Faculty Fellowship, 2013
• NSF Faculty Early Career Development (CAREER) Award, 2008
• US DOD Postdoctoral Traineeship Award, Congressionally Direc…