About

Princess U II Imoukhuede is an Adjunct Associate Professor in the Department of Bioengineering at the University of Illinois Urbana-Champaign. Her research applies systems biology to study clinically relevant questions in cancer and cardiovascular disease. Her laboratory engineers fluorescent nanosensors that quantitatively characterize the vascular microenvironment and develops computational models that integrate molecular and cellular data to inform on processes occurring in vascular pathologies. These systems biology methods, both experimental and computational, are used to predict the efficacy of angiogenic therapeutics and to identify novel drug targets and treatment schemes. Dr. Imoukhuede holds a PhD in Bioengineering from the California Institute of Technology and a BS in Chemical Engineering from MIT. Her academic positions include affiliate roles at the Institute for Genomic Biology and the Beckman Institute at the University of Illinois, as well as her role as Assistant Professor in Bioengineering since 2012. Her research interests encompass membrane biology, tyrosine kinase receptors, nanosensors, fluorescence, computational modeling, and systems biology, with a focus on tumor angiogenesis and vascular pathologies. She has contributed to the field through her work on receptor profiling, quantitative fluorescent profiling, and the development of computational models to understand vascular processes, with the goal of advancing therapeutic strategies for cancer and cardiovascular diseases.

Research topics

• Political Science
• Computer Science
• Sociology
• Aesthetics
• Mathematics
• Biology
• History
• Computational biology
• Law
• Gender studies

Selected publications

• Obesity Alters the Vascular Morphology and VEGF‐A Signaling in Adipose Tissue

  FASEB BioAdvances · 2025-05-19 · 3 citations

  articleOpen accessSenior authorCorresponding

  Obesity is a global health crisis, with its prevalence particularly severe in the United States, where over 42% of adults live with obesity. Obesity is driven by complex molecular and tissue-level mechanisms that remain poorly understood. Among these, angiogenesis-primarily mediated by vascular endothelial growth factor-A (VEGF-A)-is critical for adipose tissue expansion but presents unique challenges for therapeutic targeting due to its intricate regulation. Systems biology approaches have advanced our understanding of VEGF-A signaling in vascular diseases, but their application to obesity is limited by scattered and sometimes contradictory data. To address this gap, we performed a comprehensive analysis of the existing literature to synthesize key findings, standardize data, and provide a holistic perspective on the adipose vascular microenvironment. The data mining revealed five key findings: (1) obesity increases adipocyte size by 78%; (2) vessel density in adipose tissue decreases by 51% in mice with obesity, with vessels being 47%-58% smaller and four to nine times denser in comparison with tumor vessels; (3) capillary basement membrane thickness remains similar regardless of obesity; (4) VEGF-A shows the strongest binding affinity for VEGFR1, with four times stronger affinity for VEGFR2 than for NRP1; and (5) binding affinities measured by radioligand binding assay and surface plasmon resonance are significantly different. These consolidated findings provide essential parameters for systems biology modeling, new insights into obesity-induced changes in adipose tissue, and a foundation for developing angiogenesis-targeting therapies for obesity.

  PublisherOA PDFDOI

• Cross-family interactions of vascular endothelial growth factors and platelet-derived growth factors on the endothelial cell surface: A computational model

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-04

  preprintOpen accessSenior authorCorresponding

  Angiogenesis, the formation of new vessels from existing vessels, is mediated by vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). Despite discoveries supporting the cross-family interactions between VEGF and PDGF families, sharing the binding partners between them makes it challenging to identify growth factors that predominantly affect angiogenesis. Systems biology offers promises to untangle this complexity. Thus, in this study, we developed a mass-action kinetics-based computational model for cross-family interactions between VEGFs (VEGF-A, VEGF-B, and PlGF) and PDGFs (PDGF-AA, PDGF-AB, and PDGF-BB) with their receptors (VEGFR1, VEGFR2, NRP1, PDGFRα, and PDGFRβ). The model, parametrized with our literature mining and surface resonance plasmon assays, was validated by comparing the concentration of VEGFR1 complexes with a previously constructed angiogenesis model. The model predictions include five outcomes: 1) the percentage of free or bound ligands and 2) receptors, 3) the concentration of free ligands, 4) the percentage of ligands occupying each receptor, and 5) the concentration of ligands that is bound to each receptor. We found that at equimolar ligand concentrations (1 nM), PlGF and VEGF-A were the main binding partners of VEGFR1 and VEGFR2, respectively. Varying the density of receptors resulted in the following five outcomes: 1) Increasing VEGFR1 density depletes the free PlGF concentration, 2) increasing VEGFR2 density decreases PDGF:PDGFRα complexes, 3) increased NRP1 density generates a biphasic concentration of the free PlGF, 4) increased PDGFRα density increases PDGFs:PDGFRα binding, and 5) increasing PDGFRβ density increases VEGF-A:PDGFRβ. Our model offers a reproducible, fundamental framework for exploring cross-family interactions that can be extended to the tissue level or intracellular molecular level. Also, our model may help develop therapeutic strategies in pathological angiogenesis by identifying the dominant complex in the cell signaling. Author summary: New blood vessel formation from existing ones is essential for growth, healing, and reproduction. However, when this process is disrupted-either too much or too little-it can contribute to diseases such as cancer and peripheral arterial disease. Two key families of proteins, vascular endothelial growth factors (VEGFs) and platelet-derived growth factors (PDGFs), regulate this process. Traditionally, scientists believed that VEGFs only bind to VEGF receptors and PDGFs to PDGF receptors. However, recent findings show that these proteins can interact with each other's receptors, making it more challenging to understand and control blood vessel formation. To clarify these complex interactions, we combined computer modeling with biological data to map out which proteins bind to which receptors and to what extent. Our findings show that when VEGFs and PDGFs are present in equal amounts, VEGFs are the primary binding partners for VEGF receptors. We also explored how changes in receptor levels affect these interactions in disease-like conditions. This work provides a foundational computational model for studying cross-family interactions, which can be expanded to investigate tissue-level effects and processes inside cells. Ultimately, our model may help develop better treatments for diseases linked to abnormal blood vessel growth by identifying key protein-receptor interactions.

  PublisherOA PDFDOI

• From FAIR to CURE: Guidelines for Computational Models of Biological Systems.

  PubMed · 2025-02-21 · 3 citations

  preprintOpen access

  are key to progress. For this reason, and recognizing that such models are a very special type of "data", we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary set of guidelines. We propose the CURE principles, emphasizing that models should be Credible, Understandable, Reproducible, and Extensible. We delve into each principle, discussing verification, validation, and uncertainty quantification for model credibility; the clarity of model descriptions and annotations for understandability; adherence to standards and open science practices for reproducibility; and the use of open standards and modular code for extensibility and reuse. We outline recommended and baseline requirements for each aspect of CURE, aiming to enhance the impact and trustworthiness of computational models, particularly in biomedical applications where credibility is paramount. Our perspective underscores the need for a more disciplined approach to modeling, aligning with emerging trends such as Digital Twins and emphasizing the importance of data and modeling standards for interoperability and reuse. Finally, we emphasize that given the non-trivial effort required to implement the guidelines, the community moves to automate as many of the guidelines as possible.

  PublisherOA PDF

• Sex Differences in VEGF and PDGF Ligand and Receptor Protein Expression during Adipose Tissue Expansion and Regression

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-16 · 5 citations

  preprintOpen accessSenior authorCorresponding

  Inadequate angiogenesis in obesogenic adipose tissue (AT) has been implicated in disrupted adipogenesis and metabolic disorders. Yet, key cellular and molecular regulators of AT angiogenesis remain largely unidentified. This study sought to identify the dysregulated elements within the Vascular Endothelial Growth Factor (VEGF) and Platelet-Derived Growth Factor (PDGF) systems during obesity progression. We employ a mouse model, comprising both male and female mice, to investigate the changes in the VEGF/PDGF concentration and their receptor distribution in AT during short- and long-term weight gain and weight loss. Our results reveal pronounced sex-specific differences in obesity progression, with male and female mice exhibiting distinct angiogenic ligand and receptor profiles under identical dietary interventions. This data also lays the groundwork for developing computational models of VEGF/PDGF signaling networks in AT, allowing for the simulation of complex biological interactions and the prediction of therapeutic outcomes.

  PublisherOA PDFDOI

• Discovery of High-Affinity (Nanomolar) Interactions between Vegfs and Pdgfs

  SSRN Electronic Journal · 2025-01-01

  preprintOpen accessSenior author
  PublisherDOI

• Computational Systems Biology for the VEGF Family in Angiogenesis

  Elsevier eBooks · 2025-11-24

  book-chapterSenior author
  PublisherDOI

• Cultured endothelial cells present organ-specific RTK distributions: advancing receptor measurement and data standardization via quantitative flow cytometry

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-28 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Purpose Receptor tyrosine kinase (RTK) concentrations on the plasma membrane correlate with angiogenic functions in vitro and in rodent models. The intracellular RTK pool also regulates plasma membrane receptor availability and signaling pathways. Organs have specialized angiogenic functions essential to their distinct roles, supporting the hypothesis that plasma membrane and intracellular RTK concentrations vary across endothelial cells (ECs) from different organs. Methods Using quantitative flow cytometry on human ECs derived from dermis, umbilical vein, kidney, liver, and brain, we measured and statistically analyzed the concentrations of selected RTKs within ECs and on their plasma membranes. Results VEGFR1 exhibited the lowest concentrations on the plasma membrane (300 - 900 VEGFR1/cell) among VEGFRs. HDMECs (dermis) showed the lowest VEGFR1 level among the examined EC types. Whole-cell VEGFR1 concentrations were 2500 - 7500 VEGFR1/cell, with 12 - 26% located on the plasma membrane. The proportion of VEGFR2 located on the plasma membrane was higher at > 30%, except in HGMECs (kidney) where it was 24%. Plasma membrane VEGFR2 was significantly lower in HDMECs and HGMECs compared with HBMECs (brain), whereas whole-cell VEGFR2 levels were consistently in the range of 14,100 - 22,500 molecules/cell. VEGFR3 was the least localized to the plasma membrane, from 2% in HGMECs to 14% in HDMECs at the highest level of 4400 VEGFR3/cell. Whole-cell VEGFR3 concentrations ranged from 32,400 in HDMECs to 62,000 VEGFR3/cell in HLiSMECs (liver), with no significant differences among EC types. NRP1 was most abundant on the plasma membrane of HUVECs (umbilical vein) at 39,700 NRP1/cell; other ECs displayed 26,000 - 29,900 NRP1/cell, approximately 5-fold higher than the numbers of VEGFRs. Across EC types, Axl was present on the plasma membrane at levels (6900 - 12,200 Axl/cell) similar to those of VEGFR2. Conclusions We quantified and statistically analyzed plasma membrane and whole-cell expression of angiogenic RTKs across cultured human ECs from five different organs. Our findings suggest that RTK protein distribution might not fully reflect the differential angiogenic capacities in cultured ECs. In vitro monoculture conditions might reduce EC organ-specific features essential for refining vascular models.

  PublisherOA PDFDOI

• Predicting oxytocin binding dynamics in receptor genetic variants through computational modeling

  npj Women s Health · 2025-02-08

  articleOpen accessSenior author

  Approximately half of U.S. women giving birth annually receive Pitocin, a synthetic form of oxytocin (OXT), yet the optimal dosing remains challenging due to significant individual variability in response. To address this, we developed a mathematical model examining the effects of five OXT receptor (OXTR) variants (V45L, P108A, L206V, V281M, and E339K) on OXT-OXTR binding dynamics in human embryonic kidney cells (HEK293T) and myometrial smooth muscle cells. The model was parameterized using experimentally derived, cell-specific OXTR surface localization measurements and literature-reported OXT-OXTR-binding kinetics. The model revealed differences in time to equilibrium between HEK293T and myometrial cells, distinct dynamics among genetic variants, and that early increases in OXT could partially rescue diminished responses in V281M and E339K variants. This model provides key insights into how genetic variants influence OXT dose responses and offers a framework for tailoring OXT dosing to patient-specific genetic profiles.

  PublisherOA PDFDOI

• Exploring cross-family activation of growth factor receptors with molecular dynamics simulations

  Biophysical Journal · 2024-02-01

  articleOpen access
  PublisherOA PDFDOI

• Understanding the effects of oxytocin receptor variants on OXT–OXT receptor binding: A mathematical model

  Research Square · 2024-10-17

  preprintOpen accessSenior author
  PublisherDOI

Recent grants

• UNS:ADVANCING CELL-PRESERVING SEPARATION VIA DETACHABLE CELL ANCHORING & SPIRAL MICRO-MIXING

  NSF · $372k · 2015–2018

• CAREER: qBio+cBio=sBio; Identifying the role of cross-family signaling in angiogenesis

  NSF · $557k · 2017–2019

• CAREER: qBio+cBio=sBio; Identifying the role of cross-family signaling in angiogenesis

  NSF · $397k · 2018–2023

• Quantitative and computational characterization of oxytocin receptor signaling

  NIH · $2.8M · 2019–2025

Frequent coauthors

• J. Weddell

  13 shared

• Yingye Fang

  University of Washington

  11 shared

• Aleksander S. Popel

  Johns Hopkins University

  11 shared

• Si Chen

  China Medical University

  10 shared

• Jennifer Amos

  University of Illinois Urbana-Champaign

  7 shared

• Felipe T. Lee-Montiel

  QB3

  7 shared

• Manasi Malik

  Washington University in St. Louis

  6 shared

• Sarah K. England

  Washington University in St. Louis

  6 shared

Education

• Postdoctoral Fellowship, Biomedical Engineering

  Johns Hopkins Medicine

  2011

• PhD, Bioengineering

  Caltech

  2008

• SB, Chemical Engineering

  MIT

  2002