Sean Palecek
· Milton J. and A. Maude Shoemaker ProfessorVerifiedUniversity of Wisconsin-Madison · Biomedical Engineering
Active 1993–2026
About
Sean Palecek is the Milton J. and A. Maude Shoemaker Professor at the College of Engineering at the University of Wisconsin-Madison. His research focuses on cellular signaling networks, particularly mechano-transduction pathways, and how quantitative changes in signal flow control various cellular processes. He studies how cell-cell adhesive interactions influence disease pathogenesis and how adhesive and mechanical signals, combined with chemical signals, regulate stem cell fate choices. His work includes investigating how cell adhesion affects disease mechanisms, using genetic screens to identify adhesion receptors in the human pathogen Candida albicans, and characterizing their roles in biofilm formation, virulence, and interactions with materials used in medical devices. Palecek also studies how physical cues such as adhesive forces and mechanical strain impact the self-renewal and differentiation of human embryonic stem cells, aiming to develop methods for scalable stem cell culture and differentiation strategies. His contributions advance understanding in cellular engineering, tissue engineering, and stem cell biology, with applications in disease treatment and biomaterials design.
Research topics
- Neuroscience
- Biology
- Medicine
- Pathology
- Computational biology
- Artificial Intelligence
- Cell biology
- Computer Science
- Genetics
- Cancer research
- Virology
- Bioinformatics
- Biochemistry
Selected publications
Figshare · 2026-01-01
otherOpen accessSenior authorAbstract Background Mechanisms guiding the induction of blood-brain barrier (BBB) properties in central nervous system (CNS) endothelial cells during human development are incompletely understood. For example, there is a limited understanding of signaling pathways that influence the unique property of low vesicular endocytosis and transcytosis in brain microvascular endothelial cells (BMECs) relative to peripheral endothelial cells. Mouse studies suggest the importance of BBB-relevant developmental pathways, including Wnt and Notch signaling, for the induction of this BBB feature in developing BMECs. Methods To explore induction of reduced vesicular endocytosis and transcytosis in human in vitro model of the BBB, we used human pluripotent stem cell (hPSC)-derived endothelial progenitor cells (EPCs) in which Wnt/β-catenin signaling was activated to generate hPSC-derived CNS-like ECs (hPSC-CECs). We assessed the effects of Notch signaling through overexpression of the Notch1 receptor intracellular domain (N1ICD). Results N1ICD overexpression in hPSC-CECs resulted in upregulation of GLUT-1, a BBB-enriched glucose transporter, and decreased expression of both PLVAP and caveolin-1, two vesicular endocytosis-associated proteins. The combination of Wnt/β-catenin activation and N1ICD overexpression resulted in fewer vesicles and reduced albumin uptake. Conclusion These findings indicate that Notch signaling reduces vesicular endocytosis and transcytosis in a human model of the developing BBB and contribute to our understanding of how Notch signaling induces these specific BBB properties in this model of human CNS EC development.
Open MIND · 2026-01-01
articleSenior authorSupplementary Material 1
ChemRxiv · 2026-04-03
articleOpen accessThe accessory gene regulator (agr) quorum sensing system in Staphylococcus aureus plays a prominent role in acute infections caused by this common pathogen. In contrast, ATP synthase affects the ability of S. aureus to establish chronic infections and persist as small colony variants. In this study, we report that a synthetic small molecule, CP-20, is capable of dually inhibiting agr and ATP synthase. We demonstrate CP-20’s ability to counteract key virulence phenotypes associated with both pathways, including hemolysis, biofilm formation, and antibiotic resistance. We also show that CP-20 facilitates more efficient clearance of S. aureus by murine macrophages than genetic inactivation of either agr or ATP synthase alone, suggesting that dual inhibition may have an additive effect on ablating intracellular survival. This work demonstrates the utility of a single chemical modulator to attenuate S. aureus pathogenesis via two non-essential pathways and suggests a pathway toward non-bactericidal virulence control.
Fluids and Barriers of the CNS · 2026-01-16
articleOpen accessSenior authorMechanisms guiding the induction of blood-brain barrier (BBB) properties in central nervous system (CNS) endothelial cells during human development are incompletely understood. For example, there is a limited understanding of signaling pathways that influence the unique property of low vesicular endocytosis and transcytosis in brain microvascular endothelial cells (BMECs) relative to peripheral endothelial cells. Mouse studies suggest the importance of BBB-relevant developmental pathways, including Wnt and Notch signaling, for the induction of this BBB feature in developing BMECs. To explore induction of reduced vesicular endocytosis and transcytosis in human in vitro model of the BBB, we used human pluripotent stem cell (hPSC)-derived endothelial progenitor cells (EPCs) in which Wnt/β-catenin signaling was activated to generate hPSC-derived CNS-like ECs (hPSC-CECs). We assessed the effects of Notch signaling through overexpression of the Notch1 receptor intracellular domain (N1ICD). N1ICD overexpression in hPSC-CECs resulted in upregulation of GLUT-1, a BBB-enriched glucose transporter, and decreased expression of both PLVAP and caveolin-1, two vesicular endocytosis-associated proteins. The combination of Wnt/β-catenin activation and N1ICD overexpression resulted in fewer vesicles and reduced albumin uptake. These findings indicate that Notch signaling reduces vesicular endocytosis and transcytosis in a human model of the developing BBB and contribute to our understanding of how Notch signaling induces these specific BBB properties in this model of human CNS EC development.
ChemRxiv · 2026-04-02
articleOpen accessThe accessory gene regulator (agr) quorum sensing system in Staphylococcus aureus plays a prominent role in acute infections caused by this common pathogen. In contrast, ATP synthase affects the ability of S. aureus to establish chronic infections and persist as small colony variants. In this study, we report that a synthetic small molecule, CP-20, is capable of dually inhibiting agr and ATP synthase. We demonstrate CP-20’s ability to counteract key virulence phenotypes associated with both pathways, including hemolysis, biofilm formation, and antibiotic resistance. We also show that CP-20 facilitates more efficient clearance of S. aureus by murine macrophages than genetic inactivation of either agr or ATP synthase alone, suggesting that dual inhibition may have an additive effect on ablating intracellular survival. This work demonstrates the utility of a single chemical modulator to attenuate S. aureus pathogenesis via two non-essential pathways and suggests a pathway toward non-bactericidal virulence control.
bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-03
articleOpen accessAbstract Brain microvascular endothelial cells (BMECs) forming the blood-brain barrier (BBB) maintain brain homeostasis through specialized properties such as tight junctions, efflux transporters, and low levels of transcytosis. However, mechanisms governing induction of BBB properties during development remain poorly understood. We mined single-cell RNA sequencing datasets to identify transcription factors (TFs) critical for BBB development. Forty-four TFs were overexpressed in human pluripotent stem cell-derived endothelial cells cultured in the presence of the Wnt pathway agonist CHIR99021 to identify TFs capable of directing acquisition of BBB properties via forward programming. Individual TFs, including KLF2 , KLF4 , FOXF1 , FOXF2 , ZIC2 , ZIC3 , NR4A1 , NR4A2 , FOXC1 , and FOXQ1 , induced distinct BBB-like gene expression patterns. Combinations of these TFs induced many canonical BBB genes, yielding ECs with reduced endocytosis, increased efflux activity, and improved barrier function. The resultant forward programmed CNS-like ECs (fpCECs) offer promising tools for modeling human BBB development and neurovascular disease and for drug screening.
Biotechnology and Bioengineering · 2026-05-14
articleOpen accessSenior authorTerminal cell types derived from human pluripotent stem cells (hPSCs) are at the forefront of emerging cell and gene therapy products. hPSC-derived cardiomyocytes (hPSC-CMs) are of particular interest in understanding and treating heart disease, which is highly prevalent worldwide; however, hPSC-CM manufacturing robustness is a roadblock to these applications. Non-destructive methods to monitor hPSC-CMs and predict differentiation efficiency throughout the process are needed. Here, we demonstrate a supervised machine learning approach utilizing random projection-based feature embedding and Linear Discriminant Analysis that can predict Day 12 CM purity from phase contrast images as early as 1 day after initiation of differentiation. In contrast, a heuristic based on a live-cell cTnT-GFP reporter provided limited information until Days 7-9. In summary, we provide evidence that machine learning analysis of phase contrast images is a promising approach for predicting hPSC-CM differentiation efficiency during early differentiation stages. Future efforts could use these models to inform the improvement of CM differentiation protocols and support CM biomanufacturing.
Journal of Molecular and Cellular Cardiology Plus · 2026-03-01
articleOpen accessFigshare · 2026-01-01
otherOpen accessSenior authorAbstract Background Mechanisms guiding the induction of blood-brain barrier (BBB) properties in central nervous system (CNS) endothelial cells during human development are incompletely understood. For example, there is a limited understanding of signaling pathways that influence the unique property of low vesicular endocytosis and transcytosis in brain microvascular endothelial cells (BMECs) relative to peripheral endothelial cells. Mouse studies suggest the importance of BBB-relevant developmental pathways, including Wnt and Notch signaling, for the induction of this BBB feature in developing BMECs. Methods To explore induction of reduced vesicular endocytosis and transcytosis in human in vitro model of the BBB, we used human pluripotent stem cell (hPSC)-derived endothelial progenitor cells (EPCs) in which Wnt/β-catenin signaling was activated to generate hPSC-derived CNS-like ECs (hPSC-CECs). We assessed the effects of Notch signaling through overexpression of the Notch1 receptor intracellular domain (N1ICD). Results N1ICD overexpression in hPSC-CECs resulted in upregulation of GLUT-1, a BBB-enriched glucose transporter, and decreased expression of both PLVAP and caveolin-1, two vesicular endocytosis-associated proteins. The combination of Wnt/β-catenin activation and N1ICD overexpression resulted in fewer vesicles and reduced albumin uptake. Conclusion These findings indicate that Notch signaling reduces vesicular endocytosis and transcytosis in a human model of the developing BBB and contribute to our understanding of how Notch signaling induces these specific BBB properties in this model of human CNS EC development.
Soft Matter · 2026-01-01
articleWe report on the optical responses of nanoparticle-stabilized droplets of thermotropic liquid crystals (LCs) dispersed in water to phospholipid vesicles composed of single or mixed-lipid systems of dilauroyl phosphatidylcholine (DLPC), dioleoyl phosphocholine (DOPC), dioleoyl phosphoethanolamine (DOPE), and dioleoyl phosphoglycerol (DOPG). Our findings reveal these LC droplets to undergo bipolar-to-non-bipolar optical transitions upon exposure to vesicles in ways that depend upon phospholipid structure. Specifically, DLPC induced LC transitions at lower concentrations when compared to DOPC, while DOPE and DOPG did not trigger LC responses up to the highest lipid concentrations tested. Moreover, incorporating at least 30% DLPC into DOPC, DOPE, or DOPG vesicles significantly enhanced the sensitivity of stabilized LC droplets to these lipids. Notably, DLPC-containing DOPE and DOPG vesicles triggered LC transitions that were not observed with the corresponding single-component systems. Our findings provide fundamental insight into the behaviors of LC droplet-based systems that combine colloidal stability with sensitive optical responses to contact with model phospholipid vesicles. This work lays a foundation for exploring these nanoparticle-stabilized LC emulsions in contact with more complex lipid membrane mimics to support the design of responsive materials systems that can report the presence of lipid structures of interest in applied contexts, including vesicles, lipid nanoparticles, or mammalian or bacterial cells.
Recent grants
Prevention of Candida biofilms by localized delivery of aurein analogues
NIH · $421k · 2016–2018
NSF · $300k · 2015–2018
NIH · $1.5M · 2019–2025
UNS:Role of Cell-Mediated ECM Remodeling in Pluripotent Stem Cell Differentiation
NSF · $350k · 2015–2020
CAREER: A Cell-Based Biosensor for DNA Damaging Agents
NSF · $418k · 2003–2009
Frequent coauthors
- 70 shared
Eric V. Shusta
University of Wisconsin–Madison
- 65 shared
Timothy J. Kamp
University of Wisconsin–Madison
- 60 shared
Xiaojun Lian
Pennsylvania State University
- 55 shared
James A. Thomson
Morgridge Institute for Research
- 54 shared
Gisela F. Wilson
- 54 shared
Andrew G. Soerens
University of Minnesota Medical Center
- 54 shared
Jianhua Zhang
- 53 shared
Junying Yu
Education
- 1998
Ph.D., Chemical Engineering
Massachusetts Institute of Technology
- 1995
M.S., Chemical Engineering
University of Illinois at Urbana-Champaign
- 1993
B.S., Chemical Engineering
University of Delaware
Awards & honors
- Kellett Mid-Career Award (2023)
- Syracuse University, Stevenson Lecture (2023)
- R. Byron Bird Excellence in Research Publication Award (2021…
- Honored Instructor Award (2017)
- Fellowship, American Institute for Medical and Biological En…
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