About

Wei Guo is the Hirsch Family President's Distinguished Professor in the Department of Biology at the University of Pennsylvania. His primary research interests lie in Cell and Developmental Biology. He is based in the 304E Lynch Laboratory and can be contacted via guowei@sas.upenn.edu. Wei Guo's work focuses on understanding the cellular and developmental processes that underlie biological function and organization.

Research topics

• Biology
• Cancer research
• Cell biology
• Biochemistry
• Chemistry
• Condensed matter physics
• Quantum mechanics
• Genetics
• Immunology
• Materials science
• Physics

Selected publications

• RPPA data and analysis for melanoma cells under tryptophan deprivation

  Open MIND · 2026-01-29

  otherSenior author
  DOI

• SPTBN2 promotes an immunosuppressive tumor microenvironment and cross-resistance to anti-cancer therapies

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-01

  articleOpen access

  Immunosuppressive tumor microenvironment (TME) inactivates CD8+ cytotoxic lymphocytes (CTLs). Here, we identify SPTBN2 spectrin as a key immunosuppressive regulator induced in CTLs in response to nutritional deficit. In human pancreatic and colorectal cancers, SPTBN2 expression negatively correlated with CTL infiltration and patients' survival. In TME of mouse pancreatic and colorectal adenocarcinomas, SPTBN2 inactivated intratumoral CTLs, stimulated tumor growth and conferred cross-resistance to anti-cancer therapies. SPTBN2 knockout protected CAR T-cells from trogocytosis and increased their memory state. SPTBN2 maintained levels of cell surface proteins such as BTLA that undermine CAR T-cell cytotoxicity and promote exhaustion. Re-expression of BTLA largely reversed phenotypes in SPTBN2-deficient CAR T-cells. In manufactured CAR T cells, SPTBN2 was associated with their clinical failure in pediatric patients with leukemia. Accordingly, ablation of SPTBN2 in CAR T-cells increased their cytotoxicity, in vivo persistence and therapeutic effects indicating that SPTBN2 can be targeted to increase the efficacy of anti-cancer therapies.

  PublisherOA PDFDOI

• RPPA data and analysis for melanoma cells under tryptophan deprivation

  Zenodo (CERN European Organization for Nuclear Research) · 2026-01-29

  otherOpen accessSenior author
  PublisherDOI

• Agarose Microgel-Based In Situ Cleavable Immuno-Rolling Circle Amplification for Multiplexed Single-Molecule Quantitation on Single Extracellular Vesicles

  ACS Nano · 2025-05-05 · 7 citations

  articleOpen access

  We have developed a platform for the multiplexed and ultrasensitive profiling of individual extracellular vesicles (EVs) directly in plasma, which we call GDEVA─Agarose microGel-based Digital single-molecule–single EV Assay. GDEVA achieves single-molecule sensitivity and moderate multiplexing (demonstrated 3-plex), and can achieve a throughput of ∼104 EVs per minute necessary to resolve EVs directly in human plasma when read out using flow cytometry. Our platform integrates a rolling circle amplification (RCA) immunoassay of EV surface proteins, which are cleaved from single EVs, and amplified within agarose microgels, followed by flow cytometry-based readout or imaging after fluorescence-activated cell sorting (FACS). It overcomes steric hindrance of RCA products, nonspecific binding of RCA templates, and the lack of quantitation of multiple proteins on EVs that have plagued earlier approaches. We evaluated the analytical capabilities of GDEVA through head-to-head comparison with conventional technology and demonstrated a ∼100× improvement in the limit of detection (LOD) of EV subpopulations. We evaluate GDEVA’s potential in cancer immunology, by analyzing single EVs in plasma samples from patients with melanoma, where EV heterogeneity plays a critical role in disease progression and response to therapy. We demonstrate profiling of individual EVs for key immune markers PD-L1, CD155, and the melanoma marker TYRP-1, and showed that GDEVA can precisely quantify EVs, offering the resolution to detect rare EV subpopulations in complex clinical specimens.

  PublisherOA PDFDOI

• Overcoming extracellular vesicle-mediated fratricide improves CAR T cell treatment against solid tumors

  Nature Cancer · 2025-04-15 · 9 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Microengineered transplantation of human solid tumors for in vitro studies of CAR T immunotherapy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-29 · 1 citations

  preprintOpen access

  Treatment of solid malignancies using chimeric antigen receptor (CAR) T cells remains a significant challenge, but current efforts to advance this therapy are challenged by our limited capacity to probe and understand cancer-immune interactions in human solid tumors. Here, we present a microengineered platform for in vitro modeling of malignant solid tumors during CAR T therapy. This system makes it possible to vascularize human tumor explants and perfuse them with blood-borne immune cells in a controlled manner. We first present a microphysiological model of human lung adenocarcinomas infused with CAR-T cells and show how this system can be used to simulate, visualize, and interrogate tumor-directed trafficking and effector function of CAR T cells. We then demonstrate the proof-of-principle of testing a chemokine-directed CAR T cell engineering strategy in a model of malignant pleural mesothelioma and validating our in vitro assessment using a matching in vivo mouse model. Finally, we describe a potential therapeutic target discovered by single-cell RNA sequencing that can be pharmacologically modulated to increase the efficacy of CAR T cells for lung adenocarcinoma, for which we also present specific biomarkers identified by global metabolomics analysis. We believe that the bioengineering principle demonstrated here will make important contributions to developing new capabilities for preclinical studies of adoptive cell therapies for cancer and other complex diseases.

  PublisherOA PDFDOI

• A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors

  Nature Biotechnology · 2025-10-17 · 18 citations

  article
  PublisherDOI

• Hydrogel delivering antifibrotic agent and nano-sonosensitizer enhances efficacy of sonodynamic therapy in osteosarcoma treatment

  Bioactive Materials · 2025-10-15 · 3 citations

  articleOpen access

  generation from endogenous hydrogen peroxide while depleting intracellular GSH, thereby amplifying ROS production during SDT. Concurrently, SIS3 reprograms CAFs by blocking TGF-β/SMAD3 signaling, reducing collagen deposition and promoting immune cell infiltration. In an osteosarcoma mouse model, the combination of PMH-mediated SDT with SIS3-induced CAF reprogramming reduced collagen deposition by approximately 50 % and triggered robust antitumor immune responses, which collectively contributed to a 76 % inhibition of tumor growth. Collectively, this study demonstrates a novel CAF-targeted SDT strategy integrating ECM remodeling, ROS enhancement, and localized delivery, offering a promising therapeutic paradigm for solid tumor treatment.

  PublisherDOI

• DR5 CAR-T cells target melanoma and suppress MDSCs with minimal toxicity

  Molecular Therapy · 2025-12-11

  articleOpen access
  PublisherOA PDFDOI

• Mechanical regulation of extracellular vesicle activity during tumour progression

  Nature Biomedical Engineering · 2025-08-06 · 6 citations

  review
  PublisherDOI

Recent grants

• Exosome Trafficking and Tumor Cell Invasion

  NIH · $4.1M · 2009–2021

• NIH Grant R01GM064690

  NIH · $2.5M · 2013

• Molecular Basis and Regulatory Mechanisms of Exosome Secretion

  NIH · $3.9M · 2021–2031

• Molecular Regulation of Exocytosis

  NIH · $2.4M · 2014–2022

Frequent coauthors

• Zhongwen Feng

  The People's Hospital of Guangxi Zhuang Autonomous Region

  49 shared

• Rong-feng Chen

  Aviation General Hospital

  49 shared

• Junying Liu

  49 shared

• Weijie Tian

  Guizhou University

  49 shared

• Chengchao Zheng

  Aviation General Hospital

  49 shared

• Xiaowei Xu

  The Wistar Institute

  36 shared

• Meenhard Herlyn

  28 shared

• Wenqun Zhong

  24 shared

Awards & honors

• Fellow, American Society of Cell Biology
• Pew Scholar in Biomedical Sciences
• American Heart Association Established Investigator
• Biology Department Teaching Award (2008)