About

Anjelica Gonzalez serves as the Raymond John Wean Professor of Biomedical Engineering at Yale University and is part of the Vascular Biology and Therapeutics Program. Her research focuses on the development of biomimetic materials for investigating immunology, inflammation, and fibrosis. She has a dedicated interest in training the next generation of scientists to think interdisciplinarily and approach problems from a scientifically global perspective. Her lab combines organic chemistry, molecular biology, mathematics, computational modeling, and image analysis to develop engineered scaffolds that dissect the chemo-mechanics of immunological processes. This work has led to significant advancements related to diseases such as vascular inflammation, stroke, fibrosis, and sepsis. Additionally, her translational research has resulted in the development of new technologies deployed in underserved and low-infrastructure settings worldwide, including PremieBreathe, a low-cost neonatal respiratory device supported by major international agencies.

Research topics

• Internal medicine
• Medicine
• Biology
• Biochemistry
• Endocrinology
• Intensive care medicine
• Immunology
• Cardiology
• Cell biology

Selected publications

• Engineered microvascular basement membrane mimetic for real‐time neutrophil tracking in the microvascular wall

  Bioengineering & Translational Medicine · 2025-03-12 · 1 citations

  articleOpen accessSenior authorCorresponding

  The microvascular basement membrane (mvBM) is crucial in maintaining vascular integrity and function and, therefore, key to the health of major organs. However, the complex nature and the intricate interplay of biochemical and biomechanical factors that regulate the mvBM functional dynamics make it difficult to study. Here, we present a novel and highly tunable in vitro model of the human mvBM, enabling a bottom-up approach to assemble a composite model of the microvascular wall and explore microvascular dynamics and interactions with circulating neutrophils in real time. An electrospun polyethylene glycol (PEG)-based fibrillar network mimics the mvBM with adjustable nanofiber diameter, orientation, and density. The fidelity of the model to the human mvBM's topography and mechanics was verified through second harmonic generation imaging and atomic force microscopy. PEG was functionalized with bioactive moieties to enable endothelial cell (EC) and pericyte (PC) attachment, through which neutrophil interactions with the microvascular wall model were observed. The model, coupled with 4D microscopy, revealed nuanced and dynamic neutrophil behavior when interacting with the microvascular wall, demonstrating its utility in characterizing cell-cell interactions. As such, the model can be employed in the exploration of inflammatory and microvascular-related diseases. Therefore, this innovative approach represents a significant advancement in vascular biology research, holding profound implications for understanding mvBM dynamics in both health and disease.

  PublisherOA PDFDOI

• TGF-β1 Drives Integrin-Dependent Pericyte Migration and Microvascular Destabilization in Fibrotic Disease

  American Journal Of Pathology · 2024-03-26 · 9 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Ezrin drives adaptation of monocytes to the inflamed lung microenvironment

  Cell Death and Disease · 2024-11-29 · 4 citations

  articleOpen access

  Ezrin, an actin-binding protein, orchestrates the organization of the cortical cytoskeleton and plasma membrane during cell migration, adhesion, and proliferation. Its role in monocytes/macrophages (MΦs) is less understood. Here, we used a monocyte/MΦ-specific ezrin knock-out mouse model to investigate the contribution of ezrin to monocyte recruitment and adaptation to the lung extracellular matrix (ECM) in response to lipopolysaccharide (LPS). Our study revealed that LPS induces ezrin expression in monocytes/MΦs and is essential for monocytes to adhere to lung ECM, proliferate, and differentiate into tissue-resident interstitial MΦs. Mechanistically, the loss of ezrin in monocytes disrupts activation of focal adhesion kinase and AKT serine-threonine protein kinase signaling, essential for lung-recruited monocytes and monocyte-derived MΦs to adhere to the ECM, proliferate, and survive. In summary, our data show that ezrin plays a role beyond structural cellular support, influencing diverse monocytes/MΦ processes and signaling pathways during inflammation, facilitating their differentiation into tissue-resident macrophages.

  PublisherOA PDFDOI

• ZFYVE21 promotes endothelial nitric oxide signaling and vascular barrier function in the kidney during aging

  Kidney International · 2024-05-24 · 9 citations

  articleOpen access

  ZFYVE21 is an ancient, endosome-associated protein that is highly expressed in endothelial cells (ECs) but whose function(s) in vivo are undefined. Here, we identified ZFYVE21 as an essential regulator of vascular barrier function in the aging kidney. ZFYVE21 levels significantly decline in ECs in aged human and mouse kidneys. To investigate attendant effects, we generated EC-specific ZFVYE21-/- reporter mice. These knockout mice developed accelerated aging phenotypes including reduced endothelial nitric oxide (ENOS) activity, failure to thrive, and kidney insufficiency. Kidneys from ZFYVE21 EC-/- mice showed interstitial edema and glomerular EC injury. ZFYVE21-mediated phenotypes were not programmed developmentally as loss of ZFYVE21 in ECs during adulthood phenocopied its loss prenatally, and a nitric oxide donor normalized kidney function in adult hosts. Using live cell imaging and human kidney organ cultures, we found that in a GTPase Rab5- and protein kinase Akt-dependent manner, ZFYVE21 reduced vesicular levels of inhibitory caveolin-1 and promoted transfer of Golgi-derived ENOS to a perinuclear Rab5+ vesicular population to functionally sustain ENOS activity. Thus, our work defines a ZFYVE21- mediated trafficking mechanism sustaining ENOS activity and demonstrates the relevance of this pathway for maintaining kidney function with aging.

  PublisherOA PDFDOI

• Mechanosensing regulates tissue repair program in macrophages

  Science Advances · 2024-03-13 · 80 citations

  articleOpen access

  Tissue-resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of all tissues. Here, we find that macrophages sense the mechanical properties of the ECM to regulate a specific tissue repair program. We show that macrophage mechanosensing is mediated by cytoskeletal remodeling and can be performed in three-dimensional environments through a noncanonical, integrin-independent mechanism analogous to amoeboid migration. We find that these cytoskeletal dynamics also integrate biochemical signaling by colony-stimulating factor 1 and ultimately regulate chromatin accessibility to control the mechanosensitive gene expression program. This study identifies an "amoeboid" mode of ECM mechanosensing through which macrophages may regulate tissue repair and fibrosis.

  PublisherOA PDFDOI

• Ezrin drives adaptation of monocytes to the inflamed lung microenvironment.

  The Journal of Immunology · 2024-05-01

  article

  Abstract We have previously shown that the actin-binding protein ezrin is reduced and displaced from the plasma membrane in monocytes/macrophages (MΦs) from patients with cystic fibrosis (CF) and CF mice, impacting immune response to bacteria. However, its role in monocyte/MΦ is not fully understood. To investigate how the lack of ezrin affects monocyte/MΦ functions in response to lung infections, we developed a monocyte/MΦ-specific ezrin knock out mouse model (Ez-KOm) . We aerosolized WT and Ez-KOm mice with LPS and assessed the number of lung monocyte/MΦ by flow cytometry and their transcriptional profile via RNA-seq, followed by in vitro functional studies. In WT mice, ezrin is induced by LPS in all lung monocyte/MΦ populations, with the highest induction observed in the interstitial MΦs (IMs) (4-fold higher than monocytes). LPS treated Ez-KOm mice exhibit a significant reduction in IM numbers compared with WT and increased expression of pro-inflammatory markers (Il6, Tnfα, and Cxcl1). RNA-seq revealed differentially expressed genes in Ez-KOm monocytes/IMs related to adhesion, proliferation and cytoskeleton rearrangement. Consistently, Ez-KOm monocytes treated in vitro with LPS on collagen show stunted filopodia, altered F-actin distribution, reduced adhesion and increased cell death due to defective FAK and PI3K/AKT signaling. Our studies suggest that ezrin plays a critical role in the survival and adaptation of monocytes to the lung extracellular matrix during infections.

  PublisherDOI

• Contextual factors influencing bubble continuous positive airway pressure implementation for paediatric respiratory distress in low-income and middle-income countries: a realist review

  The Lancet Global Health · 2024-12-12 · 6 citations

  reviewOpen access

  BACKGROUND: Bubble continuous positive airway pressure (bCPAP) is a low-cost, non-invasive respiratory support therapy for children with respiratory distress, but its effectiveness is dependent on the context. We aimed to understand contextual factors influencing bCPAP implementation for children aged 1-59 months in low-income and middle-income countries (LMICs) and to develop a theory explaining how these factors influence implementation outcomes. METHODS: In this realist review, we generated an initial programme theory comprising candidate context-mechanism-outcome configurations (CMOCs) via review of key references and team discussion. On July 25, 2023, we conducted a search for peer-reviewed and grey literature, without date restrictions, describing bCPAP use for paediatric respiratory distress in LMICs. We included references describing related contexts, mechanisms, or outcomes. We coded statements from the literature supporting each CMOC, iteratively revising and adding CMOCs using inductive and deductive logic. We assembled an international, interdisciplinary panel of 22 bCPAP stakeholders to refine CMOCs using iterative surveys, focus groups, and interviews until we reached thematic saturation. This realist review is registered with PROSPERO (CRD42023403584). FINDINGS: Of 1640 peer-reviewed references and eight grey literature references retrieved, 38 peer-reviewed articles and two grey literature documents were deemed eligible for inclusion after removal of duplicates and screening. After four rounds of expert surveys and three focus groups, we identified 18 CMOCs. CMOCs were synthesised into a final programme theory operating at five levels to influence implementation feasibility, fidelity, and sustainability: (1) the bCPAP device, (2) local partnerships and infrastructure, (3) clinical and technical teams, (4) caregivers and the community, and (5) institutional practices. INTERPRETATION: Using realist methods with a diverse, international stakeholder panel, we generated a theory that could explain how bCPAP therapy works in different contexts. This theory could be leveraged to enhance the rigour of future bCPAP implementation trials. FUNDING: Yale National Clinician Scholars Program, US National Center for Advancing Translational Science (TL1TR001864), and National Heart, Lung, and Blood Institute (T32HL155000).

  PublisherOA PDFDOI

• Macrophages sense ECM mechanics and growth factor availability through cytoskeletal remodeling to regulate their tissue repair program

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-06-30 · 3 citations

  preprintOpen access

  Abstract Tissue resident macrophages play important roles in tissue homeostasis and repair. However, how macrophages monitor and maintain tissue integrity is not well understood. The extracellular matrix (ECM) is a key structural and organizational component of all tissues. Here, we find that macrophages sense the mechanical properties of the ECM in order to regulate a specific tissue repair program. We show that macrophage mechanosensing is mediated by cytoskeletal remodeling and can be performed in three-dimensional environments through a non-canonical, integrin-independent mechanism analogous to amoeboid migration. We find that these cytoskeletal dynamics also integrate biochemical signaling by CSF1 and ultimately regulate chromatin accessibility to control the mechanosensitive gene expression program. This study suggests a distinct mode of ECM mechanosensing and growth factor signaling through which macrophages may regulate tissue repair and fibrosis.

  PublisherOA PDFDOI

• Engineering multicellular living systems—a Keystone Symposia report

  Annals of the New York Academy of Sciences · 2022-09-30 · 6 citations

  articleOpen access

  The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3-6, 2022, experts in the field met at the Keystone symposium "Engineering Multicellular Living Systems" to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ-on-a-chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium "Organoids as Tools for Fundamental Discovery and Translation".

  PublisherOA PDFDOI

• Endothelial cell secreted VEGF-C enhances NSC VEGFR3 expression and promotes NSC survival

  Stem Cell Research · 2021-04-01 · 17 citations

  articleOpen accessSenior authorCorresponding

  Although delivery of neural stem cell (NSC) as a therapeutic treatment for intracerebral hemorrhage (ICH) provides promise, NSC delivery typically has extremely low survival rates. Here, we investigate endothelial cell (EC) and pericyte (PC) interactions with NSC, where our results demonstrate that EC, and not PC, promote NSC cell proliferation and reduce cytotoxicity under glucose deprivation (GD). Additionally, NSC proliferation was increased upon treatment with EC conditioned media, inhibited with antagonism of VEGFR3. In an NSC + EC co-culture we detected elevated levels of VEGF-C, not seen for NSC cultured alone. Exogenous VEGF-C induced NSC upregulation of VEGFR3, promoted proliferation, and reduced cytotoxicity. Finally, we delivered microbeads containing NSC + EC into a murine ICH cavity, where VEGF-C was increasingly present in the injury site, not seen upon delivery NSC encapsulated alone. These studies demonstrate that EC-secreted VEGF-C may promote NSC survival during injury, enhancing the potential for cell delivery therapies for stroke.

  PublisherDOI

Recent grants

• Pericyte reprogramming in fibrosis

  NIH · $971k · 2023–2028

Frequent coauthors

• Holly M. Lauridsen

  W. L. Gore & Associates (United States)

  13 shared

• Rita Matta

  Yale University

  11 shared

• Amanda S. Pellowe

  Yale University

  10 shared

• Jordan S. Pober

  Yale University

  10 shared

• Lawrence W. Green

  Louisiana Tech University

  9 shared

• David L. Katz

  9 shared

• Mary Murimi

  Texas Tech University

  9 shared

• Valentine Njike

  Yale Griffin Prevention Research Center

  9 shared

Awards & honors

• Elected, AIMBE College of Fellows (2020)
• Biomedical Engineering Society Diversity Award and Keynote A…
• USAID/Gates Foundation DevelopmentxChange Investor Pitch Com…
• Cellular and Molecular Bioengineering Young Innovator (2015)
• Yale Provost’s Teaching Prize (2014)