About

Tessa J. Barrett, PhD, is an Assistant Professor in the Department of Medicine and the Department of Pathology at NYU Grossman School of Medicine. Her laboratory investigates how platelets regulate vascular injury, inflammation, and thrombosis, with the goal of defining pathways that can be leveraged for precision cardiovascular medicine. Her research focuses on three major areas: platelet–immune cell interactions in vascular disease, mechanisms by which platelet activation reprograms leukocytes and amplifies inflammatory signaling, and novel platelet regulators of activation and signaling identified through genetic models, transcriptomics, and proteomics. Additionally, her work explores thromboinflammation across various disease contexts, including atherosclerosis, ischemia, stroke, and cancer, where platelets serve as central mediators linking clotting to immune dysregulation. Using a combination of in vivo models, single-cell and multi-omics platforms, and patient-based studies, she aims to uncover molecular mechanisms driving platelet hyperreactivity and to identify biomarkers and targets for individualized risk prediction and therapeutic strategies.

Research topics

• Medicine
• Immunology
• Biology
• Internal medicine
• Oncology
• Chemistry
• Cancer research
• Endocrinology
• Cell biology
• Biochemistry

Selected publications

• <i>LUCAT1</i> Links Interferon Signaling in Platelets to Major Adverse Cardiovascular Events

  Arteriosclerosis Thrombosis and Vascular Biology · 2026-04-09

  articleSenior author
  PublisherDOI

• The Platelet Transcriptome: Coding RNAs

  2025-01-01

  book-chapter
  PublisherDOI

• Platelets induce endothelial cell mitochondrial dysfunction in myocardial infarction

  Science Advances · 2025-11-14 · 4 citations

  articleOpen accessCorresponding

  Coronary endothelial dysfunction plays a key role in the pathogenesis of acute coronary syndromes. During myocardial infarction (MI), activated platelets release prothrombotic and proinflammatory factors, contributing to vascular injury and dysfunction. To investigate platelet-mediated endothelial dysfunction, endothelial cells (ECs) were treated with platelet-released factors from patients with MI and non-MI controls undergoing coronary angiography. RNA sequencing revealed that MI platelets induced EC mitochondrial dysfunction, confirmed by reduced mitochondrial membrane potential and disrupted mitochondrial networks. Integrating platelet transcriptomic data, we identified the C-C motif chemokine ligand 3 (CCL3) as significantly up-regulated in MI platelets and a key mediator of EC mitochondrial dysfunction. Blocking its receptor, CCR5, attenuated CCL3 effects. In an independent cohort of 261 patients with established cardiovascular disease, higher circulating CCL3 levels were associated with incident major adverse cardiovascular events. Together, these findings establish a mechanistic link between platelet activation and coronary endothelial dysfunction in MI.

  PublisherDOI

• Abstract 4368754: A Platelet Transcriptomic Signature Predicts Cardiovascular Risk in Peripheral Artery Disease

  Circulation · 2025-11-03

  article

  Background: Patients with peripheral artery disease have a markedly increased risk of cardiovascular morbidity and mortality. While platelets are key mediators in the pathogenesis of peripheral artery disease (PAD), few studies have characterized the PAD platelet transcriptome. The platelet transcriptome offers unique insights into both hemostatic, thrombotic, and inflammatory processes that may inform risk stratification in PAD patients. Hypothesis: We hypothesized that platelet gene expression patterns would uncover distinct transcriptomic signatures associated with PAD prevalence, severity and clinical outcomes. Methods: Participants with symptomatic PAD (n=171) were enrolled and had platelets collected prior to lower extremity revascularization (LER). RNA was extracted from isolated platelets and sequenced. Transcriptomic analysis identified signatures linked to PAD prevalence, severity, and cardiovascular events. Participants were followed for major adverse cardiovascular and limb events (MACLE, composite of death, MI, stroke, and major amputation). Statistical models were used to assess the association between platelet transcriptomics and clinical outcomes, with adjustments for relevant covariates. Results: Overall, mean age was 70 ± 10 years, 35% were female, 33% were non-White, 19% were Hispanic/Latino, and 50% had diabetes. In PAD patients compared to controls, 556 genes were identified as differentially expressed (padj&lt;0.05), including 394 upregulated and 162 downregulated genes (Figure 1a). Pathway analysis revealed enrichment in inflammatory responses and granule release pathways (Figure 1b). Among PAD patients, those with chronic limb-threatening ischemia (CLTI) exhibited the highest enrichment in thrombotic and inflammatory pathways (Figure 1c). A 75-gene transcriptomic signature for PAD was developed and validated, demonstrating a significant association with PAD in a separate test cohort (padj=.005; Figure 1d). Finally, individuals with a score above the median demonstrated a higher risk for MACLE after multivariable adjustment (adjHR=1.87 [1.17-2.98], p=0.009; Figure 1e). Conclusions: The platelet transcriptome in PAD patients reveals significant enrichment of pathways linked to granule release and inflammatory responses. A unique transcriptomic signature is strongly associated with PAD prevalence, severity, and cardiovascular outcomes, highlighting its potential as a novel biomarker for risk stratification in patients undergoing LER.

  PublisherDOI

• Ischaemic endothelial necroptosis induces haemolysis and COVID-19 angiopathy

  Nature · 2025-06-04 · 9 citations

  article
  PublisherDOI

• Cardiometabolic risk factor burden associates with an immature platelet profile

  Platelets · 2025-01-30 · 2 citations

  articleOpen access

  < .01). Greater cardiometabolic risk factor burden is associated with increased platelet size and immaturity and suggesting novel platelet-mediated mechanisms linking risk factor burden with CVD.

  PublisherDOI

• Platelets impair the resolution of inflammation in atherosclerotic plaques in insulin-resistant mice after lipid lowering

  JCI Insight · 2025-10-09

  articleOpen access

  Insulin resistance impairs benefits of lipid-lowering treatment, as evidenced by higher cardiovascular disease risk in individuals with type 2 diabetes versus those without. Because platelet activity is higher in insulin-resistant patients and promotes atherosclerosis progression, we questioned whether platelets impair inflammation resolution in plaques during lipid lowering. In mice with obesity and insulin resistance, we induced advanced plaques and then implemented lipid lowering to promote atherosclerotic plaque inflammation resolution. Concurrently, mice were treated with either platelet-depleting or control antibodies for 3 weeks. Platelet activation and insulin resistance were unaffected by lipid lowering. Both antibody-treated groups showed reduced plaque macrophages, but plaque cellular and structural composition differed. In platelet-depleted mice, single-cell RNA-seq revealed dampened inflammatory gene expression in plaque macrophages and an expansion of a subset of Fcgr4+ macrophages having features of inflammation-resolving, phagocytic cells. Necrotic core size was smaller and collagen content greater, resembling stable human plaques. Consistent with the mouse results, clinical data showed that patients with lower platelet counts had decreased proinflammatory signaling pathways in circulating nonclassical monocytes after lipid lowering. These findings highlight that platelets hinder inflammation resolution in atherosclerosis during lipid-lowering treatment. Identifying novel platelet-targeted therapies following lipid-lowering treatment in individuals with insulin resistance may be a promising therapeutic approach to promote atherosclerotic plaque inflammation resolution.

  PublisherOA PDFDOI

• Complement C9-mediated RBC hemolysis drives microvascular obstruction via endothelial necroptosis and hemolyzed RBC aggregation in COVID-19

  Immunobiology · 2025-07-01

  articleOpen access

  Microvascular obstruction (MVO) is a major attributor to tissue injury in ischemic diseases, including acute myocardial infarction and severe COVID-19 with multi-organ failure. Thus far, RBCs have been widely regarded as passive bystanders in MVO—mechanically trapped within compromised vessels under disturbed flow and endothelial dysfunction, without actively contributing to the obstructive process. Complement activation, particularly the terminal complement complex C5b-9, is a key mediator of vascular injury in ischemia-reperfusion (IR) and COVID-19-associated microangiopathy. While complement’s role in inflammation and endothelial damage is well recognized, its influence on RBC behavior, particularly in promoting RBC aggregation and leading to MVO in IR, remains poorly defined. Notably, our study suggests that C9-mediated RBC membrane fragmentation (hemolysis) directly contributes to MVO. IR injury models of mouse gut, heart, and brain were used alongside COVID-19 and ischemic human tissues. Multiplexed immunofluorescence and multimodal imaging identified endothelial necroptosis (pMLKL, pRIPK1), C5b-9 deposition, and RBC fragmentation marked by intensified glycophorin A (CD235). RBC aggregation was modeled using a flow platform with necrotic human microvascular endothelial cell line 1 (HMEC-1) monolayers and complement inhibition. RBC microangiopathy was evident in the microvasculature of patients with myocardial infarction, gut ischemia, stroke, and septic or cardiogenic shock. Mechanistically, IR-induced MLKL-dependent endothelial necroptosis triggered C9-mediated RBC hemolysis. Hemolyzed RBCs became intrinsically adhesive, forming aggregates with surrounding intact RBCs and creating occlusive structures that drive MVO independently of platelets or fibrin. C5b-9 deposition was found spatially associated with necroptotic endothelium and lysed RBCs, particularly in COVID-19 tissues. Genetic deficiency of C9 or endothelial MLKL significantly reduced RBC hemolysis, MVO, and tissue injury. In vitro , we recapitulated the RBC aggregation on necrotic HMEC-1 monolayers under IR relevant shear stress. Inhibition of C5b-9 formation using complement-depleted plasma or Cp40 (a C3 inhibitor) effectively prevented the RBC aggregation. Our findings identify complement C9-mediated RBC hemolysis as a key driver of MVO, revealing a novel therapeutic target in ischemic vascular disease.

  PublisherDOI

• Abstract 4370745: Aggressive Lipid Lowering Differentially Impacts the Vascular Endothelium in Diabetic vs Healthy Individuals. Findings from the American Heart Association Cardiometabolic Health Strategically Focused Research Network

  Circulation · 2025-11-03

  article

  Background: Vascular endothelial cell (EC) damage and subsequent cardiovascular (CV) events occur in patients with type 2 diabetes (T2D) despite aggressive medical therapy. This study investigated the key vascular EC pathways in T2D vs controls at baseline and after aggressive lipid lowering therapy (LLT) to improve our mechanistic understanding of CV risk reduction strategies in T2D. Methods: CHORD (CHOlesterol lowering and Residual Risk in Diabetes) is a clinical trial of LLT with PCSK9 inhibitor plus high-intensity statin or ezetimibe for 1-month to evaluate mechanisms of CV risk in T2D and non-T2D (controls) free of clinical CV disease with an LDL-C &gt; 100 mg/dL. In a subset of participants, EC harvesting was performed at baseline and follow-up by inserting a J-wire through an angiocatheter into the brachial vein. ECs were isolated with magnetic beads directed against CD146, and transcript expression assessed using next generation RNA sequencing. Results: We performed EC harvesting in 15 participants with DM (median age 55 years, 60% male, HbA1c 6.7%, LDL-C 131 mg/dL) and 25 controls (median age 37 years, 56% male, HbA1c 5.2%, LDL-C 142 mg/dL). After adjustment for age and sex, EC RNA sequencing in T2D (vs controls) demonstrated 1126 upregulated and 204 downregulated genes (nominal p&lt;0.05) with dysregulated pathways in T2D (vs controls) involved in lipid metabolic process, apoptosis, interferon signaling, and leukocyte vascular adhesion. After lipid-lowering (LDL-C decreased by 70% in both T2D and controls), 839 genes were upregulated, and 1271 genes were downregulated (nominal p&lt;0.05) with upregulated EC pathways related to EC health, nitric oxide, and IL-10 signaling. Downregulated EC pathways after LLT included interferon production, inflammasome signaling and NFkB production (Figure). When compared to controls, T2D showed preferential reduction in endothelial inflammatory pathways yet upregulation in those related to platelet activation and hemostasis (Figure). Following LLT, the dysregulated pathways between T2D and controls at baseline (lipid process, apoptosis, interferon signaling, leukocyte vascular adhesion) were no longer significantly different between groups. Conclusion: While individuals with and without T2D derive improvement in vascular endothelial function, aggressive lipid lowering appears to have a more robust anti-inflammatory impact in T2D yet no impact on those related to hemostasis.

  PublisherDOI

• Megakaryocyte phenotyping in response to SARS-CoV-2 variants

  Platelets · 2025-07-23

  articleOpen accessSenior authorCorresponding

  . Consistent with transcriptomic changes, SARS-CoV-2-incubated MKs secreted significantly elevated levels of IL-8. Among hospitalized COVID-19 patients, plasma IL-8 levels were highest in COVID-19 patients who subsequently experienced thrombotic events or died. In conclusion, WA1, Delta, and Omicron similarly induce classical MK activation responses while mediating distinct transcriptomic changes. Increased IL-8 levels may serve as a biomarker to inform platelet hyperreactivity and thrombotic events associated with COVID-19.

  PublisherDOI

Frequent coauthors

• Edward A. Fisher

  New York University

  113 shared

• Jeffrey S. Berger

  New York University

  75 shared

• Ira J. Goldberg

  New York University

  52 shared

• Clare L. Hawkins

  University of Copenhagen

  49 shared

• Prabhakara R. Nagareddy

  University of Oklahoma Health Sciences Center

  38 shared

• Diego Scerbo

  Fraternal Order of Eagles

  37 shared

• Joseph C. Obunike

  New York University

  36 shared

• Lesley A. Huggins

  New York University

  36 shared

Labs

• Barrett LabPI