About

John Knight is a Clinical Assistant Professor at the University of Michigan School of Nursing, affiliated with the Department of Systems, Populations and Leadership. His scholarship focuses on translating evidence-based practice research into professional settings to improve access to care for lower socioeconomic populations, enhance patient outcomes, and support practitioners' mental health. He has published work on improving patient compliance in ambulatory care and has presented at numerous scholarly and professional conferences on topics such as clinician burnout, informatics, and reducing patient no-shows at large academic health systems. With extensive experience in process excellence and improvement consulting within healthcare systems of varying sizes, Dr. Knight combines practical expertise with academic scholarship to catalyze practice change. His research interests include leadership improvement, project management, informatics, developing high-performance teams, and quality and process improvement techniques. He emphasizes motivating students to develop deep problem-solving and critical thinking skills, using team-based, problem-based case studies to foster engagement, teamwork, and clinical assessment skills. Dr. Knight teaches in both graduate and undergraduate programs, focusing on leadership, process excellence, and informatics.

Research topics

• Microbiology
• Surgery
• Medicine
• Biochemistry
• Internal medicine
• Biology
• Immunology
• Cell biology
• Chemistry

Selected publications

• Antiphospholipid antibodies and cardiovascular thrombosis

  Nature Reviews Cardiology · 2026-03-10 · 2 citations

  article
  PublisherDOI

• Endothelial cell-derived plasminogen activator inhibitor-1 potentiates thrombosis in antiphospholipid syndrome

  Journal of Autoimmunity · 2026-04-27

  articleOpen accessSenior authorCorresponding

  BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays a key role in modulating fibrinolysis. However, its role in the thrombotic autoimmune disease known as antiphospholipid syndrome (APS) remains understudied. METHODS: We characterized PAI-1 expression by APS endothelial cells through single-cell RNA sequencing (scRNA-seq) of skin biopsies from APS patients with active livedo racemosa and age-matched controls. Total and active PAI-1 were quantified in plasma samples from 167 patients with APS, 37 antiphospholipid antibody-positive carriers without clinical APS, 18 patients with a history of non-APS thrombosis, and 48 healthy controls. In vitro, human microvascular endothelial cells (MVECs) were cultured with IgG isolated from patients with APS, and PAI-1 mRNA and protein levels were evaluated by quantitative PCR and ELISA, respectively. Finally, a mouse model of APS IgG-accelerated venous thrombosis induced by electrolytic injury of the inferior vena cava was used to determine the impact of the PAI-1 inhibitor MDI-2268 on thrombosis. RESULTS: scRNA-seq revealed significantly increased SERPINE1 (PAI-1) expression in endothelial cells from patients with APS. Compared with healthy controls, active PAI-1 was detected at significantly higher levels in the plasma of patients with thrombotic APS, where it showed a positive correlation with absolute neutrophil count, erythrocyte sedimentation rate, and C-reactive protein. APS patients with increased antibody burden, as determined by a higher adjusted global APS score (aGAPSS ≥7 versus <7), had more active PAI-1 in their plasma. In vitro, APS IgG stimulation of MVECs increased PAI-1 transcription and secretion, which were dependent on NF-κB signaling. In mice, the administration of APS IgG significantly increased thrombus weights, which was mitigated by MDI-2268. CONCLUSION: Together, these findings suggest that endothelial cells are a likely source of increased active PAI-1 in APS. Furthermore, blocking PAI-1 activity effectively reduced APS IgG-accelerated thrombosis in mice, suggesting that PAI-1 inhibition has therapeutic potential in APS.

  PublisherDOI

• Neutrophils and monocytes in the pathogenesis of antiphospholipid syndrome

  Current Opinion in Immunology · 2026-03-26

  articleOpen accessSenior authorCorresponding

  Antiphospholipid syndrome (APS) is an autoimmune thromboinflammatory disorder in which antiphospholipid antibodies cause vascular thrombosis and obstetric morbidity. Growing evidence indicates that neutrophils and monocytes are key effector cells bridging inflammation and coagulation in APS. Neutrophils display heightened activation, enhanced glycolysis, and exaggerated NETosis, with downstream neutrophil extracellular traps promoting endothelial injury, complement activation, and trophoblast dysfunction. Dysregulated purinergic signaling in APS neutrophils further amplifies thromboinflammatory crosstalk with platelets and the endothelium. Monocytes similarly exhibit proinflammatory skewing, manifesting as increased expression of adhesion molecules and robust induction of tissue factor. Epigenetic alterations in both neutrophils and monocytes may further prime their pathogenic activation. Together, these findings implicate neutrophils and monocytes as important mediators of immunothrombosis and highlight them as potential therapeutic targets in APS.

  PublisherDOI

• Correction: A proteomic map of thromboinflammatory signatures in antiphospholipid syndrome: results from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) registry

  Frontiers in Immunology · 2026-04-10

  articleOpen access

  Correction on: Pine A, Butt A, Andreoli L, Knight JS, Gerosa M, Cecchi I, Branch DW, Lopez-Pedrera R, Belmont HM, Kello N, Petri M, Cervera R, Pengo V, Meroni PL, Cohen H, Willis R, Bertolccini ML, Goshua G, Gu S, Hwa J, Lee AI, Erkan D and Sharda AV (2025) A proteomic map of thromboinflammatory signatures in antiphospholipid syndrome: results from antiphospholipid syndrome alliance for clinical trials and international networking (APS ACTION) registry. Front. Immunol. 16:1676578. doi: 10.3389/fimmu.2025.1676578 Author Pier Luigi Meroni was erroneously assigned to affiliation "University of Milan, Milan, Italy". This affiliation has now been updated to "IRCCS Istituto Auxologico Italiano Milan, Italy."The original version of this article has now been updated.for a reason not seen here, please contact the journal's editorial office.

  PublisherOA PDFDOI

• Do ethnoracial differences exist among antiphospholipid antibody-positive patients with no other systemic autoimmune diseases: results from the APS ACTION registry

  Advances in Rheumatology · 2026-04-16

  articleOpen access

  The APS ACTION Registry was created to study long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients. The objectives of this study were to examine the ethnoracial differences in clinical and laboratory characteristics of aPL-positive patients with no other systemic autoimmune rheumatic diseases (SARDs). A web-based data capture system stores patient demographics and aPL-related medical history. Inclusion criteria are positive aPL results, based on the revised Sapporo APS classification criteria, tested at least twice within one year prior to enrollment. For this cross-sectional analysis of the baseline data, demographic, clinical, and laboratory characteristics of registry patients were analyzed based on self-reported ethnorace (White, Latin American Mestizo [LAM], Asian, and Black). 728 patients with no history of other SARD (78% with APS classification) were included in the analysis. The ethnoracial distribution was 516 (78%) White, 82 (12%) LAM, 49 (7%) Asian, and 13 (2%) Black. Based on ethnoracial comparisons: (a) there were less females among White patients; (b) livedo reticularis/racemosa was more frequent in LAM patients; and (c) triple aPL positivity was more frequent in Whites, while isolated lupus anticoagulant positivity was more common in LAM patients. In our international registry of persistently aPL-positive patients with or without APS classification, Blacks were the least frequently (2%) reported ethnoracial group. No major ethnoracial differences were found in the aPL-related clinical manifestations. Our analysis highlights the need for further investigation into the genetic and social determinants impacting the clinical and serologic phenotypes of aPL-positive patients across diverse populations.

  PublisherDOI

• Antiphospholipid syndrome (APS) is the newest member of the PF4 immunothrombotic family: Mechanistic and therapeutic insights

  Blood · 2025-11-03

  articleOpen access

  Abstract Background: APS is an autoimmune thromboinflammatory disorder characterized by venous, arterial, and microvascular thrombosis, adverse pregnancy outcomes and thrombocytopenia. A major antigenic target is b2-glycoprotein I (b2GPI). Prior observations showed: i. b2GPI can bind the platelet chemokine, platelet factor 4 (PF4), which enhances binding of APS antibodies (Abs), ii. b2GPI binds extruded chromatin from neutrophils (neutrophil extracellular traps or NETs), which also enhances APS Ab binding, and iii. PF4 binds avidly to NETs. In other immunothrombotic disorders, such as heparin-induced thrombocytopenia (HIT), PF4:NET complexes contribute to thrombosis. Aim: We proposed that PF4 released from platelets binds to NETs, enhancing the binding of b2GPI to the NETs and that PF4:b2GPI:NET complexes are important in the pathobiology of thrombosis in APS. Methods &amp; Results: Dynamic light scattering (DLS) studies showed PF4 and b2GPI form antigenic complexes with DNA that bind isolated APS IgG. These findings were confirmed in a NET-lined microfluidic system, where the NETs bound 5-10 times more b2GPI in the presence of PF4 (25 µg/ml) than in its absence (p&amp;lt;0.0001) and subsequently enhanced APS IgG binding four-fold (p&amp;lt;0.005). IgG from 16 randomly selected individuals who met clinical criteria for APS and had “triple-positive” serology required the addition of β2GPI and PF4 to initiate platelet, fibrin, C1q, and C5b-9 deposition on injured human umbilical vein endothelial cell (HUVEC)-lined microfluidic channels. This effect was not seen with IgG from healthy controls. In vivo studies in mice that express PF4: wildtype (WT) mice, mice expressing only human PF4 (hPF4+) or hPF4 plus FcgRIIA (hPF4+/FcgRIIA+) were compared to mice lacking murine PF4 (mPF4-/-). We found that passive inoculation with APS IgG slowed neutrophil rolling on the uninjured venous endothelium and enhanced neutrophil adhesion and enhanced platelet- and neutrophil-rich thrombosis in laser-injured cremaster venules and arterioles in all mice EXCEPT mPF4-/- mice, which were comparable to mice infused with healthy-donor control IgGs. hPF4+/FcgRIIA+ mice had more neutrophils and neutrophil-derived extracellular vesicles incorporated within venule and arteriole thrombi as compared to mPF4-/- mice. As an independent approach, we tested three anti-PF4 monoclonal (mo) Abs, each having different specificities and effects on PF4: RTO, which disaggregates PF4 tetramers; deglycosylated (DG) 1E12, which blocks PF4 binding to NETs; and an IgG4 version of KKO (G4KKO), which crosslinks PF4:NETs. DLS studies showed that RTO and 1E12 disaggregated PF4:b2GPI:DNA immune complexes, whereas G4KKO formed larger complexes that sterically blocked binding of APS IgG. All 3 Abs inhibited thrombosis in the injured HUVEC system. In mice, G4KKO prevented enhanced neutrophil-venous endothelial interaction when infused prophylactically. G4KKO blocked thrombosis in both venule and arteriole models, when given prophylactically or therapeutically post-APS IgG exposure. Conclusions: PF4:β2GPI:NETs complexes are recognized by triple-positive APS IgG, as demonstrated by all 16 APS IgG samples tested to date. This finding reveals a previously unrecognized similarity between APS and other PF4-mediated immunothrombotic disorders, such as HIT and vaccine-induced immune thrombotic thrombocytopenia (VITT). Notably, each of the three anti-PF4 monoclonal antibodies — each disrupting PF4:β2GPI:NET immune complexes — significantly reduced thrombosis, particularly when administered prophylactically. As these moAbs do not alter hemostasis, they are a potential complementary therapy to standard anticoagulants. Future studies will address the importance of PF4 in other forms of APS that do not involve high-titer anti-β2GPI antibodies.

  PublisherOA PDFDOI

• Supplemental Figure 4 from Liver Metastases License Neutrophils through IL1 to Potentiate Cancer Progression

  2025-12-02

  articleOpen access

  &lt;p&gt;Supplemental Figure 4: Liver metastases augment neutrophils to promote cancer progression.&lt;/p&gt;

  PublisherDOI

• Supplemental Figure 3 from Liver Metastases License Neutrophils through IL1 to Potentiate Cancer Progression

  2025-12-02

  articleOpen access

  &lt;p&gt;Supplemental Figure 3: Liver metastases augment neutrophils to promote cancer progression.&lt;/p&gt;

  PublisherDOI

• Antiphospholipid antibody-associated NETosis is palmitoylation-dependent 2047

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Antibodies targeting the phospholipid-binding protein beta-2 glycoprotein I (anti-β2GPI) are associated with thrombosis and inflammation in antiphospholipid syndrome (APS). Anticoagulation inconsistently prevents thrombosis and fails to mitigate long-term organ damage. There are limited treatment options for anticoagulant-resistant APS manifestations. We have previously shown that anti-β2GPI activate neutrophils through Toll-like receptor 4 (TLR4) to promote the release of pathogenic neutrophil extracellular traps (NETs), contributing to inflammation and thrombosis. Here, we sought to elucidate the mechanisms by which anti-β2GPI fully leverage TLR4 signaling to activate neutrophils. RNA-seq of APS neutrophils revealed upregulation of several members of the zDHHC family of enzymes, which facilitate protein palmitoylation, prompting us to further investigate the role of palmitoylation in the neutrophil response to anti-β2GPI. Palmitoylation inhibition with cyano-myracrylamide (CMA) mitigated neutrophil activation and NET formation downstream of anti-β2GPI and other TLR4-stimuli. Conversely, palmitoylation inhibition did not affect PMA-induced NETosis, highlighting a role of palmitoylation in TLR4-mediated NETosis, rather than NETosis more broadly. These findings indicate the potential of palmitoylation-associated proteins as novel therapeutic targets in APS. Ongoing work aims to identify the particular zDHHC-family and palmitoylated-target proteins implicated in these pathways. Funding Sources Supported by T32AI007413 Topic Categories Basic Autoimmunity (BA)

  PublisherOA PDFDOI

• Microvascular Endothelial Cells License APS Vasculopathy Through YAP1- and CCN2-Mediated Signaling

  Circulation · 2025-08-29 · 5 citations

  articleSenior author

  BACKGROUND: Whereas antiphospholipid syndrome (APS) is best known for increasing the risk of macrovascular thrombosis, APS vasculopathy is characterized by the abnormal proliferation of endothelial and smooth muscle cells, leading to occlusion of small blood vessels in the skin, kidneys, and heart, among other organs. The underlying mechanisms remain unclear, and targeted treatment options for patients with APS are lacking. METHODS: To identify and analyze APS microvascular endothelial cells (MVECs), skin biopsies of patients with APS complicated by livedo racemosa were characterized using single-cell RNA sequencing. CCN1 (cellular communication network factor 1) and CCN2 were identified in skin and kidney biopsies by immunofluorescence microscopy and in plasma by ELISA. Healthy dermal MVECs were cultured with APS patient-derived serum or immunoglobulin G (IgG), and relevant signaling pathways were characterized using quantitative PCR, immunoblotting, and immunofluorescence microscopy. The proliferation and migration of vascular smooth muscle cells were determined after exposure to conditioned medium from APS IgG-stimulated MVECs. A mouse model of APS IgG-accelerated neointima formation was developed. Anti-CCN2 monoclonal antibodies were tested in vascular smooth muscle cell functional assays and the mouse model. RESULTS: Increased endothelial cell expression of CCN1 and CCN2 was identified by single-cell RNA sequencing and further confirmed in APS skin by microscopy as well as in APS plasma by ELISA. Exposure of healthy MVECs to patient IgG triggered the upregulation of CCN1 and CCN2 via Toll-like receptor 4- and YAP1 (yes-associated protein 1)-mediated signaling. CCN2, originating from APS IgG-stimulated MVECs led to the proliferation and migration of vascular smooth muscle cells, phenotypes that were inhibited by an anti-CCN2 antibody or depletion of EGFR (epidermal growth factor receptor). We further observed increased expression of CCN2, along with evidence of YAP1 nuclear translocation, in kidney vessels of APS nephropathy biopsies. Finally, CCN2 inhibition with an anti-CCN2 monoclonal antibody significantly reduced neointima thickening and cell proliferation in a mouse model of APS IgG-accelerated neointima formation. CONCLUSIONS: This study revealed activation of YAP1-mediated signaling in APS dermal microvessels and demonstrated that the YAP1 target CCN2 plays a role in facilitating pro-proliferative communication between MVECs and vascular smooth muscle cells. These findings offer insights into the cellular and molecular mechanisms underlying APS vasculopathy, providing potential therapeutic targets for patients.

  PublisherDOI

Recent grants

• Innate Immunity in the Pathogenesis of Lupus and Antiphospholipid Vasculopathy

  NIH · $692k · 2014–2019

• Scientist Training in Rheumatology Research

  NIH · $7.3M · 1976–2028

• Purinergic modulation of the autoimmune vascular phenotype

  NIH · $4.8M · 2018–2027

Frequent coauthors

• Srilakshmi Yalavarthi

  University of Michigan–Ann Arbor

  74 shared

• Yogendra Kanthi

  National Heart Lung and Blood Institute

  70 shared

• Yu Zuo

  University of Michigan–Ann Arbor

  55 shared

• Doruk Erkan

  Cornell University

  46 shared

• D. Ware Branch

  University of Utah

  45 shared

• Mariana J. Kaplan

  National Institutes of Health

  42 shared

• Michelle Petri

  Johns Hopkins University

  41 shared

• Hui Shi

  Shanghai Jiao Tong University

  34 shared