About

Kandace L Gollomp, MD, is an Assistant Professor of Pediatrics in the Department of Pediatrics at the University of Pennsylvania. Her clinical expertise is in pediatric benign hematology. Her research focuses on therapies that modify neutrophil extracellular traps (NETs) to enhance their ability to capture pathogens such as viruses and bacteria, while reducing their potential to cause harm to host tissue. Her work aims to improve outcomes in conditions including sepsis, sickle cell disease, heparin-induced thrombocytopenia, and anti-phospholipid antibody syndrome. Dr. Gollomp has contributed to multiple research presentations and publications related to immunothrombosis, bacterial infections, and hematologic disorders, emphasizing her commitment to advancing understanding and treatment of complex hematological and infectious diseases in pediatric populations.

Research topics

• Medicine
• Immunology
• Virology
• Pathology

Selected publications

• Supplementary Table S5 from Corticosteroid-Dependent Association between Prognostic Peripheral Blood Cell-Free DNA Levels and Neutrophil-Mediated NETosis in Patients with Glioblastoma

  2025-04-01

  supplementary-materialsOpen access

  <p>List of all methylGSA results for (Gene Ontology,GO, gene sets) differential methylation comparing cluster 1 vs cluster 2 from unsupervised clustering of the plasma ccfDNA methylation results.</p>

  PublisherDOI

• Supplementary Table S2 from Corticosteroid-Dependent Association between Prognostic Peripheral Blood Cell-Free DNA Levels and Neutrophil-Mediated NETosis in Patients with Glioblastoma

  2025-04-01

  supplementary-materialsOpen access

  <p>Published reference methylomes used in deconvolution</p>

  PublisherDOI

• Cell-free DNA (cfDNA) and plasma proteomics reveal inflammatory heterogeneity in vaso-occlusive crises in sickle cell disease (SCD).

  Blood · 2025-11-03

  articleOpen accessSenior author

  Abstract Background: SCD is characterized by chronic hemolytic anemia and recurrent vaso-occlusive crises (VOCs), which are a leading cause of hospitalization and morbidity. The mechanisms driving VOC are complex, with a subset induced by acute inflammation, while others reflect exacerbations of chronic pain. This clinical heterogeneity complicates treatment and underscores the need for biomarkers that can distinguish between VOC subtypes to facilitate more effective interventions. cfDNA, a marker of innate immune activation, has been observed to be elevated in VOC. We hypothesize that plasma levels of cfDNA may help identify inflammation-associated VOC episodes. Aims: To perform high-throughput proteomic analysis of matched plasma samples collected from individuals with SCD at baseline and during VOC, and integrate these data with cfDNA, to both identify molecular pathways activated during crisis and distinguish inflammation-driven episodes from non-inflammatory VOC. Methods: We enrolled 46 individuals with SCD who were hospitalized or receiving outpatient infusion therapy for VOC. EDTA plasma samples were collected at enrollment and again at a follow-up hematology clinic visit during clinical baseline for 39 of these individuals. Samples were stored at –80°C prior to analysis. Proteomic profiling of the 39 matched samples was performed using the Olink® Explore platform to quantify normalized protein expression levels for over 1,000 plasma proteins. Paired student t-tests were performed to identify differentially expressed proteins with the threshold of P < 0.01. cfDNA concentrations were measured using a SYTOX™ Green fluorescent plate assay. Demographics, current medications, and clinical laboratory parameters obtained at the time of sample collection were abstracted from the electronic medical record. Results: Proteomic analysis identified expected sex differences, as well as increased levels of Arginase-1 (a known marker of hemolysis) during VOC, supporting the validity of the assay. A total of 38 proteins were significantly differentially expressed (P < 0.01) between VOC and baseline. Components of the ubiquitin–proteasome system (UPS), including multiple 19S and 20S proteasome subunits and regulatory proteins were elevated during VOC, as were post-translational modification proteins, suggesting increased ubiquitination and SUMOylation during VOC. Immune-related cytokines and modulators, including Oncostatin M and Interleukin 32, were significantly upregulated, consistent with an inflammatory state. Pathway enrichment analysis of differentially expressed proteins confirmed significant upregulation (FDR < 0.01) of several key biological pathways during VOC. These included proteasome-mediated protein degradation, cytokine-mediated signaling, regulation of apoptosis, and oxidative stress response. While some plasma proteins may have been released due to increased hemolysis or cell turnover, the overlap of related pathways supports a coordinated inflammatory response during VOC. Although cfDNA levels trended higher during VOC, these differences were not statistically significant and showed considerable overlap between time points, suggesting inflammatory heterogeneity. However, principal component analysis (PCA) was performed across the full VOC cohort (n=46) and revealed distinct clustering of individuals with high cfDNA (>0.75 µg/mL) versus low cfDNA (<0.75 µg/mL) at VOC. Patients with high cfDNA had significant changes in proteins related to inflammation, vascular stress, and vesicle trafficking, suggesting a coordinated systemic response during cfDNA elevation. Complementing these findings, Spearman correlation analysis across all samples showed that cfDNA levels were significantly correlated (P < 0.01) with over 60 plasma proteins involved in pathways related to cell adhesion, inflammation, and epithelial integrity. Conclusion: VOC is associated with increased plasma levels of proteins related to proteasome activity, cytokine signaling, and apoptosis. cfDNA correlated with a broad inflammatory proteomic signature, supporting its potential as a marker of inflammatory VOC phenotype. To our knowledge, this is the first study to integrate high-throughput plasma proteomics with cfDNA measurement to stratify VOC inflammatory subtypes. These findings enhance our understanding of VOC pathobiology and highlight potential targets for biomarker development and therapeutic intervention.

  PublisherOA PDFDOI

• Supplementary Table S8 from Corticosteroid-Dependent Association between Prognostic Peripheral Blood Cell-Free DNA Levels and Neutrophil-Mediated NETosis in Patients with Glioblastoma

  2025-04-01

  supplementary-materialsOpen access

  <p>List of all methylGSA results for (Gene Ontology,GO, gene sets) with differential methylation for % neutrophil ccfDNA dichotomized at median.</p>

  PublisherDOI

• Supplementary Table S3 from Corticosteroid-Dependent Association between Prognostic Peripheral Blood Cell-Free DNA Levels and Neutrophil-Mediated NETosis in Patients with Glioblastoma

  2025-04-01

  supplementary-materialsOpen access

  <p>Array consistent autosomal CpGs from which deconvolution signature was selected.</p>

  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 & 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<0.0001) and subsequently enhanced APS IgG binding four-fold (p<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

• Back to the drawing board: Exploring the composition and physical properties of traumatic hemothorax

  The Journal of Trauma: Injury, Infection, and Critical Care · 2025-04-02 · 2 citations

  article

  BACKGROUND: Despite a wide array of management options for traumatic hemothorax (HTX), rates of secondary intervention remain high. Exploring the composition and physical properties of HTX thrombi may inform improved management. We hypothesized that the composition and physical properties of HTX thrombi vary based upon time postinjury. METHODS: Hemothorax samples were collected during resuscitative thoracotomy or thoracic surgical procedures for rib plating or retained HTX evacuation. Hemothorax thrombi were grouped according to the timing of collection (acute <72 hours postinjury vs. subacute ≥72 hours). Hemothorax compressive yield strength was quantified with rheometry, while composition and degree of contraction were determined using scanning electron microscopy. RESULTS: Of eight HTX samples collected, five were acute (median collection, 0.5 hours postinjury [interquartile range, 0.5-0.6 hours]) and three were subacute (median collection, 108 hours postinjury [interquartile range, 77-128 hours]). Compressive yield strength was lower among acute HTX thrombi compared with subacute thrombi (median, 52.3 vs. 79.1 kPa; p = 0.01). Acute HTX thrombi exhibited a greater proportion of biconcave erythrocytes (11.0% vs. 4.0%, p = 0.006) but similar proportions of deformed erythrocytes and fibrin (38.8% vs. 42.1%, p = 0.226; 30.6% vs. 38.4%, p = 0.454). Acute HTX thrombi were also less contracted than subacute thrombi (median, 19.0% vs. 25.0%; p < 0.001). DISCUSSION: The composition and physical properties of HTX thrombi vary significantly depending on the time postinjury. These findings support the use of early mechanical adjuncts to drainage including thoracic lavage. Retained HTX thrombi were significantly contracted and less porous, suggesting that lytic therapy could be enhanced with disruptive adjuncts such as lavage, ultrasound, or vibration. The timing of this transition and the effect on various interventions warrant further characterization.

  PublisherDOI

• Platelet factor 4 modulates endothelial cell antimicrobial activity to enhance bacterial clearance and improve sepsis outcomes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-03

  preprintOpen accessSenior author

  ABSTRACT Sepsis is a life-threatening condition characterized by dysregulated host responses to infection. Here, we identify platelet factor 4 (PF4) as a key mediator of vascular antimicrobial defense. In vitro, PF4 enhanced endothelial cell internalization of Escherichia coli via interactions with the PF4 receptor CXCR3 and the endothelial glycocalyx, directing bacteria to clathrin-mediated endocytosis and lysosomal degradation. In vivo, PF4 administration improved survival and reduced sepsis severity, bacterial burden, inflammation, and thrombosis in wild-type (WT) and PF4 knockout ( PF4 − / − ) mice challenged with systemic polymicrobial infection. Using intravital microscopy, we observed that infused bacteria were rapidly sequestered in the pulmonary microvasculature. However, PF4 − / − mice exhibited impaired bacterial clearance and increased microvascular platelet adhesion and aggregation. In the liver, following Kupffer cell depletion, PF4 − / − mice had increased sinusoidal platelet accumulation, larger bacterial aggregates, and elevated hepatic bacterial burden compared to WT controls. Collectively, these findings reveal that PF4 promotes bacterial clearance and restrains immunothrombosis during sepsis in part via endothelial cell uptake and destruction of microbes. By enhancing endothelial antimicrobial function, PF4 represents a significant yet previously underrecognized host defense mechanism that limits bacterial spread and alleviates vascular injury during infection. KEY POINTS In vitro, PF4 accelerates bacterial clearance by enhancing endothelial uptake of bacteria and promoting their trafficking to the lysosome. In murine sepsis, PF4 augments pathogen clearance to reduce infection severity, limit organ injury, and improve survival.

  PublisherOA PDFDOI

• Cortisol in sickle cell disease: a systematic review and meta-analysis

  Blood Advances · 2025-06-15 · 1 citations

  reviewOpen access

  ABSTRACT: Cortisol plays a critical role in the biological link between psychosocial stress and health outcomes; however, the methods for assessing cortisol and the biopsychosocial correlates of this stress hormone among individuals with sickle cell disease (SCD) are not well developed. This review aimed to systematically evaluate the current literature for cortisol measurement and methodology among individuals with SCD and synthesize findings of biopsychosocial correlates in this population. A systematic search of medical databases was conducted, resulting in 20 studies meeting inclusion criteria, involving 710 participants with SCD and 454 control participants without SCD. Cortisol was primarily measured using serum (k = 10) and plasma (k = 8), and few studies used salivary (k = 1) or hair (k = 1) measurements. Most studies investigated cortisol in comparison with a control group (k = 14). Qualitative findings were inconsistent, and quantitative meta-analytic data (k = 12) imply no significant difference in cortisol in SCD participants relative to healthy controls (serum Hedges g = -1.51, 95% confidence interval [CI], -3.99 to 0.97; plasma Hedges g = -0.72; 95% CI, -1.56 to 0.13). Additionally, studies examined cortisol in comparison with adrenal standards (k = 5), responses to adrenocorticotropic hormone stimulation (k = 7), and correlations with vaso-occlusive crises (k = 3) and disease severity (k = 3). Few studies explored medication (k = 2) or behavioral correlates (k = 1) of cortisol. Finally, no study investigated the influence of psychosocial stressors on cortisol levels. There is a clear need for high-quality observational research to clarify cortisol findings in SCD and identify psychosocial correlates and biomedical outcomes.

  PublisherOA PDFDOI

• Activating STIM1 mutations drive the development of myelofibrosis

  Blood · 2025-11-03

  article

  Abstract Myeloproliferative neoplasms (MPNs) are typically ascribed to hyperactive JAK-STAT signaling via mutations in JAK2, CALR, or MPL. Here, we characterize how activating mutations in the calcium sensor STIM1, previously established as the cause of Stormorken Syndrome (SS), a rare congenital disorder, are sufficient to drive development of myelofibrosis (MF). We further uncover distinct interactions between STIM1 activity and JAK2 versus CALR driven MPNs. We initially identified two SS patients with activating mutations in STIM1 (R304W and S88G) and features of MF, including marked reticulin fibrosis with megakaryocytic hyperplasia and atypia. This led us to hypothesize that altered calcium signaling may play a role in the development of MF in both SS and MPNs. Single cell RNA sequencing performed on samples from both patients demonstrated elevated NFκB inflammatory signaling in monocyte populations, suggesting a link between altered STIM1 and store operated calcium entry (SOCE) activity and aberrant inflammation, thereby contributing to MF development. To corroborate these findings from our SS patients, we generated a knock-in mouse model of the heterozygous R304W mutation. Induction of hematopoietic-specific expression of mutant Stim1 with Vav-Cre recapitulated the hematological features of SS, including elevated SOCE activity and thrombocytopenia. We also recapitulated MF features including the development of bone marrow fibrosis and severe osteosclerosis, with the mice developing splenomegaly as young as 9 weeks old. In ex vivo megakaryocyte differentiation assays with our Stim1 R304W knock-in mice, we also observed aberrant cytoskeletal organization and elevated TGFβ mRNA expression. When induction was driven universally through CMV-Cre, we also validated that mice recapitulated multiple SS features, including thrombocytopenia, tubular aggregate myopathy, growth deficiency, and the development of bone marrow fibrosis as young as 10 weeks. We additionally identified a separate cohort of 9 related individuals with SS and STIM1 mutations (L92V) as well as a separate patient with the R304W mutation. In ex vivo megakaryocytic differentiation assays, cells from SS patients demonstrated defective thrombopoiesis with significantly decreased proplatelet formation, and displayed aberrant cytoskeletal formation within the pro-platelet termini, in conjunction with increased expression of TGFβ. Further supporting a role for STIM1 in MPNs, we identified upregulation of STIM1 expression in MPN patient CD34+ hematopoietic stem/progenitors' cells (HSPCs), we well as megakaryocyte progenitors and platelets, including those with CALR or JAK2 mutations. To evaluate the functional role of STIM1 in MPNs, we generated patient-derived xenograft (PDX) models with CALR and JAK2-mutantpatient samples subjected to CRISPR ablation of STIM1. In an initial CALR-mutant PDX experiment, abrogation of STIM1 led to decreased human CD45+ cell engraftment in conjunction with prolonged survival. In a second CALR-mutant PDX experiment, STIM1 targeting did not overtly impact engraftment or survival. In contrast, CRISPR ablation of STIM1 in JAK2-mutant PDX models led to exacerbated disease phenotypes, including increased human CD45+ cell engraftment, increased splenomegaly, and early lethality. Altogether, this study represents the first demonstration of MF development in patients with Stormorken Syndrome and reveals a previously unrecognized role of aberrant SOCE underlying SS and MPNs. We recapitulated these findings in a novel conditional mouse model. These findings also illustrate unique interactions between STIM1 and JAK2 and CALR driven MPNs. These observations have important implications for the development of targeted therapeutic approaches for these disorders.

  PublisherDOI

Frequent coauthors

• Mortimer Poncz

  Children's Hospital of Philadelphia

  64 shared

• M. Anna Kowalska

  Polish Academy of Sciences

  37 shared

• Lubica Rauova

  Children's Hospital of Philadelphia

  33 shared

• Veronica Bochenek

  Children's Hospital of Philadelphia

  28 shared

• Anh T. P. Ngo

  Children's Hospital of Philadelphia

  26 shared

• Michele P. Lambert

  Children's Hospital of Philadelphia

  25 shared

• Amrita Sarkar

  Children's Hospital of Philadelphia

  23 shared

• Douglas B. Cines

  University of Pennsylvania

  21 shared

Labs

• Kandace L Gollomp LabPI

Education

• Fellowship, Pediatrics

  Children's Hospital of Philadelphia

  2016

• Residency, Pediatrics

  Children's Hospital of Philadelphia

  2013