About

Hamid Bassiri, MD, PhD, is an Adjunct Associate Professor of Pediatrics (Infectious Diseases) at the University of Pennsylvania's Perelman School of Medicine. His research investigates two primary areas: the mechanisms of tumor immune surveillance and the development of cellular cancer immunotherapy, with ongoing projects focusing on natural killer T and natural killer cell responses, immunometabolic features of Natural killer T cells, and the immune microenvironment of neuroblastoma. Additionally, his work explores the immune pathogenesis of pediatric hyper-inflammatory syndromes, including those caused by genetic lesions, infections such as COVID-19, and cancer immunotherapy like CAR-T cell therapy. Dr. Bassiri's clinical expertise encompasses pediatric infectious diseases, care of immunocompromised children, and management of immune dysregulation conditions such as hemophagocytic lymphohistiocytosis and multisystem inflammatory syndrome in children (MIS-C). His contributions include advancing understanding of immune responses in pediatric infectious and inflammatory diseases, with a focus on translating these insights into therapeutic strategies.

Research topics

• Medicine
• Immunology
• Bioinformatics
• Biology
• Virology
• Pathology
• Internal medicine

Selected publications

• Multimodal analysis reveals polyclonality and inflammatory programs specific to TRBV11-2+ CD4 T cells in MIS-C

  Zenodo (CERN European Organization for Nuclear Research) · 2026-05-07

  datasetOpen access

  Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening condition presenting with multi-organ dysfunction, whose presentation shares features of other inflammatory syndromes. Expansion of TRBV11-2+ T cells has been suggested to distinguish MIS-C, but mechanisms underlying this phenomenon remain unclear. Contrasting models posit that TRBV11-2+ T cell activation is driven by peptide antigen-specific versus superantigen-induced mechanisms. However, systematic evaluation of these hypotheses has been limited without molecular insight into the relationship between T cell clonality and gene expression states in MIS-C. Here, we present a unique single-cell dataset capturing integrated expression of TCR genes, surface epitopes, and transcriptomes from peripheral blood mononuclear cells of children with MIS-C versus clinically severe COVID-19, mild COVID-19, and healthy controls. Multimodal analyses resolved a proliferative and Th1-polarized CD4 T cell subset in MIS-C with profound TRBV11-2 skewing and polyclonality, both hallmark features of superantigen-mediated expansion. Moreover, known superantigen-induced transcriptional programs were enriched in TRBV11-2+ CD4 T cells from MIS-C patients, but not TRBV11-2− cells nor COVID-19 patients. Together, these data are consistent with nonspecific expansion of TRBV11-2+ and Th1-polarized CD4 T cells in MIS-C. Our findings demonstrate the power of integrated single-cell profiling to resolve pathways of T cell activation in pediatric inflammatory diseases.

  PublisherDOI

• Multimodal analysis reveals polyclonality and inflammatory programs specific to TRBV11-2+ CD4 T cells in MIS-C

  Zenodo (CERN European Organization for Nuclear Research) · 2026-05-07

  datasetOpen access

  Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening condition presenting with multi-organ dysfunction, whose presentation shares features of other inflammatory syndromes. Expansion of TRBV11-2+ T cells has been suggested to distinguish MIS-C, but mechanisms underlying this phenomenon remain unclear. Contrasting models posit that TRBV11-2+ T cell activation is driven by peptide antigen-specific versus superantigen-induced mechanisms. However, systematic evaluation of these hypotheses has been limited without molecular insight into the relationship between T cell clonality and gene expression states in MIS-C. Here, we present a unique single-cell dataset capturing integrated expression of TCR genes, surface epitopes, and transcriptomes from peripheral blood mononuclear cells of children with MIS-C versus clinically severe COVID-19, mild COVID-19, and healthy controls. Multimodal analyses resolved a proliferative and Th1-polarized CD4 T cell subset in MIS-C with profound TRBV11-2 skewing and polyclonality, both hallmark features of superantigen-mediated expansion. Moreover, known superantigen-induced transcriptional programs were enriched in TRBV11-2+ CD4 T cells from MIS-C patients, but not TRBV11-2− cells nor COVID-19 patients. Together, these data are consistent with nonspecific expansion of TRBV11-2+ and Th1-polarized CD4 T cells in MIS-C. Our findings demonstrate the power of integrated single-cell profiling to resolve pathways of T cell activation in pediatric inflammatory diseases.

  PublisherDOI

• Macrophage Activation Syndrome–Associated Proteins and Enhanced Interferon‐γ Responsiveness in the Plasma Proteome of Patients With Multisystem Inflammatory Syndrome in Children in a Pretreatment Replication Single‐Center Cohort

  ACR Open Rheumatology · 2026-02-01

  articleOpen access

  OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory syndrome that follows SARS-CoV-2 infection. Prior plasma proteomic analysis from a 2020 cohort of patients with MIS-C at our center revealed a profile characterized by thrombotic microangiopathy (TMA), macrophage activation syndrome (MAS)-associated proteins, and dysregulated interferon-γ (IFNγ) responses. However, a limitation of that study was that samples were often acquired after treatment. The objective of this study was to identify plasma proteomic signatures that uniquely define MIS-C versus other viral syndromes unconfounded by treatment effects in an independent cohort. METHODS: Plasma proteomics was performed using the Olink Explore HT platform on plasma from patients enrolled at emergency department admission with suspected MIS-C (final diagnoses N = 12 MIS-C, N = 30 other viral syndromes). Plasma autoantibody analysis was performed using a custom microbead-based protein array. RESULTS: Consistent with findings in the 2020 cohort, TMA- and MAS-associated proteins were more highly expressed, and there was a higher CXCL9 response to IFNγ in MIS-C compared to viral infection. In contrast to the 2020 cohort, patients with MIS-C did not have lower expression of the IFNγ suppressive protein TRIM21. On reanalysis of the 2020 cohort, only patients who received intravenous Ig (IVIg) treatment before sampling had low TRIM21 (also known as Ro52/SSA). IVIg recipients also had anti-Ro52 autoantibodies. CONCLUSION: We have validated several unique features of the plasma proteome of patients with MIS-C first identified in 2020. Discrepant TRIM21 expression in these two cohorts is due to anti-Ro52 autoantibodies in IVIg-treated patients. These data support the use of plasma cytokine profiling to rapidly diagnose MIS-C.

  PublisherDOI

• Digging in the DIRT Since 2018: Form, Function, and Findings of a Complex Immune Dysregulation Program

  Journal of Human Immunity · 2025-04-25

  articleOpen access

  Inflammation and immune disturbance are common to the pathology of most diseases. Clinical understanding and ability to interrogate immune function lag far behind the rising number of available immune-directed therapies. Historically, diagnosis and management of patients with complex immune dysregulation is often siloed by specialty and inefficient. Building from a successful hemophagocytic lymphohistiocytosis response team, we describe our experience implementing a comprehensive, multidisciplinary dysregulated immunity response team (DIRT, colloquially) to improve the care of children with severe, recalcitrant, or otherwise complex immune dysregulation disorders. With seed support through a competitive internal mechanism, The Children's Hospital of Philadelphia Immune Dysregulation Program (IDP) commenced in 2018, graduating to an established program in 2021. With coordination by dedicated administrators and highly specialized nurse practitioners, the IDP now staffs a year-round inpatient consultation service and four outpatient clinics per month. Inpatient service is staffed by IDP infectious disease, immunology, rheumatology, hematology, or oncology specialists. Preparation for outpatient visits is tailored to individual patient needs and includes triage, prior authorization (for testing), medical record review, and determination of which IDP specialists are needed (as above and/or gastroenterology, hepatology, dermatology, neurology, and pulmonology). In Fiscal Year ’24, the IDP staffed 187 outpatient visits and 90 inpatient consultations. 36% of IDP patients traveled from >20 states outside PA/NJ and internationally. Additional clinical accomplishments include establishment of an in-house, rapid turn-around, clinical plasma cytokine panel; a weekly “office hours” external patient discussion; a widely attended weekly case teleconference; three institutional guidance documents (MIS-C, HLH, and antimicrobial prophylaxis); contributions to three international consensus guideline projects; and treatment of nine patients on single-patient investigational new drug protocols. Research accomplishments include enrollment of >325 subjects in a biobank/registry protocol and publication of eight primary manuscripts. Education/training accomplishments include establishment of an immune dysregulation elective, conducting a yearly 10+-part “Fellows Immunology Course,” hosting seven Immune Dysregulation Symposia, and receiving the first “Physician Scientist Training Program in Immune Dysregulation” award (T32AI170501). An integrated, multidisciplinary IDP is a feasible and sustainable approach to meeting the growing clinical, educational, and research challenges posed by caring for patients with complex immune dysregulation.

  PublisherDOI

• Circulating Free and Low-Density Lipoprotein-Bound GD2 Can Compete with Neuroblastoma Cells for Binding Therapeutic Anti-GD2 Antibodies

  2025-04-22

  preprintOpen access

  Background: GD2 is a ganglioside that is expressed on the surface of neuroblastoma cells and shed into the circulation, where it primarily circulates bound to low density lipoprotein (LDL). We questioned whether free GD2 or GD2 bound to LDL could interfere with the binding of therapeutic anti-GD2 monoclonal antibodies like dinutuximab to neuroblastoma cells. Procedure: The GD2-expressing neuroblastoma cell line IMR5 was stained with an anti-GD2 antibody tagged with allophycocyanin (APC) at the lowest possible saturating concentration, and median fluorescence intensity was measured by flow cytometry after in vitro exposure to free GD2 or GD2 bound to LDL at concentrations of 0nM, 100nM, 1μM, and 5μM. Control experiments assessed the ability of cells with GD2 surface-expressed and GD2-non-expressing cells to compete for anti-GD2-APC antibodies with a population of 2 million IMR5 cells. Results: Free and LDL-bound GD2 reduced the binding of anti-GD2-APC antibodies to IMR5 cells in vitro in a concentration-dependent manner. At 100nM, which is below the median plasma GD2 concentration measured in patients with high-risk neuroblastoma prior to therapy, reduced antibody binding to IMR5 cells by 40%. Conclusions: At physiologic concentrations found in the plasma of patients with high-risk neuroblastoma, free GD2 and LDL-bound GD2 reduced the binding of anti-GD2 antibodies to GD2-expressing neuroblastoma cells, in vitro . This suggests that circulating GD2 could impact the efficacy of therapeutic anti-GD2 antibodies administered to patients with a high disease burden during induction therapy or at relapse.

  PublisherOA PDFDOI

• A Method for Comparing Proteins Measured in Serum and Plasma by Olink Proximity Extension Assay

  Molecular & Cellular Proteomics · 2025-05-27 · 3 citations

  articleOpen access

  Accurate measurement of secreted proteins in serum and plasma is essential for understanding mechanisms and developing reliable biomarkers. Recent technological advancements, such as proximity extension assay (PEA), have enabled high-throughput multiplex protein analyses from small sample volumes in either serum or plasma. Despite the increasing use of PEA-based proteomics and the generation of extensive datasets, integrated data from these two mediums remains challenging due to inherent differences in sample processing. To address this issue, we developed and validated protein-specific transformation factors using linear modeling to normalize protein measurements between serum and plasma proteins quantified using Olink. Our analysis surveyed 1463 proteins across matched serum and plasma samples, identifying 686 transformation factors. The transformation factors were further validated using independent datasets generated from patients with different disease phenotypes and ages, and 551 of the models and transformation factors were reproducible. These transformation factors provide a valuable resource for normalizing PEA-based proteomic data across serum and plasma, ultimately enhancing the capacity for collaborative analyses and facilitating comprehensive insights across diverse disease phenotypes.

  PublisherOA PDFDOI

• Design of a new tool for the assessment of pediatric infectious diseases fellow competencies

  Academic Pediatrics · 2025-11-01

  article
  PublisherDOI

• Metabolomic and Immunologic Discriminators of MIS-C at Emergency Room Presentation

  medRxiv · 2024-01-15 · 1 citations

  preprintOpen access

  Multisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to misdiagnosis. To identify diagnostic discriminators at the time of emergency department presentation, we enrolled 104 children who met MIS-C screening criteria, 14 of whom were eventually diagnosed with MIS-C. Before treatment, we collected breath samples for volatiles and peripheral blood for measurement of plasma proteins and immune cell features. Clinical and laboratory features were used as inputs for a machine learning model to determine diagnostic importance. MIS-C was associated with significant changes in breath volatile organic compound (VOC) composition as well as increased plasma levels of secretory phospholipase A2 (PLA2G2A) and lipopolysaccharide binding protein (LBP). In an integrated model of all analytes, the proportion of TCRVβ21.3+ non-naive CD4 T cells expressing Ki-67 had a high sensitivity and specificity for MIS-C, with diagnostic accuracy further enhanced by low sodium and high PLA2G2A. We anticipate that accurate diagnosis will become increasingly difficult as MIS-C becomes less common. Clinical validation and application of this diagnostic model may improve outcomes in children presenting with multisystem febrile illnesses.

  PublisherOA PDFDOI

• Abstract 5122: Modulating anti-GD2 immunotherapy via dual DFMO and TGF-β inhibition in neuroblastoma

  Cancer Research · 2024-03-22

  article

  Abstract Neuroblastoma (NB) is an often-lethal childhood solid tumor. Anti-GD2 immunotherapy improves survival but not all responses are durable. Transforming growth factor-beta (TGFβ) has been implicated in solid tumor immunoresistance. High-risk NBs harbor activated MYC or MYCN to coordinately expand intratumoral polyamines (PA), oncometabolites with immunomodulatory roles, to support tumor progression. Difluoromethylornithine (DFMO) is an inhibitor of ornithine decarboxylase, the rate-limiting enzyme in PA synthesis, and has shown activity in preclinical NB models, including TH-MYCN+/+ transgenic mice, and is in clinical trials in children. We sought to augment anti-GD2 therapy using DFMO and the small molecule TGFβ-receptor inhibitor, galunisertib. We randomized TH-MYCN+/+ mice in two experiments (10 therapy arms; n=6-10 mice/arm) to receive combinations of DFMO, galunisertib, and anti-GD2 antibody m14G2a and to assess impact on survival. We measured 770 genes using nCounter Immuno-Oncology 360 (Nanostring), 36 cytokines using xMap bead-arrays (Luminex), and tumor-infiltrating leukocytes using flow cytometry in harvested tumors. Cell line TGFβ signaling was evaluated in tissue culture. In vitro, galunisertib consistently suppressed the upregulated TGFβ-Smad2/3 signaling cascade in MYCN-amplified neuroblastoma cell lines. In vivo, DFMO alone extends mouse survival and increases intra-tumoral neutrophils and natural killer (NK) cells. These NK cells increased surface expression of activation receptors like NKG2D (p<0.05), while tumor cells increased surface expression of NK-ligands. Tumor cells also expressed increased latency-associated peptide (LAP; p<0.05), a TGFβ precursor, suggesting NK cells were poised to kill but restrained by TGFβ. Cytotoxicity assays showed reversal of this inhibition with TGFβR1 inhibitor galunisertib in vitro. In a proof-of-concept trial, DFMO and galunisertib (DFMO/gal) demonstrated a clinical anti-tumor synergistic effect. DFMO/gal treated tumors had upregulated NK cell activity genes and downregulated TGFβ signaling genes. Cytokine analysis confirmed DFMO induced upregulation of TGFβ1 and TGFβ2 (p<0.01) that was modulated by galunisertib. IL6, GCSF, and GMCSF were markedly downregulated in tumors treated with both DFMO and galunisertib (p<0.05). An expanded trial showed DFMO/gal added to m14G2a showed no significant survival benefit over the DFMO and m14G2a combination. Ultimately, DFMO creates a pro-inflammatory cellular and cytokine milieu in TH-MYCN+/+ NBs. DFMO and TGFβR1 inhibition via galunisertib activate NK cells further and decrease the anti-inflammatory cytokine IL6. Ongoing studies are further characterizing the gene expression and cytokine levels of the NB TME under these treatment conditions. Citation Format: Om H. Gandhi, Christina S. Turn, Kangning Liu, Annette T. Vu, Hamid Bassiri, Michael D. Hogarty. Modulating anti-GD2 immunotherapy via dual DFMO and TGF-β inhibition in neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5122.

  PublisherDOI

• Serum cytokine panels in pediatric clinical practice

  Journal of Allergy and Clinical Immunology · 2024-09-18 · 13 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• Mechanisms of invariant NKT cell-mediated in vivo anti-tumor responses

  NIH · $541k · 2012–2016

Frequent coauthors

• Edward M. Behrens

  Children's Hospital of Philadelphia

  146 shared

• Caroline Diorio

  Children's Hospital of Philadelphia

  131 shared

• David T. Teachey

  Children's Hospital of Philadelphia

  121 shared

• Chakkapong Burudpakdee

  Fox Chase Cancer Center

  103 shared

• Scott W. Canna

  Children's Hospital of Pittsburgh

  83 shared

• Michele P. Lambert

  Children's Hospital of Philadelphia

  83 shared

• Kevin O. McNerney

  Lurie Children's Hospital

  75 shared

• Stephan A. Grupp

  Children's Hospital of Philadelphia

  74 shared

Education

• Ph.D.

  University of Pennsylvania

  2002

• B.A.

  University of Pennsylvania

  1991