About

Michael J. May, Ph.D., is a faculty member in the Department of Biomedical Sciences at the University of Pennsylvania's Perelman School of Medicine. His laboratory investigates signal transduction pathways that lead to altered patterns of gene expression in immune and inflammatory responses. A primary focus of his research is understanding how the loss of control of normal signaling contributes to the progression of diseases such as chronic inflammation and cancer. His work centers on the Nuclear Factor (NF)-kappa B transcription factor activation pathway, which is critical for inflammation, innate and adaptive immunity, and lymphocyte development. Dr. May's research aims to determine the specific molecular events underlying aberrant signals and to identify targets for selectively blocking abnormal responses while maintaining normal physiological functions. His laboratory combines cellular, molecular, and genetic approaches to elucidate mechanisms that redirect normal NF-kappa B activation into a constitutively active state, which is associated with chronic inflammation and various tumors, leukemias, and lymphomas. Additionally, he explores the role of NF-kappa B in regulating the phenotype and function of vascular endothelial cells. Dr. May is also interested in the therapeutic potential of peptide transduction technology as a strategy for modulating cell signaling responses, including the development of peptide inhibitors of NF-kappa B activity. His active research areas include the biochemical regulation of the I Kappa B Kinase complex, signals regulating vascular endothelial cell function in immune responses, and the development of peptide inhibitors targeting NF-kappa B.

Research topics

• Biology
• Cell biology
• Cancer research
• Medicine
• Chemistry

Selected publications

• Early Dendritic Cell Depletion Drives High Endothelial Venule Dysfunction and Failure of Naïve Lymphocyte Trafficking in Lymph Node Graft-Versus-Host Disease

  Transplantation and Cellular Therapy · 2026-02-01

  article
  PublisherDOI

• Spatial atlas of diabetic kidney disease reveals a B cell-rich subgroup

  Nature · 2026-04-29

  article
  PublisherDOI

• NF-κB Signaling is Required for X-Chromosome Inactivation Maintenance Following T cell Activation

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-02-12 · 1 citations

  preprintOpen access

  RNA and heterochromatic modifications on the inactive X chromosome (Xi), and these modifications become enriched at the Xi after cell stimulation. Here, we examined allele-specific gene expression and the epigenomic profiles of the Xi following T cell stimulation. We found that the Xi in unstimulated T cells is largely dosage compensated and is enriched with the repressive H3K27me3 modification, but not the H2AK119-ubiquitin (Ub) mark, even at promoters of XCI escape genes. Upon CD3/CD28-mediated T cell stimulation, the Xi accumulates H2AK119-Ub and H3K27me3 across the Xi. Next, we examined the T cell signaling pathways responsible for Xist RNA localization to the Xi and found that T cell receptor (TCR) engagement, specifically NF-κB signaling downstream of TCR, is required. Disruption of NF-κB signaling, using inhibitors or genetic deletions, in mice and patients with immunodeficiencies prevents Xist/XIST RNA accumulation at the Xi and alters expression of some X-linked genes. Our findings reveal a novel connection between NF-κB signaling pathways which impact XCI maintenance in female T cells.

  PublisherOA PDFDOI

• Loss of Lymphatic IKKα Disrupts Lung Immune Homeostasis, Drives BALT Formation, and Protects against Influenza

  ImmunoHorizons · 2024-07-01 · 2 citations

  articleOpen accessSenior author

  IκB kinase (IKK)α controls noncanonical NF-κB signaling required for lymphoid organ development. We showed previously that lymph node formation is ablated in IkkαLyve-1 mice constitutively lacking IKKα in lymphatic endothelial cells (LECs). We now reveal that loss of IKKα in LECs leads to the formation of BALT in the lung. Tertiary lymphoid structures appear only in the lungs of IkkαLyve-1 mice and are not present in any other tissues, and these highly organized BALT structures form after birth and in the absence of inflammation. Additionally, we show that IkkαLyve-1 mice challenged with influenza A virus (IAV) exhibit markedly improved survival and reduced weight loss compared with littermate controls. Importantly, we determine that the improved morbidity and mortality of IkkαLyve-1 mice is independent of viral load and rate of clearance because both mice control and clear IAV infection similarly. Instead, we show that IFN-γ levels are decreased, and infiltration of CD8 T cells and monocytes into IkkαLyve-1 lungs is reduced. We conclude that ablating IKKα in LECs promotes BALT formation and reduces the susceptibility of IkkαLyve-1 mice to IAV infection through a decrease in proinflammatory stimuli.

  PublisherDOI

• Maintenance of X chromosome inactivation after T cell activation requires NF-κB signaling

  Science Immunology · 2024-10-04 · 13 citations

  articleOpen access

  X chromosome inactivation (XCI) balances X-linked gene dosage between sexes. Unstimulated T cells lack cytological enrichment of X-inactive specific transcript (Xist) RNA and heterochromatic modifications on the inactive X chromosome (Xi), which are involved in maintenance of XCI, and these modifications return to the Xi after stimulation. Here, we examined allele-specific gene expression and epigenomic profiles of the Xi in T cells. We found that the Xi in unstimulated T cells is largely dosage compensated and enriched with the repressive H3K27me3 modification but not the H2AK119-ubiquitin (Ub) mark. Upon T cell stimulation mediated by both CD3 and CD28, the Xi accumulated H2AK119-Ub at gene regions of previous H3K27me3 enrichment. T cell receptor (TCR) engagement, specifically NF-κB signaling downstream of the TCR, was required for Xist RNA localization to the Xi. Disruption of NF-κB signaling in mouse and human T cells using genetic deletion, chemical inhibitors, and patients with immunodeficiencies prevented Xist/XIST RNA accumulation at the Xi and altered X-linked gene expression. Our findings reveal a previously undescribed connection between NF-κB signaling pathways, which affects XCI maintenance in T cells in females.

  PublisherOA PDFDOI

• The Bruton’s Tyrosine Kinase Inhibitor Evobrutinib Demonstrates Superior Efficacy in Targeting Compartmentalized Neuroinflammation Compared to Anti-CD20 Treatment. (S16.004)

  Neurology · 2023-04-25 · 1 citations

  article

  <h3>Objective:</h3> To evaluate the efficacy of evobrutinib, a central nervous system (CNS)-penetrant Bruton’s tyrosine kinase inhibitor (BTKi), versus anti-CD20 treatment, on compartmentalized neuroinflammation and disease outcomes in a novel mouse model recapitulating key features of disease progression in multiple sclerosis (MS). <h3>Background:</h3> In MS, compartmentalized neuroinflammation often starts early and is characterized by an accumulation of persistent B cell rich aggregates. Compartmentalized neuroinflammation is predictive of both poor clinical outcomes and rapid disability progression. B cells within the CNS may be protected from established MS therapies such as anti-CD20 antibodies. CNS-penetrant small molecules directed against BTK – with its critical role in B cell activation, proliferation, and survival – have emerged to potentially target chronic neuroinflammation. <h3>Design/Methods:</h3> Preclinical assessments compared the therapeutic potential of evobrutinib and anti-CD20 antibodies on MS progression using the experimental autoimmune encephalomyelitis mouse model with features of progression (pEAE). Clinical outcomes and their correlation with CNS immunopathological parameters were assessed in pEAE mice to recapitulate key aspects of MS disease progression. <h3>Results:</h3> Evobrutinib, versus anti-CD20 (clone: SA271G2) treatment, reduced disease severity (65% reduction; P&lt;0.0001) and immunopathological parameters of disease (56% reduction; P&lt;0.01) in pEAE mice. The beneficial effects of BTKi were paralleled by body-weight gain and a decrease in maximum disease score versus anti-CD20 treatment. Evobrutinib lessened neuroinflammation by significantly reducing the number and activation of lymphoid and myeloid cells as well as the extent of submeningeal demyelination both in the brain (44% reduction; P&lt;0.01) and the spinal cord (42% reduction; P&lt;0.01). <h3>Conclusions:</h3> The improvements in clinical, immunological, and neuropathological parameters of disease observed in pEAE mice treated with evobrutinib illustrate the importance of compartmentalized neuroinflammation for disease progression. The limited effect of anti-CD20 treatment confirms the insufficient disease inhibition potential of antibody-based therapies when targeting intrathecal B cells. These findings support the notion that evobrutinib targets persistent neuroinflammation in MS. <b>Disclosure:</b> Ms. Kebir has received research support from Fonds de Recherche du Québec-Santé. Ms. Kebir has received intellectual property interests from a discovery or technology relating to health care. Cen Li has received research support from Chinese Scholarship Council. The institution of Michael May has received research support from NIH. Molly Church has nothing to disclose. Ursula Boschert has nothing to disclose. Jorge Alvarez has nothing to disclose.

  PublisherDOI

• Opening Orai's to see B-yond current paradigms

  Cell Calcium · 2023-05-16

  articleOpen access
  PublisherOA PDFDOI

• Expression of BTK in Leptomeningeal B-cell Rich Infiltrates in Two Models of Progressive MS and its Inhibition by Evobrutinib, Underscores BTK as a Target for Compartmentalized Neuroinflammation (4162)

  Neurology · 2021-04-13 · 1 citations

  article

  We investigated BTK expression in central nervous system (CNS) tissue from two models of progressive multiple sclerosis (MS), spontaneous canine granulomatous meningoencephalomyelitis (GME) and progressive experimental autoimmune encephalomyelitis (pEAE), and tested the efficacy of evobrutinib in murine pEAE.

  PublisherDOI

• Analysis of Calcium Control of Canonical NF-κB Signaling in B Lymphocytes

  Methods in molecular biology · 2021-01-01 · 3 citations

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  PublisherDOI

• Lymph node formation and B cell homeostasis require IKK-α in distinct endothelial cell–derived compartments

  Proceedings of the National Academy of Sciences · 2021-11-22 · 2 citations

  articleOpen accessSenior authorCorresponding

  Significance Noncanonical NF-κB controls lymph node (LN) formation and B cell homeostasis. We previously demonstrated that IKK-α–dependent noncanonical NF-κB signaling is activated in vascular endothelial cells (ECs). Here, we find that ablation of IKK-α in ECs leads to complete loss of LNs and markedly reduced B cell numbers, recapitulating the phenotype of global IKK-α inactivation. Using cell type–specific conditional knockout models, we find that loss of IKK-α in hematopoietic cells underlies the B cell defect, whereas deletion in lymphatic ECs (LECs) results in the absence of LNs. Thus, our findings reveal that IKK-α in distinct EC-derived compartments is uniquely required to promote B cell homeostasis and LN development and demonstrate that LEC-intrinsic IKK-α is essential for LN formation.

  PublisherOA PDFDOI

Recent grants

• Targeting NF-kB in Atherosclerosis

  NIH · $431k · 2015–2017

• NIH Grant R01HL096642

  NIH · $1.6M · 2015

• Endothelial Cell-Intrinsic Non-Canonical NF-kB in Chronic inflammation

  NIH · $1.9M · 2017–2022

• Calcium Regulation of NF-kB Activation in Lymphocytes

  NIH · $576k · 2016–2018

• NIH Grant R01HL080612

  NIH · $2.0M · 2012

Frequent coauthors

• Sankar Ghosh

  Columbia University

  36 shared

• Floris Groenendaal

  University Medical Center Utrecht

  22 shared

• Cobi J. Heijnen

  Baylor College of Medicine

  22 shared

• Frank van Bel

  Utrecht University

  20 shared

• Albert S. Baldwin

  20 shared

• Annemieke Kavelaars

  The University of Texas MD Anderson Cancer Center

  20 shared

• Kelly A. McCorkell

  Thomas Jefferson University

  19 shared

• Anita Gaurnier-Hausser

  19 shared

Education

• PhD, Vascular Biology

  Kings College London

  1996

• MSc, Immunology

  University of Manchester

  1992

• BSc, Immunology

  University of Glasgow

  1988