Faculty

Michael J. May, Ph.D.

faculty photo
Graduate Group Affiliations

Contact information
Department of Biomedical Sciences (OVH 200E),
The School of Veterinary Medicine,
The University of Pennsylvania
3800 Spruce Street, Philadelphia PA 19104.
Philadelphia, PA 19104
Office: (215) 573 0940
Fax: (215) 573 5186
Education:
Ph.D. (Vascular Biology Research Centre)
King’s College London, UK. , 1996.
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Description of Research Expertise

The May laboratory investigates signal transduction pathways that lead to altered patterns of gene expression in immune and inflammatory responses. We are particularly interested in understanding how the loss of control of normal signaling contributes to the progression of diseases such as chronic inflammation and cancer. Our goal is to determine the specific molecular events underlying aberrant signals and to define realistic targets for selectively blocking abnormal, while maintaining physiologically normal responses. The focus of our work is the Nuclear Factor (NF)-kappa B transcription factor activation pathway that is critical for inflammation, innate and adaptive immunity and lymphocyte development. NF-kappa B activation is typically a rapid and transient response, however constitutive NF- kappa B activity occurs at sites of chronic inflammation and in various tumors, leukemias and lymphomas. We combine cellular, molecular and genetic approaches to determine the mechanisms that redirect normal NF-kappa B activation pathways into this functionally abnormal, constitutively active state. In addition to determining the basic mechanisms of NF-kappa B activation we have a long-standing interest in understanding the role of NF-kappa B in regulating the phenotype and function of vascular endothelial cells.

A second related interest is to explore the experimental and therapeutic potential of peptide transduction technology as a strategy for modulating specific cell signaling responses. We previously described a small cell-permeable peptide inhibitor of NF-kappa B activity and demonstrated the feasibility of this approach both in vitro and in vivo. We will continue to exploit this exciting novel strategy to fully dissect deregulated NF-kappa B activity in chronic inflammatory diseases.

Currently our active areas of research are:

1. Determining the biochemical and molecular mechanisms that regulate the activity of the I Kappa B Kinase complex.
2. Investigating the signals that regulate vascular endothelial cell function in immune and inflammatory responses.
3. Developing novel targets for cell-permeable peptide inhibitors of NF-kappa B.

Selected Publications

McCorkell KA, Jayachandran N, Cully MD, Freund-Brown J, Weinkopff T, Monslow J, Hu Y, Puré E, Freedman BD, Alvarez JI, Cancro MP, May MJ.: Lymph node formation and B cell homeostasis require IKK-α in distinct endothelial cell-derived compartments. Proc Natl Acad Sci U S A 118: e2100195118, Nov 2021.

Berry CT, Liu X, Myles A, Nandi S, Chen YH, Hershberg U, Brodsky IE, Cancro MP, Lengner CJ, May MJ, Freedman BD.: BCR-Induced Ca(2+) Signals Dynamically Tune Survival, Metabolic Reprogramming, and Proliferation of Naive B Cells. Cell Rep 31: 107474, Apr 2020.

Philipson BI, O'Connor RS, May MJ, June CH, Albelda SM, Milone MC.: 4-1BB costimulation promotes CAR T cell survival through noncanonical NF-κB signaling. Sci Signal 13: eaay8248, Mar 2020.

Berry Corbett T, May Michael J, Freedman Bruce D: STIM- and Orai-mediated calcium entry controls NF-κB activity and function in lymphocytes. [PMID 30048879] Cell calcium 74: 131-143, 09 2018.

Liu Xiaohong, Berry Corbett T, Ruthel Gordon, Madara Jonathan J, MacGillivray Katelyn, Gray Carolyn M, Madge Lisa A, McCorkell Kelly A, Beiting Daniel P, Hershberg Uri, May Michael J, Freedman Bruce D: T Cell Receptor-induced Nuclear Factor κB (NF-κB) Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-mediated Calcium Entry. [PMID 26826124] The Journal of biological chemistry 291(16): 8440-52, Apr 2016.

Ager Ann, May Michael J: Understanding high endothelial venules: Lessons for cancer immunology. [PMID 26155419] Oncoimmunology 4(6): e1008791, Jun 2015.

Giacomin Paul R, Moy Ryan H, Noti Mario, Osborne Lisa C, Siracusa Mark C, Alenghat Theresa, Liu Bigang, McCorkell Kelly A, Troy Amy E, Rak Gregory D, Hu Yinling, May Michael J, Ma Hak-Ling, Fouser Lynette A, Sonnenberg Gregory F, Artis David: Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity.[PMID 26371187] The Journal of experimental medicine 212(10): 1513-28, Sep 2015.

Sehnert B, Burkhardt H, Wessels J T, Schröder Ag, May M J, Vestweber D, Zwerina J, Warnatz K, Nimmerjahn F, Schett G, Dübel S, Voll R E: NF-κB inhibitor targeted to activated endothelium demonstrates a critical role of endothelial NF-κB in immune-mediated diseases. [PMID 24062461] Proceedings of the National Academy of Sciences of the United States of America 110(41): 16556-61, Oct 2013.

Gray Carolyn M, McCorkell Kelly A, Chunduru Srinivas K, McKinlay Mark A, May Michael J: Negative feedback regulation of NF-κB-inducing kinase is proteasome-dependent but does not require cellular inhibitors of apoptosis. [PMID 24942881] Biochemical and biophysical research communications 450(1): 341-6, Jul 2014.

Habineza Ndikuyeze Georges, Gaurnier-Hausser Anita, Patel Reema, Baldwin Albert S, May Michael J, Flood Patrick, Krick Erika, Propert Kathleen J, Mason Nicola J: A phase I clinical trial of systemically delivered NEMO binding domain peptide in dogs with spontaneous activated B-cell like diffuse large B-cell lymphoma. [PMID 24798348] PloS one 9(5): e95404, 2014.

Gray Carolyn M, Remouchamps Caroline, McCorkell Kelly A, Solt Laura A, Dejardin Emmanuel, Orange Jordan S, May Michael J: Noncanonical NF-κB Signaling Is Limited by Classical NF-κB Activity. [PMID 24497610] Science Signaling 7(311): ra13, Feb 2014.

Neely R J, Brose M S, Gray C M, McCorkell K A, Leibowitz J M, Ma C, Rothstein J L & May M J: The RET/PTC3 oncogene activates classical NF-kappaB by stabilizing NIK. [PMID 20818435] Oncogene 6(30): 87-96, 2011.

Gaurnier-Hausser Anita, Patel Reema, Baldwin Albert S, May Michael J, Mason Nicola J: NEMO-binding domain peptide inhibits constitutive NF-κB activity and reduces tumor burden in a canine model of relapsed, refractory diffuse large B-cell lymphoma.[PMID 21610150] Clinical cancer research : an official journal of the American Association for Cancer Research 17(14): 4661-71, Jul 2011.

Madge LA & May MJ: Classical NF-kappaB activation negatively regulates non-canonical NF-kappaB-dependent CXCL12 expression.[PMID 20923761] The Journal of biological chemistry 285 (49): 38069-077, Dec 2010.

Yatherajam G, Banerjee PP, McCorkell KA, Solt LA, Hanson EP, Madge LA, Kang S, Worley PF, Orange JS & May MJ.: Cutting edge: association with I kappa B kinase beta regulates the subcellular localization of Homer3. [PMID 20693425] Journal of immunology 185(5): 2665-9, Sept 2010.

Hanson, Eric P. Monaco-Shawver, Linda. Solt, Laura A. Madge, Lisa A. Banerjee, Pinaki P. May, Michael J. Orange, Jordan S.: Hypomorphic nuclear factor-kappaB essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity. [PMID 18851874] Journal of Allergy & Clinical Immunology 122(6): 1169-1177.e16, Dec 2008.

Bredemeyer, Andrea L. Helmink, Beth A. Innes, Cynthia L. Calderon, Boris. McGinnis, Lisa M. Mahowald, Grace K. Gapud, Eric J. Walker, Laura M. Collins, Jennifer B. Weaver, Brian K. Mandik-Nayak, Laura. Schreiber, Robert D. Allen, Paul M. May, Michael J. Paules, Richard S. Bassing, Craig H. Sleckman, Barry P.: DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes. [PMID 18849970] Nature 456(7223): 819-23, Dec 11 2008.

Madge LA, Kluger MS, Orange JS & May MJ.: Lymphotoxin-alpha 1 beta 2 and LIGHT induce classical and noncanonical NF-kappa B-dependent proinflammatory gene expression in vascular endothelial cells. [PMID 18292573] Journal of Immunology 180(5): 3467-77, March 2008.

Solt LA, Madge LA & May MJ: NEMO-binding domains of both IKKalpha and IKKbeta regulate IkappaB kinase complex assembly and classical NF-kappaB activation.[PMID 19666475] The Journal of biological chemistry 284(40): 27596-608, Oct 2009.

Wharry CE, Haines KM, Carroll RG & May MJ.: Constitutive non-canonical NFkappaB signaling in pancreatic cancer cells. [PMID 19502791] Cancer biology & therapy 8(16): 1567-76, Aug 2009.

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Last updated: 11/24/2021
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