Penn Institute for Immunology
Perelman School of Medicine at the University of Pennsylvania
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Hydar Ali

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Graduate Group Affiliations

Contact information
Robert Schattner Center
346 Levy Building
240 South 40th Street
Philadelphia, PA 19104
Office: (215) 573-1993
Fax: (215) 573-2050
Education:
B.Sc.
University College London, England, 1982.
Ph.D. (Immunology/Pharmacology)
University of London, UK, 1986.
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Description of Research Expertise

Research Interests:

Mas-related G protein coupled receptor-X2 (MRGPRX2) in host defense and chronic inflammatory diseases

Research Summary:

Surface epithelial cells, when activated by pathogen-associated molecular patterns (PAMPs) release small host defense antibacterial peptides (HDPs), known as defensins and cathelicidins. These HDPs display potent antimicrobial activity, modulate immune responses via the activation of mast cells through MRGPRX2. This GPCR also likely participates in pseudo-allergic drug reactions and in the pathogenesis of chronic inflammatory diseases such as asthma, chronic urticaria and periodontitis.

A unique feature of MRGPRX2 that distinguishes it from other GPCRs is that it is activated by multiple ligands that include HDPs, neuropeptides, major basic protein (MBP), eosinophil peroxidase (EPO) and many FDA approved peptidergic drugs. In addition, unlike other GPCRs, MRGPRX2 is expressed only in dorsal root ganglia and mast cells and are present both on plasma membrane and intracellular sites.

We are currently using cellular, molecular and imaging approached to delineate the mechanisms involved in the regulation of MRGPRX2 in vitro and humanized mice to study its function in vivo.

Selected Publications

Gupta, K., Subramanian, H., Ali, H.: Modulation of host defense peptide-mediated human mast cell activation by LPS. Innate Immun 22(1): 21-30, 2016.

Subramanian, H., Gupta, K., Ali, H.: Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol 2016.

Gupta, K., Kotian, A., Subramanian, H., Daniell, H., Ali, H.: Activation of human mast cells by retrocyclin and protegrin highlight their immunomodulatory and antimicrobial properties. Oncotarget 2015.

Subramanian, H., Gupta, K., Parameswaran, N., Ali, H.: Regulation of FcRI Signaling in Mast Cells by G Protein-coupled Receptor Kinase 2 and Its RH Domain. J Biol Chem 289(30): 20917-20927, 2014.

Gupta, K., Subramanian, H., Klos, A., Ali, H.: Phosphorylation of C3a receptor at multiple sites mediates desensitization, beta-arrestin-2 recruitment and inhibition of NF-kappaB activity in mast cells. PLoS One 7(10): e46369, 2012.

Subramanian Hariharan, Gupta Kshitij, Ali Hydar: Roles for NHERF1 and NHERF2 on the regulation of C3a receptor signaling in human mast cells. PloS one 7(12): e51355, 2012.

Kashem Sakeen W, Subramanian Hariharan, Collington Sarah J, Magotti Paola, Lambris John D, Ali Hydar: G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: roles of Mas-related genes MrgX1 and MrgX2. European journal of pharmacology 668(1-2): 299-304, Oct 2011.

Subramanian Hariharan, Kashem Sakeen W, Collington Sarah J, Qu Hongchang, Lambris John D, Ali Hydar: PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2 (MrgX2) in human mast cells. Molecular pharmacology 79(6): 1005-13, Jun 2011.

Kashem, SW, Subramanian, H., Collington, S Maggoti, P, Lambris, JD and Ali, H. : G protein coupled receptor specificity for C3a and compound 48/48-induced degranulation in human mast cells: roles of Mas-related genes MrgX1 and MrgX2. Eur. J. Pharm. 668: 299-304, 2011.

Guo, Q, Subramanian, H, Gupta, K and Ali, H. : Regulation of C3a receptor signaling in human mast cells by G Protein coupled receptor kinases. PLoS ONE 6: e22559, 2011.

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Last updated: 08/26/2016
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