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:

Mast cells in host defense and chronic inflammatory diseases

Research Summary:

Mast cells are granulated cells of hematopoietic lineage that reside close to blood vessels primarily at sites exposed to the external environment, such as the skin, oral/gastrointestinal mucosa and respiratory tract. They contribute to vascular homeostasis, innate/adaptive immunity and wound healing. Mast cells are, however, best known for their roles in allergic and inflammatory diseases such as anaphylaxis, food allergy, rhinitis, itch, urticaria, periodontitis, atopic dermatitis and asthma. Mast cells express a newly discovered G protein coupled receptor (GPCR) known as Mas-related G protein coupled receptor X2 (MRGPRX2) and the high affinity IgE receptor (FceRI). As the only mast cell lab at Penn, we are interested in delineating how MRGPRX2 and FceRI contribute to host defense and allergic/inflammatory diseases.

MRGPRX2: Activation of surface epithelial cells by pathogen-associated molecular patterns (PAMPs) results in the generation of host defense antimicrobial peptides (HDPs). These HDPs display potent antimicrobial activity and modulate immune responses via the activation of mast cells through MRGPRX2. In addition to its immunomodulatory function, MRGPRX2 likely participates in pseudo-allergic drug reactions and chronic inflammatory diseases such as urticaria, periodontitis and asthma exacerbation. A unique feature of MRGPRX2 that distinguishes it from other GPCRs is that it is activated by multiple cationic ligands including HDPs, neuropeptides (substance P and hemokinin-1), eosinophil major basic protein (MBP), eosinophil peroxidase (EPO), the neutrophil-derived cathelicidin LL-37 and many FDA approved peptidergic drugs. We are currently using cellular, molecular and imaging approaches to delineate the mechanisms involved in the regulation of MRGPRX2 in vitro and humanized mice to study its function in vivo.

FceRI: Aggregation of FceRI on mast cells by antigen and the release of proinflammatory mediators contribute to the pathogenesis of anaphylaxis and allergic asthma. It is well documented that GPCR kinases (GRKs) and the adapter protein β-arrestin contribute to the desensitization of most GPCRs. We recently made the unexpected observation that GRK2 and β-arrestin2 regulate FceRI-mediated mast cell chemotaxis, degranulation and cytokine gene expression. We are currently utilizing both in vitro and in vivo approaches to delineate how GRK2 and β-arrestin2 regulate FceRI signaling in mast cells to modulate anaphylaxis and allergic asthma.



Current lab members:

Saptarshi Roy, Ph.D. (Postdoctoral Researcher)

Ibrahim Alkanfari DDS (DScD student)
Chalatip Chompunud Na Ayudhya DDS (DScD student)
Manorak, Wichayapha DDS (MSOB student)

Tahsin Jahan M.S. (Research Specialist)
Anirban Ganguly B.S. (Research Specialist)

Projects are available for interested undergraduate, dental and graduate students to study mast cell MRGPRX2 and FceRI

Selected Publications

Ali, H: Mas-related G protein coupled receptor-X2: A potential new target for modulating mast cell-mediated allergic and inflammatory diseases. Journal of Immunobiology 1(4), December 2016.

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.

Shenker Bruce J, Ali Hydar, Boesze-Battaglia Kathleen: PIP3 regulation as promising targeted therapy of mast-cell-mediated diseases. Current pharmaceutical design 17(34): 3815-22, Nov 2011.

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.

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Last updated: 02/14/2017
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