Hydar Ali, Ph.D.

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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
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, Pseudo-allergy, Anaphylaxis, Neurogenic Inflammation, itch and rosacea

Research Summary:

Mast cells are tissue-resident cells found close to blood vessels primarily at sites exposed to the external environment such as the skin and the respiratory tract. Although mast cells contribute to tissue homeostasis, immunomodulation and wound healing, they are perhaps best known for their roles in allergic diseases such as anaphylaxis, food allergy, rhinitis and asthma. Mast cells express high affinity receptors for IgE (FceRI) and their aggregation by antigen results in the explosive release of granules (degranulation/histamine release), generation of leukotrienes and production of proinflammatory cytokines. Currently used drugs that directly or indirectly target mast cells include omalizumab, (monoclonal anti-IgE antibody), Claritin/Zyrtec (anti-histamine), Montelukast/Zafirukast/Zileuton (leukotriene inhibitors) and epinephrine.

In addition to FceRI, mast cells exress a recently described G protein coupled receptor (GPCR), known as Mas-related GPCR-X2 (MRGPRX2). Our lab was the first to show that host defense antimicrobial peptides (HDPs) and their synthetic small molecule mimetics activate human mast cells via MRGPRX2. These peptide-mimetics could serve as novel targets for the treatment of drug-resistant fungal and bacterial infections because of their ability to harness mast cells' immunomodulatory properties. However, inappropriate activation of MRGPRX2 is associated with a number of pathologic conditions. Thus, activation of MRGPRX2 by FDA-approved peptidergic drugs leads to pseudo-allergic drug reactions. MRGPRX2 is an “atypical opioid receptor” and some of the side effects of opioids are likely mediated via mast cell degranulation through this receptor.

Emerging evidence suggests that MRGPRX2-mediated local mast cell degranulation and chemokine production by neuropeptides leads to neurogenic inflammation. Furthermore, adrenomedullin peptide 9-20 (PAMP9-20; released from keratinocytes)activates MRGPRX2 to cause allergic contact dermatitis and itch. A unique feature of mast cell is that it is the only known cell type that expresses both MRGPRX2 and FceRI. The focus of our lab is to determine mechanisms involved in the regulation and cross-regulation of MRGPRX2 and FceRI function in mast cells in vitro and to determine their impact on drug-induced pseudo-allergy, anaphylaxis, neurogenic inflammation, allergic contact dermatitis and rosacea in vivo.

Current lab members:

Saptarshi Roy, Ph.D. (Postdoctoral Researcher)
Shaswati Chaki, Ph.D. (Postdoctoral Researcher)
Vishwa Deepak Ph.D. (Postdoctoral Researcher)

Monica Thapaliya, BS (Ph.D. student/Pharmacology)
Chalatip Chompunud Na Ayudhya DDS (DScD student)
Aetas Amponnawarat, DDS (DscD student)
Bushra Alghamdi DDS, (DScD rotation student)
Maram Bawazir, DDS, (DScD rotation student)

Projects are available for interested undergraduate, dental and graduate students to study mast cell MRGPRX2/FceRI regulation in vitro and drug-induced pseudo-allergy, anaphylaxis, neurogenic inflammation, allergic contact dermatitis, itch and rosacea in vivo.

Selected Publications

Deepak, V., Komarow, H. D., Alblaihess, A. A., Carter, M. C., Metcalfe, D. D., Ali, H.: Expression of MRGPRX2 in skin mast cells of patients with maculopapular cutaneous mastocytosis. J Allergy Clin Immunol Pract 2021.

Roy, S., Chompunud Na Ayudhya, C., Thapaliya, M., Deepak, V., Ali, H.: Multifaceted MRGPRX2: New insight into the role of mast cells in health and disease. J Allergy Clin Immunol 148(2): 293-308, 2021.

Thapaliya, M., Chompunud Na Ayudhya, C., Amponnawarat, A., Roy, S., Ali, H.: Mast Cell-Specific MRGPRX2: a Key Modulator of Neuro-Immune Interaction in Allergic Diseases. Curr Allergy Asthma Rep 21(1): 3, 2021.

Babina, M., Wang, Z., Roy, S., Guhl, S., Franke, K., Artuc, M., Ali, H., Zuberbier, T.: MRGPRX2 Is the Codeine Receptor of Human Skin Mast Cells: Desensitization through beta-Arrestin and Lack of Correlation with the FcepsilonRI Pathway. J Invest Dermatol 141(5): 1286-1296 e4, 2021.

Ali, H.: Revisiting the role of MRGPRX2 on hypersensitivity reactions to neuromuscular blocking drugs. Curr Opin Immunol 72: 65-71, 2021.

Chompunud Na Ayudhya, C., Amponnawarat, A., Roy, S., Oskeritzian, C. A., Ali, H.: MRGPRX2 Activation by Rocuronium: Insights from Studies with Human Skin Mast Cells and Missense Variants. Cells 10(1), 2021.

Chompunud Na Ayudhya, C., Amponnawarat, A., Ali, H.: Substance P Serves as a Balanced Agonist for MRGPRX2 and a Single Tyrosine Residue Is Required for beta-Arrestin Recruitment and Receptor Internalization. Int J Mol Sci 22(10), 2021.

Lazki-Hagenbach, P., Ali, H., Sagi-Eisenberg, R.: Authentic and Ectopically Expressed MRGPRX2 Elicit Similar Mechanisms to Stimulate Degranulation of Mast Cells. Cells 10(2), 2021.

Amponnawarat, A., Chompunud Na Ayudhya, C., Ali, H.: Murepavadin, a Small Molecule Host Defense Peptide Mimetic, Activates Mast Cells via MRGPRX2 and MrgprB2. Front Immunol 12: 689410, 2021.

Roy, S, Gupta, K. Ganguly, A and Ali, H. : β-Arrestin-2 expressed in mast cells regulates ciprofloxacin-induced pseudo-allergy and IgE-mediated anaphylaxis. J. Allergy and Clin. Immunol. 10.1016/j.jaci.2019.04.024, May 2019.

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Last updated: 08/09/2021
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