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, 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)

Ibrahim Alkanfari DDS (DScD student)
Chalatip Chompunud Na Ayudhya DDS (DScD student)
Monica Thapaliya, BS (Ph.D. student/Pharmacology)
Abdulaziz Alblaihess, DDS (MSoB student)


Anirban Ganguly BS. (Research Specialist)
Anwar Hossain MB.BS (Volunteer)
Sayeda Humaira MB.BS. (Volunteer)

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.

Selected Publications

Subramanian, H., Gupta, K., Quo, Q., Price, R., and Ali, H : MAS-Related gene X2 (MrgX2) as a novel Receptor for the antimicrobial Peptide, LL-37: Resistance to Receptor Phosphorylation, Desensitization and Internalization J. Biol. Chem. 286: 44739 - 44749, 2011.

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.

Alkanfari, I, Freeman, K., Roy, S, Jahan, T, Scot, RW and Ali, H: Small molecule host defense peptide mimetics activate human and mouse mast cells via Mas-related GPCRs. Cells 8(311. ): pii E311, April 2019.

Ali, H: Emerging Roles for MAS-Related G Protein-Coupled Receptor-X2 in Host Defense Peptide, Opioid, and Neuropeptide-Mediated Inflammatory Reactions. Advances in Immunology. Arun Shukla (eds.). Elsevier, 136: 123-162, September 2017.

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.

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.

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

Manorak, W., Idahosa, C., Gupta,K., Roy, S., Panettieri Jr, R and Ali, H: Upregulation of Mas-related G Protein coupled receptor X2 in asthmatic lung mast cells and its activation by the novel neuropeptide hemokinin-1 Respiratory Research 19(1): doi: 10.1186/s12931-017-0698-3. January 2018.

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Last updated: 06/27/2019
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