Investigating the role of cell adhesion molecule 1 and focal adhesion kinase in mast cell-sensory neuron interactions to drive IGE mediated anaphylaxis

Active Project Grant Awarded Last action

Award ID
F31AI197258
Recipient
Awarding agency
Obligated
$87,370

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 1% complete
Originally
Place of performance
Ann Arbor, MI 48109, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Nearly 11% of the adult US population have a food allergy, resulting in 200,000 emergency room visits a year from anaphylaxis. Anaphylaxis is a rapid allergic reaction caused by allergen crosslinking of the fcεri receptor on mast cells, leading to mast cell degranulation. Recent studies have demonstrated the importance of mast cell-neuron interactions in phenomena ranging from itch to allergen avoidance behavior and anaphylaxis-related temperature drop. This F31 proposal seeks to identify a role for mast cell-sensory neuron (MC-SN) interactions in the systemic spread and rapid speed of anaphylaxis. Two moieties of interest are cell adhesion molecule-1 (CADM1), as a binding partner between mast cells and neurons, and focal adhesion kinase (FAK) as a regulator of mast cell degranulation. Mast cell adhesion to sensory neurons requires CADM1 and enhances mast cell degranulation, while inhibition of FAK, the initiator of focal adhesion complexes, decreases degranulation. Preliminary data from our group suggest that the use of a FAK inhibitor is sufficient to block anaphylaxis in mice and validates the expression of CADM1 on both sensory neurons and mast cells. This data indicates a role for both molecules in MC-SN communication that assists the propagation of IGE-mediated anaphylaxis this proposal will test the hypothesis that the formation of a MC-SN "synapse" via CADM1 binding propagates anaphylaxis through FAK-mediated activation. This hypothesis will be tested through two specific aims: 1) determine CADM1'S role in MC-neuron binding during the sensitization phase prior to anaphylaxis and 2) define the role of FAK and sensory neurons in the effector phase of IGE mediated anaphylaxis. To accomplish these aims, in vitro CO-cultures and in vivo engineered mouse models will be used to study cell-cell interactions and anaphylaxis reactions with manipulation of FAK and CADM1. The results of these studies will further elucidate the mechanisms behind anaphylaxis propagation and the role of mast cells as a sensing extension of the nervous system in allergic diseases. Better understanding of the pathophysiology behind anaphylaxis will allow for the development of more effective treatments and repurposing of already existing drugs. The experimental design for this research project was independently created. All research will be conducted in the lab of DR. Charles schuler at the university of michigan. Support will be provided by other senior lab members, core facilities, and collaborators in the neuroscience and bioinformatics department. Bioinformatic courses and career development seminars will be provided by the program in biomedical sciences and office of graduate and postdoctoral studies. A dissertation committee has been formed and will meet twice each year to assess and guide research and career development progress.

Transactions

Action Obligated Date
Amendment $43,685
Amendment $0
Original award $43,685

Quick answers

Who received award F31AI197258?

F31AI197258 was awarded to Regents Of The University Of Michigan by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on October 23, 2026.

How much is award F31AI197258 worth?

$87,370 has been obligated on F31AI197258.

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