Associate Professor

Office:    Jones Building Room 113
Phone:   860-486-1814
Email:    clinton.mathias@uconn.edu
Lab Website: https://mathiaslab.nusc.uconn.edu/

Mast cells are heterogeneous cells present throughout vascularized tissues and close to surface areas such as the skin, intestine, and airways where they are well-positioned as sentinel cells against invading pathogens. While the role of mast cells in promoting IgE-mediated immune responses has been well established, novel roles for mast cells in both host defense as well as a number of other diseases are now being uncovered, suggesting that mast cells can confer distinct immune responses by virtue of their inherent plasticity and depending on the immune microenvironment.

Dr. Mathias’ research interests follow two main directions: 1) further exploring the mechanisms that govern mast cell homeostasis and function during allergic responses; and 2) uncovering the dynamics of mast cell interactions with other immune cells. More specifically, we have been interested in studying various factors that can modulate mast cell homeostasis and behavior, with a particular emphasis on the role of diet and nutritional components, the effects of epigenetic modifications, and the role of immunomodulatory factors such as microbiota and cytokines. Recently published papers demonstrate the effects of dietary antigens as well as a novel role for the cytokine IL-10 in modulating IgE-mediated mast cell activation and function during food allergy. We are interested in further quantifying the variables that modulate mast cell function during diverse immune responses at both the single cell, genomic, and epigenetic levels. It is hoped that a better understanding of these processes would lead to further insight into how mast cells are modulated and better approaches to fine-tune their function therapeutically. Current projects in the lab are aimed at further exploring the role played by cytokines such as IL-10 as well as diet in modulating mast cell responses during both IgE-dependent and independent responses in the airway and the gut. These include the role of IL-10 as a mast cell growth factor and its regulation by diet, the effects of diet on epigenetic modifications and protein disulfide isomerases in mast cells, and the interplay between IL-10 and other cytokines such as IL-33 in regulating mast cell function.

Research Support

• • Principal Investigator, RO1, National Institutes of Health, 2022-2027: Differential regulation of mast cell-mediated allergic responses by IL-10.
  • Principal Investigator, R15 AREA Award, National Institutes of Health, 2014-2019: Inhibitory Effects of Curcumin on Th2 sensitization and mast cell function in a mouse model of food allergy.
  • Principal Investigator, Bridge Funding, Western New England University, 2019-2010: Effects of IL-10 on IL-33-mediated mast cell responses.
  • Co-investigator: RUI Award, National Science Foundation, 2015-2018: Effects of vision loss on astrocyte maturation and oligodendrocyte myelination via BDNF-associated mechanisms in the visual cortex.

PROFESSIONAL SERVICE

Professional Service

• • 2012-2018: Director, High School Teachers Summer Research Program, American Association of
    Immunologists (AAI)
  • 2012-2017: Member, Education Committee, AAI

Peer-review Activities

• • Grant Reviewer, Dutch Research Council
  • Grant Reviewer, NIH Study Section, Asthma and Allergic Diseases Cooperative Research Centers Special Emphasis Panel
  • Associate Editor, Nutritional Immunology, Frontiers in Immunology
  • Grant Reviewer, NIH Study Section, Maternal-Fetal Immunity, Special Emphasis Panel
  • Topic Editor, Frontiers in Immunology: Insights into the Mechanisms underlying the Pathogenesis, Regulation, Prevention and Treatment of Allergic Disease
  • Grant Reviewer, Asthma UK Grants
  • Grant Reviewer, New Investigator Award, American Association of Colleges of Pharmacy
  • Textbook Reviewer, Oxford University Press, Immunology by Stephen Juris
  • Ad-hoc reviewer: Journal of Immunology, Trends in Immunology, Clinical and Experimental Allergy, Medical Microbiology and Immunology, Frontiers in Immunology, PLoS One Journals, Nature Scientific Reports, Clinical and Experimental Immunology, Respiratory Research, American Journal of Pharmaceutical Education, Nutrients

AWARDS & HONORS

• • AAI Laboratory Travel Grant, American Association of Immunologists, 2022
  • AAI Distinguished Service Award, American Association of Immunologists, 2019
  • Professor of the Year nomination, 2019 and 2022, Western New England University College of Pharmacy and Health Sciences
  • Excellence in Scholarship Award, 2019, Western New England University College of Pharmacy and Health Sciences
  • AACP Excellence in Innovative Research Award, Eastern Colleges Science Conference, 2016
  • Undergraduate Faculty Travel Grant 2016, 2014, and 2013, American Association of Immunologists
  • Excellence in Service Award, 2016, Western New England University College of Pharmacy
  • Professor of the Year Award, 2014, Western New England University College of Pharmacy
  • Excellence in Scholarship Award, 2013, Western New England University College of Pharmacy

PATENTS

• • Mathias CB: Thiol isomerase inhibitors for the treatment and prevention of food allergies, Western New England University

EDITORIAL ACTIVITIES

Textbook

• • Mathias, McAleer, and Szollosi: Pharmacology of Immunotherapeutic Drugs, Springer Nature Publishing Company; Website: https://www.springer.com/us/book/9783030199210#aboutBook

Book Chapters

(corresponding author denoted by asterisk)

• • Mathias CB*. Chapter 1: Overview of the Immune System and its Pharmacological Targets; Pharmacology of Immunotherapeutic Drugs. Edited by Mathias, McAleer, and Szollosi; Springer Nature
  • Szollosi D and Mathias CB. Chapter 2: Modulation of the Innate Immune System; Pharmacology of Immunotherapeutic Drugs. Edited by Mathias, McAleer, and Szollosi; Springer Nature.
  • Szollosi D, Mathias CB, and McAleer J. Chapter 3: Modulation of the Adaptive Immune System; Pharmacology of Immunotherapeutic Drugs. Edited by Mathias, McAleer, and Szollosi; Springer Nature.
  • Mathias CB*. Chapter 4: Respiratory Disorders of the Immune System and its Pharmacological Targets; Pharmacology of Immunotherapeutic Drugs. Edited by Mathias, McAleer, and Szollosi; Springer Nature.
  • Mathias CB*. Chapter 5: Inflammation of the Skin and its Therapeutic Targets; Pharmacology of Immunotherapeutic Drugs. Edited by Mathias, McAleer, and Szollosi; Springer Nature.
  • Mathias CB*, McAleer J, and Szollosi D. Chapter 6: Inflammatory Diseases of the Gastrointestinal Tract and Pharmacological Treatments; Pharmacology of Immunotherapeutic Drugs. Edited by Mathias, McAleer, and Szollosi; Springer Nature.
  • Mathias CB* and McAleer J. Chapter 8: Transplantation: Immunologic Principles and Pharmacologic Agents; Pharmacology of Immunotherapeutic Drugs. Edited by Mathias, McAleer, and Szollosi; Springer Nature.
  • Szollosi D, Mathias CB, Lucero V, Ahmad S, Donato J. Chapter 9: Immunopathogenesis, Immunization, and Treatment of Infectious Diseases; Pharmacology of Immunotherapeutic Drugs. Edited by Mathias, McAleer, and Szollosi; Springer Nature.

Research Topics

• • Frontiers in Immunology: Insights into the Mechanisms underlying the Pathogenesis, Regulation, Prevention and Treatment of Allergic Disease; Website: https://www.frontiersin.org/researchtopics/7958/insights-into-the-mechanisms-underlying-the-pathogenesis-regulation-prevention-andtreatment-of-alle

SELECTED PUBLICATIONS

• • Krajewski D, Polukort SH, GelzinisJ, RovattiJ, Kaczenski E, Galinski C, Pantos M, Shah NN, Schneider SS, Kennedy DR and Mathias CB. Protein disulfide isomerases regulate IgEmediated mast cell responses and their inhibition confers protective effects during food allergy development. Frontiers in Immunology 2020. doi: 10.3389/fimmu.2020.606837
  • Murphy MT, Qin X, Kaul S, Barrientos G, Zou Z, Mathias CB, Thomas D, Bose DD. The Polyphenol Ellagic Acid Exerts Anti-Inflammatory Actions via Disruption of Store-Operated Calcium Entry (SOCE) Pathway Activators and Coupling Mediators. Eur J Pharmacol. 2020 May 15;875:173036. doi: 10.1016/j.ejphar.2020.173036. Epub 2020 Feb 23.
  • Krajewski D, Kaczenski E, Rovatti J, Polukort S, Thompson C, Dollard C, Ser-Dolansky J, Schneider SS, Kinney SRM, Mathias CB. Epigenetic Regulation via Altered Histone Acetylation Results in Suppression of Mast Cell Function and Mast Cell-Mediated Food Allergic Responses. Front Immunol. 2018 Oct 23;9:2414.
  • Thangam EB, Jemima AE, Singh H, Bag MS, Khan M, Mathias CB, Church MK and Saluja R. The role of histamine and histamine receptors in mast cell-mediated allergy and inflammation: the hunt for new therapeutic targets. Front. Immunol. 2018 Aug 13;9:1873.
  • Poddighe D, Mathias CB, Brambilla I, Marseglia GL, Oettgen HC. Importance of basophils in eosinophilic asthma: the murine counterpart. J Biol Regul Homeost Agents. 2018 MarApr;32(2):335-339.
  • Mathias CB, Schramm CM, Guernsey LA, Wu CA, Polukort SH, Rovatti J, Ser-Dolansky J, Secor E, Schneider SS, Thrall RS, Aguila HL. IL-15-deficient mice develop enhanced allergic responses to airway allergen exposure. 2017. Clinical and Experimental Allergy. Jan 17. doi: 10.1111/cea.12886.
  • Polukort SH, Rovatti J, Carlson L, Thompson C, Ser-Dolansky J, Kinney SRM, Schneider SS and Mathias CB. IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10–Deficient Mice. 2016. Journal of Immunology; published ahead of print May 6, 2016, doi:10.4049/jimmunol.1600066
  • Kinney S, Carlson L, Ser-Dolansky J, Shah S, Gambrah G, Thompson C, Xing W, Schneider SS and Mathias CB. Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy. 2015. PLoS One. Jul 6;10(7):e0132467.
  • Mathias CB. A Learner-Led, Discussion-based Elective on Emerging Infectious Disease. 2015. American Journal of Pharmaceutical Education. Volume 79, Issue 6, Article 81.
  • Mathias CB. Natural killer cells in the development of asthma. 2015. Curr Allergy Asthma Rep. Feb;15(2):500.
  • Mathias CB, Guernsey LA, Zammit D, Brammer C, Wu CA, Thrall RS, Aguila HL. Proinflammatory role of natural killer cells in allergic airway disease. 2014. Clinical and Experimental Allergy. 44(4):58 the role of IL-10 as a mast cell growth factor and its regulation by diet 9-601.
  • Poddighe D, Mathias CB, Freyschmidt EJ, Kombe D, Caplan B, Marseglia GL, Oettgen HC. Basophils are rapidly mobilized following initial aeroallergen encounter in naïve mice and provide a priming source of IL-4 in adaptive immune responses. 2014. Journal of Biological Regulators and Homeostatic Agents. 28(1):91-103.
  • Mathias CB, Hobson SA, Garcia-Lloret M, Lawson G, Poddighe D, Freyschmidt EJ, Xing W, Gurish MF, Chatila TA, Oettgen HC. IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling.2011. J Allergy Clin Immunol. Mar;127(3):795-805.
  • Freyschmidt EJ, Mathias CB, Diaz N, MacArthur DH, Laouar A, Manjunath N, Hofer MD, Wurbel MA, Campbell JJ, Chatila TA, Oettgen HC. Skin inflammation arising from cutaneous regulatory T cell deficiency leads to impaired viral immune responses.2010. Journal of Immunology. Jul 15;185(2):1295-302. Epub 2010 Jun 14.
  • Tachdjian R, Mathias CB, Al Khatib S, Bryce PJ, Kim HS, Blaeser F, O’Connor BD, Rzymkiewicz D, Chen A, Holtzman MJ, Hershey GK, Garn H, Harb H, Renz H, Oettgen HC, Chatila TA. Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma. 2009. Journal of Experimental Medicine. 206(10):2191-204. Epub 2009 Sep 21.
  • Tachdjian R, Al Khatib S, Schwingshackl A, Kim HS, Chen A , Mathias CB, Kim HY, Umetsu D, Oettgen HC and Chatila TA. In vivo Regulation of the Allergic Response by the Interleukin 4 Receptor Alpha Chain Immunoreceptor Tyrosine-based Inhibitory Motif. 2009. Journal of Allergy and Clinical Immunology. 125(5):1128-1136.e8. Epub 2010 Apr 14.
  • Jin H, Oyoshi MK, Le Y, Bianchi T, Koduru S, Mathias CB, Kumar L, Le Bras S, Young D, Collins M, Grusby MJ, Wenzel J, Bieber T, Boes M, Silberstein LE, Oettgen HC, Geha RS. IL21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice. 2009. Journal of Clinical Investigation. 119(1):47-60.
  • Jin H, Kumar L, Mathias CB, Oettgen HC, Gorelik L and Geha RS. Toll-like receptor 2 is important for the Th1 response to epicutaneous sensitization. 2009. Journal of Allergy and Clinical Immunology. 123(4):875-882.
  • Mathias CB, Freyschmidt EJ and Oettgen HC. IgE antibodies enhance pulmonary inflammation induced by inhalation of a chemical hapten. 2009. Clinical and Experimental Allergy. 39(3):417-25.
  • Mathias CB, Freyschmidt EJ, Caplan B, Jones T, Poddighe D, Xing W, Harrison KL, Gurish MF, Oettgen HC. IgE influences the number and function of mature mast cells but not progenitor recruitment in allergic pulmonary inflammation. 2009. Journal of Immunology. 182(4):2416-24.
  • Freyschmidt EJ, Mathias CB, MacArthur DH, Laouar A, Narasimhaswamy M, Weih F, and Oettgen HC. Skin inflammation in RelB-/- mice leads to defective immunity and impaired clearance of vaccinia virus. 2007. Journal of Allergy and Clinical Immunology .19(3):671-9.
  • Bryce PJ, Mathias CB, Harrison KL, Watanabe T, Geha RS and Oettgen HC. The H1 histamine receptor regulates allergic lung responses. 2006. Journal of Clinical Investigation. 116(6):1624-32.
  • Mehrotra S, Chhabra A, Chakraborty A, Chattopadhyay S, Slowik M, Stevens R, Zengou R, Mathias C, Butterfield LH, Dorsky DI, Economou JS, Mukherji B, Chakraborty NG. Antigen presentation by MART-1 adenovirus-transduced interleukin-10-polarized human monocytederived dendritic cells. 2004. Immunology. 113(4):472-81.