Dr. Adriana Larregina is a Professor with tenure of Dermatology and Immunology at the University of Pittsburgh School of Medicine and she is also a faculty member of the Graduate Program in Immunology and Microbiology (IMM).

Dr. Larregina earned her medical degree at National University of La Plata in Buenos Aires, Argentina, where she graduated magna cum laude. Following, she completed a four-year residency in pathology at the Center of Medical Education and Clinical Investigation (CEMIC) University of Buenos Aires, and she was chief resident during the four years. She then completed a fellowship in pediatric pathology and was an attending in surgical pathology. Dr. Larregina earned her PhD in Immunology at the University of Buenos Aires School of Medicine, a degree that she obtained summa cum laude. Following, Dr. Larregina completed a postdoctoral research fellowship in gene therapy at the Molecular Medicine Unit, Department of Medicine of the Victoria University of Manchester (UK). Upon completion of her postdoctoral fellowship, she accepted a position of Visiting Research Instructor in the Department of Dermatology School of Medicine at the University of Pittsburgh in 1998. During the following years, she secured funding through several grants to support her research and was promoted to Assistant Professor in tenure stream, Associate Professor with Tenure, and Professor of Dermatology. In 2003 she joined the Department of Immunology that had been recently established, and in 2009, Dr. Larregina joined the McGowan Institute for Regenerative Medicine.

Research interests:

Cutaneous immunology. Role of cutaneous neuroinflammation. Study of the relevance of pro-inflammatory neuropeptides as stimulators of dendritic cell, mast cell and T cell immune function. Use of antagonists of the pro-inflammatory neurokinin-1 receptor for the prevention and treatment of skin inflammatory and autoimmune diseases. Study of cell-cell communication via extracellular vesicles.

Specific Research Projects

Study of the relevance of pro-inflammatory neuropeptides released in the skin [i.e. substance P (SP)] and hemokinin-1 (HK-1) to promote immunostimulatory function of mouse and human dendritic cells generated ex-vivo.  This project evaluates the relevance and the mechanism involved in the immune-stimulatory functions of SP signaling via the neurokinin 1 receptor (NK1R) to promote skin inflammation and autoimmunity.

Development of negative immunizations using CMC microneedles arrays (MNAs).  The purpose of the research project is to use a novel method using self-dissolvable MNAs to deliver efficiently biologics in the skin microenvironment to engineer cutaneous neuroimmune networks for the treatment of skin chronic inflammatory diseases.

Relevance of signaling the NK1R in specific skin cells in the context of cell-cell communication via extracellular vesicles.

Recent relevant publications from Dr. Larregina’s laboratory

Montecalvo A, Larregina AT (First Co-author), Shufesky WJ, Beer Stolz D, Sullivan ML, Karlsson JM, Baty CJ, Gibson GA, Erdos G, Wang Z, Milosevic J, Tkacheva OA, Divito SJ, Jordan R, Lyons- Weiler J, Watkins SC, and Morelli AE. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood. 119: 756-766, 2012.

Janelsins BM, Sumpter TL, Tkacheva OA, Erdos G, Mathers AR, Shufesky WJ, Storkus WJ, Falo LD Jr., Morelli AE, and Larregina AT (Corresponding author). Neurokinin-1 receptor agonists bias therapeutic dendritic cells to induce type-1 immunity by licensing host dendritic cells to produce IL- 12. Blood. 121: 2923-2933, 2013.

Sumpter TL, Ho CH, Pleet A, Tkacheva OA, Shufesky WJ, Rojas-Canales DM, Morelli AE, and  Larregina AT (Corresponding author). Autocrine hemokinin-1 functions as endogenous adjuvant for IgE-mediated mast cell inflammatory responses. J Allergy Clin Immunol. 135: 1019-1030, 2015.

Divito SJ and Morelli AE Larregina AT (Corresponding author). Nociceptive neurons as targets to control immunity: Potential relevance for transplantation. Am J Transplant. 15: 1472-1474, 2015.

Liu Q, Rojas-Canales DM, Divito SJ, Shufesky WJ, Stolz DB, Erdos G, Sullivan ML, Gibson GA, Watkins SC, Larregina AT, and Morelli AE. Donor dendritic cell-derived exosomes promote allograft-targeting immune response. J Clin Invest. 126: 2805-2820. 2016.

Li G, Larregina AT, Domsic RT, Stolz DB, Medsger TA Jr, Lafyatis R, Fuschiotti P. Skin-Resident Effector Memory CD8+CD28- T Cells Exhibit a Profibrotic Phenotype in Patients with Systemic Sclerosis. J Invest Dermatol. 2017: 137:1042-1050.

Friedrich AD, Campo VA, Cela EM, Morelli AE, Shufesky WJ, Tckacheva OA. Leoni J, Paz M, Larregina AT, and Daniel H. González Maglio. (Larregina AT last Co-autor). Oral administration of Lipoteichoic acid from Lactobacillus rhamnosus GG overcomes UVB-induced immunosuppression and impairs skin tumor growth in mice. Eur. J Immunol. 49:2095-2102. 2019.

Chen Z, Larregina AT, Morelli AE. Impact of extracellular vesicles on innate immunity. Curr Opin Organ Transplant. 24:670-678. 2019.

Morelli AE, Sumpter TL, Rojas-Canales, DM, Bandyopadhyay M, Chen Z, Tkacheva O, Shufesky WJ, Wallace C, Watkins SC, Berger A, Paige CJ, Falo Jr. LD and Larregina, AT (Corresponding author). Neurokinin-1 receptor signaling is required for efficient Ca flux in TCR-activated T cells. Cell Rep. 10:3448-3465.e8. doi:10.1016/j.celrep.2020.02.054.PMID: 32160549. 2020.

Bandyopadhyay M, Larregina AT (Corresponding author). Keratinocyte-Polyamines and Dendritic Cells: A Bad Duet for Psoriasis. Immunity. 53:16-18. 2020.

Zeng F, Chen Z,  Rao C, Shufesky WJ, Bandyopadhyay M, Camirand G, Oberbarnscheidt G, Mara Sullivan M, Baty C, Yang M, Calderon M, Beer Stolz D, Geza E, Pelanda R, Todd VB, Catz SD, Watkins SC, Larregina AT (Co-Corresponding author)  and Morelli AE. Graft-derived extracellular vesicles transported across subcapsular sinus macrophages elicit B-cell allo-immunity after transplantation. Sci. Transl. Med. 17 Mar 2021: Vol. 13, Issue 585, eabb0122).

Bandyopadhyay M, Morelli AE, Balmert SC, Ward NL, Erdos G, Korkmaz E, Sumpter TL, Kaplan DH, Oberbarnscheidt M, Tkacheva O, Shufesky WJ, Falo Jr. LD, and Larregina AT.  Skin co-delivery of hapten and neurokinin1 receptor antagonists by microneedle arrays suppresses neurogenic inflammation and contact dermatitis. J Allergy Clin Immunol. Advanced on line publication Jan 29, 2022.

View Dr. Larregina’s complete list of publications in MyBibliography.

Funding

Current

NIH/NIAID 5R01AI148690-02 (PI: Morelli). Title: Placental Extracellular Vesicles as Regulators of Maternal Adaptive Immunity. Role: Co-Investigator. Years inclusive: 7/1/2020 – 6/30/2024.

Pending

NIH/NIAID. 1R01AI168142-01A1. Title: Role of neurokinin 1 receptor in keratinocytes in allergic contact dermatitis. Role: Principal Investigator. Years inclusive: 2022-2027. This grant was in the percentile 3 following scientific review.

NIH/NIAID. 1R01AI174273-01. Title: Graft extracellular vesicles as promoters of anti-donor immunity in cardiac and skin transplantation. Morelli AE (PI). Role: Co-Investigator. Years inclusive: 2022-2027. This grant was in the percentile 3 following scientific review.

Recently Completed

NIH/NIAMS. R01AR071277 Title: MNA Delivery of Neurokinin 1 Receptor Antagonists to Treat Atopic Dermatitis. This grant explores the possibility of manipulating the skin microenvironment to treat atopic dermatitis. Role: Co-Principal Investigator. Years inclusive: 7/1/2017 – 6/30/2022.

NIH/NIAMS. R01AR068249.  Title: Manipulating Cutaneous Neuroimmunity to Treat Contact Dermatitis. This grant explores the biology of skin resident T cell expressing neuropeptide receptors and the possibility of eliminating skin memory Th1 and Tc1 lymphocytes that have survived immune contraction and cause contact dermatitis. Role: Co-Principal Investigator. Years inclusive: 7/1/2015 – 6/30/2020.

NIH/NIHL. R01HL130191-01 (PI: A. Morelli). Title: Exosomes as paracrine signal mediators in cardiac allograft rejection. We propose to test the hypothesis that after heart transplantation, donor exosomes (and other extracellular vesicles) function as paracrine mediators for passage and dissemination of donor MHC Ag and APC-stimulating signals to recipient APCs. Role: Co-Investigator. Years inclusive: 2/8/2016 – 01/31/2020.

View Dr. Larregina’s complete list of publications in MyBibliography.