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Matthew Garth Brewer, Ph.D.

Matthew Garth Brewer, Ph.D.

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About Me

My background in science began in 2006 when I enrolled at the Rochester Institute of Technology (RIT) and studied Biotechnology. During my undergraduate studies I focused on developing a cyclopropene backbone molecule that could be easily modified to develop derivatives that prevent crop ripening. I...
My background in science began in 2006 when I enrolled at the Rochester Institute of Technology (RIT) and studied Biotechnology. During my undergraduate studies I focused on developing a cyclopropene backbone molecule that could be easily modified to develop derivatives that prevent crop ripening. I worked on this project under Dr. Michael Coleman until my graduation in 2010.
Upon graduating from RIT, I started a technical position under Dr. Stephen Dewhurst at the University of Rochester (UoR). During that time, I investigated novel platforms for HIV vaccines. Specifically, I worked on using lambda phage to display HIV-1 envelope (Env) protein. I discovered that this delivery platform, while displaying a dense distribution of protein, was no better than soluble Env at initiating an anti-HIV immune response. I then joined the PhD program at the UoR in 2011 and continued to work under Dr. Dewhurst. I transitioned my studies from lambda phage to nanoparticle-based vaccine platforms to avoid the problems inherent to biological vectors. Through my studies on nanoparticles displaying either Env or Influenza hemagglutinin (HA) protein, I discovered that a sparse display of vaccine antigen was more efficient in stimulating an immune response. This was a truly unique finding since the general belief in the scientific community is that highly dense, multivalent vectors are the most ideal for vaccine candidates. Clearly, from my work, this was not always true. When I achieved my Masters of Science in 2014, I then began to teach (adjunct professor) at Saint John Fisher College, which I maintained up to the fall of 2021.
I finished my PhD in 2017 and then transitioned to a Postdoctoral Associate position working with Drs. Lisa Beck and Ben Miller. I utilized my knowledge on vaccine platforms and delivery to develop a new skin-based method of vaccination through targeting a microdomain (tight junctions) in the epidermis important for barrier formation. With this method I demonstrated that epicutaneous delivery of vaccine antigens was able to stimulate an immune response similar in magnitude to intramuscular administration.
In August 2021 I was promoted to Research Assistant Professor in the Department of Dermatology. My research currently focuses on continuing the epicutaneous vaccine delivery studies. Additionally, I have become intensely interested in chronic inflammatory skin diseases (such as atopic dermatitis and psoriasis) and pathogenesis studies. The reason for this is during my Postdoctoral position I was made aware that patients with inflammatory skin diseases, such as atopic dermatitis, were overly susceptible to skin infections from both bacteria and viruses. Importantly, the mechanism behind this observation is not known. I now focus on identifying how epidermal cells become infected by different pathogens (vaccinia virus, herpes simplex virus-1, S. aureus) and the affects that skin inflammation has on this process.
I am currently a member of the Society of Investigative Dermatology and serve as an ad hoc reviewer for the following journals: International Journal of Molecular Sciences, BBA-Biomembranes, Frontiers in Cellular and Infection Microbiology, and the Journal of Clinical Medicine.

Faculty Appointments

Research Assistant Professor - Department of Dermatology (SMD)

Credentials

Education

PhD | University of Rochester. Microbiology and Immunology. 2017

MS | University of Rochester. Microbiology and Immunology. 2014

BS | Rochester Institute of Technology. Biotechnology. 2010

Research

My research focuses on the intersection between chronic inflammatory skin diseases (such as atopic dermatitis and psoriasis) and the underlying immune environment during times of stimulation (such as vaccination) and disease (both viral and bacterial pathogens).
Utilizing the skin as the primary ...
My research focuses on the intersection between chronic inflammatory skin diseases (such as atopic dermatitis and psoriasis) and the underlying immune environment during times of stimulation (such as vaccination) and disease (both viral and bacterial pathogens).
Utilizing the skin as the primary site of antigen delivery represents an underappreciated practice in vaccine biology. To correct this lack of knowledge, I am working on methods enabling antigen delivery into the epidermis. My unique approach targets a microdomain in the epidermis called tight junctions, which serve as a critical source of skin barrier. I have demonstrated that disruption of tight junctions via a targeted peptide delivers influenza antigens into the skin and elicits an anti-influenza humoral response similar to intramuscular delivery. Ongoing studies include how this technology alters the cellular and inflammatory environment of the skin. Importantly, antigen type (protein, carbohydrate, lipid) and source (bacterial, viral, protozoan) can cause alterations in acquisition, processing, and presentation from different cell types of the immune system. Whether these attributes affect the efficacy of an immune response initiated in the skin are unknown and the focus of ongoing studies. Finally, drug delivery into the epidermis represents a safer route due to diminished side effects, which typically arise after systemic delivery. Unfortunately, drug delivery into the skin is usually inefficient because of the molecular characteristics of most therapeutics. Current studies using small molecule inhibitors delivered into the skin by tight junction disruption are expected to support this technique as a method to enhance cutaneous drug delivery and decrease the necessity of oral or intravenous routes.
Individuals with chronic inflammatory skin diseases have been shown to be overly susceptible to bacterial and viral infections. The underlying mechanism behind this occurrence is poorly understood. To address this gap in knowledge, my group has developed a number of models including CRISPR/Cas9 knockout cell lines, primary cell cultures from neonatal/adult skin tissue, a mouse AD model, and an adult skin explant infection platform. I focus my viral pathogenesis studies on skin-specific viruses (vaccinia and herpes simplex, respectively). In addition, I have been studying how bacterial pathogens (S. aureus, S. epidermidis, etc.) are able to invade, persist, and disseminate in the skin. These studies are expected to identify host factors or pathways in epidermal cells (i.e. keratinocytes) that are critical for protection against or susceptibility to pathogens, which would open up new druggable targets to prevent cutaneous infections.

Publications

Journal Articles

The mycobiome affects viral susceptibility of skin epithelium.

Peterson LF, Beck LA, Brewer MG

Journal de mycologie me?dicale.. 2024 September 34 (3):101499. Epub 07/09/2024.

CLDN1 knock out keratinocytes as a model to investigate multiple skin disorders.

Arnold KA, Moran MC, Shi H, van Vlijmen-Willems IMJJ, Rodijk-Olthuis D, Smits JPH, Brewer MG

Experimental dermatology.. 2024 May 33 (5):e15084. Epub 1900 01 01.

Differentiation of keratinocytes or exposure to type 2 cytokines diminishes internalization.

Morgenstern AR, Peterson LF, Arnold KA, Brewer MG

mSphere.. 2024 April 239 (4):e0068523. Epub 03/19/2024.

Electrical Impedance Spectroscopy Quantifies Skin Barrier Function in Organotypic In Vitro Epidermis Models.

van den Brink NJM, Pardow F, Meesters LD, van Vlijmen-Willems I, Rodijk-Olthuis D, Niehues H, Jansen PAM, Roelofs SH, Brewer MG, van den Bogaard EH, Smits JPH

The Journal of investigative dermatology.. 2024 April 19 Epub 04/19/2024.

virulence factors decrease epithelial barrier function and increase susceptibility to viral infection.

Moran MC, Brewer MG, Schlievert PM, Beck LA

Microbiology spectrum.. 2023 September 2211 (5):e0168423. Epub 09/22/2023.

Stage of Keratinocyte Differentiation Is a Key Determinant of Viral Susceptibility in Human Skin.

Moran MC, Chinchilli E, Kenney HM, Pope EM, Scott G, Brewer MG, Beck LA

The Journal of investigative dermatology.. 2023 September 143 (9):1838-1841.e7. Epub 03/28/2023.

JAK Signaling Is Critically Important in Cytokine-Induced Viral Susceptibility of Keratinocytes.

Arnold KA, Peterson LF, Beck LA, Brewer MG

International journal of molecular sciences.. 2023 May 2524 (11)Epub 05/25/2023.

A photonic biosensor-integrated tissue chip platform for real-time sensing of lung epithelial inflammatory markers.

Cognetti JS, Moen MT, Brewer MG, Bryan MR, Tice JD, McGrath JL, Miller BL

Lab on a chip.. 2023 January 1723 (2):239-250. Epub 01/17/2023.

Supply Chain Disruptions During COVID-19 Pandemic Uncover Differences in Keratinocyte Culture Media.

Moran MC, Pope EM, Brewer MG, Beck LA

JID innovations : skin science from molecules to population health.. 2022 November 2 (6):100151. Epub 08/22/2022.

Monkeypox: Considerations as a New Pandemic Looms.

Brewer MG, Monticelli SR, Ward BM

The Journal of investigative dermatology.. 2022 October 142 (10):2561-2564. Epub 08/24/2022.

Conditions That Simulate the Environment of Atopic Dermatitis Enhance Susceptibility of Human Keratinocytes to Vaccinia Virus.

Brewer MG, Monticelli SR, Moran MC, Miller BL, Beck LA, Ward BM

Cells.. 2022 April 1411 (8)Epub 04/14/2022.

An increase in glycoprotein concentration on extracellular virions dramatically alters vaccinia virus infectivity and pathogenesis without impacting immunogenicity.

Monticelli SR, Bryk P, Brewer MG, Aguilar HC, Norbury CC, Ward BM

PLoS pathogens.. 2021 December 17 (12):e1010177. Epub 12/28/2021.

Research Techniques Made Simple: Delivery of the CRISPR/Cas9 Components into Epidermal Cells.

Shi H, Smits JPH, van den Bogaard EH, Brewer MG

The Journal of investigative dermatology.. 2021 June 141 (6):1375-1381.e1. Epub 1900 01 01.

Characterization of Human Keratinocyte Cell Lines for Barrier Studies.

Moran MC, Pandya RP, Leffler KA, Yoshida T, Beck LA, Brewer MG

JID innovations : skin science from molecules to population health.. 2021 June 1 (2):100018. Epub 04/28/2021.

Peptides Derived from the Tight Junction Protein CLDN1 Disrupt the Skin Barrier and Promote Responsiveness to an Epicutaneous Vaccine.

Brewer MG, Anderson EA, Pandya RP, De Benedetto A, Yoshida T, Hilimire TA, Martinez-Sobrido L, Beck LA, Miller BL

The Journal of investigative dermatology.. 2020 February 140 (2):361-369.e3. Epub 08/02/2019.

Staphylococcal Virulence Factors on the Skin of Atopic Dermatitis Patients.

Moran MC, Cahill MP, Brewer MG, Yoshida T, Knowlden S, Perez-Nazario N, Schlievert PM, Beck LA

mSphere.. 2019 December 114 (6)Epub 12/11/2019.

Antagonistic Effects of IL-4 on IL-17A-Mediated Enhancement of Epidermal Tight Junction Function.

Brewer MG, Yoshida T, Kuo FI, Fridy S, Beck LA, De Benedetto A

International journal of molecular sciences.. 2019 August 2120 (17)Epub 08/21/2019.

Vaccinia Virus Phospholipase Protein F13 Promotes Rapid Entry of Extracellular Virions into Cells.

Bryk P, Brewer MG, Ward BM

Journal of virology.. 2018 June 192 (11)Epub 05/14/2018.

Display of the HIV envelope protein at the yeast cell surface for immunogen development.

Mathew E, Zhu H, Connelly SM, Sullivan MA, Brewer MG, Piepenbrink MS, Kobie JJ, Dewhurst S, Dumont ME

PloS one.. 2018 13 (10):e0205756. Epub 10/18/2018.

Nanoparticles decorated with viral antigens are more immunogenic at low surface density.

Brewer MG, DiPiazza A, Acklin J, Feng C, Sant AJ, Dewhurst S

Vaccine.. 2017 February 135 (5):774-781. Epub 01/03/2017.

Display of HIV-1 Envelope Protein on Lambda Phage Scaffold as a Vaccine Platform.

Mattiacio JL, Brewer M, Dewhurst S

Methods in molecular biology.. 2017 1581 :245-253. Epub 1900 01 01.

Use of bacteriophage particles displaying influenza virus hemagglutinin for the detection of hemagglutination-inhibition antibodies.

Domm W, Brewer M, Baker SF, Feng C, Martínez-Sobrido L, Treanor J, Dewhurst S

Journal of virological methods.. 2014 March 197 :47-50. Epub 12/06/2013.

9G4+ antibodies isolated from HIV-infected patients neutralize HIV-1 and have distinct autoreactivity profiles.

Alcéna DC, Kobie JJ, Kaminski DA, Rosenberg AF, Mattiacio JL, Brewer M, Dewhurst S, Dykes C, Jin X, Keefer MC, Sanz I

PloS one.. 2013 8 (12):e85098. Epub 12/26/2013.

Highly selective synthesis of tetra-substituted furans and cyclopropenes: copper(I)-catalyzed formal cycloadditions of internal aryl alkynes and diazoacetates.

Swenson AK, Higgins KE, Brewer MG, Brennessel WW, Coleman MG

Organic & biomolecular chemistry.. 2012 October 710 (37):7483-6. Epub 08/17/2012.

9G4 autoreactivity is increased in HIV-infected patients and correlates with HIV broadly neutralizing serum activity.

Kobie JJ, Alcena DC, Zheng B, Bryk P, Mattiacio JL, Brewer M, Labranche C, Young FM, Dewhurst S, Montefiori DC, Rosenberg AF, Feng C, Jin X, Keefer MC, Sanz I

PloS one.. 2012 7 (4):e35356. Epub 04/18/2012.

Dense display of HIV-1 envelope spikes on the lambda phage scaffold does not result in the generation of improved antibody responses to HIV-1 Env.

Mattiacio J, Walter S, Brewer M, Domm W, Friedman AE, Dewhurst S

Vaccine.. 2011 March 2129 (14):2637-47. Epub 02/18/2011.