Jonelle Mattiacio

Dr. Mattiacio has been at Fisher since 2014 and is involved in teaching a variety of courses to first-year, sophomore, junior, and senior students beginning with General Biology I during the fall semester for first-year students and culminating in elective coursework in Microbiology and Virology for Biology majors. She is also involved in the Microbes and Disease course for nursing majors. When not in the classroom, she is in the lab teaching students how to study and manipulate viruses. Her research interests lie in understanding virus-host interactions using influenza as a model RNA virus, isolating and characterizing bacteriophage, and investigating the use of bacteriophage therapy to treat multi-drug resistant bacterial infections.

Teaching

• BIOL 151 - General Biology I w/ lab
• BIOL 107L - Microbes and Disease
• BIOL 298 - Introduction to Research
• BIOL330 - Advanced Cell
• BIOL 333 - Microbiology
• BIOL 333L - Microbiology lab
• BIOL 412 - Virology

Research

Viruses are complex pathogens that are responsible for many devastating human diseases. Each year in the US, influenza or “flu” kills more than 36,000 people and hospitalizes 200,000 more. Along with the annual seasonal epidemics, influenza is also responsible for occasional lethal global pandemics, such as those of 1918, 1957, 1968, and the most recent 2009 (swine-origin H1N1). Even though we currently have an effective seasonal influenza vaccine, continued research on influenza biology is essential to find better ways to prevent, diagnose, and treat both seasonal and pandemic influenza.

Viruses are obligate intracellular parasites and therefore depend exclusively on host cellular machinery to replicate. Host cells in turn develop multi-layered antiviral mechanisms to control or prevent viral infection. Studying virus-host interactions is therefore essential for developing more effective virus control strategies. The focus of Dr. Mattiacio’s research is to study influenza-host interactions particularly involving the viral polymerase complex. The viral polymerase complex (3P) consisting of three proteins (PB1, PB2, PA), is responsible for viral mRNA transcription & replication of the viral genome. It is also known to play an important role in viral pathogenesis & host adaptation. The 3P complex assembles in the host cell nucleus, where transcription and replication occur. Several events must occur inside the host cell in order to support viral replication and these events require the viral RNA polymerase to interact with numerous host cell factors, many of which have yet to be identified. In the Mattiacio laboratory, students utilize basic molecular biology techniques (such as PCR, DNA preparation and analysis, gene cloning, protein expression and analysis), mammalian cell culture and luciferase reporter gene assays to investigate these interactions.

Current projects ongoing in the Mattiacio lab:

1. Investigation into the interaction between influenza virus polymerase subunit, PA, and host factor AIFM1.

Previous studies have shown that the RNA virus’ heterotrimeric polymerase interacts with host proteins including apoptosis inducing factor, AIFM1, a flavoprotein critical in initiating apoptosis. However, little is known about the mechanism or purpose for this interaction. Localizing the site of interaction between AIFM1 and influenza polymerase may shed light on these questions. AIFM1 is a protein endogenous to the mitochondria but is known to translocate to the nucleus upon induction of apoptosis. The localization of this interaction is being investigated through cell fractionation and coimmunoprecipitation of mitochondrial and cytosolic fractions for the proteins of interest. We are also looking into immunofluorescence to visualize the localization of the interaction in cells.

2. Investigating the phytochemical constituents of Kalanchoe plant species for anti-viral properties

Although a vaccine for influenza exists, the virus’ ability to reassort its surface proteins poses strains that are unpredictable and resistant to annual vaccination. These viral infections may be treated with antivirals, however, many of these drugs are both expensive and can be cytotoxic. We also witness a significant number of strains that have drug resistant. For these reasons, the development of new, safe, and effective antiviral drugs is important. Kalanchoe brasiliensis and Kalanchoe daigremontiana are medicinal plants of the Crassulaceae family that are commonly used in folk medicine to treat inflammation and infection. Extracts from these plants have successfully shown antiviral activity against Enterovirus 71 and Coxsackievirus A16 in vitro. A similar study is being performed to test extracts of K. daigremontiana at varying concentrations for antiviral activity against influenza A virus in Madin-Darby Kidney Cells (MDCK). Cell viability post infection is being measured using an MTT assay to measure cellular metabolic activity. This project is also helping provide a system for testing anti-viral activity against influenza from a variety of samples in addition to plant extracts.

3. Investigation into the disruption of bacterial biofilms using bacteriophage and quorum sensing inhibitors.

The spread of antibiotic-resistant bacteria threatens all aspects of modern medicine, including advances in the treatment of infectious disease. Due to the rise in antibiotic resistance, new treatment options need to be developed and used to combat bacterial infections. A worrying trend is the spread of multidrug-resistant (MDR) bacteria that show resistance to several classes of antibiotics. Of MDR bacteria, Pseudomonas aeruginosa is a nosocomial opportunistic pathogen associated with pneumonia, bacteremia, and urinary tract infections. One of the possible alternatives includes bacteriophage therapy, a treatment that involves the use of bacterial viruses (phage) that infect and lyse the bacteria to cure or prevent infectious disease. There are numerous benefits to phage therapy, one being that bacteriophages are extremely species specific, often only infecting a single bacterial species. One issue with using bacteriophages to treat nosocomial chronic illnesses, like those caused by P. aeruginosa is that the bacteriophages are unable to get past the extracellular layer of the biofilm that these pathogens are known to form. This project focuses on an antibacterial cocktail consisting of bacteriophage and quorum sensing inhibitor (QSI) to interfere with the bacterial communication allowing the bacteriophage access to the biofilm and potential lysis of the pathogen. We have isolated P. aeruginosa (PAO1 and PA14 strains) phage and are using them along with different quorum sensing chemicals, to find an optimal combination of the two that may prove to be a novel treatment mechanism. A second issue with phage therapy, is a clear understanding of the effects of bacteriophage on the human host immune response. We, therefore, also plan to gain a better understanding of the effects of bacteriophage therapy on the human immune response in cell culture.

Publications

• Lifespan extending properties of Kalanchoe diagremontiana plant extracts in S. cerevisiae, BIOS, July 2022. Co-authored with O. Marziale, X* Somoulay, A. Sridhar, M. Herman, and J. Millen.
• ERBB2 signaling drives supporting cell proliferation in vitro and apparent supernumerary hair cell formation in vivo in the neonatal mouse cochlea, Eur J Neurosci, 2018. Co-authored with J. Zhang, Q. Wang, D. Abdul-Aziz, ASB Edge, PM, White.
  Display of HIV-1 Envelope Protein on Lambda Phage Scaffold as a Vaccine Platform, Methods Molecular Biology, Recombinant Virus Vaccines, 2017. Co-authored with Matt Brewer and Stephen Dewhurst.
• 9G4+ antibodies isolated from HIV-infected patients neutralize HIV-1 and have distinct autoreactivity profiles, PLoS One, 2013. Co-authored with DC Alcena, JJ Kobie, DA Kaminski, AF Rosenberg, M Brewer, S Dewhurst, C Dykes, X Jin, MC Keefer, I Sanz.
• Anti-Idiotype Monobodies Derived from a Fibronectin Scaffold, Biochemistry, 2013. Co-authored with MA Sullivan, LR Brooks, P Weidenborner, W Domm, Q Xu, M Tiberio, T Wentworth, J Kobie, P Bryk, B Zheng, M Murphy, I Sanz, S Dewhurst.
• Autoreactive 9G4+ B Cells and Antibodies are Increased in HIV-Infected Patients and Correlate with HIV Broadly Neutralizing Serum Activity, PLOS One, 2012. Co-authored with JJ Kobie, DC Alcena, B Zheng, P Bryk, M Brewer, C LaBranche, FM Young, S Dewhurst, DC Montefiori, A Rosenberg, X Jin, MC Keefer, I Sanz.
• Comprehensive Proteomic Analysis of Influenza Virus Polymerase Complex Reveals a Novel Association with Mitochondrial Proteins and RNA Polymerase Accessory Factors, J Virol, 2011. Co-authored with BG Bradel-Tretheway, A Krasnoselsky, C Stevenson, D Purdy, S Dewhurst, and MG Katze.
• PA residues in the 2009 pandemic influenza virus enhance avian virus polymerase activity in mammalian cells, J Virol, 2011. Co-authored with KA Bussey, EA Desmet, A Hamilton, B Bradel-Tretheway, HE Bussey, B Kim, S Dewhurst, and T Takimoto.
• Dense display of HIV-1 envelope spikes on lambda phage scaffold does not result in the generation of improved antibody responses to HIV-1, Env. Vaccine, 2011. Co-authored with S Walter, M Brewer, W Domm, AE Friedman, and S Dewhurst. 

(* indicates St. John Fisher University undergraduate student author)