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New study highlights potential of inhaled nanoparticle vaccine to confer immunity to influenza

Monday, July 26, 2021

A new paper by T32 graduate student Sean Nelson, working with P.I. Dr. Andrea Sant, reported that intranasal immunization with a novel nanoparticle vaccine in mice elicited long-lived anti-viral CD4 T cell responses in the lung ( Using a mouse model of influenza infection, the research showed that CD4 T cell responses to nanoparticle vaccination outperformed CD4 T cell responses to conventional live-attenuated intranasal vaccines both in terms of establishing lung-resident CD4 T cells and the ability of these CD4 T cells to protect from influenza virus challenge upon transfer into naive hosts. The mechanisms leading to the establishment of lung-resident memory CD4 T cells are not well known, and this study adds important new knowledge in this areas. These findings show that protection from influenza virus infection can be fostered by conserved influenza virus protein-based vaccines introduced into the respiratory tract. The article was highlighted on the cover of the Journal of Virology, and was selected as an article of special interest 

Read More: New study highlights potential of inhaled nanoparticle vaccine to confer immunity to influenza

New microplastics working group formed in collaboration between the University of Rochester and the Rochester Institute of Technology

Wednesday, June 30, 2021

T32 post-doctoral fellow Samantha Romanick, Ph.D. directs the Rochester Microplastics Working Group, a joint effort of over 30 investigators from the University of Rochester and the Rochester Institute of Technology. The Working Group aims to increase our awareness of microplastics, some of which are manufactured at a small scale, and others of which are formed by the breakup of macro materials due to weathering, wear, and mechanical forces. These microparticles, classified as anything smaller than 5 mm, may not even be visible to the eye. The Working Group also aims to draw attention to microplastics in freshwater systems, including rivers and lakes. Plastics behave differently in freshwater systems, in part because the density of the water itself is lower than ocean water, making it more likely that plastics will sink, rather than float. Finally, the group also aims to raise awareness that microplastics are small enough to travel suspended in water, or even air, and are ingested or inhaled by humans. The potential adverse effects of inhaled microplastics on lung health are not well known, but an important area of future research.

Read More: New microplastics working group formed in collaboration between the University of Rochester and the Rochester Institute of Technology

New Coronavirus Vaccine Study Seeks to “Boost” Immune Response

Wednesday, February 24, 2021

The University of Rochester Medical Center (URMC) and Rochester Regional Health (RRH) have begun a new clinical trial that will evaluate the safety and efficacy of a third dose of the Pfizer/BioNTech COVID-19 vaccine. The vaccine is currently approved for a two dose regimen. This study represents an important step in the development of long-term vaccination strategies, including the creation of booster doses that target coronavirus variants.

"While widespread vaccination is the key to moving past the current health crisis, COVID-19 has the potential to become a seasonal and mutating virus," said Ed Walsh, M.D., and infectious disease specialist at URMC. "This study will help us understand important questions about the safety and immunogenicity of multiple doses of an mRNA vaccine, information that could ultimately enable us to extend the protection of vaccines and develop tailor-made, variant-specific boosters."

URMC and RRH have been involved in the development of the Pfizer/BioNTech vaccine since the launch of phase 1 clinical trials in May 2020 when volunteers in Rochester were among the first in the nation to receive the then experimental vaccine. Rochester was also a site for the phase 2/3 clinical trials that ultimately led to the vaccine's emergency use authorization (EUA) by the U.S. Food and Drug Administration last December. Since then, tens of millions of people across the globe have received at least one dose of the Pfizer/BioNTech vaccine.

The new study will involve individuals who participated in the phase 1 trials last spring, all of whom were fully vaccinated more than 6 months ago. Over the next several weeks, researchers will dose 144 volunteers, including 35 in Rochester, with a booster dose of the EUA-approved Pfizer/BioNTech vaccine. Rochester is one of four sites in the U.S. involved in the study.

The local studies are led by Walsh and Ann Falsey, M.D.; both hold faculty appointments in the URMC Department of Medicine, Infectious Diseases and are members of the Infectious Disease Unit at RRH. Pfizer contracted with URMC to conduct the clinical trial in Rochester and the recruitment of study volunteers and testing of the vaccine will occur at Rochester General Hospital.

While the duration of protection provided by the Pfizer/BioNTech vaccine is unknown, it is assumed that immunity wanes over time, a phenomenon common in vaccines for other infectious diseases. The trial will measure the boost to the immune system and evaluate in the lab whether antibodies and other immune cells generated after the third dose provide protection against coronavirus variants. The study will also seek to answer is how well a third dose of the vaccine is tolerated in healthy volunteers and researchers will closely monitor participants for side effects.

The findings of the study will also be important as vaccine developers have turned their focus to the development of vaccines that can be tailored to meet the threat of emerging strains of the virus. Pfizer and BioNTech announced today that the companies had begun discussions with regulatory agencies regarding an early stage clinical study to evaluate a modified version of approved vaccine.

"While we have not seen any evidence that the circulating variants result in a loss of protection provided by our vaccine, we are taking multiple steps to act decisively and be ready in case a strain becomes resistant to the protection afforded by the vaccine. This booster study is critical to understanding the safety of a third dose and efficacy against circulating strains," said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. "At the same time, we are making the right investments and engaging in the appropriate conversations with regulators to help position us to potentially develop and seek authorization for an updated mRNA vaccine or booster if needed."

Can Mother’s Milk Help Fight COVID? New Evidence Suggests ‘Yes’

Wednesday, February 10, 2021

URMC co-authored study indicates that breastfeeding is safe for COVID positive mothers

A study conducted by researchers at the University of Rochester Medical Center (URMC) -- in collaboration with several other universities - indicates that breastfeeding women with COVID-19 do not transmit the SARS-CoV-2 virus through their milk, but do confer milk-borne antibodies that are able to neutralize the virus.

Breast Milk Research Team

Drs. Bridget Young, Kirsi Jarvinen-Seppo and Antti Seppo were part of the breast milk research team

The study, "Characterization of SARS-CoV-2 RNA, antibodies, and neutralizing capacity in milk produced by women with COVID-19," published on February 9 in the journal mBio -- analyzed 37 milk samples submitted by 18 women diagnosed with COVID-19. None of the milk samples were found to contain the virus, while nearly two thirds of the samples did contain two antibodies specific to the virus.

Critically, this study provides evidence that COVID-19 positive mothers should not be separated from their newborn children. At the onset of the pandemic, major health organizations have often provided contradictory advice on whether this separation was necessary. This report will hopefully offer new clarity on guidance for post-natal mothers.

"We only want to sequester a mother from her baby if it's medically necessary," said co-investigator Bridget Young, Ph.D., assistant professor in the Department of Pediatrics at URMC, "However, the issue was very confusing for practitioners who don't have sufficient evidence. These early results suggest that breast milk from mothers who have had a COVID-19 infection contains specific and active antibodies against the virus, and that they do not transfer the virus through milk. This is great news!"

URMC was funded over $130,000 by the Bill and Melinda Gates Foundation for this research. The initial study published in mBio reported on the first group of 18 women who submitted milk samples. Results from the larger study will be forthcoming, which will hopefully reinforce the initial findings, according to Young.

The URMC research group is led by Antti Seppo, Ph.D., in the Department of Pediatrics. Other co-investigators include Casey Rosen-Carole. M.D., medical director of lactation services and programs at URMC, and Kirsi Jarvinen-Seppo M.D., Ph.D., research associate professor in the Department of Pediatrics.

Mark Sangster, PhD, and David Topham, PhD, both research professors in the Department of Microbiology and immunology, did the primary work measuring antibody assay levels in their lab.

"We found high levels of IgA -- a common antibody in blood and other body fluids -- in their breast milk. IgAs migrate in mucosal transfer, therefore this is encouraging information that mothers transfer these antibodies," said Sangster.

The full research team also included scientists from the University of Rochester School of Medicine and Dentistry, Brigham and Women's Hospital and Harvard Medical School, and the University of Idaho. The team now has enrolled nearly 50 women who were diagnosed with COVID-19 and has followed their progress with the disease for as long as two months.

The study was initiated to address the lack of existing research into COVID-19 in breastmilk. The next steps will be to see if the initial results are replicated in larger samples.

"This work needs to be replicated in larger cohorts. Additionally, we now need to understand if the COVID-19 vaccine impacts breast milk in the same way," said Young.

Read More: Can Mother’s Milk Help Fight COVID? New Evidence Suggests ‘Yes’

Medical Center faculty, Anthony Fauci to discuss coronaviruses on TV program

Thursday, February 4, 2021

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, will join David Topham, the Marie Curran Wilson and Joseph Chamberlain Wilson Professor in the Department of Microbiology and Immunology, and Lou Papa, a professor of clinical medicine, for a discussion of coronaviruses, a family of viruses that cause illnesses such as the common cold and COVID-19. Tune in to the health care program "Second Opinion" at 8 p.m. tonight, February 4, on WXXI-TV.

Read More: Medical Center faculty, Anthony Fauci to discuss coronaviruses on TV program

UR Center for RNA Biology RNA Presentation Contest Results

Tuesday, February 2, 2021

Thank you to those who participated in and/or viewed the UR Center for RNA Biology's RNA Presentations on Jan 6th, 13th, and 27th, sponsored by the RNA Society and Lexogen. The judging committee was impressed with the quality of the presentations given on all three dates, making final decisions difficult.

All nine of the graduate student, postdoc, and technician presenters, chosen based on their quality of their abstract, will be receiving a one-year membership to the RNA Society. Of these, four who were chosen based on the quality of their presentation will be awarded $375 each to be used toward the attendance of an RNA-centric meeting, in person or virtually.

The four to be awarded a one-year membership in the RNA Society and $375, in alphabetical order, are:

Kamel Awayda (presented Jan 6th )

Technician, Mitch O'Connell Lab

"Characterization of THUMP Domain-Containing Protein 1, and Putative Modulator of RNA Modification"

Chen Bao (presented Jan 13th)

Biochemistry Grad Student, Dmitri Ermolenko Lab

"mRNA Stem-Loops Can Induce Translational Pause through Two Pathways"

Xavier Rambout, PhD (presented Jan 27th)

Postdoc, Lynne Maquat Lab

"Transcriptional Coactivator PGC-1α Contains a Novel CBP80-Binding Motif that Orchestrates Efficient Target-Gene Expression"

Arica VanderWal (presented Jan 13th)

Biochemistry Grad Student, Mitch O'Connell Lab

"The Role of Csx28 in CRISPR-Cas13b Anti-Bacteriophage Defense"

The remaining to be awarded a one-year membership in the RNA Society, in alphabetical order, are:

Lily Cisco (presented Jan 6th )

Pharm-Phys Grad Student, John Lueck Lab

"Testing Therapeutic Intervention for Myotonic Dystrophy Type 1 in a Novel Mouse Model"

Xueyang He (presented Jan 6th )

Biophysics Grad Student, Paul Boutz Lab

"A Novel Method to Capture and Sequence Intron Lariats"

Shon Koren (presented Jan 6th )

Technician, Gail Johnson Lab

"Tau-Ribosome-tRNA Associations Underlie Common Features of Dys sincening Protein Synthesis in Dementia"

Sean Lindley (presented Jan 13th )

Biology Grad Student, Doug Anderson Lab

"StitchR: Ribozyme-Mediated RNA Trans-Splicing and Expression in Mammalian Cells"

Debanjana Maji (presented Jan 27th )

Biophysics Grad Student, Clara Kielkopf Lab

"Representative Cancer-Relevant U2AF2 Mutations Alter RNA Interactions and Splicing"

Will the Covid-19 vaccine work on new strains of the virus?

Monday, January 25, 2021

Dave Topham was recently quoted on as to whether the current COVID-19 vaccines will be effective for the variants.

As researchers become more aware of strains of SARS-CoV-2, the virus that causes Covid-19, public health officials have one question: Will vaccines offer protection against them?

At the moment, there are two broad kinds of mutations scientists are keeping an eye on: Some that make the virus more infectious, and others that appear to make it capable of evading antibodies generated by vaccines.

These new strains are somewhat expected—viruses mutate constantly. Their only evolutionary goal is to be a glorified genetic copy-and-paste machine; destroyed cells and illness are just collateral damage. It's understandable that sometimes, viruses make copying mistakes in their genetic code along the way—and sometimes, those bugs end up being perks for them instead.

"What's going on now is the virus is adapting to a new host," says David Topham, a microbiologist and immunologist at the University of Rochester in New York. SARS-CoV-2 didn't start out as a virus infectious to humans—it began as an animal virus. Now that it's had over a year of practice copying itself in people, it's not surprising that it's gotten better at replicating and surviving among us.

New Research Funding Initiative to Support Young Investigators

Friday, January 15, 2021

Thanks to a partnership between pediatric researchers and the GCH Advancement division, a new funding initiative will seek to provide $25,000 -- matched with grant funds -- to support individual young investigators who are undertaking pediatric research.

These young investigators would be tenure-track assistant professors or post-doctoral fellows who already have a PhD degree and are on the path to obtain a tenure track position. This type of "seed" funding will be critical for fostering the careers of young researchers at URMC and could potentially pay dividends for institutional growth in the long-term, according Tom Mariani, PhD, professor of Neonatology and director of research for the Department of Pediatrics.

"In addition to funding discovery and innovation which could potentially save millions of lives, the career development of one investigator can be leveraged many times over to merit additional external funding, creation of new labs, and stimulate economic growth in the Rochester community."

Alan Wood, owner of the Realty company RE/Max Plus and supporter of GCH, and Lynne Maquat, PhD, endowed chair and professor in the Departments of Biochemistry and Biophysics, Oncology, and Pediatrics, developing this funding idea after Wood and his children visited Maquat's Fragile X Syndrome lab this Fall. Fragile X Syndrome is the most common single-gene cause of autism and intellectual disability, and Wood's family got a thorough education on the scope of Maquat's work, which is examining disease-causing mutations in children, and what those mutations do to gene expression via RNA production.

"My children loved getting first-hand experience touring the lab and seeing real-world visualizations of the work Maquat and her team are doing. Wearing lab coats and gloves, they isolated genetic material from bananas, which turn out to have more genetic material than us humans," said Wood.

Wood will be leading the effort to develop the program and secure funding. Donors who sponsor a young investigator will be able to establish a relationship to learn more about their research as it evolves.

"We have several talented young researchers in the Department of Pediatrics," said Maquat, "providing early support for their career is a long-term goal. The results won't be immediate, but over time, this support will build the foundation for discovery that will improve kids' lives."

Read More: New Research Funding Initiative to Support Young Investigators

Ashley Rackow Publishes her first paper “The self-fulfilling prophecy of pulmonary fibrosis: a selective inspection of pathological signalling loops” in ERJ

Wednesday, January 6, 2021

Congratulations to Ashley Rackow for her first authored publication "The self-fulfilling prophecy of pulmonary fibrosis: a selective inspection of pathological signalling loops", published in the European Respiratory Journal in November 2020. This review article summarizes how normal wound healing pathways become corrupted in lung fibrosis, and outlines new ways to think about therapeutic interventions.

Read More: Ashley Rackow Publishes her first paper “The self-fulfilling prophecy of pulmonary fibrosis: a selective inspection of pathological signalling loops” in ERJ