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Congratulations to Alan Brooks, M.D., Ph.D. for receiving a URMC CTSI Pilot Project award "Identifying Biomarkers Predictive of Right Heart Failure in Left Ventricular Assist Device Patients?" in 2020. The URMC CTSI is supported by UL1 TR002001 from the National Center for Advancing Translational Sciences of the National Institutes of Health.

John Lueck

Joanne Ladolcetta, a freelance writer based out of San Francisco, wanted to put together information to help address circulating fears and misconceptions about the recently FDA approved COVID-19 mRNA vaccines. She reached out to friends Bryant Johnson (Cartoonist) and John Lueck (Researcher at the University of Rochester Medical Center) to tackle some of the most common vaccine questions. The collaboration resulted in an approachable informative write-up with creative illustrations and helpful links to provide readers the ability to do a deeper dive into the generation and application of the novel COVID-19 mRNA vaccines.

Courtesy of Bryant Johnson

Read More: Blog: Are the new mRNA vaccines safe?

Two new studies from the University of Rochester Medical Center (URMC) have uncovered an association between vaping and mental fog. Both adults and kids who vape were more likely to report difficulty concentrating, remembering, or making decisions than their non-vaping, non-smoking peers. It also appeared that kids were more likely to experience mental fog if they started vaping before the age of 14.

While other studies have found an association between vaping and mental impairment in animals, the URMC team is the first to draw this connection in people. Led by Dongmei Li, Ph.D., associate professor in the Clinical and Translational Science Institute at URMC, the team mined data from two major national surveys.

"Our studies add to growing evidence that vaping should not be considered a safe alternative to tobacco smoking," said study author Li.

The studies, published in the journals Tobacco Induced Diseases and Plos One, analyzed over 18,000 middle and high school student responses to the National Youth Tobacco Survey and more than 886,000 responses to the Behavioral Risk Factor Surveillance System phone survey from U.S. adults. Both surveys ask similar questions about smoking and vaping habits as well as issues with mental function.

Both studies show that people who smoke and vape -- regardless of age -- were most likely to report struggling with mental function. Behind that group, people who only vape or only smoke reported mental fog at similar rates, which were significantly higher than those reported by people who don't smoke or vape.

The youth study also found that students who reported starting to vape early -- between eight and 13 years of age -- were more likely to report difficulty concentrating, remembering, or making decisions than those who started vaping at 14 or older.

"With the recent rise in teen vaping, this is very concerning and suggests that we need to intervene even earlier," said Li. "Prevention programs that start in middle or high school might actually be too late."

Adolescence is a critical period for brain development, especially for higher-order mental function, which means tweens and teens may be more susceptible to nicotine-induced brain changes. While e-cigarettes lack many of the dangerous compounds found in tobacco cigarettes, they deliver the same amount - or possibly more - nicotine.

While the URMC studies clearly show an association between vaping and mental function, it's not clear which causes which. It is possible that nicotine exposure through vaping causes difficulty with mental function. But it is equally possible that people who report mental fog are simply more likely to smoke or vape -- possibly to self-medicate.

Li and her team say that further studies that follow kids and adults over time are needed to parse the cause and effect of vaping and mental fog.

In addition to Li, authors of the youth study include Catherine Xie, and Zidian Xie, Ph.D. For the adult study, Li was joined by co-authors Zidian Xie, Ph.D., Deborah J. Ossip, Ph.D. Irfan Rahman, Ph.D., and Richard J. O'Connor, Ph.D. Both studies were funded by the National Cancer Institute and the U.S. Food and Drug Administration's Center for Tobacco Products.

Congratulations to Tim Smyth for his first authored publication "Diesel exhaust particle exposure reduces expression of the epithelial tight junction protein Tricellulin", published in Particle Fibre Toxicology in October 2020. This research article reports the new finding that diesel exhaust particles lead to epithelial barrier dysfunction, and inhibit expression of the tight junction protein Tricellulin both in vitro and in vivo.

WXXI hosts a live, televised forum addressing COVID-19 vaccines.

Local experts on the latest COVID-19 vaccine research gathered for a live forum on WXXI-TV and radio Thursday night. Those on the panel said they see reason for hope, but they also caution it will take some time for the community to build up immunity to the virus.

Researchers on the program from the University of Rochester Medical Center included Dr. Angela Branche, co--director of the URMC Vaccine Trials and Evaluation Unit. Branche talked about the challenge to get past the mistrust that some people in the Black community have regarding medical research, when the vaccine becomes more widely available.

"And we're really going to have to work with our community partners, leaders and activists in the community who already have established trust with these groups that we're talking about and partnering with them and giving them educational tools and helping them deliver the message is really what's going to be the most effective," Branche said.

Monroe County's commissioner of Public Health, Dr. Michael Mendoza also sees a need to provide as much outreach and education to the community as possible about the vaccine. And he emphasized the need to continue following guidelines about wearing masks and physical distancing, because it will take a while to get most people inoculated.

"We have a vaccine on the ground, there are people who are getting the vaccine now, but the reality is that there is still so much time between now and when this is over."

Mendoza said that right now he is concerned about the rapidly increasing numbers of people being hospitalized and how that could impact health care in general in the Finger Lakes region.

Ashley Rackow, current TOX PhD and Pulmonary T32 graduate student, has had a review article, "The self-fulfilling prophecy of pulmonary fibrosis: a selective inspection of pathological signalling loops," published in the European Respiratory Journal. Ashley currently works in Dr. Kottmann's Lab focusing on the endogenous function and manipulation of pH-sensing G-protein coupled receptors (GPCRs) in the context of pulmonary fibrosis. Congrats Ashley!

Rackow AR, Nagel DJ, McCarthy C, Judge J, Lacy S, Freeberg MAT, Thatcher TH, Kottmann RM, Sime PJ. The self-fulfilling prophecy of pulmonary fibrosis: a selective inspection of pathological signalling loops. Eur Respir J. 2020 Nov 26;56(5):2000075. doi: 10.1183/13993003.00075-2020. PMID: 32943406.

Abstract: Pulmonary fibrosis is a devastating, progressive disease and carries a prognosis worse than most cancers. Despite ongoing research, the mechanisms that underlie disease pathogenesis remain only partially understood. However, the self-perpetuating nature of pulmonary fibrosis has led several researchers to propose the existence of pathological signalling loops. According to this hypothesis, the normal wound-healing process becomes corrupted and results in the progressive accumulation of scar tissue in the lung. In addition, several negative regulators of pulmonary fibrosis are downregulated and, therefore, are no longer capable of inhibiting these feed-forward loops. The combination of pathological signalling loops and loss of a checks and balances system ultimately culminates in a process of unregulated scar formation. This review details specific signalling pathways demonstrated to play a role in the pathogenesis of pulmonary fibrosis. The evidence of detrimental signalling loops is elucidated with regard to epithelial cell injury, cellular senescence and the activation of developmental and ageing pathways. We demonstrate where these loops intersect each other, as well as common mediators that may drive these responses and how the loss of pro-resolving mediators may contribute to the propagation of disease. By focusing on the overlapping signalling mediators among the many pro-fibrotic pathways, it is our hope that the pulmonary fibrosis community will be better equipped to design future trials that incorporate the redundant nature of these pathways as we move towards finding a cure for this unrelenting disease.

Minsoo Kim, Ph.D was recognized recently with the Davey Award, an honor bestowed on University of Rochester/Wilmot Cancer Institute faculty members who have made outstanding contributions to cancer research.

The University of Rochester Medical Center (URMC) has created a new institute that will strengthen and accelerate the study of viral, bacterial, and fungal pathogens. The Translational Immunology and Infectious Diseases Institute (TIIDI) will build upon decades of scientific research leadership in the human immune system, respiratory viruses, and vaccine development, and, more recently, the Medical Center's role in the national response to the coronavirus pandemic.

The new Institute -- which is led by David J. Topham, Ph.D., and was approved by the University of Rochester Board of Trustees last month -- will bring together multi-disciplinary teams of scientists and clinicians that will take the knowledge gained from basic research in immunology, microbiology, and virology and apply it to problems in human diseases caused by infectious pathogens. TIIDI will also strengthen education and training programs to build a pipeline that produces the next generation of adult and pediatric clinician-researchers in the field.

Researchers will study infectious diseases across several areas of medicine, including immunodeficiency, cancer, transplant, orthopedics, ophthalmology, dermatology, gastroenterology, autoimmunity, neonatology, and public health. TIIDI will focus on the development of new treatments and vaccines, and strategies to better control the spread of infectious diseases, such as HIV, respiratory pathogens, and hospital acquired infections. Researchers will also study the pathology of infectious diseases to better assess risk factors for severe outcomes and develop more effective early interventions.

What are you and your institution currently working on regarding COVID-19?

The Topham Lab launched a coronavirus research study to understand how the immune system responds to acute COVID-19 infection, including how long immunity lasts once a person has been infected and recovered. We have evidence of pre-existing cross-reactive memory B cells and Original Antigenic Sin in infected subjects. We are also collaborating with researchers at New York University and University of Idaho to examine whether mothers can transmit COVID-19 through breast milk (they don't) and whether the breast milk itself has immunological properties against the disease (it does). Funded by the Bill and Melinda Gates Foundation and the NIH, the study could result in critical guidance for current and soon-to-be mothers. Physicians at URMC and Rochester Regional Health are investigating a new coronavirus vaccine developed by Pfizer and BioNTech. The URMC Vaccines and Treatments Evaluation Unit is testing Remdesivir combined with other drugs, as well as a Phase III clinical trial of the Astra Zeneca ChAdOX-1 SARS-CoV-2 vaccine. Rochester engineers and medical scientists are collaborating closely with clinicians to develop tests to detect coronavirus. Projects include (1) research on a finger-stick test to detect and study immunity to COVID-19; (2) the creation of tiny sensor chips that use coronavirus proteins to "very quickly" detect the presence of antibodies that help humans fight against the virus; and (3) testing samples of sputum, nasal mucus, or blood using ultrathin silicon nanomembranes to "instantly" determine if an individual has been infected. The Lung Development Molecular Atlas Program (LungMAP) and the Human BioMolecular Atlas Program (HuBMAP) collaboratives received funding from the NIH to examine human lung tissue in order to determine why children seemingly contract COVID-19 at a lower rate and remain more asymptomatic than the older population. Gloria Pryhuber, professor of Neonatology, will lead URMC's involvement in this multi-institutional project. The New York State Emerging Infections Program (EIP) is part of the federal Centers for Disease Control & Prevention's national effort to provide population-based communicable disease data to identify disease patterns, to evaluate vaccine programs, and to identify at-risk populations. The URMC EIP will be performing laboratory and population-based surveillance for COVID-19 as a part of multi-site national study. The group will collect a variety of demographic and clinical data that will be reported to the Centers for Disease Control & Prevention and the Monroe County Department of Public Health.

Please describe your research involving antibodies, memory B-Cells and the S-Subunit?

Dr. Mark Sangster in the Topham Lab has been studying acute and memory B cell (MBC) responses to COVID-19. We found evidence of pre-existing cross-reactive MBC specific for the S2 subunit of the spike glycoprotein and seasonal beta coronaviruses. This cross-reactive MBC responds more rapidly to infection and may affect responses to other SARS-CoV-2 proteins. Antibodies to the S2 subunit can be neutralizing. We are now trying to understand whether this immune memory is correlated with disease outcomes. We are also beginning studies of T cell responses to SARS-CoV-2 in acute and convalescent subjects.

Professional Summary

David Topham joined the faculty at the University of Rochester Medical Center in 1999 and was appointed in 2009 as Vice Provost and Executive Director of the Health Science Center for Computational Innovation (HSCCI), a partnership between New York State, the University and IBM. As Executive Director of the HSCCI, Dr. Topham's responsibility is to support collaboration in biomedical research using High Performance Computational Resources. He will bring together academic biomedical and health-related Research Investigators, High Performance Computational Biologists, and HP Research Computing resources. Dr. Topham provides strategic direction to the HSCCI and facilitates the development of research projects between UR scientists and its corporate partners, as well as support from state and federal agencies.

Dr. Topham is a Professor of Microbiology and Immunology, a member of the David H. Smith Center for Vaccine Biology and Immunology, and directs the New York Influenza Center of Excellence--one of the five national Centers of Excellence in Influenza Research and Surveillance supported by the NIH.

Dr. Topham was recently appointed as the Founding Director of the UR Translational Immunology and Infectious Diseases Institute whose mission is to foster collaborative team based approaches to translational research on infectious diseases and immunology.

About Topham Lab

Viruses that infect the respiratory tract are responsible for extensive morbidity and mortality in human population worldwide. Influenza virus is a particular concern because of its ability to periodically cause deadly pandemics, most recently in 2009 after the spread of a swine-origin H1N1 virus to humans. Novel avian influenza viruses such as H5N1 and H7N9 continue to cause sporadic cases of severe disease in humans and are an ongoing pandemic threat. An understanding of how the immune system controls influenza and other respiratory viruses and provides long-term protection is critical for the rational development of effective vaccination and treatment strategies.

Studies in our lab are primarily aimed at understanding the multiple roles of virus-specific B and T cells in determining the outcome of viral infection of the respiratory tract. In particular, we are interested in the character, longevity, and protective capacity of B and T cell memory induced by infection and vaccination. A large component of work in the lab focuses on the response of the human immune system to infection and vaccination; other work uses a variety of animal model systems to investigate basic immunological mechanisms. A recent initiative in the lab is the identification of viral genes and host responses that influence the severity of respiratory virus infections. This work will identify strategies for engineering new antivirals and improving vaccines.

Many projects involve strong collaborative interactions within centers at the University of Rochester that focus on immunity to respiratory pathogens. These centers include the Respiratory Pathogens Research Center (RPRC), the New York Influenza Center of Excellence (NYICE), and the University of Rochester Genomics Research Center (URGRC).

Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection. New research appearing in the journal Nature Immunology describes how different cells in the immune system work together, communicate, and -- in the case of cells called neutrophils -- bring about their own death to help fight off infections. The findings could have important implications for the development of vaccines and anti-viral therapies.

"The immune system consists of several different types of cells, all acting in coordination," said Minsoo Kim, Ph.D., a professor of Microbiology and Immunology at the University of Rochester Medical Center (URMC) and senior author of the study. "These findings show that cells called neutrophils play an important altruistic role that benefits other immune cells by providing key resources for their survival and, in the process, enhancing the body's immune response against a virus."

Neutrophils are a key component of the innate immune system, the part of the body's defenses that is always switched on and alert for bacterial and viral invaders. The vast majority of white cells circulating in blood are neutrophils and, as a result, these cells are the first on the scene to respond to an infection.

However, neutrophils are not fully equipped to eliminate a viral threat by themselves. Instead, when the respiratory tract is infected with a virus like influenza or COVID-19, a large number of neutrophils rush to the infection site and release chemical signals. This triggers the production of specialized T cells, which are part of the body's adaptive immune system, which is activated to produce a more direct response to specific infections. Once mobilized in sufficient quantities, a process that typically takes several days, these T cells target and ultimately destroy the infected cells.

The new study, which was conducted in mice infected with the flu virus, shows that in addition to jump-starting the adaptive immune response, neutrophils have one more important mission that requires that they sacrifice themselves. As T cells arrive at the infection site, the neutrophils initiate a process called apoptosis, or controlled death, which releases large quantities of a molecule called epidermal growth factor (EGF). EGF provides T cells with the extra boost in energy necessary to finish the job.

"This study represents an important paradigm shift and shows that the adaptive immune system doesn't generate a successful response without instruction and help from the innate immune system," said Kim. "The findings reveal, for the first time, how different immune cells work together, and even sacrifice themselves, to accomplish the same goal of protecting the host from the viral infection."

Clinical Trials on a Chip researchers plan to build and test common and rare disease models to help improve the clinical trial process.

Approximately 85% of late-stage clinical trials of candidate drugs fail because of drug safety problems or ineffectiveness, despite promising preclinical test results. To help improve the design and implementation of clinical trials, the National Institutes of Health has awarded 10 grants to support researchers' efforts in using tiny, bioengineered models of human tissues and organ systems to study diseases and test drugs. One major goal of the funded projects is to develop ways to better predict which patients are most likely to benefit from an investigational therapy prior to initiating clinical trials.

The awards total more than $6.9 million in the first year, and approximately $35.5 million over five years, pending available funds. They are administered through a new program, Clinical Trials on a Chip, which is led by NIH's National Center for Advancing Translational Sciences (NCATS) in conjunction with several other NIH Institutes and Centers, including the National Cancer Institute, the National Institute of Child Health and Human Development, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Tissue chips, or organs-on-chips, are 3-D platforms engineered to support living human tissues and cells and mimic complex biological functions of organs and systems. Tissue chips are currently being developed for drug safety and toxicity testing and disease modeling research, including on the International Space Station. Clinical Trials on a Chip is one of several initiatives that are a part of the NCATS-led Tissue Chip for Drug Screening program, which was started in 2012 to address the major gaps in the drug development process.

What do vapers, smokers, and non-smokers with chronic conditions such as high blood pressure or diabetes have in common? They all are at higher risk for COVID-19.

The scientific explanation behind this is complex and not yet certain — but it may boil down to an enzyme known as ACE2, that lives on the surface of many cells in the lungs and serves as the entry point for the coronavirus.

Evidence shows that people with chronic inflammatory illnesses, vulnerable older adults, and those who smoke or vape, all have an abundance of ACE2 receptor proteins to serve as a gateway to the deadly virus.

A research team at the University of Rochester Medical Center, led by Irfan Rahman, Ph.D., published a series of studies during the pandemic that focus on the vital role of ACE2 — which is already at the center of many other scientific investigations — to shape a clearer picture of the critical cellular mechanisms that regulate the deadly virus and its link to vaping.

While Rochester investigators are working in lockstep with scientists around the world, Rahman's special interest is on the growing problem of young people who test positive and may be spreading coronavirus at alarming rates. Even some older children and teens who have higher levels of the ACE2 receptor seem to be more vulnerable to the virus.

"Our next step is to investigate whether ACE2 is normally low in young people, hence their relatively low infection and mortality rates from COVID-19, but to find out if ACE2 is increased by smoking or vaping rendering them more susceptible to the virus," said Rahman, Dean's Professor of Environmental Medicine, Medicine (Pulmonary), and Public Health Sciences. "This would be in contrast to older people with lung diseases such as COPD and pulmonary fibrosis, who we already know are at higher risk for severe viral illnesses and death."

When the first COVID-19 cases hit the University of Rochester Medical Center's ICU back in March of 2020, there were no proven treatments available, but experimental therapies were cropping up around the world. Quickly, a team of URMC clinicians and researchers mobilized to bring the most promising clinical trials - that address the broadest swath of patients' needs - to URMC. Since then, URMC has joined three clinical trials that provide extra treatment options for some of the sickest COVID-19 patients.

COVID-19 causes a wide range of outcomes: some infected people never show a single symptom, while many battle the disease for weeks in the ICU. The difference between those outcomes seems to lie in a careful balance of the immune response. In the beginning of the disease, the immune system helps fight off the virus. But for those who land in the hospital, this early, helpful immune response gives way to uncontrolled over-activation of the immune system, causing system-wide inflammation and severe complications.

The three COVID-19 inpatient clinical trials currently running at URMC attack the disease at both ends of this balance.

"Our goal has always been to promote effective therapies through clinical trials," said Martin Zand, M.D., Ph.D., senior associate dean for Clinical Research and co-director of the Clinical & Translational Science Institute. "Our team is working hard to make sure that the trials we bring to URMC have the greatest chance of benefiting our own patients, and significantly advancing the science of COVID-19 to benefit patients around the world."

Quieting Inflammation at All Ages

While researchers have high hopes that baricitinib can quell the over-exuberant immune activity of COVID-19, that trial is only open to patients who are 18 years old and up. Another trial, sponsored by Incyte Corp, is testing a very similar drug, called ruxolitinib, in patients as young as 12 who have very severe COVID-19 disease and need to be on a ventilator.

When the immune system runs amok in the late stages of COVID-19, the lining of the lungs can become leaky, allowing fluid to build up in the lungs' air sacs. This phenomenon, called acute respiratory distress syndrome, starves the body of oxygen and mechanical ventilation can even fail to rescue these patients.

The URMC team, led by Christopher Palma, M.D. and Steve Georas, M.D., expects to enroll up to 20 severely ill COVID-19 patients in the trial to see if ruxolitinib can keep them alive and get them off ventilators and out of the ICU sooner.

Action for AT Foundation awards a grant for an exciting new collaboration between the O'Reilly and Mayer-Proschel labs that will investigate how recurrent respiratory viral infections causes ataxia-telangiectasia mutated neurologic disease.

On 16 June 2020, EHP welcomed three Deputy Editors, Dana Boyd Barr, Manolis Kogevinas, and Paige Lawrence, on their first official day of service in their new positions. Editor-in-Chief (EIC) Joel Kaufman, MD, MPH, introduced the new Deputy Editor role and named the appointees in a recent webinar with the Board of Associate Editors.

As recognized leaders in their respective disciplines of exposure science, environmental epidemiology, and experimental toxicology, the Deputy Editors will act as ambassadors to colleagues in their scientific communities to ensure that EHP continues to publish the most influential environmental health research. With a wealth of leadership, editorial, and peer review experience at EHP and other journals, the new Deputy Editors are expected to complement existing editorial workflows.

Working closely with the EIC and EHP Science Editors, they will evaluate new and revised manuscripts, participate in triage and interim editorial decisions, and collaborate with Associate Editors to oversee peer review. The Deputy Editors will also provide leadership for the consideration of submissions in their areas of expertise.

The new Deputy Editor role represents the next step in changes to the journal's operating structure that began when Joel assumed the EIC role in February 2020. As the first offsite EIC, Joel maintains his faculty position at the University of Washington while serving the journal.

Research at the University of Rochester Medical Center has found evidence of why COVID-19 is worse for people who smoke and vape than for the rest of the population.

Irfan Rahman, who runs a lab at URMC that studies the effects of tobacco products on the lungs, said people who smoke and vape often have elevated levels of receptors for an enzyme called ACE2.

Those receptors also allow the novel coronavirus to enter lung cells. More receptors means more viral load, which means more severe infections, Rahman said.

"It's pretty bad, actually," he said.

Rahman said early evidence from novel coronavirus infections showed that smokers were particularly at risk from COVID-19, but the mechanism behind the vulnerability was unclear.

Now, Rahman and other researchers said, a growing body of evidence shows inhaling nicotine increases the lungs' receptiveness to the virus and the lethality of the disease.

Other articles on this topic:

https://www.rochestercitynewspaper.com/rochester/why-smokers-and-vapers-are-more-susceptible-to-covid-19/Content?oid=11961338

https://www.wxxinews.org/post/urmc-research-uncovers-links-between-covid-19-and-vaping-smoking#:~:text=Irfan%20Rahman%2C%20a%20researcher%20at,gain%20entry%20to%20the%20lungs.&text=Those%20receptors%20also%20allow%20the%20novel%20coronavirus%20to%20enter%20lung%20cells.

https://www.wxxi.org/category/tags/covid-19

Please congratulate Tom Mariani, who is this year's recipient of the Andy Tager Award for Excellence in Mentoring!

Tom's dedication to scientific inquiry into lung biology, and his enduring effort to lift all boats with a rising tide made him the perfect fit for this award!

"Assembly on Respiratory Cell & Molecular Biology Andy Tager Award for Excellence in Mentoring"

Dr. Andy Tager was a remarkable physician scientist who combined his talent as an astute and caring physician, with that of a creative and insightful scientist, and with a lifelong dedication to helping others. Dr. Tager received multiple national awards for his discovery of bioactive lipids as potential targets of therapy in interstitial pulmonary fibrosis and distinguishing himself as one of the few to fulfill the dream of taking his work from bench to bedside. He was a selfless mentor to trainees and colleagues at his home institution, caring for the careers of those he was mentoring at least as much as his own. Less obvious to others, through his many leadership roles at ATS, Dr. Tager helped promote the professional careers ATS of members, particularly the RCMB Assembly, from all over the world. The Andy Tager Award for Excellence in Mentoring is our tribute to the brilliant, caring man, whose selfless dedication touched so many hearts, in more ways than one."

NIAID is funding a CEIRS network wide COVID-19 and influenza Southern Hemisphere surveillance study, "Natural history of SARS-CoV-2 in comparison to influenza A virus: a multi-site study focused in the Southern Hemisphere and equatorial regions."

The New York Influenza Center of Excellence, at the University of Rochester, under the direction of Dr. David Topham, will receive just over $1M in funding. Dr. Topham's lab has partnered with investigators in Australia and Vietnam to carry out the proposed research, which will include samples from Vietnam that will be shipped to Rochester for immune response analysis. The Australian samples will be analyzed at the WHO collaborating center for influenza located at the Doherty Institute in Melbourne.

Together, the CEIRS Network offers a unified human surveillance effort designed to gather critical information on the spectrum of disease, risk factors, duration of viral shedding, viral genomics, viral dynamics within and between populations and innate and memory immune responses to infection. By targeting international locations where seasonality is muted or winter is just beginning, we will gain much-needed insight into the impact of the seasons on SARS-CoV-2 spread. We will furthermore capture co-circulation of SARS-CoV-2 with other respiratory viruses, including influenza viruses, allowing a valuable comparative approach to be taken in our clinical, virological and immunological analyses.

Congratulations to Lung Biology Program members Drs. Georas, Mariani and Dean who all received the following grants:

P.I.: Steve Georas, MD
NIH/NIAA

Award Number : 1 R01 AI144241-01A1

Title of Project: Novel role of protein kinase D in airway inflammation and antiviral immunity

Project Period: 3/13/20 -- 2/28/25?

P.I.: Tom Mariani, PhD

Agency: CTSI Pilot Project Program/NIH

Award Period: 7/1/20 -- 1/31/21

Total Award (TPC): $50,000

Title: Airway Biomarkers for Prediction of ARI Etiology (Internal Grant)

The overall goal of this project is to show that airway sampling will provide optimal diagnostic biomarkers for determining bacterial involvement in ARI.

P.I.: David Dean ,PhD

Agency: NIH/NHLBI

Award Period: 4/5/20- 3/31/24

Total Award (TPC): $2,298,764

Title: A multimodal delivery and treatment approach for Acute Lung Injury (R01)

This projects investigates how gene transfer of the b1 subunit of the Na,K-ATPase to the lung increases not only alveolar fluid clearance, but also improves alveolar-capillary barrier function by up regulating abundance and activity of tight and adherent junction complexes.

P.I.: David Dean, PhD

Agency: NIH/NIDDK

Award Period: 4/15/20 -- 3/31/23

Total Award (TPC): $1,588,524

Title: Gene therapy for GERD-associated esophageal epithelial barrier dysfunction (R01)

Gen transfer of the b1 subunit of the Na,K-ATPase can upregulate tight and adherence junctions abundance and activity in the lung. Since a hallmark of gastroeosphageal reflux disease (GERD) is reduced barrier function in the distal esophagus (which may play a role in ultimate transition to esophageal adenocarcinoma), this project investigates whether gene delivery of the b1 subunit of the Na,K-ATPase can restore esophageal barrier integrity and therefore reduce GERD.

P.I.: David Dean, PhD

Agency: Cystic Fibrosis Foundation

Award Period: 2-1-20 -- 1-31-23

Total Award (TPC): $840,000

Title: : Electroporation-mediated gene delivery to the airways to treat Cystic Fibrosis (grant)

This project investigates whether electroporation-mediated gene transfer can be used to effectively sustain long-term expression of CFTR in animal models. If successful, the project may lead to the development of new therapies designed to treat people with cystic fibrosis.

University scientists are adapting existing research to develop tests to detect and improve our understanding of COVID-19. Examples include projects led by Martin Zand, senior associate dean for clinical research at the Medical Center; Benjamin Miller, a professor of dermatology and biomedical engineering; and James McGrath, a professor of biomedical engineering.

Zand is working on the finger-stick test, which uses patented technology that detects immunity to more than 50 strains of flu. The test comes in an easy-to-mail kit similar to those that test blood sugar for diabetes. "We're hoping this could make COVID-19 vaccine trials faster and more convenient for those who volunteer for them," says Zand.

Miller's lab hopes to find the virus with optics at the nanoscale. The lab is developing tiny sensor chips that use coronavirus proteins to "very quickly" detect the presences of immunoglobulin G and M antibodies that humans develop within two days of exposure to the virus. "The problem right now is actually getting patient samples," says Miller. "Meanwhile we are optimizing our assays with 'normal' serum samples doped with coronavirus antibodies—basically making artificial patient samples."

McGrath is using ultrathin membranes—less than 200 nanometers thick—to determine whether individuals have been infected with COVID-19. He can apply the membranes as a sensor and as a platform for discovering pathogenic mechanisms. McGrath is eyeing an inexpensive device similar to a pregnancy test that could be used in low-resource communities around the world.

"It will likely take more than a year to develop a vaccine, so COVID-19 is going to be with us for some time," says McGrath. "If we move quickly but deliberately, I think the device could be ready in time to help with the current pandemic."

The University of Rochester Medical Center (URMC) have launched a new study to understand how the body's immune system responds to COVID-19, including if and when a person could be re-infected with the virus and whether some people have pre-existing immunity. The findings could have significant implications for the public health response to the pandemic, the development of COVID-19 vaccines, and decisions related to re-opening the economy and society.

This study was featured on 13WHAM.

The new coronavirus research is being led by David Topham, Ph.D., Angela Branche, M.D., and Ann Falsey, M.D., under the URMC New York Influenza Center of Excellence(NYICE), one of the five international centers in the Centers of Excellence in Influenza Research and Surveillance network. The research is supported by approximately $5 million in funding from the National Institute of Allergy and Infectious Diseases (NIAID), the institute headed by Anthony Fauci, M.D.

"This research will seek to answer several important questions, including the durability of immunity from the virus once a person has been infected and recovered, whether the virus is mutating, whether previous exposure to other seasonal coronaviruses provides a degree of protection from COVID-19, and how long potential vaccines could provide immunity from the virus," said Topham.

The study will recruit up to 100 COVID-19 positive individuals across all age groups from the Rochester community and follow them for 90 days. The researchers will collect samples that will enable them to isolate and study the virus, and measure immune response to the infection.

Specifically, it will track the production of antibodies that seek out and flag the virus for destruction by immune cells. Once produced in sufficient quantity, these antibodies and other cells generated by the immune system provide protection from re-infection. These cells are also activated after vaccination. However, as is the case with other viral infections such as the flu, it is speculated that immunity to COVID-19 will weaken over time.

This research builds on more than a decade of influenza and respiratory pathogens research by the NYICE. For the past 13 years, URMC researchers have been conducting surveillance studies in an effort to better understand the immune response to the flu and vaccination. At the request of NIAID, URMC researchers have retooled and expanded the influenza study to include on COVID-19.