News

The National Institutes of Health-funded New York Influenza Center of Excellence (NYICE), led by David Topham, Ph.D., received $5.4 million in new awards from the NIH to conduct a variety of projects related to the immune response to flu infection and vaccination. NYICE is a multidisciplinary and multi-institutional center that emphasizes basic and clinical research on human influenza.

The funding covers 13 new projects that will be conducted by investigators at URMC, as well as scientists from institutions that are members of NYICE, such as the University of Pennsylvania, University of Chicago, Duke and the University of Minnesota. Research will be conducted in the U.S. and abroad, including studies in Melbourne, Australia and Stockholm, Sweden.

Development of a universal flu vaccine is the focus of several of the new projects. The comparison of different types of vaccines (egg-based vaccine; cell culture vaccine; vaccine made in insect cells) is another important study, as the widely-used egg-based vaccine wasn't particularly effective in the 2017-2018 flu season. Investigators will also work to better understand how the viruses we're exposed to as children influence immunity later on in life.

In addition to Topham, URMC researchers Andrea J. Sant, Ph.D.,Jennifer Nayak, M.D.,Angela Branche, M.D.,Luis Martinez-Sobrido, Ph.D. and James J. Kobie, Ph.D. will spearhead several of the new projects.

Irfan Rahman, Ph.D., professor of environmental medicine, public health sciences, dentistry and medicine has been designated as an American Thoracic Society Fellow for his pulmonary science accomplishments and services to international lung community.

Dr. Rahman's lab is interested in understanding the redox signaling, mechanism of proinflammatory gene expression by studying the chromatin remodeling-epigenetic changes (histone acetylation/deacetylation) on pro-inflammatory genes, involvement of anti-inflammatory and anti-aging proteins sirtuins, and steroid resistance in chronic inflammatory diseases/COPD. Recent research includes in understanding the role of sirtuins in aging and accelerated decline in lung function and regulation of circadian genes. Our long-term goal is to understand the cellular and molecular mechanisms involved in pathogenesis of COPD, and the potential benefit of therapeutic interventions in this debilitating disease.

Congratulations Irfan!

David Topham, Ph.D. was recently featured in the Medical Center "Make a Difference Campaign.

Viruses and bacteria that infect the respiratory tract are a leading cause of death worldwide, despite advances in antibiotics and vaccines. At the University of Rochester, our history of vaccine development is responsible for saving hundreds of thousands of lives each year around the world. Today, we are using data science innovation to gain new insights into how the immune system works to reduce the global burden of respiratory pathogens and develop more effective treatments and vaccines.

Read the flyer.

The expertise of two regional research teams has earned a federal grant of nearly $20 million to create the nation's first program dedicated to the study of flavored tobacco. One of only nine projects to earn funding through the federal Tobacco Centers of Regulatory Science (TCORS) program, the WNY Center for Research on Flavored Tobacco Products, or CRoFT, will unite teams from Roswell Park Comprehensive Cancer Center and the University of Rochester Medical Center in an effort to better document and understand one of the fastest-growing trends in tobacco use.

The five-year, $19.05 million competitive grant, awarded by the National Cancer Institute, will be shared by Roswell Park and URMC. Based at Roswell Park, the program will be led by Richard O'Connor, Ph.D., and Maciej Goniewicz, Ph.D., Pharm.D., both internationally recognized experts on tobacco use and its health consequences. The Roswell Park team will analyze various combustible and electronic tobacco products, their consequences for health and how users interact with these products. Collaborators from URMC, led by Irfan Rahman, Ph.D., and Deborah Ossip, Ph.D., will contribute critical resources in biomarker screening, genetic analysis and toxicology assessment.

"We're really excited about initiating this work, because no one has ever looked at flavored tobacco in such a comprehensive and systematic way. There are so many different flavorings, delivery systems and product options, and so much we don't know about them," says O'Connor, professor of Oncology with Roswell Park's Health Behavior and Epidemiology & Prevention programs and director of the Buffalo cancer center's Tobacco Research Laboratory.

Current federal regulations prohibit the sale and manufacture of flavors other than menthol in combustible cigarettes but not in other tobacco products, including e-cigarettes. Data published last year from the PATH Study, the largest prospective U.S. study of tobacco use, indicated that use of flavored products was highest among youth and young-adult tobacco users, with 80% of tobacco users ages 12-17 and 73% of tobacco users ages 18-24 reporting that they'd used a flavored tobacco product in the previous 30 days.

"There are a number of flavoring chemicals that are regarded as safe for incorporation into food and drink, but we have such limited data about what happens when these products are inhaled," adds Rahman, professor of Environmental Medicine, Dentistry, Medicine (Pulmonary) and Public Health Sciences at URMC. "We're going to study the impact on public health when these chemicals are added to e-cigarettes, vape pens, Juul and other pods, hookahs, waterpipes, cigars and cigarillos (little cigars) to be a resource for both policymakers and the general public."

Why does preterm birth increase the severity of respiratory viral infections in children?

Michael O'Reilly, Ph.D., professor of Pediatrics and Environmental Medicine has received a $2 million grant to investigate how early exposure to oxygen changes how the lung responds to influenza A virus later in life. The grant continues a line of research that began 12 years ago when his own son Thomas was born preterm.

A growing body of evidence suggests exposure to environmental pollutants during critical stages of fetal and postnatal lung development can permanently change health of the lung later in life. The transition to air at birth is one of the most profound environmental changes that the developing lung will ever experience. While the newborn lung is prepared to breathe oxygen, the preterm lung transitions too soon. This aberrant exposure to oxygen at birth can increase the severity of viral infections through poorly understood mechanisms.

Using a novel mouse model, Dr. O'Reilly and his colleagues discovered high levels of oxygen at birth increases the severity of influenza A virus infection by depleting epithelial stem cells needed to repair the infected lung. The goal of the new grant is to figure how oxygen depleted these cells with the hope that such knowledge will increase our ability to prevent or treat lung disease in people born preterm.

Additional collaborators on this project include B. Paige Lawrence, Ph.D., Luis Martinez-Sobrido, Ph.D., Andrew McDavid, Ph.D., and Martha Susiarjo, Ph.D.

Department of Public Health Sciences faculty and staff (David Rich, Philip Hopke, Edwin van Wijngaarden, Ann Dozier, Mauro Masiol, Stefania Squizzato, Kelly Thevenet-Morrison), in collaboration with others from URMC (Sally Thurston, Daniel Croft, Mark Utell, Frederick Ling, Scott Cameron, David Chalupa) and the University at Albany, State University of New York (Shao Lin, Wangjian Zhang) are conducting several studies examining the health effects of ambient air pollution in New York State. Funded by the New York State Energy Research and Development Authority, they are examining whether the concentrations and composition of air pollutants emitted from electricity generation and fuel combustion, and changes in them following implementation of air quality policies and economic changes due to a recession, have had measurable health impacts on New York State residents and measurable impacts on ambient air pollution concentrations across the state. From these studies, several URMC faculty and students presented oral presentations (Edwin van Wijngaarden, Meng Wang) and poster presentations (Daniel Croft, Rui Li) at the joint conference of the Internal Society of Exposure Science and the International Society of Environmental Epidemiology in Ottawa Canada from August 26-30, 2018, and the International Aerosol Conference in St. Louis, Missouri from September 2-7, 2018 (Mauro Masiol, Stefania Squizzato).

At Opening Convocation on September 6, 2018, Paige Lawrence received the award for Outstanding T32 Program Director. This award is presented to the T32 principal investigator with the best impact score for a new grant or competing renewal in the past year.

Irfan Rahman was also recognized at Convocation for receiving a Dean's Professorship this past year. Dean's Professorships were established in 1982 and are designated by the Dean to be assigned to individuals of outstanding research excellence.

Congratulations to both!

Paige Lawrence, Ph.D.

Irfan Rahman, Ph.D.

Professor Jim McGrath has received a Health Sciences Center for Computational Innovation (HSCCI) Grant for his project, "Database of Fluid Flow in Nanomembrane-based Microdevices." This project seeks to build a database of computational 3D flow profiles for microfluidic devices featuring the laboratory's silicon nanomembranes. Nanomembranes are ultrathin porous membranes with orders of magnitude higher permeability than conventional membranes. A two-channel, microfluidic device with a 5.4 mm square membrane 'chip' separating the channels has become a standard format for multiple projects in the McGrath laboratory. Specifically, the device format is used for: 1) benchtop evaluations of toxin clearance in hemodialysis, 2) capture of exosomes from raw biofluids in tangential flow, 3) a 'tissue-chip' mimetic of the microvasculature. Future microfluidic applications of this device include: 1) enhancement of DNA detection by a novel dual membrane system, and 2) an electrodialysis system for desalinization.

The Health Sciences Center for Computational Innovation (HSCCI) facilitates access to high-performance computational resources for biomedical research. HSCCI is the result of a partnership between the University of Rochester, IBM, and New York State. The University seeks to develop the center further through corporate partnerships, institutional support, federal research grants, and New York State programs.

2D COMSOL simulation of flow near membrane (yellow). Flow is left to right on top with some transmembrane flow. Fluid streamlines are shown as black lines.

The Lawrence Lab's article, "Developmental Exposure to a Mixture of 23 Chemicals Associated With Unconventional Oil and Gas Operations Alters the Immune System of Mice", has been chose as one of NIEHS "Papers of the month."

The paper deals with prenatal exposure to chemicals used in unconventional oil and gas (UOG) extraction, also known as fracking, affected immune system development in mice, according to a new study by NIEHS grantees. The study provided the first evidence that early-life exposure to a mixture of 23 commonly used UOG chemicals may hinder the ability to ward off diseases later in life.

Congratulations to the entire lab, Dr. Lawrence and co-authors, including Drs. Steve Georas, Jacques Robert and Susan Nagel (Missouri).

By Susanne Pritchard Pallo

The MSTP 2017 incoming class, with former UR CTSI Academic Research Track participants Samuel Weisenthal and Ian De Andrea-Lazarus (far right).

Over the past several decades, concerns have risen about the declining population of physician-scientists, with reports pointing to early career training and support as a possible solution. The UR CTSI Academic Research Track, which allows medical students to try their hands at research, has helped two University of Rochester School of Medicine and Dentistry students take the next step toward a research career: joining an MD-PhD program.

The pair, Ian De Andrea-Lazarus and Samuel Weisenthal, joined the University of Rochester Medical Scientist Training Program after finishing their Academic Research Track projects. This is a move that a new study from the Association of American Medical Colleges suggests will help them stay in science. The study tracked MD-PhD program graduates over 50 years and showed that most stuck with their research careers.

Ian and Sam explain what drove them to pursue a career as physician-scientists.

Why did you join the UR CTSI's Academic Research Track?

Ian: I've always craved knowledge and enjoy the challenge of pushing the boundaries of existing human knowledge. I had several years of research experience before applying for medical school - as an undergraduate research assistant in the Linguistics Department at Gallaudet University and as a post-baccalaureate fellow at the National Cancer Institute. For two years, I worked in the Laboratory of Cancer Biology and Genetics at NCI, studying a non-selective cation channel found mainly in the peripheral nervous system that is involved in the transmission and modulation of pain.

Sam: Like Ian, I was inspired by my time as a post-baccalaureate trainee at the NIH, where I worked for a year in a computational radiology lab. I also had a great time doing a summer research project in health informatics at Rochester. I joined the Academic Research Track because I wanted to study the vast amount of data being collected through the electronic health record. In a single year, the University of Rochester Medical Center alone accrues more than two terabytes of non-image data (a lot). I was particularly interested in how this data could be used to predict -- and hopefully help prevent -- adverse health events in patients.

How did your experience in the Academic Research Track drive you to join the University of Rochester Medical Scientist Training Program?

Ian: I had originally wanted to apply for the University of Rochester Medical Scientist Training Program but I was afraid that my application would not be competitive enough. The Academic Research Track was the bridge that allowed me to pursue my goal of becoming a physician-scientist and reinvigorated my interest in research. The program allowed me to obtain a master's degree in Public Health along with the tools and drive I needed to apply for the MD-PhD program.

Sam: I had also previously considered an MD-PhD program, but did not have a cohesive story to tell in an application. The Academic Research Track year allowed me to obtain a master's degree in Data Science from the Goergen Institute for Data Science at the University of Rochester, which provided a foundation for more advanced study. It also helped me discover the UR CTSI's Translational Biomedical Science PhD Program, which was a good fit, and to fully engage in a research project in a great lab.

What did you study during the Academic Research Track program?

Sam: We were initially interested in predicting readmission to the intensive care unit, which is a quality metric used by some hospitals. Ultimately, however, we decided to focus on predicting acute kidney injury, which is common, deadly, and sometimes completely preventable with simple interventions like fluid administration or medication review. Insights from our studies could be used to hopefully develop a better predictive tool that could help prevent acute kidney injury in the future.

Ian: We explored the association between low levels of lead in the serum of 3- to 5-year-old children and their mental capacity to focus attention, remember instructions, and juggle multiple tasks. We used a well-characterized tool for assessing these mental executive functions in children, called the Stroop day-night task, but found that the tool may not be sensitive enough to detect lead's effects on neurodevelopment.

What are you studying now?

Sam: I am pursuing a joint degree between the Translational Biomedical Science PhD Program and Computer Science Department, with Computer Science as a minor. This includes select coursework in computer science, biostatistics, and medicine. My research focus is a continuation of my Academic Research Track project with Martin Zand, Ph.D., co-director of the UR CTSI and professor of Nephrology and Public Health Sciences at the University of Rochester Medical Center. Our goal is to improve acute kidney injury prediction by reformulating the standard approach and performing more rigorous error analysis. Ultimately, we hope to squeeze maximal predictive value out of electronic health record data to assist physicians in making the best decisions for at-risk patients.

Ian: I am pursuing a doctoral degree in the UR CTSI's Translational Biomedical Science PhD Program and working with John Foxe, Ph.D., Killian J. and Caroline F. Schmitt chair of Neuroscience, and Edward Freedman, Ph.D., associate professor of Neuroscience, on a mobile brain/body imaging (MoBI) study. We are interested in understanding how the brains of people with decreased cognitive function, like those with Alzheimer's disease, handle the cognitive demands of multitasking while walking, which requires continuous processing of information about the environment and body position.

Amid predictions of a second fracking boom in the U.S., the first evidence that chemicals found in ground water near fracking sites can impair the immune system was published today in Toxicological Sciences. The study, performed in mice, suggests that exposure to fracking chemicals during pregnancy may diminish female offspring's ability to fend off diseases, like multiple sclerosis.

Fracking, also called hydraulic fracturing or unconventional oil and gas extraction, involves pumping millions of gallons of chemical-laden water deep underground to fracture rock and release oil and gas. About 200 chemicals have been measured in waste water and surface or ground water in fracking-dense regions and several studies have reported higher rates of diseases, like acute lymphocytic leukemia and asthma attacks, among residents in these areas.

"Our study reveals that there are links between early life exposure to fracking-associated chemicals and damage to the immune system in mice," said Paige Lawrence, Ph.D., chair of Environmental Medicine at the University of Rochester Medical Center, who led the study. "This discovery opens up new avenues of research to identify, and someday prevent, possible adverse health effects in people living near fracking sites."

Irfan Rahman addresses the crowd at the Tobacco 21 Forum

On March 21^st at the Thomas P Ryan R-Center, 530 Webster Avenue in Rochester, NY, Dr. Irfan Rahman participated in the Kick Butts Day Point of Sale & Tobacco 21 Forum. The event was organized to address tobacco's impact on youth & the community as well as research and evidence-based policy solutions.

Dr. Rahman's talk was on Local Youth Impact & E-cigarette Usage.

The goals and objectives of the event were:

Goals:

• Develop knowledge that will more fully equip community members and leaders to create healthier and safer approaches to protecting local populations from the dangers of tobacco use
• Improve awareness of the interconnectedness between tobacco-related influences: social, economic, public health, and youth-based impacts

Objectives:

As a result of the forum, participants will be able to:

• Engage community leaders and organizations on present tobacco-related health disparities
• Comprehend Tobacco 21 efforts and emerging trends toward this movement
• Understand e-cigarette research and data to better educate our county parents and adolescents
• Recognize tobacco marketing and retailer density consequences on our youth, communities, and neighborhoods
• Become knowledgeable of effective evidence-based policy solutions on the local level

By Lisa Rapaport (Reuters Health)

E-cigarette liquids sweetened with flavorings like vanilla and cinnamon may harm the lungs even when they don't contain nicotine, a U.S. study suggests.

Researchers examined what happened to monocytes, a type of white blood cell, upon exposure to flavoring chemicals used in popular e-cigarette liquids. None of the liquids contained nicotine, but the flavoring chemicals still appeared to increase biomarkers for inflammation and tissue damage, and many of them also caused cells to die.

Over time, this type of cell damage can lead to wide range of lung problems including fibrosis, chronic obstructive pulmonary disorder, and asthma, said senior study author Irfan Rahman, an environmental health researcher at the University of Rochester Medical Center in upstate New York.

"Nicotine-free e-liquids have generally been considered safe; however, the impact of flavoring chemicals, especially on immune cells, has not been widely researched," Rahman said by email. "This study shows that even though flavoring compounds are considered safe for ingestion, it is not safe for inhalation."

If you skipped this year's flu shot and then came down with the virus, you may think there's no point to getting the vaccine now.

But you'd be wrong.

There are good reasons to get a flu shot, even if you've already been sick, says David Topham, Ph.D., professor of microbiology and immunology at the University of Rochester and director of the New York Influenza Center of Excellence.

You can catch the flu more than once in a season—because having one "type" of flu doesn't provide immunity against the other types that may be circulating. "The way your immune system sees them is very different," Topham says. Two types commonly make people ill: type A and type B. This flu season, as is typical, most cases of flu so far have been type A (the H3N2 strain).