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NIH grant will help identify new strategies to enhance immune response

Cutting-edge imaging technologies that allow scientists to watch the immune system work in real time are leading to a greater understanding of how we combat infection and disease. With a new $12 million grant, researchers will use this knowledge to explore strategies to better fight infections like the flu and beat back overactive immune responses in disorders like rheumatoid arthritis and lupus.

The five-year project, led by Deborah J. Fowell, Ph.D., Dean's Professor in the department of Microbiology and Immunology at the University of Rochester Medical Center, builds on a $9 million grant that her team received in 2014. Both program project grants were awarded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

"When we take cells out of their natural environment and study them in a dish we're missing out on a lot of biology," said David J. Topham, Ph.D., a study project leader and professor of Microbiology and Immunology at URMC. "Imaging and tracking live cells is an emerging theme in immunology and one that I think is going to move forward meaningful discoveries in the field."

In addition to Fowell and Topham, project leaders include Minsoo Kim, Ph.D.,James F. Miller, Ph.D., and Patrick Oakes, Ph.D. Scientists from Cornell and Loyola University will collaborate with the team, as well.

Congratulation to Hen Prizant, Postdoctoral Fellow in the Fowell Lab who is this year's recipient of the Outstanding Postdoctoral Researcher Award. This award was established in 2015 to recognize a School of Medicine and Dentistry postdoc for outstanding research contributions. Selection is based on the originality, creativity, and significance of the individual's research accomplishment.

Anuj has been selected to receive the 2019 Rochester Vaccine Fellowship in honor of Dr. Porter Anderson. The Rochester Vaccine Fellowship is awarded annually to an outstanding postdoctoral fellow working in the area of vaccine-related research, who is mentored by a faculty member with a primary or secondary appointment in the Department of Microbiology and Immunology. This fund was created by a donation from Dr. Michael Pichichero in honor of Dr. Porter Anderson (Professor Emeritus of Pediatrics in Infectious Diseases), who co-invented the widely administered vaccine for bacterial meningitis.

When immune cells get recruited to infections, tumors, or other sites of inflammation they exit the blood stream and begin searching for the damage. But how they effectively traverse the body's tissue and home in on their targets is unclear. A new study led by Deborah Fowell, Ph.D. suggests that T cells have distinct navigation systems that help them pinpoint their targets.

Fowell's research team, based in the David H. Smith Center for Vaccine Biology and Immunology in the Department of Microbiology and Immunology made the discovery by visualizing the immune system in real time using intravital multiphoton microscopy. The technology allows you to look directly into the skin and observe the dynamic behavior of immune cells 'live.' Their findings were published earlier this month in the journal Immunity.

"We thought that locating the infection foci was a passive event for immune cells; that they used the tissue as a scaffold to weave their way through this complex matrix to get to their target," said Fowell, Dean's professor in the Department of Microbiology and Immunology. "We discovered that they are pre-programmed to respond to certain cues within the tissue microenvironment that help them find their targets more efficiently."

The team hopes that discovering these specialized programs for migration in tissues will provide new therapeutic targets that enable manipulation of the immune response in a disease-specific or tissue-specific fashion, rather than globally suppressing the immune system. Possibilities include boosting protective immunity in diseases where the immune system is inefficient, such as chronic infections and tumors, and limiting immunity in diseases that are exacerbated by the immune system, like autoimmunity and heart disease.

Hen Prizant, Ph.D., a postdoctoral fellow in Fowell's lab and Alison Gaylo-Moynihan, M.D., Ph.D., a former student in the lab are co-first authors. Graduate students Ninoshka R.J. Fernandes, Hannah Bell, Dillon C. Schrock, Tara Capece, Brandon Walling, and Christopher Anderson contributed to the study. Faculty members David Topham, Minsoo Kim, Alan Smrcka and James Miller are also authors.

Fowell credits the new finding to the power of NIH Program Project Grants (P01), which allow faculty, trainees and students to explore uncharted scientific territory and branch out among different disciplines. For example, the team reached across Elmwood Avenue to have conversations with astrophysicists and engineers on River Campus about how objects move through and are found in space. The P01 that funded the research was awarded to Fowell (PI) and Kim, Topham and Miller in 2014.

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007872

https://www.ncbi.nlm.nih.gov/pubmed/31194844

Fascinating new study on the compensatory roles of TLRs and inflammasomes during infection.

Originally called Provost's Multidisciplinary Awards, the University Research Awards provide "seed" grants for promising, high-risk projects.

The fund has been increased from $500,000 annually to $1 million. Half of the funding comes from the President's Fund, with the rest being matched by the various schools whose faculty members are recipients.

Applications were sought from faculty across the University, and funding is awarded to recipients who demonstrate their projects favor new research with a high probability of being leveraged by future external funding. A review committee of faculty from across the University provides peer review of the applications.

Two professors from CVBI were among this year's recipients. Sally Quataert, research associate professor, and Mark Sangster, research professor, both of microbiology and immunology, for Advancing Translational Research to Drive Universal Influenza Vaccine Development: Novel Methods for Assessing Clinical Antibody Responses.

One of the leading candidates for a universal influenza vaccine is the conserved stem/stalk region of the HA protein that mediates fusion of the virus with endosomal membrane, an important step in infection. This study's multiple goals include developing clinical assay methods to detect and quantitate anti-stalk antibodies in sera and to assess antibody affinity/avidity and functional anti-fusion activity.