It has been an excellent year for the Immunology Department and we want to share some of our news with you in our annual newsletter. We also want to thank our students, postdocs and research scientists for their talents, hard work and energy that has allowed our research to flourish, and for making this a fun place to work and learn.

Thanks also to our administrative staff for supporting everything we do, and handling the challenges of running a complex enterprise with a high degree of professionalism.

Finally, we greatly appreciate those who have donated to us this past year in support of our efforts; we have put your resources to good use. To donate this year there is a link within the newsletter or click here, your support is critical to us in helping us achieve our mission.

Department of Immunology Newsletter November 2017

Event Details

12/31/1969
4:00pm-4:00pm

Michael Gale Jr., Ph.D.
Professor, Department of Immunology
University of Washington

“The Center for Innate Immunity and Immune Disease”

November 30, 2015

3:30 p.m., Orin Smith Auditorium, SLU 
4:30 p.m., Reception in Orin Smith Lobby (Reception sponsored by Kineta, Inc. and the CIIID)

The Center for Innate Immunity and Immune Disease (CIIID) is new focus center to serve the UW School of Medicine and the Seattle research community. The Center serves to link multiple biomedical disciplines for research, training, and program development. Our focus within the growing field of innate immunity aims to support collaboration for the advancement and translation of basic concepts in immune regulation and immunologic disease into clinical applications for improving human health. This presentation will preview the Center’s structure, research focus, service cores, educational programs, and membership opportunities. (ciiid.uw.edu)

The Department of Immunology gratefully acknowledges the generous contributions in support of this series from the Benaroya Research Institute and the Weiser Education Fund.

The NIH Director's New Innovator Award is part of the High-Risk, High-Reward Research program, the award supports exceptionally creative early career investigators who propose innovative, high-impact projects.

Dr. Jakob von Moltke's work focuses on parasitic worms (helminths) and allergens which both induce a “type 2” immune response, however very little is known about how the immune system first senses these agonists. The Moltke lab aims to uncover how intestinal tuft cells detect helminth infection, thereby employing an entirely new and innovative entry point to understanding type 2 immune sensing. If successful, this work would establish a novel paradigm for the initiation of type 2 immune responses and could provide new targets for therapeutic intervention in helminth infection and allergy. 

Read more about the Moltke Lab project: Sensing of Helminths by Tuft Cells.

   

More About the NIH Director's New Innovator Award

NIH Director's New Innovator Award

The NIH Director's New Innovator Award, established in 2007, supports unusually innovative research from early career investigators who are within 10 years of their final degree or clinical residency and have not yet received a research project grant or equivalent NIH grant.

Department of Immunology announces the 2017-18 seminar series schedule. Check out the 2017–18 Immunology 573 Seminar Series Schedule

RESEARCH TRIANGLE PARK, NC -- As part of its continuing effort to stimulate fundamental research into human infectious diseases, the Burroughs Wellcome Fund — a private foundation making investments in biomedical research and careers for more than 60 years — has invested $6 million in grants to top pathogenesis investigators in the United States.

The 12 recipients of the 2017 Investigators in the Pathogenesis of Infectious Disease Award (PATH) are assistant professors from Columbia, Duke University Medical Center, Harvard School of Public Health, Princeton, Stanford, University of Michigan-Ann Arbor, University of Pennsylvania, University of Utah, University of Washington, University of Wisconsin, Washington University in St. Louis, and Yale.

The PATH program awards $500,000 over a period of five years for faculty at the assistant professor level to study pathogenesis — with the intent of boosting early-career, multidisciplinary scientists, whose innovation in biochemical, pharmacological, immunological, and molecular approaches can create new research pathways to understanding infectious diseases.

“Infectious disease research has to be nimble—new diseases are appearing faster than ever before, and we still don’t know enough about diseases that have been with us for thousands of years,” said BWF President Dr. John Burris. “By focusing on the principles underneath—on understanding the how, where, and why our relationship with infectious agents becomes destructive, the BWF Investigators can get at understanding today’s diseases and tomorrow’s.”

Learn more about PATH and see a list of past awardees at www.bwfund.org/path.

The 2017 PATH Awardees and their Research Focus

Listed by alphabetical order of awardee name.

Catherine Blish, M.D., Ph.D. | Stanford University Training natural killer cells to fight HIV

Caroline Buckee, Ph.D. | Harvard School of Public Health The impact of human red blood cell heterogeneities and dynamics on malaria parasite virulence

Jason M. Crawford, Ph.D. | Yale University A functional metagenomic screen to systematically identify human-bacteria interactions

Elizabeth A. Grice, Ph.D. | University of Pennsylvania Skin microbiome functions in colonization resistance to pathogens

Stacy M. Horner, Ph.D. | Duke University Medical Center Regulation of antiviral host response by RNA modifications

Adam S. Lauring, M.D., Ph.D. | University of Michigan-Ann Arbor The evolution of pathogen virulence and transmissibility

Andrew Mehle, Ph.D. | University of Wisconsin Defining the functional landscape between intracellular pathogens and the host

Marion Pepper, Ph.D. | University of Washington

The development and function of Plasmodium-specific memory B cells

June Round, Ph.D. | University of Utah Influence of the microbiota on neuro-inflammation

Mohammad R. Seyedsayamdost, Ph.D. | Princeton University Deciphering the small molecule vocabulary of human microbiome Streptococci

Christina Stallings, Ph.D. | Washington University Consequences of neutrophil-mycobacteria interactions

Harris Wang, Ph.D. | Columbia University Mapping host-microbe and inter-microbial networks atultra-high spatial resolution

###

Russ Campbell | news@bwfund.org

Insect-transmitted viruses, like Powassan and West Nile, which can attack the brain in some cases, are becoming a growing public health concern. Medical scientists are trying to understand how brain cells try to fend off invading viruses. Recently they have learned that, in a turnabout, a biochemical self-destruct trigger found in many other types of cells appears to guard the lives of brain cells during infection with West Nile virus. 

UW Medicine scientists who this led research found that this chemical pathway doesn’t have to sacrifice brain cells to destroy the viruses and recruit the body’s defenses against infection.

The same chemical pathway can preserve the brain’s nerve cells, or neurons, by using an alternative approach to summon protection.

The self-destruct trigger, a protein called RIPK3 (pronounced rip-3), is better known for activating a certain type of cell death during infection or other damaging events in other parts of the body.  The death of infected cells in this manner is a protective mechanism that helps the body eliminate the infection.

During a West Nile virus infection, however, the activation of RIPK3 in brain cells doesn’t cause them to die. That’s because its signaling within the central nervous system is not the same as in cell types elsewhere in the body. Its brain-specific role implies that there are central nervous system functions for RIPK3 not observed in other tissues.

“There is something special about neurons, perhaps because they are non-renewable and too important to undergo cell death,“ said Andrew Oberst, assistant professor of immunology at the University of Washington School of Medicine. He is the senior author of a recent Cell paper on how brain cells ward off West Nile virus.

“RIPK3 acts as part of the milieu of signals that support anti-viral inflammation in the brain,” said the lead author of the paper, Brian Daniels, a UW Medicine postdoctoral fellow in immunology.   

RIPK3 responds to the presence of West Nile virus in the brain by placing an order for chemokines, the researchers observed.

Daniels explained that these chemicals underlie a successful ousting of West Nile virus. Chemokines attract an influx of infection-fighting white blood cells.

These efforts contribute to the clearance of the virus from the brain, but not by directly stopping replacement virus from reproducing within brain cells. Instead, the brain tissue undergoes a kind of inflammation that restricts the West Nile virus infection.

In a different cell type, such as a fibroblast, the entry of a West Nile virus would result in the cell initiating its own demise.

Their findings, the researchers noted, suggest that additional care might need to be taken in developing and testing drugs against RIPK3 to treat neurodegenerative disorders, brain damage from stroke or injury, and autoimmune diseases of the nervous system such as multiple sclerosis.  Too much interference with RIPK3 in the brain could make it prone to certain viral infections.

Yueh-Ming Loo (left), Andrew Oberst (center) and Brian Daniels in their immunology laboratory at UW Medicine South Lake Union.Yueh-Ming Loo is a UW research assistant professor of immunology and another key scientist on the study. Like Oberst, she is from the UW Center for Innate Immunity and Immune Disease. She’s interested in why certain pathogens like West Nile virus gravitate toward and invade the central nervous system in some people and animals, but not in others.

Not everyone infected with the West Nile virus develops neurological disease. Some don’t even realize they were exposed.

How the body controls brain infections when they do occur, especially with the blood-brain barrier restricting access, is also still poorly understood.

Loo explained that the efforts to subdue the virus in the brain can be a delicate balance.  An inappropriately zealous immune response to the pathogen can inadvertently cause long-term neurological problems.

The UW Medicine researchers conducted part of their studies in mice to learn more about the role of RIPK3 in fighting brain infections. They found that mice that were genetically deficient in RIPK3 were highly susceptible to having West Nile virus overtake the brain. These mice displayed a fatal defect in their ability to produce a chemokine-generated neuroinflammation.

The mouse studies and related lab work, the researchers noted, provide evidence that RIPK3 coordinates the infiltration of disease-fighting cells into the central nervous system during West Nile virus infection.

Central nervous system infections are a “profound and growing burden to global public health,” the researchers noted in discussing the significance of this scientific question.

The project was supported by several grants from the National Institutes of Health (RO1 AI108685, R21 NS101524, U19 AI083019, 1ZIAES1038601) and a National Science Foundation graduate research fellowship (DGE-1256082).

The findings were reported in the Cell paper, “RIPK3 Restricts Viral Pathogenesis via Cell Death-Independent Neuroinflammation.”

By Leila Gray  |  HSNewsBeat  |  Updated 10:00 AM, 05.18.2017

Tagged with: West Nike virusbrainimmunology

 

Contact us about this story.

Patty Murray with Dr. Maron Pepper and Immunology Graduate Students Nicole Arroyo and Fahd al QureshahImmunology graduate students Nicole Arroyo and Fahd al Qureshah, greeted U.S. Senator Patty Murray and Dr. Marion Pepper on April 12, 2017. One by one, several UW Medicine researchers told U.S. Senator Patty Murray (D-Wash) about what cuts to the National Institutes of Health’s budget would mean for their research and their careers. Dr. William Hahn, an infectious disease fellow with the University of Washington’s School of Medicine, works with immunologist Dr. Marion Pepper. He said lack of NIH funding would mean he’d have to find another line of work. He is currently looking at why the body’s defenses don’t seem to remember contact with the malaria parasite from one exposure to the next. 

“Once we figure out the immune memory, and why the body doesn’t seem to have it with this disease, we’re on the way to making a better treatment,” he told Murray, who was in Seattle to visit the immunology labs at UW Medicine’s South Lake Union research campus. 

“You can see I have a lab of 10 people – they are the bright young stars of research – but their training and research depends on NIH grants,” Pepper told Murray after the tour. Cutting NIH funding would mean curtailing or ending new discoveries the researchers might make during their careers, Pepper added.

Read the full article on UW Health Sciences Newsbeat.

Photos: Clare McLean

Article: Barbara Clements, HSNewsBeat

A new Cell paper published by the Oberst Lab reveals breakthrough findings indicating an unexpected diversity in the outcomes of RIPK1 and RIPK3 signaling within the central nervous system not observed in other tissues. Congratulations to Brian P. Daniels, Annelise G. Snyder, Tayla M. Olsen, Susana Orozco, Thomas H. Oguin III, Stephen W.G. Tait, Jennifer Martinez, Michael Gale Jr., Yueh-Ming Loo, and Andrew Oberst.

Cell DOI: (10.1016/j.cell.2017.03.011) Copyright © 2017 Elsevier Inc

Highlights

- Mice lacking RIPK3 are highly susceptible to neuroinvasive West Nile virus
- RIPK3 signaling in WNV-infected neurons results in inflammatory chemokine expression
- WNV-infected, RIPK3-deficient mice display a fatal defect in chemokine-dependent neuroinflammation
- Direct activation of RIPK3 in neurons triggers chemokine production but not cell death

Summary

Receptor-interacting protein kinase-3 (RIPK3) is an activator of necroptotic cell death, but recent work has implicated additional roles for RIPK3 in inflammatory signaling independent of cell death. However, while necroptosis has been shown to contribute to antiviral immunity, death-independent roles for RIPK3 in host defense have not been demonstrated. Using a mouse model of West Nile virus (WNV) encephalitis, we show that RIPK3 restricts WNV pathogenesis independently of cell death. Ripk3−/− mice exhibited enhanced mortality compared to wild-type (WT) controls, while mice lacking the necroptotic effector MLKL, or both MLKL and caspase-8, were unaffected. The enhanced susceptibility of  Ripk3−/− mice arose from suppressed neuronal chemokine expression and decreased central nervous system (CNS) recruitment of T lymphocytes and inflammatory myeloid cells, while peripheral immunity remained intact. These data identify pleiotropic functions for RIPK3 in the restriction of viral pathogenesis and implicate RIPK3 as a key coordinator of immune responses within the CNS.

Read the full Cell article here.

Visualizing Tumor Microenvironments: A postdoctoral position is available in the laboratory of Dr. Michael Gerner to investigate how the spatial organization of innate and adaptive immune cells in tumors influences cancer development and the outcome of immunomodulatory therapy. This is an industry-sponsored collaborative opportunity, the major aim of which is to use multiplex confocal imaging and quantitative image analysis (Gerner et al., Immunity 2012, Immunity 2015) to understand tumor microanatomy during disease and after therapy. An additional goal of this project is to develop novel statistical image analysis platforms to better study the spatial relationships and intercellular interactions of cells in complex 3D tissues.

This position requires PhD level training in immunology, cancer biology, or a related field, and/or extensive expertise in imaging and image processing. Experience with bioinformatics and implementation of customized statistical algorithms is desirable. The successful applicant will join a collaborative and dynamic research environment, and will be able to take advantage of the extremely collegial surroundings provided by the UW’s Department of Immunology and the thriving research environment in Seattle. Opportunity has potential for international travel.

Applications should be sent by email to Dr. Gerner at gernermy@uw.edu. Applicants are requested to send a cover letter, CV, one or two representative publications, and names and contact information of three references.

University of Washington is an affirmative action and equal opportunity employer. All qualified applicants will receive consideration for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, age, protected veteran or disabled status, or genetic information.

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