In addition to our regular CRI Activities Update, this month’s Research Focus highlights collaborative work from the team led by Aravinda de Silva, PhD, MPH, Professor of Microbiology and Immunology and a member of the UNC Institute for Global Health and Infectious Diseases.

Activities Update: We held our Medical Foundation Board of Visitors meeting on February 23. In addition to an update on the Children’s Hospital provided by Kevin Kelly, MD, Interim Chair Department of Pediatrics, presentations were given by Elizabeth Fitzgerald, MD, Assistant Professor in Pediatrics, Emergency Medicine; Cheryl Jackson, MD, Chief, Division of Pediatric Medicine, Medical Director, Pediatric Emergency Department; and Nina Jain, MD, Associate Professor of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Director UNC Children’s Diabetes Program. They spoke to the needs of our Children’s Hospital, the ground breaking work we are doing, and the heartbreak and benefits of our global pediatric health initiative. The CRI was also highlighted as a research initiative in the UNC Children’s Campaign goals.

For our CRI lecture series, we are thrilled to have identified speakers for the remainder of the year, see: https://childrensresearch.unc.edu/lecture-series/. Going forward into 2019, we are looking into collaborations with other schools/departments/centers for the CRI lecture series. Also on our web site, we have added a funding page that lists funding opportunities brought to our attention: https://childrensresearch.unc.edu/research/funding-opportunities/. Despite progress on our web site, our research page remains in the works while we program a function to be able to list all of our researchers by photo in a “tiled” manner. We have information on many researchers that needs to be added.  The build for this has taken longer than anticipated due to platform migration of the SOM to WordPress. The good news is we should have increased functionality with the migration, and are hopeful to be able to include more of our researchers on our website in the near future.

New this winter, we have begun meeting individually with junior researchers to develop Individual Development Plans (IDP), review timelines, identify mentors, and flesh out specific aims. The concept is to serve as “process mentors,” complementing the existing mentorship services and faculty mentors, and focusing on our pediatric Clinician Scientists to provide support and guidance. We will continue to meet as needed with the Pediatric Scholars Program (PSP) and Pay-it-Forward, Move-it-Forward to review specific aims, proposals, presentations, and manuscripts.

Finally, we continue to identify themes for Pediatric Team Science and look to be proactive for funding opportunities. We are looking across the department, school, and beyond at potential ways to collaborate (eg, Child Environmental Health and Development; Immunity and Inflammation; Molecular Medicine and Gene Therapy; Developmental Precision Medicine; Family-centered Pediatric Care and Preventive Health). We continue to work closely with NC TraCS, the Office of Research Development, the Medical Foundation, and Corporate & Foundation Relations Office to align researchers and funding opportunities. We are also navigating the university system to gather pilot data towards the ultimate goal of developing and funding a patient registry.

Reminder: Aravinda de Silva, PhD, MPH is presenting at our next CRI monthly luncheon seminar series, on Tuesday, March 13, 2018 at 12:15 pm in the Bioinformatics Auditorium (room 1131). Please mark your calendars. We look forward to seeing you there!

Research Focus of the Month:

Aravinda de Silva, PhD

The Children’s Research Institute is dedicated to pediatric research collaborations across the university and beyond, which is why we are excited to highlight the research of Aravinda de Silva, PhD, MPH in this month’s update. Dr. de Silva is a Professor of Microbiology and Immunology and a member of the UNC Institute for Global Health and Infectious Diseases. He has a long-standing interest in vector-borne infectious diseases, including disease pathogenesis and human immunological response. Currently, research in the de Silva lab centers on 2 mosquito-transmitted viruses belonging to the flavivirus family of arthropodborne viruses, dengue and Zika.  This family of viruses also includes West Nile virus, yellow fever virus, and tick-borne encephalitis virus.

Although traditionally uncommon in the United States, these viruses represent a significant threat to global health. Dengue viruses cause a spectrum of symptoms that range from sub-clinical infections to dengue fever and dengue hemorrhagic fever/dengue shock syndrome. Dengue hemorrhagic fever, which can be fatal, is more common in babies and young children. Children with chronic diseases (eg, diabetes, asthma) appear to be at greater risk of severe dengue disease as well.  While Zika is commonly asymptomatic or mild and self-limited, Zika is distinct from other flaviviruses in that it is not solely transmitted by mosquitoes, but is also transmitted sexually, as well as by crossing the placenta in pregnant women and resulting in developmental abnormalities (congenital Zika syndrome). Primary prevention for both dengue and Zika is through community efforts to control vector mosquito populations. A vaccine is available for dengue; however, the response to the vaccine has been limited because there are multiple distinct serotypes of dengue virus and the immune system’s response to dengue virus is complex.

To further elucidate the pathological mechanisms and immune responses, for developing potential treatments/preventative measures, Dr. de Silva’s lab studies human B cell and antibody response to dengue and Zika viruses.  They are particularly interested in understanding how dengue antibodies protect people from infection under some conditions yet enhance viral replication and disease under other conditions. By studying dengue and Zika both in the lab and in the field, Dr. de Silva and his collaborators are able to take their research from bench to bedside. The main translational impact of their work is pursuing the development of safe and effective vaccines.

Through his collaborations with colleagues at UNC, La Jolla Institute of Allergy and Immunology, Ministry of Health of Sri Lanka, and Sri Lanka’s Genetech Research Institute, Dr. de Silva’s lab has been able to identify genotypes of dengue serotypes, DENV1 and DENV3, which correspond to mild versus severe outbreaks. Additional collaborations at UNC include clinical researchers in the Departments of Infectious Disease, Obstetrics and Gynecology and Family Medicine as well as researchers of basic science in Departments of Public Health, Microbiology, Genetics and Cell Biology. Dr. de Silva has also partnered with investigators at the NIH, Johns Hopkins, UC Berkeley, Duke University, Vanderbilt University, and the University of Vermont. In addition, Dr. de Silva has long standing international collaborations in Colombia and Nicaragua, as well as Sri Lanka, where he has worked with colleagues over the past 20 years to study changing epidemiology of dengue in the region. His lab is also partnering with Sanofi and Takeda Pharmaceutical Company towards the development of dengue and Zika vaccines.

Links to more information about Dr. de Silva and a selection of publications are listed below:

Dr. de Silva’s Laboratory

Matthew H. Collins, Eileen McGowan, Ramesh Jadi, Ellen Young, Cesar A. Lopez,
Ralph S. Baric, Helen M. Lazear, Aravinda M. de Silva. Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection. Emerging Infectious Diseases. 2017:23 (5) 773–781.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403059/pdf/16-1630.pdf

Patel B, Longo P, Miley MJ, Montoya M, Harris E, de Silva AM (2017) Dissecting the human serum antibody response to secondary dengue virus infections. PLoS Neglected Tropical Diseases 2017:11(5) e0005554.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444852/pdf/pntd.0005554.pdf

Grifoni A, Angelo MA, Lopez B, et al. Global Assessment of Dengue Virus-Specific CD4+ T Cell Responses in Dengue-Endemic Areas. Frontiers in Immunology. 2017;8:1309. doi:10.3389/fimmu.2017.01309.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646259/

Gallichotte EN, Widman DG, Yount BL, et al. A New Quaternary Structure Epitope on Dengue Virus Serotype 2 Is the Target of Durable Type-Specific Neutralizing Antibodies. Lipkin WI, ed. mBio. 2015;6(5):e01461-15. doi:10.1128/mBio.01461-15.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620467/