$20.6M NIH Grant Establishes School of Dentistry-Led Human Virome Characterization Center

The National Institutes of Health (NIH) has awarded a $20.6M million grant over five years to establish one of five Human Virome Characterization Centers (HVCC), leveraging UCLA leadership and the collective expertise of interdisciplinary scientists nationwide to advance understanding of the virome's role in human health and disease across the oral–gut–brain axis. (NIH U54 AG089335 Human Virome Characterization Center for the Oral-Gut-Brain Axis)

Dr. Yvonne Hernandez-Kapila – UCLA School of Dentistry Associate Dean of Research and holder of the Felix and Mildred Yip Endowed Chair – will serve as contact primary investigator (PI) for the largest NIH grant awarded to the School of Dentistry in its 60-year history. Among the four multiple primary investigators (MPIs) is Dr. Clara Lajonchere, deputy director of UCLA’s Institute for Precision Health (IPH). The Center's discovery team will comprise diverse specialists from UCLA, Baylor College of Medicine, the Mayo Clinic, UC San Diego, USC, Penn State, and the NIH/National Institute of Dental and Craniofacial Research (NIDCR).

This initiative is part of the NIH Common Fund  Human Virome Program (HVP), which seeks to identify the diversity of viruses that naturally inhabit the human body, often referred to as the virome. Of the five HVCCs, the UCLA-led initiative is the only one headquartered in a dental school.

“This novel effort is an enormous undertaking and it promises to change medicine. The HVP aims to characterize the ‘healthy’ human virome, remove technological roadblocks, and define the virome’s role in human health,” Dr. Hernandez-Kapila said.

Building on the achievements of the NIH Human Microbiome Project (HMP) – which transformed knowledge of the human bacteriome – the HVCCs will address the largely uncharted human virome and its potential effects on health. Although estimates suggest that over 380 trillion viruses inhabit the human body, much remains unknown about what constitutes a “healthy” virome – viruses that infect bacteria, viruses that replicate in human cells, and viruses that pass through the body without replicating – especially across the lifespan.

“The HMP led to the discovery of new biomarkers for health and disease and gave us novel approaches for developing therapeutics, and we expect the HVP will have a similar impact on public health,” Hernandez-Kapila added. “The first step is to define what constitutes a ‘normal’ virome to establish a baseline for health. This foundational knowledge will be critical for maintaining health and developing novel therapeutics and diagnostic tools.”

HVCC research specific to Dr. Hernandez-Kapila’s team will concentrate on the oral, gut, and brain systems where viral communities may play significant roles in immune regulation, neurodevelopment, and disease processes. The Center aims to characterize virome richness, diversity, and structure in healthy individuals across different age groups and ethnic backgrounds. This will establish a baseline for identifying virome alterations associated with disease, potentially enhancing early detection, diagnosis, and treatment.

Dean and Professor Paul H. Krebsbach praised the achievement, saying: “This NIH grant underscores the outstanding thought leadership at the UCLA School of Dentistry, particularly the groundbreaking human virome research already conducted by the Hernandez-Kapila Lab. Being selected as one of only five nationwide studies is a significant recognition of our institution’s expertise. With this grant, UCLA, our project partners, and other sites are poised to drive transformative discoveries with boundless potential for societal impact.”

Five Core Functions of the HVCC
The HVCC anchored at the UCLA School of Dentistry will comprise five overlapping, interacting cores, each designed to support a specific aspect of research and operations:

1. Administrative: This central hub will coordinate between research teams, patient cohorts, and other cores across the country, ensuring smooth operations and integrating efforts with the broader HVP initiative.
2. Biospecimen Collection: This core will source high-quality biospecimens from both existing and prospective cohorts. It will leverage resources from diverse populations, including those at UCLA, Mayo Clinic, NIH/NIDCR, and future cohorts like the All of Us program, to build a rich dataset of virome samples.
3. Biospecimen Analysis: Using state-of-the-art sequencing technologies, this core will analyze biospecimens to profile the virome, uncovering new insights into virus types and interactions within the oral–gut–brain axis.
4. Data Analysis and Submission: This core will process complex datasets, applying advanced bioinformatics, data science, and machine learning techniques. The goal is to analyze viral diversity and community structures, assess their stability across time, and understand their clinical and physiological interactions.
5. Ethical, Legal, and Social Implications (ELSI): To ensure ethical oversight and address social determinants of health, the ELSI Core will conduct research and create guidelines for ethically handling participant data and biospecimens. This core’s research will examine social, ethical, and legal aspects to foster inclusivity and transparency.

Timeline and Resource Sharing
Commencing in the first quarter of 2025, the initiative's first year will focus on establishing essential infrastructure including dedicated staff, defining research protocols and data management, and activating an HVCC website for sharing updates. Monthly meetings between PIs and core leaders will continue throughout the life of the project to ensure constant and closed-loop communication.

At the one-year anniversary and every year thereafter, the HVCC will host a meeting for all team members to present summaries of their activities and discuss areas of collaboration, synergies, and engagement with other HVP consortium members. In conjunction with the annual meeting in years three, four, and five, a joint symposium hosted by HVCC member institutions will be organized to ensure effective communication and dissemination of findings and to highlight other expert speakers in the field.

During this discovery phase, $250,000 in funding will be set aside each year to support multiple Collaborative Pilot Projects (CPPs) to capitalize on findings, validate new tools, methods, and approaches, and characterize novel viruses.

Aligning with NIH’s commitment to data sharing, the HVCC will establish a robust open access infrastructure for sharing findings and best practices in virome research with the scientific community and the public.

About the MPIs

• Yvonne Hernandez-Kapila, D.D.S., Ph.D., (Contact PI) is a professor in the UCLA School of Dentistry’s Sections Biosystems and Function and Periodontics, associate dean of research, and holder of the Felix and Mildred Yip Endowed Chair. With over 30 years of NIH-funded research and more than 150 peer-reviewed publications, her work has significantly advanced the understanding of the oral microbiome's role in oral cancer and periodontal disease.
   
• In addition to her leadership role with the Institute for Precision Health at UCLA, Clara Lajonchere, Ph.D., serves as an adjunct professor in the David Geffen School of Medicine Department of Neurology. Her research has focused on psychiatric genetics and neurogenomics, leading clinical and research programs for organizations such as Autism Speaks and directing the NIH Center for Genomic and Phenomic Studies in Autism at USC.
  
  "The collaboration among members of this expert team will help unlock the mysteries of the human virome, revealing its profound impact on disease and health across diverse populations,” Dr. Lajonchere said. “Together, our shared expertise will drive breakthroughs that benefit all of humanity”.
   
• Joseph Petrosino, Ph.D., chief scientific innovation officer, professor and chair of Virology and Microbiology at Baylor College of Medicine and director of the Alkek Center for Metagenomics and Microbiome Research, which has pioneered the use of sequencing technologies to study microbial communities. As a founding member of the Human Microbiome Project, he is recognized for advancing microbiome-based therapeutic research.
  
  “We are thrilled that the NIH supports this important research area; the role of viruses in human health and disease,” Dr. Petrosino said. “We are excited to work with Dr. Hernandez-Kapila and the talented team she has assembled on this novel oral-gut-brain program and expect many novel therapeutic and diagnostic targets to emerge from these provocative studies.”
   
• James Cerhan, M.D., Ph.D., is a professor of epidemiology and the Ralph S. and Beverly Caulkins Professor of Cancer Research at the Mayo Clinic in Rochester, Minn., where he also serves as the enterprise deputy director for population science and cancer control in the Mayo Clinic Comprehensive Cancer Center and founding director of the Mayo Clinic Biobank, a longitudinal biobank of over 50,000 participants. His research uses epidemiologic methods to investigate cancer causes and outcomes in human populations.
   
• Janice Lee, D.D.S., M.D., M.S., (Lead Intramural Co-investigator, unfunded), is NIDCR clinical director and chief of the Craniofacial Anomalies and Regeneration Section, and is the deputy director for Intramural Clinical Research at NIH.  She is an oral/maxillofacial surgeon with expertise in the treatment and study of craniofacial disorders who oversees large cohort studies at the NIDCR, managing healthy craniofacial tissue biospecimens studies and data systems.

Daniel J. Weisenberger, Ph.D. – a distinguished molecular biologist and genomics expert with over 20 years of experience in scientific writing, program management, and education – began serving as HVCC program manager on Jan. 21 and is based at the UCLA School of Dentistry. Additional info on the MPIs and leadership teams in each of the HVCC’s five core functional areas is available in this downloadable PDF.