February 13, 2018 (SEATTLE, WASH.) — The Center for Infectious Disease Research (CID Research) has been awarded a grant from the National Institute of Allergy and Infectious Diseases, one of the U.S. National Institutes of Health, to take a systems-level approach to the critical problem of tuberculosis (TB) infection, specifically focusing on the progression from infection to disease, and variability of treatment. The research ultimately seeks to catalyze new, transformative interventions, such as diagnostics, drugs and vaccines.
This award results from an international competition and allows CID Research to build on the success of a program originally started in 2008. The new grant is for $17.2 million over another five-year period and will address unanswered questions about TB progression and treatment response. Titled “Omics for TB: Response to Infection and Treatment,” the grant allows researchers to study many sides of TB infection simultaneously, uncovering the mysteries of how and in whom TB causes illness. It brings together leaders in the techniques and approaches that will be required to tackle this pandemic, with an explicit mandate to apply sophisticated, systems-level approaches to complex human samples.
Globally, three in 10 people harbor latent TB; 10 million new cases of active TB are diagnosed each year; and nearly 500,000 cases are multidrug-resistant. Drug resistance is an enormous treatment challenge, with 3.7 percent of new cases and 20 percent of previously treated cases resistant to at least one course of drug treatment. Totally drug resistant TB has also emerged in several countries. The research will focus on defining the critical steps on the path from TB infection to disease, and on understanding how the TB bacterium thwarts drug treatment.
“To combat the global health crisis that is TB and deliver new diagnostics, drugs and a vaccine, we desperately need new approaches and new understanding of the disease,” said John Aitchison, president of CID Research and co-investigator on the program. “Systems biology approaches enable big data generation, analysis and modeling that enable insights and prediction not possible any other way. This consortium will apply systems biology and predictive modeling to understand TB pathogenesis, and will lead to new methods for diagnoses, treatment and prevention.”
TB’s transitions, from initial infection, to active disease, to treatment success or failure involve complex processes and nuanced interactions between the bacterium, the human immune system, and anti-TB therapies.
The grant integrates the expertise of several scientists at CID Research, in collaboration with the Institute for Systems Biology (ISB), Stanford University and Weill Cornell Medical College.
- Alan Aderem, Ph.D., CID Research, is the Co-Principal Investigator (Co-PI) of the program and Co-PI of the Disease Progression project
- David Sherman, Ph.D., CID Research, is the Co-PI of the program and PI of the Treatment Response project
- Kevin Urdhal, M.D., Ph.D., CID Research, is the Co-PI of the Disease Progression project.
- John Aitchison, Ph.D., CID Research, is the PI of the Technology Core
- Garry Nolan, Ph.D., Stanford University, is a co-investigator in the Technology Core
- Kyu Rhee, M.D., Ph.D., Weill Cornell Medical College, is a co-investigator in the Technology Core and in the Treatment Response project
- Nitin Baliga, Ph.D., Institute for Systems Biology, is the PI of the Modeling Core
The team of researchers comprises experts in TB pathogenesis, host response and drug response, along with authorities in the field of systems biology and biotechnology.
“With this program, we hope to identify genes and networks in both humans and bacteria that make TB a uniquely devastating disease,” said Sherman. “We have an incredible opportunity to apply the most sophisticated tools to the most complex disease samples and provide the first comprehensive picture of how this notoriously elusive pathogen evades both the immune system and drug treatment.”
The OTB program has had a significant and widespread impact on the field of TB research in the five years since the program commenced: more than 10,000 people from more than 100 different counties have accessed data on the OTB online research portal. Publications generated through OTB have already produced 100-plus citations, and consortium members receive requests for input or assistance on a weekly basis, often leading to new collaborations and publications. This active engagement and interaction with the TB research community is one extremely valuable outcome of the OTB program.
Although TB is the leading infectious disease killer worldwide, and the biggest disease killer of HIV-positive people, it receives far less research funding than either HIV/AIDS or malaria.