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New centers to help understand biology, improve diagnoses, of rare mysterious diseases

The National Institutes of Health (NIH) recently awarded approximately $6.8 million in grants to several research teams to study the biology of rare and undiagnosed diseases. The new grants, pending available funds, support studies to better understand the causes and development of these diseases, and to improve the ability of doctors to diagnose them.

Solving Medical Mysteries

The funding establishes two new research centers, including a Model Organisms Screening Center and a Metabolomics Core, as part of the NIH Undiagnosed Diseases Network (UDN). In addition, six new awards fund research to explore how specific genes and their variations may cause disease in UDN patients. Finally, a one-year grant supports a central biorepository for storing UDN research participant tissue samples.

"The Undiagnosed Diseases Network is aimed at improving the diagnoses of patients with unsolved diseases," said UDN co-coordinator Anastasia Wise, Ph.D., a program director at the National Human Genome Research Institute (NHGRI), a part of NIH. "The recently funded projects support research studies in the laboratory to understand how these diseases work and to help with diagnoses."

UDN investigators collaborate with specialists from many medical disciplines to diagnose patients with unknown disorders. The UDN, established in 2012, now consists of seven clinical sites located throughout the country, in addition to two DNA sequencing centers, a Model Organisms Screening Center, a Metabolomics Core, a central biorepository and a coordinating center. The UDN is supported by the NIH Common Fund and builds on the success of the Undiagnosed Diseases Program, an NIH initiative that focuses on identifying and treating patients with difficult-to-diagnose diseases at the NIH Clinical Center.

Model Organisms Screening Center

At the Model Organisms Screening Center, scientists use zebrafish and fruit flies as models to examine how differences in the DNA code - called variants - can cause a disease. Scientists at the center, led by Hugo Bellen, D.V.M., Ph.D., at the Baylor College of Medicine in Houston, and Monte Westerfield, Ph.D., at the University of Oregon in Eugene, will eventually study the potential disease-causing effects of approximately 200 gene variants per year that are thought to be involved in unknown diseases in UDN patients.

Scientists genetically modify the zebrafish and fruit fly to study the gene variant in question. They add a human gene variant or turn off the gene activity of a similar zebrafish or fly gene variant, and watch the resulting effects, if any, on the organism.

"It's often very difficult to know which genes and variants contribute to disease," said Dr. Wise. "By using these model organisms, we can test the gene variants and potentially help narrow down which variants are the most promising to follow up on for more in-depth studies examining their function."

Center investigators will receive approximately $2.5 million over three years. The National Institute of Neurological Disorders and Stroke (NINDS) manages the center.

Metabolomics Core

UDN Metabolomics Core investigators, led by Thomas Metz, Ph.D., at the Department of Energy's Pacific Northwest National Laboratory in Richland, Washington, and David Koeller, M.D., at Oregon Health & Science University in Portland, will receive approximately $1.8 million over three years to study metabolites - products in cells from various biochemical activities in the body - to try to determine their potential connection to diseases in patients.

To do this, researchers will use different types of information from several sources. They will pool test results from analyzing metabolites in UDN patients with information about the patients' genomic make-up and results from various medical tests. Taken together, this information will provide clues to physicians and researchers about disease mechanisms and diagnoses in patients, said Dr. Wise. The core is managed by the NIH National Center for Advancing Translational Sciences.

Gene Function Research Grants

As genome sequencing reveals new gene variants in UDN patients, researchers want to understand how the variants' function or dysfunction affects a disease or condition. The NIH Common Fund and NINDS awarded six, two-year gene function research grants totaling approximately $2.5 million to study what specific genes do in rare, difficult-to-diagnose diseases. In this third round of UDN gene function research awards, scientists will study the role of genes in central nervous system development and neurological disorders.

The grants, managed by NINDS and the National Institute of General Medical Sciences, include awards to the following centers:

  • University of Michigan, Ann Arbor: $418,838
    Principal Investigator: Bing Ye, Ph.D.
  • University of Kansas Medical Center, Kansas City: $407,700
    Principal Investigator: Peter Smith, Ph.D.
  • Roswell Park Cancer Institute Corp., Buffalo, New York: $458,460
    Principal Investigator: Y. Eugene Yu, Ph.D.
  • University of Oregon, Eugene: $391,500
    Principal Investigator: Monte Westerfield, Ph.D.
  • Boston University (Charles River Campus), Boston: $441,990
    Principal Investigator: Angela Ho, Ph.D.
  • Emory University, Atlanta: $390,000
    Principal Investigator: Randy Hall, Ph.D.

The NIH Common Fund also awarded just over $72,000 for one year to Vanderbilt University Medical Center in Nashville, Tennessee, to oversee and manage a central biorepository for storing UDN participant biological tissue samples used in DNA sequencing and other studies. This allows the samples to be collected and stored in one place, where they can be distributed to other investigators and allow easier access for UDN investigators.

Last updated: April 20, 2016