A pair of NIH awards for JAX

The Jackson Laboratory gets $12.8 million in grants to research chronic fatigue and eye disease

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FARMINGTON, Conn.—Bolstering its mission to discover genomic solutions for disease, The Jackson Laboratory (JAX), a non-profit medical research facility, has been awarded two National Institutes of Health (NIH) grants. The first, a $10.6-million research center five-year grant to JAX professor Dr. Derya Unutmaz, is part of a multi-institutional research effort to understand and treat myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a highly debilitating and poorly understood chronic disease. The second is a $2.2-million grant from the NIH’s National Eye Institute toward developing a treatment for macular degeneration.
Both of these syndromes—chronic fatigue and macular degeneration—have been diagnosed more frequently as the baby boomer population ages.
The JAX location in Farmington, Conn., will be one of three ME/CFS Collaborative Research Centers that will be awarded $10.6 million, together with a Data Management and Coordinating Center.
Between 836,000 and 2.5 million Americans suffer from ME/CFS, according to the U.S. Centers for Disease Control and Prevention. Symptoms include profound fatigue, cognitive dysfunction, sleep abnormalities and pain, which may vary widely in severity.
One theory attributes the cause of ME/CFS to the components and interplay among a patient’s immune system, metabolism and microbiome (the collection of microorganisms that live on or inside the body).
“For a long time we knew very little about the biological basis of ME/CFS,” Unutmaz says. “Patients presented with a combination of cognitive and debilitating but general physical symptoms. Thus, it has been very difficult to diagnose and there is a great need to develop reliable biomarkers for diagnosis.”
But by using systems biology approaches, “we now have the opportunity to determine the biological correlations of this chronic disease that can pave the way for precise diagnosis and develop novel therapies to help patients,” Unutmaz adds.
Working with another JAX professor, Dr. Peter Robinson—who is considered a leader in computational biology—and assistant professor and microbiome expert Dr. Julia Oh, as well as researchers at collaborating institutions, Unutmaz and colleagues will generate one of the largest and most highly detailed collections of clinical and biological ME/CFS patient data that can be analyzed using novel computational technologies such as machine learning approaches.
The goal of the research center is to “transform the landscape of knowledge of ME/CFS” by tracking down the immune, metabolic and microbiome changes that lead to the disease “so that the knowledge gained through the work of the centers becomes an inflection point towards the goal of treating a disease that causes terrible suffering in millions of patients,” Unutmaz says.
Under the grant, Unutmaz will collaborate with Dr. Cindy Bateman and Dr. Suzanne Vernon at Bateman Horne Center of Salt Lake City; Dr. Xudong Yao of the department of chemistry at the University of Connecticut in Storrs, Conn.; and Dr. Alison Motsinger-Reif of the statistics department at North Carolina State University in Raleigh, N.C.
“ME/CFS is unique to each person, from what caused their disease to the array of symptoms,” says Vernon. “Despite this, we’ve put one ‘label’ on it. This has hindered our ability to diagnose and treat it effectively. We need patients to help us identify these unique characteristics of ME/CFS. [This effort] puts patients at the center of this fundamental first step for a deeper understanding of this disease.”
The National Eye Institute grant went to JAX associate research scientist Dr. Krish Kizhatil to support research into glaucoma, an eye disease expected to affect 80 million people by the end of the decade. His research could lay the groundwork for identifying more effective glaucoma treatments.
The disease of glaucoma is manifested by a progressive, irreversible vision loss resulting from damage to the optic nerve which occurs from an increase in intraocular pressure (IOP) resulting from poor drainage of aqueous humor, the clear fluid that fills the front of the eye, he says. A structure known as Schlemm’s canal is an important gatekeeper in the drainage process.
“Current glaucoma therapy is based on reducing elevated IOP,” Kizhatil says. “But no current drug is able to reduce IOP very effectively, indicating the pressing need for improved therapies.”
Unfortunately, drug development has been hampered by a limited understanding of the molecular basis of IOP elevation, he adds.
For this reason, Kizhatil is focused on determining the molecular mechanisms functioning in the Schlemm’s canal inner wall that facilitate aqueous humor drainage and control IOP. Elevated IOP likely results when these molecular pathways do not function properly. Thus, the identification of these molecular pathways will allow identification of new targets for a more rational approach to development of effective IOP reducing drugs.
Kizhatil’s glaucoma research really began picking up speed when mice were introduced to the lab of JAX professor and Howard Hughes Medical Institute investigator Dr. Simon W.M. John. The John lab was a pioneer in using mouse for glaucoma studies and among the first to show that mice have a Schlemm’s canal that is very similar to humans.
In 2014 Kizhatil was the first author of a paper from the John lab which, using mice, determined that the Schlemm’s canal was a unique vessel with features common to both blood and lymphatic vessels. Kizhatil has identified a gene that is a key regulator of lymphatic development and function is expressed in the inner wall of the Schlemm’s canal. This gene appears to control IOP.
Kizhatil will use the NIH grant to fund his exploration of this candidate gene, which he expects to yield critical new information on the mechanisms regulating IOP.

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