Children’s Health

It’s a trap! New laboratory technique captures microRNA targets

by Heather Buschman on May 9, 2012 at 9:43 am | 3 Comments

Huricha Baigude, Ph.D., postdoctoral researcher and first author of the study

Human cells are thought to produce thousands of different microRNAs (miRNAs)—small pieces of genetic material that help determine which genes are turned on or off at a given time. miRNAs are an important part of normal cellular function, but they can also contribute to human disease—some are elevated in certain tumors, for example, where they promote cell survival. But to better understand how miRNAs influence health and disease, researchers first need to know which miRNAs are acting upon which genes—a big challenge considering their sheer number and the fact that each single miRNA can regulate hundreds of target genes. Enter miR-TRAP, a new easy-to-use method to directly identify miRNA targets in cells. This technique, developed by Tariq Rana, Ph.D., professor and program director at Sanford-Burnham, and his team, was first revealed in a paper published May 8 by the journal Angewandte Chemie International Edition.

“This method could be widely used to discover miRNA targets in any number of disease models, under physiological conditions,” Rana said. “miR-TRAP will help bridge a gap in the RNA field, allowing researchers to better understand diseases like cancer and target their genetic underpinnings to develop new diagnostics and therapeutics. This will become especially important as new high-throughput RNA sequencing technologies increase the numbers of known miRNAs and their targets.”

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Drug discovery case study: high-throughput screening of TNAP

by Patrick Bartosch on April 11, 2012 at 11:52 am | 0 Comments

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Presence of calcium deposits in a mouse aorta, as revealed by alizarin red staining.

Editor’s note: this is the second in a series of posts highlighting drug screening studies in our Conrad Prebys Center for Chemical Genomics. Read the first post here.

Calcification of the medial layer of arteries is increasingly recognized as an important clinical problem. Medial vascular calcification (MVC) is the major cause of morbidity and mortality in generalized arterial calcification of infancy (GACI), and contributes to cardiovascular deterioration in Kawasaki disease (KD), chronic kidney disease (CKD), as well as in diabetes, obesity, and aging. MVC is thought to result from decreased circulating levels of the mineralization inhibitor, inorganic pyrophosphate (PPi).

Researchers at Sanford-Burnham have revealed that the development of MVC in mouse and rat models is accompanied by up-regulation of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme whose primary function is to hydrolyze PPi, and thus, crucial in determining where mineralization occurs. Preliminary data have proven that upregulation of TNAP is sufficient to cause MVC and Sanford-Burnham scientists have developed potent drug-like inhibitors of TNAP.

Rare bone disorder reveals new insights into autism

by Heather Buschman on March 12, 2012 at 12:00 pm | 0 Comments

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A mouse model of multiple hereditary exostoses (MHE), a rare bone disorder, exhibits autism-like social deficits. Shown here is a comparison of nest-building abilities—one measure of social behavior—by normal and autistic MHE mice.

Children with multiple hereditary exostoses (MHE), an inherited genetic disease, suffer from multiple growths on their bones that cause pain and disfigurement. But beyond the physical symptoms of this condition, some parents have long observed that their children with MHE also experience autism-like social problems.

Buoyed by the support of these parents, researchers at Sanford-Burnham recently used a mouse model of MHE to investigate cognitive function. They found that mice with a genetic defect that models human MHE show symptoms that meet the three defining characteristics of autism: social impairment, language deficits, and repetitive behavior. The study, published online the week of March 12 in the Proceedings of the National Academy of Sciences, also defines the molecular and physiological basis of this behavior, pinpointing the amygdala as the region of the brain causing autistic symptoms.

“There is growing evidence that many autistic people have related genetic defects, or defects that are exacerbated by this one,” said Yu Yamaguchi, M.D., Ph.D., professor in the Sanford Children’s Health Research Center at Sanford-Burnham. Yamaguchi led this study, along with colleagues Fumitoshi Irie, Ph.D. and Hedieh Badie-Mahdavi, Ph.D.

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Exciting clinical trial news for children with inherited bone disease

by Heather Buschman on March 8, 2012 at 9:58 am | 0 Comments

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Enyme replacement therapy ENB-0040 enhances bone formation in patients with hypophosphatasia.

José Luis Millán, Ph.D. and his lab have studied hypophosphatasia, an inherited disease that makes bones dangerously fragile, for the past 15 years. The researchers developed a mouse model of the disease—mice that, like their human counterparts, lack an enzyme called alkaline phosphatase. Then, just about five years ago, scientists from Enobia Pharma approached Millán. They had developed an enzyme replacement therapy called ENB-0040 and they needed someone who could help them test it—someone with a model and with extensive knowledge of hypophosphatasia and the alkaline phosphatase enzyme. So Millán and his team administered it to their mice. Mice with hypophosphatasia usually survive for 20 days at most. When the treated mice were alive at day 21, Dr. Millán knew they were onto something promising.

Mason’s wish

by Heather Buschman on March 2, 2012 at 9:09 am | 4 Comments

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Mason with Dr. Hudson Freeze (left) and philanthropist T. Denny Sanford, big supporter of children's health research, at Sanford-Burnham's third annual Rare Disease Day Symposium

Ten year-old Mason Barto is a sweet Pennsylvania fifth grader almost like any other. Except that he’s lived with a tracheotomy, a permanent feeding tube, and a number of other health problems since birth. Mason’s condition was inherited, but for most of his life no one could pinpoint the genetic cause of his health problems. They didn’t even have a name for it.

Then, a few months ago, Sanford-Burnham’s Dr. Hudson Freeze and his team finally discovered the genetic defect underlying Mason’s health problems and diagnosed him with what’s called a congenital disorder of glycosylation (CDG). In other words, Mason has a mutation in a gene that directs glycosylation—the process by which cells coat proteins with sugars. Lack of sugars disrupts cell growth, differentiation, and communication. There are several different types of CDG and symptoms and severity can vary widely.

While it doesn’t mean there’s an immediate cure for Mason, he is now taking a simple sugar therapy and is beginning to show early signs of improvement. The finding also gives new hope to other children living with this condition.

Today is Rare Disease Day

by Heather Buschman on February 29, 2012 at 10:54 am | 0 Comments

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Rare diseases are roughly defined as conditions affecting fewer than 200,000 people in the United States. Although a relatively small number of people are diagnosed with each individual disorder, there are 6,000 different rare diseases. Added together, these affect 1 in 10 Americans—30 million people.

Today, February 29, is the rarest day of the year and also Rare Disease Day. Last week, we held our 3rd annual Rare Disease Symposium. Today, there are events being held all over the U.S. and the world. Here are just a few:

National Institutes of Health (NIH) is holding a day-long celebration and recognition of the various rare diseases research activities supported by the NIH.

National Organization for Rare Disorders (NORD) will be live-streaming the Rhode Island Rare Disease Foundation Awareness event taking place 6:00-8:00 p.m. ET today in Cranston, RI. NORD is also sponsoring a Handprints on the Hill campaign to encourage everyone to join us in sending an important message to President Obama, members of Congress, and other elected officials.

For more information, check out:
Pictures from Sanford-Burnham’s Rare Disease Day Symposium 2012
Keynote talk by Dr. Eric Green, director of the National Human Genome Research Institute
Video, blog posts, and more from Sanford-Burnham’s Rare Disease Day Symposium 2011
Rare disease research at Sanford-Burnham

5 research areas bringing us closer to personalized medicine

by Heather Buschman on February 24, 2012 at 2:28 pm | 2 Comments

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Eric Green, M.D., Ph.D., director of the National Human Genome Research Institute at the NIH

At Sanford-Burnham’s 3rd annual Rare Disease Day Symposium, held today in La Jolla, Calif., keynote speaker Eric Green, M.D., Ph.D., director of the National Human Genome Research Institute at the NIH, spoke about genomic medicine. Sometimes called “personalized medicine,” or even “precision medicine,” Dr. Green defined this revolutionary field as the idea that health care can be tailored to the individual based on his or her own genomic information.

Dr. Green was there when the human genome was first sequenced in 2001 and he’s now leading the next step—figuring out how to use that information. In his talk, Dr. Green outlined five active research areas that are taking us from what he called “helix to health:”

When the disease is only half the battle…

by Heather Buschman on February 17, 2012 at 10:33 am | 1 comment

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Jennifer Yashari, M.D., both a doctor and a patient, will represent the Neuromuscular Disease Foundation at Sanford-Burnham's annual Rare Disease Day Symposium on February 24.

On February 24, we are holding our 3rd Annual Rare Disease Day Symposium in La Jolla, Calif. One of the speakers will be Jennifer Yashari, M.D., representing the Neuromuscular Disease Foundation. Jennifer is not only a doctor, she’s also a patient. Read excerpts from her story below and join us for the main event next week. If you can’t make it, check back here the following week for video of each talk and more stories.

I grew up being told one thing over and over again by my parents, “All that matters is that you’re healthy. Nothing is as important as your health.” I never fully understood or appreciated the extent to which that was true until six years ago, when I became someone with a disease…

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Finding the cause of Liam’s metabolic disease

by Guest Blogger on February 7, 2012 at 6:39 am | 0 Comments

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Liam

provided by Emory University

Sequencing a patient’s entire genome to discover the source of his or her disease is not routine – yet. But geneticists are getting close.

A case report, published February 2 in the American Journal of Human Genetics, shows how researchers can combine a simple blood test with an “executive summary” scan of the genome to diagnose a type of severe metabolic disease. In the study, researchers at Emory University School of Medicine and Sanford-Burnham used whole-exome sequencing to find the mutations causing a glycosylation disorder affecting Liam, a boy born in 2004.

Whole-exome sequencing reads only the parts of the human genome that encode proteins, leaving the other 99 percent of the genome unread. This method is cheaper and faster than whole-genome sequencing, but is still an efficient strategy for reading the parts of the genome scientists believe are the most important for diagnosing disease. It is estimated that most disease-causing mutations (around 85 percent) are found within the regions of the genome that encode proteins, the workhorse machinery of the cell. The report illustrates how whole-exome sequencing, which was first offered commercially for clinical diagnosis in 2011, is entering medical practice. Emory Genetics Laboratory is now gearing up to start offering whole-exome sequencing as a clinical diagnostic service.

How antipsychotics cause side effects such as obesity and diabetes

by Heather Buschman on January 31, 2012 at 3:15 pm | 3 Comments

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Fred Levine, M.D., Ph.D., director of the Sanford Children’s Health Research Center at Sanford-Burnham

In 2008, roughly 14.3 million Americans were taking antipsychotics—typically prescribed for bipolar disorder, schizophrenia, or a number of other behavioral disorders—making them among the most prescribed drugs in the U.S. Almost all of these medications are known to cause metabolic side effects such as obesity and diabetes, leaving patients with a difficult choice between improving their mental health and damaging their physical health. In a paper published January 31 in the journal Molecular Psychiatry, researchers reveal how antipsychotic drugs interfere with normal metabolism by activating a protein called SMAD3, an important part of the transforming growth factor beta (TGFβ) pathway.

The TGFβ pathway is a cellular mechanism that regulates many biological processes, including cell growth, inflammation, and insulin signaling. In this study, all antipsychotics that cause metabolic side effects activated SMAD3, while antipsychotics free from these side effects did not. What’s more, SMAD3 activation by antipsychotics was completely independent from their neurological effects, raising the possibility that antipsychotics could be designed that retain beneficial therapeutic effects in the brain, but lack the negative metabolic side effects.

New muscle research center opens in San Diego

by Heather Buschman on January 27, 2012 at 6:23 am | 0 Comments

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The new San Diego Skeletal Muscle Research Center will be made up of three core facilities shared by five local institutions.

The National Institutes of Health (NIH) recently awarded a new grant to establish the San Diego Skeletal Muscle Research Center. This new center, led by UC San Diego’s Rick Lieber, Ph.D., Sanford-Burnham’s Mark Mercola, Ph.D., and The Scripps Research Institute’s Velia Fowler, Ph.D., will allow 21 scientists at five different research institutions to combine their expertise and state-of-the-art methods to accelerate research that advances our understanding of skeletal muscles and the diseases that affect them.

Third Annual Rare Disease Day Symposium: February 24

by Heather Buschman on January 18, 2012 at 1:35 pm | 2 Comments

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Gianna Dragatto, a young patient with a rare disease called Congenital Disorders of Glycosylation

What: Third Annual Sanford-Burnham Rare Disease Day Symposium: Identifying and Treating Genetic Diseases in Children
Where: Sanford-Burnham Medical Research Institute, La Jolla, Calif., Building 12 (map)
When: February 24, 2012 – registration opens at 8:00 a.m. PT, program begins at 9:00 a.m. PT
Keynote speaker: Dr. Eric Green, director of the National Human Genome Research Institute

Program and free registration: click here
Symposium flyer: download PDF
Can’t make it? Submit your genetic disease-related questions for panel discussion to Nick at nburchfi@sanfordburnham.org. The symposium will be recorded and available on Sanford-Burnham’s website shortly after the event.

Sanford-Burnham’s successful series of Rare Disease Day symposia is based on the concept that treatment of rare diseases requires participation and exchange among all stakeholders—scientists, physicians, affected patients and their families, support groups, granting agencies, industry, and philanthropists. This year’s event, organized by Hudson Freeze, Ph.D., will focus on glycosylation-based disorders.

A few highlights:

Attendance by several children with Congenital Disorders of Glycosylation who are now benefiting from new therapies
Lunchtime panel discussion for patients and researchers
Presentation by patient advocacy group
Discussion of how one rare disorder relates to Parkinson’s disease

Video and media coverage of last year’s event are available here. For more information about Rare Disease Day USA (February 29, 2012), visit the National Organization for Rare Disorders.

Muscling up with MyoD

by Faculty Contributor on January 13, 2012 at 8:49 am | 1 comment

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Lorenzo Puri, M.D., Ph.D.

Every cell in your body contains the same DNA, with genes coding for many thousands of proteins. Yet a muscle cell makes a very different set of proteins from say, a bone cell, enabling it to perform its muscle-specific job. Lorenzo Puri, M.D., Ph.D. and his lab members study what makes stem cells (precursor cells) choose to produce the proteins that turn them into muscle cells. In doing so, they hope their research will one day help improve strategies for muscle regeneration in patients with muscle wasting diseases, such as muscular dystrophy. While a cure for muscular dystrophy is not yet in sight, the ability to stimulate muscle stem cells to generate mature muscle cells could make a big difference in the lives of patients. By repairing muscles damaged by the disease, muscle regeneration therapy would extend the lives of patients and allow them to function effectively in a whole range of activities that are currently unthinkable for victims of the disease.

A rare approach for a rare disease

by Kristina Meek on November 23, 2011 at 12:29 pm | 2 Comments

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Mayor Hall of Bakersfield cuts the ribbon to open Salon Gianna. Beside him is Gianna, with Dr. Hudson Freeze and her mother, Natalie. On the right are Rocket’s parents, Mia and Taylor Williams, and Gianna’s father, David.

People who care about curing disease can be very creative in finding ways to raise money for research. Whether someone raises money and awareness by walking 60 miles, growing a mustache, or spending $50,000 on a pair of novelty sneakers, people’s passions fuel research funding.

The family that owns Salon Gianna, a beauty salon in Bakersfield, California, is on a mission to find a cure for Congenital Disorders of Glycosylation (CDG). All of their proceeds are earmarked for The Rocket Fund at Sanford-Burnham, which is overseen by Dr. Hudson Freeze. CDG is actually a group of more than 30 rare diseases caused by inherited defects in glycosylation, the process cells use to coat proteins with sugars. Young patients have a broad spectrum of clinical problems often including developmental delay, serious intestinal and liver complications, clotting defects, eye, skin, and other defects. Dr. Freeze’s lab seeks to treat and cure these diseases, often working closely with the families of affected children.

Sisters in science

by Heather Buschman on November 4, 2011 at 9:41 am | 0 Comments

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Dr. David Pearce, Vice President of Research at Sanford Health and Director of Sanford Children’s Health Research Center in Sioux Falls

In late 2007, the Sanford Children’s Health Research Center was established at Sanford-Burnham’s La Jolla campus with a $20 million gift from South Dakota philanthropist T. Denny Sanford through Sanford Health. The gift was the foundation for a long-term partnership between Sanford Health, a large healthcare system based in South Dakota, and Sanford-Burnham. In addition to the center in La Jolla, in 2009 Sanford Health created a sister Children’s Health Research Center in Sioux Falls.

On October 27-28, researchers from both research centers gathered at Sanford-Burnham’s La Jolla campus to share new research directions and stimulate further collaboration at the fourth annual Sanford Children’s Health Research Center Scientific Symposium. Attendees heard overviews from the leaders of both Sanford-Burnham and Sanford Health and learned about Sanford Health’s new BioBank, a repository for patient samples that will help drive personalized medicine and provide fodder for population genomics studies. More than a dozen scientists presented their ongoing studies of embryonic development, type 1 diabetes, brain tumors, lung injury in newborns, and rare inherited conditions such as Batten disease. Hot topics also included stem cells and RNA biology.

Top Stories - Children's Health

It’s a trap! New laboratory technique captures microRNA targets

Drug discovery case study: high-throughput screening of TNAP

Rare bone disorder reveals new insights into autism

Exciting clinical trial news for children with inherited bone disease

Mason’s wish

Today is Rare Disease Day

5 research areas bringing us closer to personalized medicine

When the disease is only half the battle…

Finding the cause of Liam’s metabolic disease

How antipsychotics cause side effects such as obesity and diabetes

New muscle research center opens in San Diego

Third Annual Rare Disease Day Symposium: February 24

Muscling up with MyoD

A rare approach for a rare disease

Sisters in science

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