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Top Stories - Children's Health

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.
Rare bone disorder reveals new...

Sanford-Burnham researchers discover the molecular basis of autistic symptoms in children with a...

The three children in this study, from left to right: Oliver, Edward, and Amira-Zoe.
Children with rare disease CDG...

Sanford-Burnham researchers discover that several children born with rare diseases called Congenital...

Normal cells containing green fluorescent protein (left) don't glow. In contrast, cells from a child with a glycosylation disorder (right) light up, signaling a genetic defect.
Molecular “Bat Signal”...

Dr. Hudson Freeze and his lab use green fluorescent proteins to search for known and previously...

Skeletal myospheres ("mini muscles") generated by adding MyoD and BAF60C to embryonic stem cells
Building “mini muscles”...

Researchers discover that the protein BAF60C is necessary for generating "mini muscles" from stem...

Children with rare disease CDG don’t have mutation in every cell type

by Heather Buschman, Ph.D. on May 10, 2013 at 6:01 am | 1 comment
Full Article
The three children in this study, from left to right: Oliver, Edward, and Amira-Zoe.

The three children in this study, from left to right: Oliver, Edward, and Amira-Zoe.

Children born with rare, inherited conditions known as Congenital Disorders of Glycosylation, or CDG, have mutations in one of the many enzymes the body uses to decorate its proteins and cells with sugars. Properly diagnosing a child with CDG and pinpointing the exact sugar gene that’s mutated can be a huge relief for parents—they better understand what they’re dealing with and doctors can sometimes use that information to develop a therapeutic approach. Whole-exome sequencing, an abbreviated form of whole-genome sequencing, is increasingly used as a diagnostic for CDG.

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Building “mini muscles” from stem cells

by Heather Buschman, Ph.D. on March 20, 2013 at 8:48 am | 0 Comments
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Skeletal myospheres ("mini muscles") generated by adding MyoD and BAF60C to embryonic stem cells

Skeletal myospheres ("mini muscles") generated by adding MyoD and BAF60C to embryonic stem cells

To make “mini muscles” from stem cells, you need the protein BAF60C.

Pier Lorenzo Puri, Ph.D., and his team study what makes a muscle cell just that—a muscle cell. They’re especially interested in applying that information to regenerate new muscle for people with muscular dystrophy.

Last year, the team discovered that two proteins called MyoD and BAF60C work together to mark the DNA of precursor cells, setting them on a course to become muscle cells. When the MyoD/BAF60c complex receives the right signals, it unwinds the cell’s genome and begins the process of producing muscle-specific proteins. This chain of events eventually triggers these precursor cells—those that hang out in our normal muscle tissue—to mature into new muscle cells.

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3 common health conditions that are benefiting from rare disease research

by Heather Buschman, Ph.D. on February 28, 2013 at 3:15 pm | 0 Comments
Full Article
José Luis Millán, Ph.D. (left) and William A. Gahl, M.D., Ph.D., Rare Disease Day 2013

José Luis Millán, Ph.D. (left) and William A. Gahl, M.D., Ph.D., Rare Disease Day 2013

Today we held our fourth annual symposium marking Rare Disease Day. As keynote speaker William A. Gahl, M.D., Ph.D., noted, “it takes a village” to diagnose, treat, and care for people with rare diseases. By “village,” he meant parents, advocates, doctors, basic scientists, clinical researchers, government officials, and philanthropists—all of whom were represented at the event. Gahl is clinical director of the National Human Genome Research Institute (NHGRI) and director of the NIH Undiagnosed Diseases Program

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Rare Disease Day 2013: live webcast

by Heather Buschman, Ph.D. on February 20, 2013 at 11:52 am | 0 Comments
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Dr. José Luis Millán and a young patient with hypophosphatasia

Dr. José Luis Millán and a young patient with hypophosphatasia

February 28 is Rare Disease Day and you’re invited to join our fourth annual Rare Disease Day Symposium by live webcast.

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Top 10 most-read blog posts of 2012: #4

by Heather Buschman, Ph.D. on December 28, 2012 at 5:00 am | 0 Comments
Full Article
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.

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.

Rare bone disorder reveals new insights into autism

Originally published March 12, 2012

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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Top 10 most-read blog posts of 2012: #5

by Heather Buschman, Ph.D. on December 27, 2012 at 5:00 am | 0 Comments
Full Article
Fred Levine, M.D., Ph.D., director of the Sanford Children’s Health Research Center at Sanford-Burnham

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

How antipsychotics cause side effects such as obesity and diabetes

Originally published January 31, 2012

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.

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Top 10 most-read blog posts of 2012: #10

by admin on December 22, 2012 at 5:00 am | 0 Comments
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Liam

Liam

Finding the cause of Liam’s metabolic disease

Originally published February 7, 2012

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.

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“Junk DNA” drives embryonic development

by Heather Buschman, Ph.D. on December 3, 2012 at 6:04 am | 0 Comments
Full Article
Differentiating mouse embryonic stem cells (green = mesoderm progenitor cells, red = endoderm progenitor cells). The microRNAs identified in this study block endoderm formation, while enhancing mesoderm formation.

Differentiating mouse embryonic stem cells (green = mesoderm progenitor cells, red = endoderm progenitor cells). The microRNAs identified in this study block endoderm formation, while enhancing mesoderm formation.

An embryo is an amazing thing. From just one initial cell, an entire living, breathing body emerges, full of working cells and organs. It comes as no surprise that embryonic development is a very carefully orchestrated process—everything has to fall into the right place at the right time. Developmental and cell biologists study this very thing, unraveling the molecular cues that determine how we become human.

“One of the first, and arguably most important, steps in development is the allocation of cells into three germ layers—ectoderm, mesoderm, and endoderm—that give rise to all tissues and organs in the body,” explains Mark Mercola, Ph.D., professor and director of Sanford-Burnham’s Muscle Development and Regeneration Program in the Sanford Children’s Health Research Center.

In a study published November 14 in the journal Genes & Development, Mercola and his team, including postdoctoral researcher Alexandre Colas, Ph.D., and Wesley McKeithan, discovered that microRNAs play an important role in this cell- and germ layer-directing process during development.

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Five things learned at Sanford-Burnham’s annual postdoc & grad student symposium in La Jolla

by Heather Buschman, Ph.D. on November 14, 2012 at 6:11 am | 0 Comments
Full Article
Symposium attendees await the announcement of Best Talk and Best Poster awards (Photo by Karolina Kucharova)

Symposium attendees await the announcement of Best Talk and Best Poster awards (Photo by Karolina Kucharova)

Each year, the Sanford-Burnham Science Network, our organization of postdoctoral researchers and graduate students, holds a symposium for young scientists to practice presenting their work and gain valuable feedback from their peers and our faculty members. This year, the La Jolla group’s event was held at the Sanford Consortium for Regenerative Medicine.

Here are five random things we learned last week at the 11th annual symposium:

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Stem cells 101

by Communications Staff on October 8, 2012 at 10:52 am | 2 Comments
Full Article
Sanford-Burnham's Stem Cell Research Center

Congratulations to John B. Gurdon and Shinya Yamanaka on winning the 2012 Nobel Prize in Physiology or Medicine! They received the award today for their “discovery that mature cells can be reprogrammed to become pluripotent.” In other words, these scientists figured out how to turn a normal adult cell, such as a skin cell, into a stem cell that has the potential to become any other type of cell in the body. Read below to learn more about stem cells and how they are revolutionizing medical research.

What are stem cells?

Stem cells are special because each is like a blank slate. Once it’s given the proper instruction, a stem cell can specialize and become any type of cell in the body—brain, heart, muscle, and more. Stem cells also have the ability to reproduce themselves indefinitely, renewing the supply.

Are there different types of stem cells?

Embryonic stem cells only exist during an organism’s development, when it is an embryo. These cells are pluripotent, meaning they have the capacity to become any cell type in the body.

Adult stem cells exist in fully developed organisms. They are more limited than embryonic stem cells—they are multipotent rather than pluripotent. These stem cells usually can only become a few types of specialized cells, based on the tissue from which they originate.

Induced pluripotent stem cells (iPSCs) are pluripotent, much like embryonic stem cells. iPSCs are produced in the laboratory by genetically reprogramming any adult cell, such as a skin cell.

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Long-term investments in research pay off

by Kristina Meek on September 26, 2012 at 10:43 am | 0 Comments
Full Article
Dr. Fred Levine worked tirelessly to discover a potential therapeutic for diabetes.

Dr. Fred Levine worked tirelessly to discover a potential therapeutic for diabetes.

Dr. Fred Levine, director of our Sanford Children’s Health Research Center, started searching for potential diabetes drugs in 2005. Back then, Sanford-Burnham didn’t have a high-throughput drug screening center. It didn’t even have a children’s health research center.

One day, Dr. Levine was conferring with his colleague Dr. Mark Mercola, a heart researcher. Dr. Mercola was using some modest drug screening equipment set up in a converted office down the hall from his laboratory. He was screening chemical compounds with the hope of finding a few they could further explore as potential drugs for treating heart disease. Dr. Levine thought the same technique might lead to potential treatments for type 1 (juvenile) diabetes.

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Making it easier to make stem cells

by Heather Buschman, Ph.D. on September 25, 2012 at 8:01 am | 1 comment
Full Article
Induced pluripotent stem cells (iPSCs) generated using a kinase inhibitor

Induced pluripotent stem cells (iPSCs) generated using a kinase inhibitor

The process researchers use to generate induced pluripotent stem cells (iPSCs)—a special type of stem cell that can be made in the lab from any type of adult cell—is time consuming and inefficient. To speed things up, researchers at Sanford-Burnham turned to kinase inhibitors. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth. As they outline in a paper published September 25 in Nature Communications, the team found several kinase inhibitors that, when added to starter cells, help generate many more iPSCs than the standard method. This new capability will likely speed up research in many fields, better enabling scientists around the world to study human disease and develop new treatments.

“Generating iPSCs depends on the regulation of communication networks within cells,” explained Tariq Rana, Ph.D., program director in Sanford-Burnham’s Sanford Children’s Health Research Center and senior author of the study. “So, when you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier.”

According to Tony Hunter, Ph.D., professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and director of the Salk Institute Cancer Center, “The identification of small molecules that improve the efficiency of generating iPSCs is an important step forward in being able to use these cells therapeutically. Tariq Rana’s exciting new work has uncovered a class of protein kinase inhibitors that override the normal barriers to efficient iPSC formation, and these inhibitors should prove useful in generating iPSCs from new sources for experimental and ultimately therapeutic purposes.” Hunter, a kinase expert, was not involved in this study.

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NIH New Innovator Award helps Sanford-Burnham scientist pursue high-risk, high-reward project

by Heather Buschman, Ph.D. on September 13, 2012 at 6:01 am | 0 Comments
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Duc Dong, Ph.D.

Duc Dong, Ph.D.

The National Institutes of Health (NIH) Office of the Director today announced that Duc Dong, Ph.D., assistant professor at Sanford-Burnham Medical Research Institute (Sanford-Burnham), will receive a New Innovator Award. These awards are intended to help researchers pursue big ideas with the potential to transform scientific fields and speed the translation of research into improved health.

Dong’s big idea is to grow replacement organs in an adult animal, using a new technology his lab recently developed. He and his team will genetically reprogram cells in zebrafish to induce new tissue development. Zebrafish, a valuable model for studying human development and disease, will allow the researchers to rapidly screen genes and chemicals important for efficient genetic reprogramming in a living organism.

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Mending a broken heart—with a molecule that turns stem cells into heart cells

by Heather Buschman, Ph.D. on August 2, 2012 at 9:01 am | 1 comment
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Stem cell-derived cardiomyocytes (heart muscle cells) expressing a green fluorescent protein

Stem cell-derived cardiomyocytes (heart muscle cells) expressing a green fluorescent protein

For years, scientists have been looking for a good source of heart cells that can be used to study cardiac function in the lab, or perhaps even to replace diseased or damaged tissue in heart disease patients. To do this, many are looking to stem cells. Researchers at Sanford-Burnham Medical Research Institute, the Human BioMolecular Research Institute, and ChemRegen, Inc. have been searching for molecules that convert stem cells to heart cells for about eight years—and now they’ve found one. Writing in the August 3 issue of Cell Stem Cell, the team describes how they sifted through a large collection of drug-like chemicals and uncovered ITD-1, a molecule that can be used to generate unlimited numbers of new heart cells from stem cells.

“Heart disease is the leading cause of death in this country. Because we can’t replace lost cardiac muscle, the condition irreversibly leads to a decline in heart function and ultimately death. The only way to effectively replace lost heart muscle cells—called cardiomyocytes—is to transplant the entire heart,” said Mark Mercola, Ph.D., director of Sanford-Burnham’s Muscle Development and Regeneration Program and senior author of the study. “Using a drug to create new heart muscle from stem cells would be far more appealing than heart transplantation.”

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Meet 7 trail-blazing female scientists

by Heather Buschman, Ph.D. on July 9, 2012 at 12:28 pm | 0 Comments
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Dr. Alessandra Sacco

Dr. Alessandra Sacco

Can you name a present-day female scientist? If not, check out today’s issue of U-T San Diego to meet seven female scientists blazing new trails in San Diego, including our own Dr. Alessandra Sacco:

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