RNA Biology

Stem cells 101

by Communications Staff on October 8, 2012 at 10:52 am | 2 Comments

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.

Making it easier to make stem cells

by Heather Buschman, Ph.D. on September 25, 2012 at 8:01 am | 1 comment

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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.

AACR award boosts pediatric cancer research

by Heather Buschman, Ph.D. on May 17, 2012 at 6:11 am | 0 Comments

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Jing Crystal Zhao, Ph.D., assistant professor

At their recent meeting, the American Association for Cancer Research (AACR) named Jing Crystal Zhao, Ph.D. as a recipient of the 2012 AACR-Aflac Inc. Career Development Award for Pediatric Cancer Research. This award will allow Zhao and her research team to study the role of long non-coding RNA in gene regulation and the development of pediatric cancer.

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

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

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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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Sisters in science

by Heather Buschman, Ph.D. 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.

An easier (and safer) route to stem cell therapies

by Bruce Lieberman on October 31, 2011 at 9:32 am | 0 Comments

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Chao-Shun Yang, graduate student in Dr. Tariq Rana's lab and first author of the study

Many research labs around the world are focused on finding the most effective ways to reprogram an adult cell (a skin cell, for example) into induced pluripotent stem cells (iPSCs)—that is, cells that have the ability to develop into other tissues in the body. These cells not only offer researchers powerful tools to study a particular patient’s individual disease, but they have the potential to therapeutically replace diseased or damaged tissue in the patient from whom the cells originated.

Most experiments to reprogram adult cells employ viruses as vehicles to carry four particular genes—called reprogramming factors—into the nucleus of a cell. But genetic engineering carries its own risks, including the chance that these cells will continue replicating, eventually forming a tumor. What’s more, scientists are not exactly sure what the reprogramming factors do, on the molecular level, to promote the generation of iPSCs.

Could there be a safer and more predictable way to alter the expression of genes in cells, thereby reprogramming their DNA so they revert to their earlier, more malleable state?

A medical revolution

by Josh Baxt on May 18, 2011 at 8:04 am | 1 comment

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Nanoparticles, like this micelle, may be the future of medicine. (Image by Peter Allen, UC Santa Barbara College of Engineering)

A syndicated article that recently appeared in the Orlando Sentinel, the Los Angeles Times and other outlets described several revolutionary technologies that will change medicine in the coming decade.

In particular, the piece highlighted how new genomic technologies can personalize treatment to individual patients; how robotic surgery will help surgeons perform complex procedures on people thousands of miles away; and how new classes of diagnostic tests will allow physicians to discover diseases earlier, when they are most treatable.

The article included insights from Dr. Ranjan Perera, associate professor at Sanford-Burnham’s Lake Nona campus, and Dr. Jamey Marth, who directs the U.C. Santa Barbara–Sanford-Burnham Center for Nanomedicine. Dr. Marth is particularly excited about nanomedicine’s potential to enhance both diagnosis and treatment:

“Today’s scientists work at the molecular and atomic level with nanoparticles, to harness these biomachines that detect and bind to diseased cells. The nanoparticle then fuses with that sick cell and delivers its cargo — drugs or imaging agents.”

Read ‘Revolution is at hand’ for breakthroughs in medicine.

One cell’s junk is another’s treasure

by Heather Buschman, Ph.D. on May 10, 2011 at 10:02 am | 0 Comments

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Melanoma cells, with nuclei in blue and SPRY4-IT1 in green. (Image courtesy of the Perera lab)

Melanoma cells, with nuclei in blue and the lncRNA SPRY4-IT1 in green. (Image courtesy of the Perera lab)

Scientists used to think RNA was mostly just a messenger molecule that carries protein-making instructions from a cell’s nucleus to the cytoplasm. But scientists now estimate that 97 percent of human RNA doesn’t actually code for proteins at all. A flurry of research in the past decade has revealed that some types of non-coding RNAs switch genes on and off and influence protein function.

The best studied non-coding RNAs are the microRNAs, but Dr. Ranjan Perera and his collaborators are discovering that levels of a relatively understudied group of RNAs – long, non-coding RNA (lncRNA) – are altered in human melanoma. Their study, published online May 10 by the journal Cancer Research, shows that one lncRNA called SPRY4-IT1is elevated in melanoma cells, where it promotes cellular survival and invasion.

“Non-coding RNA used to be considered cellular junk. But we and others have been asking the question – if it doesn’t code for proteins, what does it do in the cell?” said Dr. Perera, associate professor at Sanford-Burnham’s Lake Nona campus in Orlando, Fla. “We’re especially interested in determining what roles microRNAs and lncRNAs play in the genesis and development of human melanomas.”

Melanoma is one of the rarest forms of skin cancer, but it is also the most deadly.

New recipe for iPS cells

by Heather Buschman, Ph.D. on February 2, 2011 at 4:00 am | 2 Comments

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Stem cells are ideal tools to understand disease and develop new treatments because they can self-renew (generate more cells in a dish) and differentiate (become a wide variety of cell types). They can be differentiated into heart muscle cells, for example, which could then be used to replace damaged heart tissue. Where do scientists get stem cells? In the early days of stem cell research, investigators could isolate stem cells from pathological specimens of the brain or bone marrow. More recently, they have figured out how to make a special kind of stem cell called an induced pluripotent stem cell (iPS cell) from almost any type of adult cell, such as a skin cell. Researchers can then use iPS cells to study human development or to create “disease in a dish”, a technique that allows them to model an individual patient’s specific disease and screen for personalized treatments.

But generating iPS cells can be an arduous task. Reprogramming differentiated adult cells into iPS cells requires so many steps and so much time that the efficiency rate is very low – you might end up with only a few iPS cells even if you started with a million skin cells. So a team set out to improve the process. In a paper published February 1, 2011 in The EMBO Journal, they uncovered microRNAs (miRNAs) that are important during reprogramming and exploited them to make the transition from skin cell to iPS cell more efficient.

“We identified several molecular barriers early in the reprogramming process and figured out how to remove them using miRNA,” said Dr. Tariq Rana, senior author of the study. “This is significant because it will enhance our ability to use iPS cells to model diseases in the laboratory and search for new therapies.”

Reining in melanoma with MicroRNA

by Heather Buschman, Ph.D. on November 1, 2010 at 2:12 pm | 2 Comments

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Dr. Ranjan Perera (left) with post-doctoral researcher Dr. Joseph Mazar

Dr. Ranjan Perera with post-doctoral researcher Dr. Joseph Mazar

Skin cancer is the most common cancer in the United States. Melanoma is one of the rarest forms of skin cancer, but it is also the most deadly. At Sanford-Burnham’s Lake Nona campus, Dr. Ranjan Perera’s lab is studying what causes melanocytes (pigment-producing skin cells) to divide abnormally, ultimately forming melanoma. In a study published today in the journal PLoS ONE, a team led by Dr. Perera and post-doctoral researcher Dr. Joseph Mazar show that melanocyte growth and the cancer’s ability to invade other tissue is at least partially controlled by abnormal expression of microRNAs (miRNAs) – small strands of genetic material that may play a major role in numerous diseases by interfering with proteinproduction.“We’ve identified one specific miRNA, called miR-211, that could be used not only as a novel diagnostic marker for early melanoma detection, but also as a therapeutic target,” explains Dr. Perera, associate professor in Sanford-Burnham’s RNA Biology Program and senior author of the study.

Hibernating herpes viruses

by Heather Buschman, Ph.D. on October 14, 2010 at 9:39 am | 1 comment

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Herpes viruses are good at hiding. They infect human cells and lay dormant there until replication is activated by stress or some other environmental factor. One type, Kaposi’s sarcoma-associated herpesvirus (KSHV), is one of only a few viruses known to cause cancer.

In a study that appeared online September 17 in the journal EMBO Reports, Sanford-Burnham’s Dr. Tariq Rana and colleagues found that KSHV stays quiet by expressing certain microRNAs (miRNAs), small strands of genetic material that interfere with protein production.

“KSHV dormancy is believed to be essential for tumor formation, yet some forms of cancers caused by the virus have also been linked to viral reactivation,” explains Dr. Rana, professor and director of Sanford-Burnham’s RNA Biology Program. “This study helps us better understand the KSHV life cycle, thus providing new insight into how the virus causes cancer in some populations.”

RNApalooza

by Josh Baxt on May 13, 2010 at 1:14 pm | 1 comment

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Until recently, RNA had been thought of simply as a messenger, transferring encoded information from our DNA to ribosomes, which produce proteins. But in the past 10 years, scientists have found that specific types of RNA, called microRNA and RNAi, play a significant role in controlling which genes are turned on or off—processes that could have a profound impact on human health.

On May 7, scientists from around the country came to Sanford-Burnham’s 32nd Annual Scientific Symposium to discuss the implications of these small RNAs and how we can use them to fight disease.

It’s a small RNA world

by Josh Baxt on April 23, 2010 at 6:00 am | 0 Comments

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We’re oversimplifying a little, but our genetic code works like this: DNA codes for messenger RNA (mRNA); mRNA takes that coded message out of the nucleus; tiny machines called ribosomes read the message in the mRNA and produce proteins; proteins do most of the work in the cell. However, there is another player in this pathway that has only come to light relatively recently—microRNAs(miRNAs).

Top Stories - RNA Biology

Stem cells 101

What are stem cells?

Are there different types of stem cells?

Read More

Making it easier to make stem cells

AACR award boosts pediatric cancer research

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

Sisters in science

An easier (and safer) route to stem cell therapies

A medical revolution

One cell’s junk is another’s treasure

New recipe for iPS cells

Reining in melanoma with MicroRNA

Hibernating herpes viruses

RNApalooza

It’s a small RNA world

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