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Sanford-Burnham Science Blog

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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.

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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.”

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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.

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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.”

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DNA 101

by Heather Buschman, Ph.D. on September 21, 2010 at 4:04 pm | 44 Comments
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DNA is short for deoxyribonucleic acid. Two chains of four chemical bases (abbreviated A, T, C and G) make up DNA and act as a cell’s recipe book to make proteins. The particular sequence of a DNA chain – meaning the precise order of the four chemical bases – determines what protein will be made. A DNA segment beginning with ATTCGC would produce a very different protein than one that starts with CCGTAT. This can be likened to adjusting the order of letters in a word. Though the letters are the same, the meaning changes. For example,  act means something very different than cat.

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Two Paths to Drug Discovery

by Josh Baxt on July 8, 2010 at 3:54 pm | 1 comment
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The Conrad Prebys Center for Chemical Genomics was recently profiled in the Orlando Sentinel. In the article, Dr. Greg Roth described how the center’s robotic screening systems can sift through thousands of chemical compounds to find the few that can alter a protein’s behavior and perhaps even become a new treatment.

“The robotic arms can fill miniature test-tube “wells” so tiny that 1,536 of them fit on a plate the size of an index card. Using such small test tubes allows researchers to save money on chemicals and compounds.”

In a separate article, the MIT Technology Review profiled Regulus Therapeutics, a startup biotech investigating the therapeutic potential of microRNAs (miRNAs), small, non-coding nucleic acids that are involved in cell signaling. Understanding how they function could have a profound impact on how we treat a variety of diseases. Dr. Peter Linsley, Chief Technology Officer for Regulus, recently presented at Sanford-Burnham’s annual scientific symposium. In the article, Sanford-Burnham faculty member Dr. Sumit Chanda explained the importance of miRNAs:

“First discovered in the 1990s, misbehaving miRNAs have been linked to several diseases, including cancer and heart failure. Drug developers hope these molecules will prove to be particularly effective drug targets because manipulating just one seems to suppress several disease-linked proteins–whereas most biotech drugs only target individual proteins.”

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