Heart Disease

Patients’ own skin cells are transformed into heart cells to create “disease in a dish”

by Heather Buschman, Ph.D. on January 27, 2013 at 10:01 am | 4 Comments

In this study, researchers used an ARVD/C patient's skin cells to make induced pluripotent stem cells. Then they used those stem cells to generate ARVD/C patient-specific heart cells (shown here in green). These heart cells provide a valuable “disease in a dish” model that can be used to study ARVD/C and test new treatments.

Most patients with an inherited heart condition known as arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) don’t know they have a problem until they’re in their early 20s. The lack of symptoms at younger ages makes it very difficult for researchers to study how ARVD/C evolves or to develop treatments.

A new stem cell-based technology created by 2012 Nobel Prize winner Shinya Yamanaka, M.D., Ph.D., helps solve this problem. With this technology, researchers can generate heart muscle cells from a patient’s own skin cells. However, these newly made heart cells are mostly immature. That raises questions about whether or not they can be used to mimic a disease that occurs in adulthood.

In a paper published January 27 in Nature, researchers unveil the first maturation-based “disease in a dish” model for ARVD/C. The model was created using Yamanaka’s technology and a new method to mimic maturity by making the cells’ metabolism more like that in adult hearts. For that reason, this model is likely more relevant to human ARVD/C than other models and therefore better suited for studying the disease and testing new treatments.

Diabetic fruit flies support buzz about dietary sugar dangers

by Heather Buschman, Ph.D. on January 17, 2013 at 5:33 am | 1 comment

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Cardiac fibrosis (shown in purple), a hallmark of heart disease, is clearly increased in fruit flies on a high-sugar diet (right), as compared to flies on a normal diet (left).

First fruit fly model of diet-induced type 2 diabetes shows how high-sugar diet affects the heart and reveals new therapeutic opportunities

Regularly consuming sucrose—the type of sugar found in many sweetened beverages—increases a person’s risk of heart disease. In a study published January 10 in the journal PLOS Genetics, researchers at Sanford-Burnham Medical Research Institute and Mount Sinai School of Medicine used fruit flies, a well-established model for human health and disease, to determine exactly how sucrose affects heart function. In addition, the researchers discovered that blocking this cellular mechanism prevents sucrose-related heart problems.

“Our study reveals a number of specific sugar-processing enzymes that could be targeted with therapies aimed at reducing sucrose’s unhealthy effects on the heart,” said Karen Ocorr, Ph.D., research assistant professor at Sanford-Burnham and the study’s corresponding author.

Stem cells 101

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

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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.

California’s stem cell agency boosts heart disease research at Sanford-Burnham

by Heather Buschman, Ph.D. on September 12, 2012 at 6:29 am | 0 Comments

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Huei-Sheng Vincent Chen, Ph.D.

The California Institute for Regenerative Medicine (CIRM) has awarded a $1.58 million grant to Huei-Sheng Vincent Chen, Ph.D., associate professor at Sanford-Burnham. Chen’s proposal was one of 28 new projects funded as part of CIRM’s Basic Biology IV awards program, which supports basic research aimed at increasing our understanding of stem cells and how to work with them. This new funding will allow Chen and his team to develop personalized models of inherited heart conditions using stem cells derived from patients’ own skin cells. They will also use these models to develop new therapies.

“Most heart conditions that cause sudden death in young people—those under age 35—are caused by inherited genetic mutations. But doctors have a hard time treating these types of heart conditions because not much is known about how genetic mutations cause them and because they’re usually diagnosed late in the disease process,” Chen said. “At the moment, the only way to treat these inherited heart diseases is to implant a heart-shocking device to prevent sudden death. More frequently, however, no therapy is available to slow the disease’s progression.”

New heart failure trigger could change the way cardiovascular drugs are made

by Heather Buschman, Ph.D. on July 18, 2012 at 10:01 am | 1 comment

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APJ’s yin-yang role in cardiac function: the receptor APJ serves a dual function in heart health, depending on how it’s activated. While APJ enhances heart health upon binding the hormone apelin (green), APJ can also trigger heart enlargement and failure when it senses certain mechanical changes (red).

In their quest to treat cardiovascular disease, researchers and pharmaceutical companies have long been interested in developing new medicines that activate a heart protein called APJ. But researchers at Sanford-Burnham Medical Research Institute and the Stanford University School of Medicine have now uncovered a second, previously unknown, function for APJ—it senses mechanical changes when the heart is in danger and sets the body on a course toward heart failure. This means that activating APJ could actually be harmful in some cases—potentially eye-opening information for some heart drug makers. The study appears July 18 in Nature.

“Just finding a molecule that activates APJ is not enough. What’s important to heart failure is not if this receptor is ‘on’ or ‘off,’ but the way it’s activated,” said Pilar Ruiz-Lozano, Ph.D., who led the study. Ruiz-Lozano, formerly assistant professor at Sanford-Burnham, is now associate professor of pediatrics in the Stanford University School of Medicine and adjunct faculty member at Sanford-Burnham.

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Personalized Medicine 101

by Amelia Tomas on April 21, 2011 at 3:54 pm | 1 comment

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Dr. Steven Smith, Scientific Director for the Florida Hospital Sanford-Burnham Translational Research Institute, demonstrates sophisticated equipment used in metabolic studies.

Dr. Steven Smith, Scientific Director for the Florida Hospital Sanford-Burnham Translational Research Institute, cares for a patient.

In 2003, the completion of the human genome project gave us an unprecedented amount of genetic information. From this, a new clinical concept is emerging: personalized medicine.

Conventional medical care generalizes treatment to all patients with a particular disease. But since a disease is as individual as the person who has it, casting a wide therapeutic net has its limitations. For one, patients with a certain genetic makeup might not respond to a particular drug as well as patients with different genetics, or they might experience different side effects. As personalized medicine becomes a reality, it could rectify these less-than-ideal situations.

From the diagnostic point-of-view, personalized medicine is a shift from reactive to proactive. Based on a person’s health, genetic, and environmental profiles, doctors practicing personalized medicine could assess a patient’s risk for acquiring a genetic disease before any symptoms develop. This might allow them to target the specific genes that account for illness (the BRCA1/BRCA2 genes that predispose a woman to breast cancer, for example), incorporate a prevention strategy, and monitor those genes over time. When it comes to treatment, personalized drugs could be prescribed based on an individual’s molecular “build” and targeting treatment where it will do the most good and the least harm.

Targeting Arterial Plaque

by Josh Baxt on April 19, 2011 at 4:00 am | 1 comment

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Dr. Erkki Ruoslahti

Atherosclerotic plaque is the fatty material that builds up on arterial walls, where it can lead to heart disease and stroke. Atherosclerosis is currently treated with dietary changes, angioplasty (which uses a balloon to move the plaque aside) or more invasive procedures. Using drugs to break up these fatty plaques would be an enticing alternative, but delivery poses a problem. How do we precisely target the therapeutic agent to the diseased areas, leaving healthy tissues unaffected?

Dr. Erkki Ruoslahti and colleagues at Sanford-Burnham and UC Santa Barbara may have found a solution. For many years, Dr. Ruoslahti has been using specially designed peptides (pieces of proteins) to target cancer and other diseases. In a paper published online on April 11 by the Proceedings of the National Academy of Sciences, the Ruoslahti lab reports the discovery of a new peptide that can guide drugs or imaging agents specifically to atherosclerotic plaques.

Patients’ own skin cells are transformed into heart cells to create “disease in a dish”

Diabetic fruit flies support buzz about dietary sugar dangers

Stem cells 101

What are stem cells?

Are there different types of stem cells?

Read More

California’s stem cell agency boosts heart disease research at Sanford-Burnham

New heart failure trigger could change the way cardiovascular drugs are made

Personalized Medicine 101

Targeting Arterial Plaque

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