Children's Pediatric Research & Clinical Care
ERVIN EPSTEIN, MD
He'd like to cure skin cancer.
"If you take a number of Caucasians of European descent and sit in them in the sun, some of them will develop basal carcinomas, some will develop melanomas and some won't develop anything at all," said Dr. Epstein. "If you do the same with people from Japan or China, the number developing skin cancers will be one-tenth the number in the Caucasian group of cancer developers. Some of this is random, but some of it is genetic, and we'd like to understand that."
At CHORI's Center for Cancer and Center for Genetics, Dr. Epstein’s research focuses primarily on skin carcinomas and on identifying therapeutic options that might help prevent tumors from developing. This research will also help us better understand internal cancers. More>>
JULIE SABA, MD, PhD
By studying the humble fruit fly, researchers discovered a new
therapeutic agent that may help prevent cancer.
"Studying developmental biology – the fruitfly, the worm, yeast – is often given a bad rap, but these kinds of studies can be surprisingly enlightening and clinically relevant if the investigative team approaches the research from a translational perspective,” says Dr. Saba. That's the approach Dr. Saba’s group took when they discovered that certain kinds of cells were dying in a study of the developmental biology of a mutant fruit fly with very high levels of SDs.
"Sphingolipid metabolites are small molecules in the cell that serve signaling functions in the control of life and death pathways,” explains Dr. Saba. “This means that they play a role in turning cell death on or off, which was why we were interested in their elevations being so high in this particular fruit fly.”
On further investigation, Dr. Saba discovered that they could actually use the SDs to induce cell death in the fly. When Dr. Saba’s group realized that SDs were also found in soy products, they put two and two together in a rather innovative way.
"Soy has been touted as one of the foods that may be protective against colon cancer, and there are many things in soy that could be responsible for that," Dr. Saba says. “We suspected, however, that perhaps one of the critical components to the benefits of soy was this same family of lipids, which in this case might be inducing cell death and increasing cell turnover in the epithelial, or surface cells, of the colon.”
Although cell death does not sound like a good thing and can indeed contribute to pathology, it is also part of the normal process the body uses to remove unhealthy or mutant cells, providing what Dr. Saba refers to as a "cancer surveillance" function. Preventative colon cancer strategies often focus on the same process – ways to get rid of those cells that might be damaged – and thus more prone to turning into cancer – as quickly as possible, which was why Dr. Saba’s team was particularly interested in SDs. In a series of different experiments described in detail in the Cancer Research publication, Dr. Saba and her colleagues evaluated SDs both at the cellular level and in animal models of colon cancer with promising results.
BRUCE AMES, PhD
He’d like everyone to know Popeye was right... "I'm strong to the finish cause I eats me spinach!"
Bruce Ames and Joyce McCann have been looking closely at Vitamin K. Vitamin K is concentrated in dark green plants such as spinach or Swiss chard, and is either not present or present in only small amounts in most multivitamin pills.
Their new analysis of research suggests that optimal dietary intakes of vitamin K can help prevent age-related conditions such as bone fragility and heart disease.
Vitamin K is known as the "Koagulation" vitamin because about half of the 16 known proteins that depend on vitamin K are necessary for blood coagulation. The other vitamin K-dependent proteins are involved in a variety of different functions involving the skeletal, arterial, and immune systems. What this suggests is that optimal dietary intakes of vitamin K can help prevent age-related conditions such as bone fragility and heart disease—and let us all get to the finish a bit stronger.
JULIE SABA, MD, PhD
She’d like to decode the mysteries of genetics to learn new ways to detect, monitor and treat cancer.
Cell death, known as apoptosis, is a natural part of life. Cells suffering cellular or DNA damage, and those dislodged from their natural environment, may undergo apoptosis.
This means apoptosis may even kill cancer cells if they’re dislodged from a primary tumor during metastasis, the spread of cancer to other parts of the body. Chemotherapy and radiation, which cause DNA damage in cells, can also cause apoptosis in cancer cells.
But DNA damage may also lead to cancer-causing mutations, including those that slow or prevent apoptosis.
This means researchers like Dr. Saba may learn new ways to fight cancer by better understanding how apoptosis works. Loss of apoptotic responses can help cancer develop, progress and even become resistant to anti-cancer drugs.
This makes it critical that scientists like Dr. Saba are able to better understand apoptosis: It will help them learn new ways to detect, monitor and treat cancer. More>>
TRUDY FORTE, PhD
She’d like to use nano-science to kill brain tumors.
Traditional treatment of the brain tumor gioblastoma multiforme (GBM), has limited success. Normally there is no better than a one-year survival rate from the time of diagnosis.
But CHORI scientist Trudy Forte, PhD, and her colleagues may have discovered a path to a new drug delivery system. It’s a Trojan Horse method for delivering anti-tumor drugs to GBM.
GBM cancer cells readily take up low density lipoproteins (LDL) through their skins, while normal brain cells don’t. So if you wrap LDLs around an anti-GBM drug, the GBM tumor will suck up the hidden drugs, but normal brain cells won’t
Unfortunately, natural LDL derived from plasma is very difficult to work with. So Forte designed an artificial LDL nanoparticle — the Trojan Horse.
For the first time, Forte’s research team has successfully demonstrated that synthetic LDL nanoparticles — loaded with a potent cancer-killing drug — can be directed into cancer cells for targeted drug delivery.
Once safety and effectiveness has been established in lab animals, clinical studies using nano-LDL could provide new hope to cancer patients. Dr. Forte’s work could open a whole new frontier in the treatment of GBM and other cancers. More>>
GREGORY MOE, PhD
He’d like to change sugar into an effective cancer vaccine.
CHORI researcher Gregory R. Moe, PhD, and his team have been pioneering research on a little known sugar molecule found in cancer cells and other pathogens. This work could hold the key to developing a broadly applicable cancer vaccine, as well as other therapies for cancer.
Dr. Moe, of the CHORI Centers for Cancer, and Immunobiology and Vaccine Development, discovered the sugar molecule — called Neu (short for de-N-acetyl sialic acid or neuraminic acid) — while working on a meningitidis vaccine .
“Sialic acid is one of the most important carbohydrates in the human body because it is involved in so many different processes critical to cell development,” said Dr. Moe.
Three things make Neu very interesting in the fight against cancer.
• Normal human cells don’t appear to make Neu.
• Where Neu is found – and in great quantity – is in the cells of many different cancers.
• Neu has a unique structure that makes it ideally suited for vaccine development.
Targeting Neu for cancer therapies or vaccines is so promising that the Moe lab is already working on development with two different biotech companies.
Dr. Moe plans to test the vaccines and therapies in animals, with the longer-term goal of establishing a safety and effectiveness threshold to take it to the final step of clinical trials with humans. More>>
JAMES FEUSNER, MD
He’d like to offer the greatest opportunity for survival to every cancer patient.
James Feusner, MD, is the director of Children Hospital’s nationally renowned Oncology department. He is responsible for the major clinical research efforts of the Cancer Center at Children’s Hospital Oakland Research Institute (CHORI).
Center researchers strive to identify the most effective treatment for specific types of cancers. They also investigate which tumor characteristics may be connected to patient ethnicity or to patient exposure to environmental carcinogens.
As members of the Children’s Oncology Group (COG) — the largest cooperative pediatric clinical trials group in the nation — clinicians and scientists at Children’s Hospital design and conduct clinical research trials that aim to improve long-term outcomes for all children with malignant tumors. Dr Feusner is the principal investigator for all Children’s Oncology Group protocols at Children’s Hospital.
Dr. Feusner also chair’s Children’s Hospital’s Tumor Board, a multidisciplinary team that makes formal treatment recommendations for clinical patients. Dr. Feusner is working toward meaningful advances in the prevention, diagnosis and treatment of pediatric malignancies. More>>