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Previous TTCF Award Recipients

2012 TTCF Grand Prize Recipient

Tom Belle Davidson, M.D.
Assistant Professor of Pediatrics
Division of Pediatric Hematology/OncologyTom Belle Davidson with Dr. Devaskar and Beth Friedman

Dendritic Cell Vaccination for Pediatric High-Grade Glioma Patients

Brain tumors in the pediatric population have poor prognosis and account for the highest mortality rate of all childhood cancers. Those who do achieve long-term survival often suffer from severe side
effects, including intellectual impairment, motor and hormonal deficits, and growth delay, from aggressive therapies. Of all the pediatric brain tumors, high-grade gliomas remain the largest challenge, with few treatment options available and an overall five-year survival rate of just 10-30 percent.

We have seen little improvement over the last 30 years in the ability to provide a cure for this devastating condition. The lack of effective treatment remains a largely unmet medical need and highlights the urgency for novel and effective therapies. A possible alternative to conventional toxic cancer treatments is utilizing a patient's own immune system to target and eliminate tumor cells. This approach has the potential to completely transform our traditional methods of attacking cancer, which are laden with extreme side effects, and may lead to a new era of safer, more personalized anti-cancer treatment.

In this study, immune system cells (dendritic cells - DCs) taken from the patient's own blood will be treated with broken-down cells isolated from his/her tumor tissue during surgery. By combining DCs and tumor cells, we will stimulate the child's own immune system to recognize and destroy the intracranial brain tumor. These stimulated DCs will then be injected back into the patient as a vaccine in order to teach the host immune system to identify the malignant brain tumor cells as "foreign" to the body. Theoretically, this method will lead to the patient's own immune system attacking any residual tumor cells.

UCLA has been at the forefront of this field with the use of DC-based therapies for adult brain tumors in pre-clinical models and in clinical trials. Previous studies focused on vaccination in adult patients with high-grade gliomas. A pilot study led by Dr. Theodore Moore and enabled by Today's and Tomorrow's Children Fund (TTCF) in 2007 demonstrated both feasibility and tolerability among pediatric patients, establishing a foundation for the next phase of research. We now have the expertise and staff resources to move forward, optimizing the use of DC vaccination in a larger number of patients at multiple institutions, while using small amounts of DNA obtained from their tumor tissue to search for specific genetic mutation signatures. Funding from TTCF will help foster this pioneering research, the results of which may lead to improved targeted therapy for children with high-grade gliomas, and ultimately to vaccines being incorporated in standardized care.

Furthermore, we plan to investigate the use of Imiquimod, a topical immunomodulatory compound, that stimulates the innate immune system and has been shown to display antiviral and antitumor activity. We hypothesize that the combination of DC anti-tumor vaccination and applied Imiquimod cream to the vaccination site in children with high-grade gliomas will be tolerable and may induce better immune responses. Moreover, we expect subsequent improved outcomes with fewer toxic side effects than current standard therapies with chemotherapeutics and radiation alone.

 

2012 TTCF Prize Recipient

Joyce Wu, M.D.
Associate Professor
Division of Pediatric NeurologyJoyce Wu with Dr. Devaskar and Beth Friedman

High-Frequency Oscillations: A Potential Noninvasive Biomarker of Pediatric Epilepsy

Childhood epilepsy is a particularly disabling group of chronic disorders. With a 1-percent incidence of epilepsy in the general population, about 50 percent begins in the pediatric years (18 and younger). While the incidence is four-fold that of breast cancer, the 2011 National Institutes of Health funding for pediatric epilepsy was less than one-tenth of that for breast cancer. Furthermore, in a significant 25-30 percent of children, their epilepsy cannot be controlled with anticonvulsants, which means about a half-million youngsters in the United States continue with frequent seizures despite multiple concurrent medications. In addition to disabling seizures, these children often have other epilepsyrelated conditions, such as cognitive impairment and autism, a triple threat that takes an emotional and financial toll on families, as well as schools and society. Despite the introduction of multiple new anticonvulsants over the last decade, the proportion of intractable epilepsy has remained relatively unchanged.

Unfortunately, the causes of medically refractory epilepsy remain largely unknown. A reliable biomarker for epileptogenesis development of epilepsy) that is able to assess, monitor, and even predict the condition is needed; the molecular basis underlying this marker will open the door to new treatment. High-frequency oscillations (HFOs) have emerged as such a potential biomarker. First seen in animal models, HFOs are an ultra-fast brain electrical activity (100-500 Hz), which is localized in the seizure onset zone and predicts which animals will develop epilepsy. Findings from our group advanced this field by first finding HFOs in children with epilepsy. We also were the first to detect HFOs throughout the brain; they were previously limited to one particular structure. Compared to HFO
detection with invasive surgical implants inside patients' heads for days to weeks as part of their epilepsy surgery evaluation, our findings significantly reduced that time to about 10 minutes just prior to resection in the operating room, without the risky surgical implantation. We also correlated the complete surgical resection of HFOs with seizure freedom, probably the most resounding feature of such a biomarker.

Our current plan to expand the concept of HFOs as a biomarker is two-fold: 1) to further establish HFOs as a spatially localizing biomarker of the epileptogenic zone, ultimately leading to noninvasive localization with scalp electroencephalographs (EEGs); and 2) to establish HFOs as a temporally predictive biomarker of epileptogenesis, by correlating its presence with later-life epilepsy in preepileptic
high-risk children due to birth hypoxia, traumatic brain injury, and tuberous sclerosis complex (formation of tumors in various organs). Additionally, the first objective includes "live" HFO interpretation in the operating room, which will enable brain tissue resected during surgery to be studied, potentially leading to a better understanding of epileptogenesis and new antiepileptic drug design. Both objectives hold promise for future clinical trials for better surgical mapping and potential disease-modifying therapy to prevent epileptogenesis altogether, not merely stopping seizures with anticonvulsant medications. HFO detection requires special equipment and recording parameters, and the analysis is 10 times more time and labor-intensive than traditional EEGs. Thus, both personnel and the EEGs themselves depend heavily on research dollars. Support from Today's and Tomorrow's Children Fund will greatly empower us to move forward on these research objectives, which may establish HFOs as a noninvasive, spatially localizing, and temporally predictive biomarker for pediatric epilepsy - unimaginable just a decade ago.


2012 TTCF Prize Recipient

Julian Martinez-Agosto, M.D., Ph.D.
Assistant Professor
Department of Human Genetics and Department of PediatricsJulian Martinez-Agosto with Dr. Devaskar and Beth Friedman

Genetic Risk Factors for Autism and Cancer Predisposition

Autism and cancer are the most common causes of illness in children. One out of every 110 children
will be diagnosed with autism, and cancer is the leading cause of death in those aged one to 14. Both conditions have been increasing in incidence over the past decade.

Autism can be inherited; siblings of children with this condition are 19 percent at risk of also having it, often because of delays in diagnosis. While recent advances in diagnosis and treatment have enhanced developmental outcomes, the causes for autism remain largely elusive. The study of rare genetic conditions with signs of autism, however, provides some insight. One group of genetic entities that can present with autism is overgrowth syndromes. They are characterized by large size at birth, excessive
postnatal growth, and increased weight, length, and/or head circumference for age and also are associated with an increased risk of specific solid tumors and leukemia. A late diagnosis may cause affected children to develop tumors that are too advanced for treatment to be effective. In this sense, a prompt diagnosis could have a significant positive impact.

While the causes in a limited number of cases have been revealed, the genetic basis for the vast majority is unknown. Our laboratory studies focus on genetic conditions in which children experience overgrowth (their bodies grow faster than their peers'). A subset of these children have autism and large head-size. Based on this knowledge, we have developed a clinical website that provides related information to parents of such children and promotes their evaluation at UCLA. We now use the most novel technologies to identify the genetic changes in order to expand our understanding of the causes of autism and, in some cases, predisposition to cancer. Support from Today's and Tomorrow's Children Fund will enable us to use "Next Generation Whole Exome" sequencing and chromosomal microarray analysis to identify mutations in pediatric patients with overgrowth syndromes. This technology will allow us to look at
each letter in a patient's genes, sequencing DNA to identify rare mutations that are predicted to cause autism, overgrowth, and/or cancer predisposition. Once we have identified the affected genes, we will be able to pursue additional funding to analyze their function.
We collaborate with a psychiatrist, neurologist, and oncologist, who provide genetic services to overgrowth patients.

Our findings are expected to enhance our understanding of the genetic risk factors for autism and the biology of pediatric growth disorders, as well as provide new potential targets for therapies. Revealing the causative genes will immediately lead to a medical test that will allow physicians to identify those children at highest risk. These results also will provide parents with critical information for planning future pregnancies. Finally, clarifying the genetic basis of how our bodies grow and develop will allow for the 1) harnessing of regenerative capabilities of tissues, 2) elucidation of the causes of cancer, and 3) further insight into the process of childhood maturation.

 

2011 TTCF Grand Prize Recipient

Kuk-Wha Lee, M.D., Ph.D
Assistant Professor
Division of Pediatric Endocrinology

Humanin, a Potential Therapy for Type 1 Diabetes (T1D)

Type 1 diabetes is an autoimmune disease in which the body's immune system attacks and destroys the insulin-producing cells of the pancreas (beta cells). Its causes are not yet entirely understood. As many as 3-million Americans may have T1D, and each year, more than 15,000 children - approximately 40 per day - are diagnosed in the United States. This disease causes dependence on injected or pumped insulin for life and carries the constant threat of devastating complications.

Despite paying constant attention to maintaining a meal plan and exercise regimen and always injecting the proper amount of insulin, these children face many other factors that can adversely affect efforts to tightly control blood sugar levels. These factors include stress, hormonal changes, periods of growth, physical activity, medications, illness/infection, and fatigue. So we are committed to finding better treatments for T1D and, ultimately, a cure. We, along with others, discovered a unique protein called Humanin (HN).  It is one of several proteins that are made from the mitochondrial (not nuclear) genome. It protects nerve cells, blood-derived cells, and muscle cells against stresses (including strokes). We are the only group to investigate 1) its potential use for a pediatric indication and 2) its effects on the pancreas. It is important to note that HN protects pancreatic insulin-producing cells from dying, and when we gave it to a mouse model of T1D, it delayed the onset of diabetes. We propose that HN will protect insulin-producing cells from dying in the process that leads to T1D.

Ours is the only laboratory in the world that can measure HN levels from blood (humans and mice). We think that HN levels will be decreased in patients with T1D compared to age-matched controls and could be utilized as a biomarker to identify those children who will develop T1D. Interval funding of this major project will allow us to apply for large grants from the Juvenile Diabetes Research Foundation (JDRF), which has partnered in a unique relationship with the National Institutes of Health (NIH) to target research for T1D.

Despite the formation of large international clinical trial networks and administered interventions, T1D is still treated with injected insulin. The protection of functional, healthy insulin-producing cells remains a fundamental quest that has implications for the prevention of T1D, the treatment of T1D post-onset, islet transplantation strategies, and a cure. Support from the Today's and Tomorrow's Children Fund will enable us to move forward on this project which has a potential for this new agent Humanin to be rapidly translated into a clinical trial in newly diagnosed children with T1D.

To read more about Dr. Lee's research progress, please see page 3 of our November 2011 newsletter.

 

2011 TTCF Prize Recipient

Paul Krogstad, M.D.        Paul Krogstad with Co-Chairs
Professor
Division of Pediatric Infectious Diseases

Discovery and Development of Drugs to Treat Enterovirus Infections

The enteroviruses are a group of more than 100 readily transmitted, seasonal viruses that usually produce common cold symptoms, hand-foot-and-mouth diseases, and other mild conditions in adolescents and adults. For newborns, infants, and young children, however, enteroviruses can be deadly. In this vulnerable population, they frequently produce central nervous system infections, hepatitis, and other life-threatening illnesses. Serious consequences are well-known among physicians who work at referral medical centers like Mattel Children's Hospital UCLA, since there are currently no medications to treat enterovirus infections. The survival of infected newborns often depends upon supportive care until the infection resolves. Unfortunately, infections of the heart in infants and older children sometimes cause progressive injury and heart failure despite this care, resulting in the need for heart transplantation. Dismayed by the lack of antiviral medications for treatment, members of my laboratory and I are studying the chemistry of enteroviruses, searching for potential therapeutic targets.

Enteroviruses are intracellular parasites that specialize in taking over the machinery used by cells to make proteins. We have identified a little-used experimental antibiotic that dramatically reduces the growth of enteroviruses in cells. In pursuit of our general goal of being able to produce effective treatments, we now wish to confirm these initial studies in animal models and identify other compounds, as well.

Treatments for enteroviruses are unlikely to arise from the pharmaceutical industry, which in recent years has relied upon Public Sector Research Institutions such as UCLA to perform the initial research needed for development of new products. Support from the Today's and Tomorrow's Children Fund would provide the critical initial push to garner the larger-scale funding needed to optimize lead molecules we identify and turn them into candidate medications to be tested in human clinical trials.

To read more about Dr. Krogstad's research progress, please see page 4 of our November 2011 newsletter.

 

2011 TTCF Prize Recipient

Yonca Bulut, M.D.        Yonca Bulut with Co-Chairs
Associate Clinical Professor
Division of Pediatric Critical Care

Do No Harm: Is Iron Supplementation Worsening Infections in Children?

Childhood infections and their severe form, sepsis, are major causes of hospital admissions. In the United States, more than 40,000 children develop severe sepsis each year, with a 10% mortality rate, especially among infants. The reasons why some boys and girls develop more severe infections are not well understood. Iron supplementation is a common health practice for the prevention of anemia in children, and it is also used in hospitals, even during severe infections; however, iron is an essential nutrient for bacteria, and its availability is a rate-limiting factor in bacterial growth and their ability to cause disease. Thus, if the current practice of iron supplementation in infected children increases iron availability to bacteria, this practice could be harmful. The aim of our study is to examine if iron supplementation and high body iron stores are risk factors for infection severity and mortality. In other words, we are asking: Is iron supplementation worsening infections?

Our laboratory has been at the forefront of iron research for the last decade. At UCLA, we discovered the critical regulator of iron metabolism, the hormone hepcidin. The discovery has brought on a revolution in our understanding of iron metabolism and its relevance to infection. Hepcidin increases early during infections and causes the disappearance of iron from blood, to keep microbes from getting this essential nutrient. Iron supplementation may subvert hepcidin's effect, enhance iron availability to microbes, and reduce the ability of our body to fight infection. Our proposal highlights a very important question about the safety of iron supplementation during severe infection. Our lab has the cutting-edge methodology as well as the experience to find out if these concerns are warranted.

The ultimate goal is to examine the safety of iron supplementation in healthy and ill children. If iron promotes infections, this result will lead to decreasing the routine use of iron supplements as well as have a major beneficial impact on the frequency and severity of infection and sepsis in hospitalized infants and children. Support from TTCF will allow us to obtain critical preclinical data to lay the framework for human studies.

To read more about Dr. Bulut's research progress, please see page 5 of our November 2011 newsletter.

 

2010

Christopher C. Giza, M.D.
Associate Professor in Residence
Department of Neurology and Division of Pediatric Neurology

Activating the Injured Brain: Restoring Plasticity after Developmental Brain Injury

Traumatic brain injury (TBI) is the #1 cause of death and disability in children and adolescents; however, there is currently no brain-specific therapy for TBI, and its victims struggle with chronic disabilities. The predominant therapeutic strategy for years has been to block neurotransmission in the injured brain, with the goal of providing 'neuroprotection;' unfortunately, this avenue has not led to any effective new treatments. Our work in the basic science laboratory and in young patients indicates that the immature brain actually shows impaired neural activation after TBI, which suggests that promoting (not blocking) neurotransmission is necessary to facilitate recovery.

To read more about Dr. Giza's research progress, read the [Mid-Year Update]

 

Christopher Giza, MD, 2010 UCLA TTCF grand prize recipient

   

2010

Robert S. Venick, M.D.        
Assistant Clinical Professor
Division of Pediatric Gastroenterology, Hepatology and Nutrition

Omega-3 Fatty Acid and Parenteral Nutrition Associated Liver Disease

Children whose intestines do not work must be fed intravenously through parenteral nutrition. While this treatment is often life-sustaining and provides sufficient calories to maintain growth and promote adequate neurodevelopment, it can be associated with life-threatening parenteral nutrition associated liver disease (PNALD). In fact, 100% of infants who develop significant PNALD and remain dependent on parenteral nutrition for more than a year will die unless they receive a timely liver and intestinal l transplant. Such transplants are not a panacea, as donor organs remain in short supply, and challenges with post-transplant infection and rejection mean that the five-year post-transplant survival rates are as low as 50%. Post-transplant care poses a large economic burden to society and the healthcare system as a whole; the cost of a transplant is estimated at $200,000, and post-transplant medications at $15,000/year per child.

To read more about Dr. Venick's research progress,read the [Mid-Year Update] 

 

Mattel Children's Hospital UCLA: 2010 TTCF prize recipient Dr. Robert Venick. 

   
 2010

Gary M. Satou, M.D., FASE
Director, Pediatric Echocardiography
Mattel Children's Hospital UCLA
Associate Clinical Professor, Pediatric Cardiology

Telemedicine with Echocardiography (Heart Ultrasound) for Real-time Evaluation of Newborns

Newborn infants with congenital heart defects often require urgent evaluation and lifesaving interventions. This particular problem is in isolated, rural, and frontier areas, where medical resources are limited and infants must quickly be transported to large specialized medical centers for care. Telemedicine with echocardiography (heart ultrasound) for real-time evaluation represents an innovative technology, permitting specialty care to be rendered at a distance to stabilize and treat these critically ill infants until a neonatal aero-medical evacuation team can be sent. In addition, unnecessary transports may be avoided, when the ultrasound shows there is no heart problem or when treatment can be directed and managed remotely by pediatric heart specialists.

To read more about Dr. Satou's research progress, read the [Mid-Year Update]

 Mattel Children's Hospital UCLA: 2010 TTCF prize recipient Dr. Gary Satou.
 

 

2009

Noah Federman, M.D.
Assistant Professor of Pediatrics
Division of Pediatric Hematology/Oncology

Fighting Cancer in Children Using NanotechnologyDr. Noah Federman

Childhood cancer patients often suffer severe side effects with chemotherapy treatment. Strategies that would improve the delivery of anti-cancer agents specifically to tumor cells would not only increase the effectiveness of a chemotherapy, but also would reduce its systemic toxicity. A molecular vehicle is needed that could target tumor cells - nanoparticles provide such a potential vehicle. Dr. Federman will develop and test targeted nanoparticles to treat pediatric sarcomas (aggressive and often lethal bone and soft tissue cancers), in which the survival rate for patients is less than 20% despite incredibly aggressive chemotherapy, surgery, and radiation treatments. This completely novel and high-risk project would be a breakthrough in our current treatment of pediatric cancers, leading to the development of powerful new therapeutic strategies in aggressive childhood malignancies. If successful, we hope to rapidly translate this technology from the laboratory bench to the patient's bedside.

More about Dr. Noah Federman

UCLA Pediatric Cancer Doctor Wins Research Award

 

A special message from Dr. Noah Federman 

This video is also available in Windows Media at
http://streaming.uclahealth.org/ttcf

Click here to post a comment 

 

 

 2008
Jacqueline Casillas, M.D, M.S.H.S. 
Assistant Professor of Pediatrics
Division of Pediatric Hematology/Oncology

Late Effects of Childhood Cancer

Dr. Casillas, Associate Program Director of the UCLA-LIVESTRONG Survivorship Center of Excellence, focuses her research on the various aspects of childhood cancer survivorship. Her study follows how the barriers to long term follow-up care, the pathophysiology of late effects and its increase in mortality, and the psychosocial growth of young adult survivors converge to impact quality of life for survivors. 

 Dr. Jacqueline Casillas - Recipient of the 2008 TTCF Award
   
 

2007
Theodore B. Moore, M.D.
Associate Clinical Professor
Division of Pediatric Hematology/Oncology

Methods of Utilizing a Person's Own Immune System to Fight Cancer 

Dr. Moore, Clinical Director of Pediatric Hematology-Oncology, has developed a new dendritic cell vaccine protocol for children with the usually fatal anaplastic astrocytoma and glioblastoma multiform brain tumors. This new therapy takes stem cells from a patient's blood and develops them into dendritic cells that are professional antigen processing cells. The dendritic cells are incubated with lysates of tumor from the patient, so that they can process the tumor antigens and, when inoculated into the patient, can teach the patient's immune system to attack the cancer.

 Dr. Theodore Moore - Recipient of the 2007 TTCF Award
   
 

2006
Daniel S. Levi, M.D.
Assistant Professor
Division of Pediatric Cardiology

Utilizing Innovative Technology to Eliminate the Need for Pediatric Cardiothoracic Surgery

Dr. Levi's research focuses on the design of new devices to help children with heart disease avoid surgery.  He is collaborating with UCLA Mechanical and Aerospace Engineering the space-age material thin film Nitinol to create tiny replacement heart valves.  These new valves will one day be inserted with a catheter through small incisions in the groin, and will therefore not require the opening of the chest, or the cutting of a little one's heart. 

 Dr. Daniel Levi - Recipient of the 2006 TTCF Award