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Previous TTCF Award Recipients
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 exerfcise 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. 
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. 
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 TTCF Grand Prize Recipient
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.
Our research involves both basic science and clinical investigations to bridge the gap from the lab to the clinic. Using neurotransmission-enhancing drugs (already approved for human use), we propose to develop a new technology, pharmacological magnetic resonance imaging (phMRI), to monitor brain activation in laboratory animals. Pilot experiments with medications that promote neurotransmission are showing restored brain activation using these new phMRI techniques. To translate these findings into a clinically relevant setting, the second part of this project would then involve initiating a clinical trial of brain activation in young TBI patients, using a combination of phMRI, functional MRI, and cognitive testing to monitor the effectiveness of the medications.
The major objectives of this project are:
1. to establish the technique of utilizing phMRI/fMRI to monitor drug effectiveness in activating the developing brain; this strategy can be used for pediatric TBI patients and for other types of pediatric brain injuries;
2. to target therapies to selected patients by distinguishing treatment-responders from non-responders;
3. most importantly, to noninvasively identify pediatric TBI patients who can then be enrolled in a therapeutic trial of neural-activating medications, with the goal of promoting more rapid recovery and an improved long-term outcome.
Despite the fact that most TBI occurs in young persons, the majority of traditionally funded research in this area has focused on adults. Proposals containing both basic neuroscience and clinical trial components often face substantial hurdles in obtaining traditional start-up funding. Support from the Today's and Tomorrow's Children Fund would provide the critical initial push to launch this project. Being able to advance the laboratory and patient-based research together will greatly accelerate these efforts to devise brain-specific treatment strategies for pediatric patients.
To read more about Dr. Giza's research progress, click here. [Mid-Year Update]
2010 TTCF Prize Recipient
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.
There is emerging evidence that the type of lipid (fat) present in parenteral nutrition is the major culprit in PNALD. The standard lipid formulation used in the United States is composed of soybean oil, which is high in omega-6 fatty acids and phytosterols (plant sterols). Currently, there is a non-FDA approved alternative lipid formulation called Omegaven, which is refined fish oil that lacks phytosterols and is rich in omega-3 fatty acids. Preliminary studies from Europe, Canada, and a handful of U.S. centers have demonstrated that Omegaven can reverse PNALD in children, thereby avoiding transplantation - and death.
At UCLA, a multidisciplinary team comprising Dr. Kara Calkins of Neonatology, Dr. James Dunn and Dr. Steve Shew of Pediatric Surgery, and me have provided Omegaven to three patients with outstanding results, which have enabled these children to survive and avoid transplantation. Within the past month, we have received permission from both the FDA and the UCLA Institutional Review Board to embark on a pilot study that would provide Omegaven to 15 subjects with PNALD. The primary aim is to evaluate if Omegaven can safely reverse liver disease in this high-risk population. Currently, there are only five institutions that are providing Omegaven in the U.S. under a protocol.
Our goal is to enhance patient care at UCLA and to contribute to the care of these children and to the fields of pediatric nutrition, gastroenterology, surgery, and neonatology. With additional funding, UCLA Hospital System will be the first medical center on the West Coast to offer this potentially lifesaving treatment under an official protocol.
To read more about Dr. Venick's research progress, click here. [Mid-Year Update]
2010 TTCF Prize Recipient
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.
The Southern Sierra Telehealth Network (SSTN) serves the remote, rural, and frontier high desert regions east of the Southern Sierra Mountains (Eastern Kern, Inyo, and Mono Counties, which cover more than 10% of the land area of California). The SSTN includes Ridgecrest Regional Hospital (RRH) and four critical access hospitals. RRH transfers 10-20 neonates a year to medical centers in Southern California, and Mammoth Hospital (three hours north of RRH) sends approximately the same number. Each of these hospitals, along with Kern Medical Center in Bakersfield and Marion Medical Center in Santa Maria, have similar issues in that they are rural, remote facilities without specialty pediatric heart care. All of these locations are interested in developing a telemedicine connection with the pediatric echocardiography laboratory at Mattel Children's Hospital UCLA; however, initial financial support is required to accomplish this goal.
TTCF grant funding has the potential to both improve patient care and support clinical research to measure the efficacy of telemedicine in this setting. The moneys would specifically allow the purchase and maintenance of hardware, software, and broadband connections. It also would develop IT support and database management. As an integral part of the project, the training of neonatal and obstetrics sonographers located in these remote areas will be provided, enabling them to learn and perform neonatal and prenatal ultrasounds and to diagnose congenital heart defects.
Because the heart can fail rapidly, better timing, guidance, and decision making for these critically ill babies can be lifesaving. Comprehensive patient outcome variables will be collected, analyzed, and reported in an effort to establish the accuracy and success of this telemedicine program. It is hoped that the establishment and review of this pilot data will encourage hospital administrators, other grant sources, and medical providers to develop a long-standing, comprehensive telemedicine network for rural California that will be in place for years to come.
To read more about Dr. Satou's research progress, click here. [Mid-Year Update]
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A special message from Dr. Noah FedermanThis video is also available in Windows Media at |
| 2008 Jacqueline Casillas, M.D, M.S.H.S. Assistant Professor of Pediatrics Division of Pediatric Hematology/Oncology Late Effects of Childhood CancerDr. 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. |
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2007 Methods of Utilizing a Person's Own Immune System to Fight CancerDr. 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. |
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2006 Utilizing Innovative Technology to Eliminate the Need for Pediatric Cardiothoracic SurgeryDr. 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. |
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