Research

Research at Texas Children’s Hospital, the largest children’s hospital in the United States, spans more than 800 ongoing clinical trials, over 800,000 square feet of lab space, and one of the largest and most diverse pediatric patient populations in the country. The ability to develop and advance major medical discoveries is an integral component to Texas Children’s Hospital giving back to the community ─ locally, nationally and globally.

Texas Children’s is affiliated with Baylor College of Medicine and is its primary pediatric training site. With funding of more than $148 million annually, over 295 Texas Children's and Baylor College of Medicine principal investigators are conducting over 1,800 clinical, basic science and translational research projects at any given moment. The research dollars awarded to Texas Children’s fund research that develops better treatments and creates better outcomes for our young patients and their families.C

Community Impact 2014

Texas Children’s research is conducted primarily at 4 facilities: Feigin Center, the Jan and Dan Duncan Neurological Research Institute (NRI), Children’s Research Center (CRC) and the Children’s Nutrition Research Center (CNRC). In FY14, Texas Children’s invested over $58 million in more than 1,800 clinical, basic and translational research projects, exploring a wide range of children’s health issues. Researchers and scientists are conducting some of the world’s most innovative ongoing research in these facilities.
Texas Children’s Hospital Research Highlights 2014

• Baylor College of Medicine, Texas Children’s Hospital join national collaboration to solve most difficult, rare medical cases. Baylor College of Medicine and Texas Children's Hospital became part of a new national network of clinicians and scientists joining forces to address prolonged undiagnosed medical conditions as part of a newly awarded $7.3 million, four-year National Institutes of Health (www.nih.gov) grant. The grant to Baylor and Texas Children's Hospital is one of six awarded in July 2014 as part of the NIH's Undiagnosed Diseases Network.

The network was established to help address the most rare and difficult-to-solve medical cases from around the country and develop effective approaches to diagnose them. It will focus on undiagnosed diseases that are rarely seen and often unrecognized.

Dr. Brendan Lee, professor and chair of molecular and human genetics at Baylor, a Howard Hughes Medical Institute Investigator and founder and director of the Skeletal Dysplasia Clinic at Texas Children's Hospital, will lead the Baylor/Texas Children's study site, which will contribute its advanced resources and expertise in clinical genetics and genomics research.

The program is a collaborative effort between the Departments of Molecular and Human Genetics, Pediatrics, Medicine, and Neurology at Baylor. Co-leaders of the program include Dr. Carlos Bacino, professor of molecular and human genetics, Dr. Jordan Orange, professor of pediatrics, Dr. Gary Clark, professor of pediatrics and neurology, Dr. Ashok Balasubramanyam, professor of medicine, and Dr. Paolo Moretti, assistant professor of neurology, all of Baylor.

"In the last 30 years, we have made significant strides in molecular diagnosis of undiagnosed and rare diseases with the advancement of research and implementation of next generation genetic testing. We are able to make a diagnosis (identify a potential molecular DNA lesion) in approximately 25 to 30 percent of cases, whereas before it was less than 1 to 2 percent," said Lee, also the Robert and Janice McNair Endowed Chair in Molecular and Human Genetics at Baylor. "Baylor and Texas Children's Hospital have been pioneers in this effort and have robust research and clinical programs focused on improving this field."

"Newly developed methods for genome sequencing now provide us amazingly powerful approaches for deciphering the causes of rare undiagnosed conditions," said Dr. Eric D. Green, director of the National Human Genome Research Institute. "Along with robust clinical evaluations, genomics will play a central role in the UDN's mission."

The network will address both childhood and adult cases.  Other institutions with Undiagnosed Disease Network clinical sites that are a part of the network include:  the National Institutes of Health in Bethesda, MD; Harvard Teaching Hospitals in Boston; Duke University in Durham, N.C.; Stanford University, in Palo Alto, Calif.; The University of California in Los Angeles and Vanderbilt University Medical Center in Nashville, Tenn.

Doubling Shank3 corresponds with mania seen in bipolar patients. A collaborative effort led by researchers in the lab of NRI Medical Director Huda Zoghbi, including faculty members Christian Schaaf, Jianrong Tang, and Hui-Chen Lu, led to publication in the October 2013 issue of the top-tier scientific journal Nature.  The article, entitled “SHANK3 over expression causes manic-like behavior with unique pharmacogenetic properties”, links a genetic mutation to hyperkinetic neuropsychiatric disorders with profound effects seen after treatment with a mood-stabilizing drug.  The finding is significant because mutations of this type are known to cause a spectrum of neuropsychiatric disorders and SHANK3 over expression has not been established as a cause of human disorders.

Landmark study reveals first genetic snapshots of unique placental microbiome. The placenta is not as sterile as once thought. New research shows that the placenta harbors a unique, low abundant microbiome, said researchers from Baylor College of Medicine and Texas Children’s Hospital.  The findings, published in the journal Science Translational Medicine, provide important new insights on the structure of the placental microbial community, the organisms present, and how they might be capable of impacting a pregnancy. “After we completed our studies of the vaginal microbiome in pregnancy, we noted that the most abundant microbes in the mom’s vagina were not what populated the baby’s intestinal microbiome,” said Dr. Kjersti Aagaard, associate professor of obstetrics and gynecology in the section of maternal fetal medicine at Baylor and the Texas Children’s Pavilion for Women, and the lead and corresponding author on the report. “We reasoned that there must be another source ‘seeding’ the infant’s gut at birth, so we sought to examine the placenta.”

The microbiome is the population of microbes – bacteria, viruses and fungi – that cohabit with human cells and help cells complete their tasks. Understanding what characterizes the microbiome communities is essential for understanding human development, Aagaard said. Aagaard and her colleagues are key members in the collaborative National Institutes of Health funded Human Microbiome Project (http://commonfund.nih.gov/hmp/index) which seeks to further characterize these communities and how they relate to health and healing human disease.

In this study, the first and largest study to focus on the placental microbiome, 320 human subjects’ samples were analyzed comprehensively following a process called shotgun metagenomic sequencing. This technology enables microbiologists to uniquely evaluate bacterial diversity and detect the abundance of specific microbes and all their genetic pathways in a community. The researchers showed that the placenta is not sterile (free from bacteria or other living organisms), but rather harbors a diverse and very unique microbiome.

“Interestingly, when we looked very thoroughly at the placenta in relation to many other sites of the body, we found that the placental microbiome does not bear many similarities to microbiomes closest in terms of anatomic location. Specifically, it is not much like the vaginal or intestinal microbiome, but rather is most similar to the oral microbiome,” said Aagaard. The finding has important implications on the likely importance of oral health during pregnancy, she said. “It reinforces long-standing data relating periodontal disease to risk of preterm birth.”

“Exposure of the fetus to a placental microbiome may have fundamental implications for early human development and the physiology of pregnancy,” said Dr. James Versalovic, co-author on the report, professor of pathology at Baylor and head of pathology at Texas Children’s Hospital.

A larger study is currently underway to expand these findings to describe the placental and microbiome profiles across pregnancy and in relation with preterm birth.

“The hope is that we will get a clearer picture of how several of the microbial communities in women and their placentas change over the course of the entire pregnancy among those at risk for preterm birth. These discoveries could lead to rapid breakthroughs in not only identifying women at risk for preterm birth, but developing new and worthwhile strategies to prevent preterm birth,” said Aagaard. “As we catch glimmers of the microbial biology of pregnancy, we can start to see a not too distant future where we will prevent preterm birth (or its complications in newborns) with truly novel approaches aimed at enhancing the healthy microbes of not just the vagina, but the mouth and gut. As we unravel the mysteries of pregnancy, we are learning that our microbes may be as much friend as foe. That is fantastic news for our moms and their babies.” 

Funding for this work was provided by the National Institutes of Health Director’s New Innovator Award (to Aagaard); the Burroughs Welcome Fund Preterm Birth Initiative (to Aagaard and Versalovic); the National Institutes of Health’s National Human Genome Research Institute as well as the Director’s Common Fund (to Aagaard, Versalovic, and Petrosino); and the Alkek Center of Metagenomics

Feigin Center

Texas Children's Feigin Center is a hub for pediatric research. The facility provides researchers space to intensify their research in areas of fundamental importance in microbiology, immunology, cell biology and sciences of infection and inflammation. Feigin Center-based researchers are making landmark discoveries and fundamental contributions to the fields of pediatric cancer, women's health and blood disorders. They are also learning how to genetically manipulate tumor cells to make effective cancer vaccines and how to enhance patients' own immune cells to enable them to attack cancers directly. A few of the exciting research projects and programs being conducted and housed at the Feigin Center include:

Sabin Vaccine Institute awarded funding to advance therapeutic vaccine development for Chagas disease.  The Sabin Vaccine Institute (Sabin) announced in September 2014, that its product development partnership (Sabin PDP) received $2 million from the Global Health Innovative Technology Fund (GHIT Fund) to develop a new therapeutic vaccine formulation for Chagas disease. Baylor College of Medicine, Eisai Co., Ltd. (Eisai) and Aeras are partnering on this project with the Sabin PDP, based at the Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development in Houston, Texas.

This two-year preclinical study will use a favorable protein-based antigen (Tc24) formulated with a novel TLR4 agonist adjuvant (E6020) developed by Eisai to elicit a stronger and more effective immune response compared to conventional aluminum-based adjuvant formulations. Protein-based vaccines are best positioned for clinical translation because of their excellent safety record, history of advancing to licensure and ability to produce protective immunity in humans.

The Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, led by faculty at Baylor College of Medicine, will lead on process development optimization and scale up, and on formulation and characterization studies, including preclinical evaluation for the selected vaccine targets. Aeras’ manufacturing unit will reproduce the technology and process development and scale-up activities for the partnership.

Ultimately, a therapeutic vaccine could solve current challenges of drugs used to combat Chagas disease, including high toxicities, prolonged treatment regimens, low efficacy in preventing severe cardiac complications and contraindication in pregnancy.

Chagas disease is an NTD estimated to infect 7.5 million people and cause more than seven billion dollars in annual economic losses globally. Chronic Chagas cardiomyopathy, present in approximately 30 percent of those infected with Chagas disease, causes arrhythmias, aneurysms, heart failure and sudden death. The T. cruzi parasite, which causes Chagas disease, is present in approximately 11 percent of pregnant women in Latin America and 40,000 women in North America and Japan at any given time, and between five to 10 percent of those pregnant women pass the infection to their unborn fetus.

Chagas disease is predominantly found in North America and Europe, but a few thousand cases have appeared in Japan. In the Latin America region, based on disability adjusted life years (DALYs), the burden of Chagas disease is five times greater than malaria.

Texas Children’s Hospital launches immunotherapy study - food desensitization trial could mean new hope for children with peanut allergies. For children with food allergies, a trace amount of a substance can trigger deadly anaphylaxis within minutes of ingestion – the fear of which can be life altering for many families. To give hope to these patients and their families, researchers at Texas Children’s Hospital and Baylor College of Medicine are embarking on a landmark peanut immunotherapy trial, using a process known as desensitization where patients swallow tiny, increasing amounts of peanut over time. For more information about Texas Children’s Hospital’s Immunology, Allergy and Rheumatology Department, please visit texaschildrens.org

The research team, led by Dr. Carla Davis, a specialist in the Pediatric Medicine, Immunology, Allergy and Rheumatology Department at Texas Children’s and assistant professor of pediatrics at Baylor, begin enrolling children with peanut allergies in the trial this month. The study will investigate the ability of peanut allergic children to take peanut flour, the mechanism by which the body develops tolerance, and measure the effect of viral infections. The goal of the trial is to find a standard of care that may lower the risk of severe allergic reactions in patients and eventually cease the allergy completely.

“No other immunotherapy trial has used the state of the art laboratory testing of immune cells to improve the process of desensitization that Texas Children’s has,” said Davis. “We believe the information gained from this trial will help make the process of desensitization faster and more efficient in the future.”

Davis and her team will collaborate with the Center for Cell and Gene Therapy and Texas Children’s Center for Human Immunobiology, directed by Dr. Jordan Orange who is also chief of Allergy, Immunology and Rheumatology at Texas Children’s and professor of pediatrics, pathology and immunology at Baylor, to evaluate more than 25 markers of cells called lymphocytes, which are central to controlling immune responses. Patients will have blood drawn and these markers will be evaluated by a process called flow cytometry. The markers will provide insight into how the immune system works to cause food allergies.

One in 13 U.S. children has a food allergy according to recent data from the national organization FARE (Food Allergy Research and Education). This reflects a nearly 50 percent increase in childhood food allergies between 1997 and 2011, leading to $25 billion per year in related health costs in treatment and diagnosis. Children can be allergic to any type of food, but eight foods account for nearly 90 percent of all allergic reactions to food in the U.S., with peanuts being the food that is most associated with life threatening food related anaphylaxis. More than 400,000 school-aged children in the U.S. have this allergy, according to the American College of Allergy, Asthma and Immunology.

Texas Children’s is the first center in the southwest region with approval from the Food and Drug Administration to dispense peanut flour as an investigational new drug. The major funding of this study has been provided by the Wareing Family and Scurlock Foundation, with additional generous support provided by families in the Texas Children’s Hospital Food Allergy Advisory Group as well as gifts provided by concerned members of the greater Houston Community. Initially, 20 patients will be enrolled, with the potential to enroll hundreds more over the next three years, with the help of expanded funding.

New study advances safety, efficacy profile of virus-specific T cells for post-transplant recipients. Patients who have received a bone marrow transplant, a lifesaving treatment for certain types of blood cancers and other hematologic and immunodeficiency disorders, are vulnerable to life-threatening infections due to their immunocompromised state post-transplant. Using specialized, virus-specific immune cells called T cells, researchers in the Center for Cell and Gene Therapy  (CAGT) at Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital have identified a novel safe, effective and rapid approach to protect from the threat of multiple severe infections at once.   Results from this clinical trial were published in June, in the journal Science Translational Medicine.

In healthy individuals, T cells help the body fight infection by recognizing viruses and destroying virally infected cells. In immunocompromised patients such as those who have undergone a bone marrow transplant, these cells are lacking and thus cannot provide the same protection.

CAGT researchers sought to develop a new therapy where they could grow a patient new virus-specific killer T cells in the laboratory using CAGT’s novel manufacturing technology. Then, they transferred these cells back to the patient to restore their anti-viral immunity.  The cells developed in the laboratory located in the Feigin Center, made in just 10 days, targeted five viruses that cause significant morbidity and mortality - Epstein-Barr virus, adenovirus, cytomegalovirus, BK virus, and Human Herpesvirus 6 (HHV6.)

They studied 11 patients who received an allogeneic transplant (transfer of stem cells from a healthy "donor" to the patient) as treatment for a variety of conditions including leukemia, lymphoma, sickle cell disease and other hematologic and immunodeficient disorders. T cells were obtained from the blood of each patient's bone marrow donor.  Eight of the patients had up to four active infections with the targeted viruses. Three patients received the modified T cell therapy to prevent infection.  In all, the virus-specific T cells produced an overall 94 percent virological and clinical response that was sustained long term.

"This study translated improved manufacturing techniques developed in the Feigin Center laboratory to the clinic and showed that virus specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days," said Dr. Helen Heslop, director for the Center for Cell and Gene Therapy and clinical principal investigator of the study. "These advances mean that this therapy could be available for more patients to treat viral infections and provide long lasting protection."

Additionally, the team demonstrated for the first time that the BK virus and HHV6 reactivations could be controlled using adoptively transferred T cells.

Funding for this study was provided by the Production Assistance for Cellular Therapies (PACT) program of The National Heart, Lung, and Blood Institute; the Clinical Research Center at Texas Children's Hospital and the Dan L. Duncan Institute for Clinical and Translational Research at Baylor.

Chipping away at the cause behind rare tumors. A new study by an international collaboration of researchers, including those from Baylor College of Medicine, has uncovered the underlying mutations in intracranial germ cell tumors, which could lead to new therapeutic targets.  The findings were published in the top tier journal Nature.  Intracranial germ cell tumors (GCT) are relatively rare tumors affecting children and young adults but the incidence of these tumors is about 8 to 10 times higher in Japan than in the Western world. The tumors are divided into two subgroups - germinoma and non-germinomatous germ cell tumors (NGGCT). While the prognosis of germinoma is good with long-term survival about 90 percent following treatment of surgery and radiation/chemotherapy, the prognosis for NGGCT is poor, with a survival rate of less than 25 percent.  Researchers identified frequent mutations in the KIT/RAS and AKT/mTOR signaling pathways as well as rare germline variants in JMJD1C, suggesting potential therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.

"This is the first time a large series of intracranial GCTs have been genomically analyzed with next generation sequencing which shows recurrent mutations in these tumors that are potential therapeutic targets," said Dr. Ching Lau, associate professor of pediatrics at Baylor and Texas Children's Cancer Center and senior author of the paper. "In addition, this is also the first time that predisposition genes in cancer were identified by next generation sequencing. These rare variants in the Japanese patient population could potentially explain the much higher incidence of this type of tumors in that population compared to the Western world." These results put researchers in the position to explore targeted therapy for intracranial GCTs by carrying out preclinical evaluation of various drug candidates in preparation for clinical trials, Lau said.   International collaboration in a focused study could yield very important results of rare tumors that would not be otherwise possible by individual centers.

The research was supported by funding from National Human Genome Research Institute, National Library of Medicine, Cancer Prevention and Research Institute of Texas, the Children's Brain Tumor Foundation, the Gillson Longenbaugh Foundation and Anderson Charitable Foundation, and the St. Baldrick's Foundation.

Texas Children's Hospital establishes Center for Human Immuniobiology to translate novel discoveries to effective clinical therapies.  The new, state-of-the-art center pairs world-class basic science immunologists with cutting-edge technologies and integrates them into a clinical setting. “Today is an exciting day as we demonstrate our commitment to continuing research for the future,” said Dr. Jordan Orange, chief of the immunology, allergy and rheumatology service at Texas Children’s Hospital and director of the Texas Children’s Hospital Center for Human Immunobiology. “Through advanced technologies, our team works to understand more deeply the functions of the human immune system thereby providing patients and families with the most current expertise.”

The center will serve as a central hub for research throughout Texas Children’s and Baylor College of Medicine (BCM), enabling investigations and findings that will translate into high-impact biology and novel approaches to the diagnosis and treatment of pediatric diseases. The lab space focuses on several key technologies including microscopy, flow cytometry, as well as molecular and genomic analysis. One of the technologies is the Leica Microsystems Gated Stimulation Emission Depletion (G-STED) microscope. In 2012, Texas Children’s became the first institution in North America to acquire the microscope, which allows researchers to take never before seen, super-resolution photos below 40 nanometers within a cell.

Faculty and staff of the Center for Human Immunobiology includes expert clinicians in the field of immunotherapy, in addition to new scientists and scientific support staff. The team will integrate with existing clinical services to be able to advance new mechanistic understanding of the human immune system. The center will focus on all investigative areas in the context of human Immunobiology including primary immune deficiencies, HIV, pancreatic cancer and the basic activation and inhibition of immune cell responses.

The Jan and Dan Duncan Neurological Research Institute (NRI)

The Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital (NRI) opened in December 2010. Dedicated to improving the lives of patients facing devastating neurological disorders, the NRI is a basic research institute committed to understanding the pathogenesis of neurological diseases with the ultimate goal of developing treatments.

Collaboration and leadership in genetics and neuroscience have allowed faculty at Baylor College of Medicine and Texas Children's Hospital to discover the underlying causes of dozens of neurological disorders.

The Jan and Dan Duncan Neurological Research Institute at Texas Children’s is the world’s first basic research institute dedicated to childhood neurological diseases, with the goal of accelerating the pace of discoveries related to brain development and function. In its first four years, the NRI has demonstrated its ability to fulfill that mission with accomplishments that include significant research breakthroughs, grants and faculty awards. Dr. Huda Y. Zoghbi, director of the NRI, professor of neurology, neuroscience, pediatrics, and molecular and human genetics at Baylor College of Medicine (BCM), and Howard Hughes Medical Institute investigator, credits the institute’s progress to its multi-disciplinary research team, its collaborative approach and a strong infrastructure of core facilities.

The NRI’s 27 principal investigators and over 150 researchers represent varied disciplines such as genetics, neurobiology, physics, mathematics, bioinformatics and behavioral psychology. NRI investigators work across a spectrum of diseases including autism, epilepsy, Rett syndrome, cerebral palsy, ataxias, intellectual disabilities and Batten disease. Such studies also impact many adult disorders that share similar symptoms. The goal of the NRI is to hasten the progress of new clinical studies and trials. Several clinical studies are under way at Texas Children's Hospital and other institutions for treatment of diseases such as epilepsy and Rett syndrome based on discoveries from NRI researchers. NRI research highlights for FY14 include:

Family makes donation to fund research on rare neurological disorder at Texas Children's Hospital, Baylor College of Medicine.  A rare and mysterious neurological disorder inspired the Wilsey family of San Francisco to fund researchers at the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and the Department of Molecular & Human Genetics at Baylor College of Medicine to study and develop treatments for NGLY1 deficiency. The Wilseys' daughter, Grace, is one of only 14 known children worldwide affected by the rare condition, which is characterized by a mutation in the gene coding for N-glycanase 1, an enzyme that is thought to help recycle defective products from a cellular assembly line. Children who lack this enzyme experience varying degrees of movement disorders, suffer from developmental delays, have liver and gastrointestinal problems and cry without producing tears.

After a lengthy saga of visiting with physicians across the nation searching for answers about Grace's condition, the Wilsey family finally found the answer after a meeting with Dr. Huda Zoghbi, Howard Hughes Medical Institute investigator and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital.  Dr. Zoghbi examined Grace and recommended a new test called whole genome sequencing, which helped identify Grace as the second child in the world diagnosed with NGLY1 deficiency. Experts at Texas Children's Hospital and Baylor College of Medicine in Houston used the new test to decode the DNA sequence of her genome allowing them to identify abnormal genes. The technology helps patients and families understand the cause of neurologic diseases, as well as the risk of recurrence.  In Grace's case, the testing provided researchers eight different genes, including NGLY1, and they began investigating the genes in order of the likelihood that they might explain her disease.
The research was published in a recent issue of the journal Genetics in Medicine.

"Whole geome sequencing has been a powerful tool in diagnosing some of the most challenging cases and we are increasingly finding patients with rare syndromes who have been through a battery of previous tests without a diagnosis," said Dr. Richard Gibbs, Director of the Human Genome Sequencing Center at Baylor. Conducted by the Whole Genome Laboratory at Baylor, the academic partner of Texas Children's Hospital, the test results are interpreted by bioinformatics and clinical genetics experts who transmit the findings to a referring physician.

Hamed Jafar-Nejad, M.D., in consultation with Dr. Zoghbi, is leading research efforts for NGLY1 deficiency at Baylor and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. The Baylor/NRI group is using fruit flies to understand the cellular and physiological defects caused by the loss of NGLY1 and to identify potential therapeutic targets for the disease. These studies are coordinated with those of a group of researchers around the world who are using biochemical, cell biological, mouse genetics and systems biology approaches to understand the biology of NGLY1 and the pathophysiology of NGLY1 deficiency. It is hoped that this multidisciplinary approach, which has been made possible by generous funds from the Wilsey family, will significantly expedite the progress of this project and will lead to the identification of a therapy for NGLY1 deficiency.

"We are grateful to finally have a diagnosis for Grace and we are committed to funding research efforts that will lead to a more advanced understanding of this disease and potentially a treatment or cure for Grace and other children who are affected," said Matt Wilsey, Grace's father.

• Two new faculty joined the NRI in 2014, including, Akash Patel, M.D., Assistant Professor of Neurosurgery, and Mingshan Xue, Ph.D., Assistant Professor of Neuroscience. Dr. Patel's research focuses on the molecular causes of inherited and sporadic brain tumors in effort to develop targeted therapy for aggressive cases. Dr. Xue's research focuses on abnormal development or dysfunction of the cerebral cortex and pathogenesis of neurological disorders. 

• Joshua Shulman, MD, PhD, NRI faculty member, published an article entitled “Functional screening in Drosophila identifies Alzheimer's disease susceptibility genes and implicates Tau-mediated mechanisms” in Human Molecular Genetics.  His results highlight the importance of cell adhesion pathways in neurodegenerative disorders and demonstrate the power of model organism genetic screens for the functional follow-up of human genome-wide association studies.

• A collaborative effort led by researchers in the lab of NRI Medical Director Huda Zoghbi, including NRI faculty members Christian Schaaf, Jianrong Tang, and Hui-Chen Lu, led to publication in the top-tier scientific journal Nature.  The article, entitled “SHANK3 over expression causes manic-like behavior with unique pharmacogenetic properties”, links a genetic mutation to hyperkinetic neuropsychiatric disorders with profound effects seen after treatment with a mood-stabilizing drug.  The finding is significant because mutations of this type are known to cause a spectrum of neuropsychiatric disorders and SHANK3 over expression has not been established as a cause of human disorders.

• The Aicardi Syndrome Research Symposium, hosted by Ignatia Van den Veyver, MD, NRI faculty member, was held at the NRI on October 11, 2013.   The event was a success, attended by international researchers and several families with children affected by Aicardi, a rare neurodevelopmental disorder that primarily affects girls.  Although the cause remains elusive, it is presumed to have a genetic basis that affects the X chromosome. The symposium provided a unique opportunity for the multidisciplinary group to collaborate and develop creative new approaches to the field of Aicardi Syndrome research.

• NRI faculty member and McNair Scholar, Ben Arenkiel, and several members of his lab were published in the scientific journal Developmental Cell. The article entitled, “Local CRH Signaling Promotes Synaptogenesis and Circuit Integration of Adult-Born Neurons,” validates the role of neuropeptide signaling in adult neural circuitry development.

• Huda Zoghbi, MD, and Christian Schaaf, MD, PhD, published the article, “NR2F1 Mutations Cause Optic Atrophy with Intellectual Disability,” in the American Journal of Human Genetics.  This article identifies the critical role of the NR2F1 gene in the neurodevelopment of the visual system, a previously unknown relationship.

• NRI Fellow, Shinya Yamamoto, along with his mentor, Dr. Hugo Bellen and several colleagues from the Bellen Lab, was published in the Public Library of Science/Biology journal.  The article, entitled, “Drosophila Tempura, a Novel Protein Prenyltransferase α Subunit, Regulates Notch Signaling Via Rab1 and Rab11,” identifies a previously uncharacterized function of the protein that affects Notch signaling, a basic function of neuronal activity.  The discovery is quite impactful as abnormal Notch signaling activity can lead to numerous neurodegenerative diseases and developmental defects.

• Drs. John Swann (NRI co-director) and Huda Zoghbi hosted the Second Biennial NRI Symposium on catastrophic epilepsies, held April 28 – 29.  Speakers included leading investigators in genetics, neuroscience and pediatric neurology with broad expertise in clinical and basic science.  The meeting objectives were to review the current state of knowledge and identify key barriers that limit a full understanding of the neurobiological mechanisms underlying epileptic disorders.  Potential avenues for therapy development including targeted drug development, ontogenetic, stem cell transplants and gene therapy were also discussed. NRI Administration raised $87,250 in sponsorships from private donors, non-profit organizations and the pharmaceutical industry.  Meeting co-sponsor, Science Translational Medicine, published the meeting transcript as a special edition of the journal.

• The Intellectual and Developmental Disabilities Research Center (IDDRC), a collaborative NIH grant initiated in 1998 and led by Huda Zoghbi, NRI Medical Director, was awarded $1.4M on September. The IDDRC is committed to advancing multidisciplinary research to address problems encountered by individuals with intellectual and developmental disabilities, and elucidate the underlying mechanisms to prevent and provide interventions and ameliorate disabilities whenever possible.  The IDDRC consists of a clinical translational core, a rodent neurobehavioral core, a neurovisualization core which includes neuropathology, confocal microscopy, and RNA in situ hybridization, and a neuroconnectivity core which includes viral production, optogenetics, and in vivo physiology.

Honors and Awards:
o The McGovern Institute for Brain Research at Massachusetts Institute for Technology awarded the prestigious 2014 Edward M. Scolnick Prize in Neuroscience to NRI Medical Director Huda Zoghbi. Awarded annually by the McGovern Institute to honor outstanding advances in the field of neuroscience, the prize recognizes the significant contributions and insight she’s provided into the mechanisms of hereditary neurodegenerative and neuropsychiatric diseases.

o Hugo Bellen, DVM, PhD, professor of Genetics at Baylor College of Medicine, Howard Hughes Medical Institute investigator, and NRI faculty, was awarded the George W. Beadle Award by the Genetics Society of America.  The prestigious award honors scientists who have made outstanding contributions to the community of genetics researchers. Recipients are recognized for having provided a contribution or service to the genetics community beyond an exemplary research career. Dr. Bellen’s lab has addressed fundamental questions regarding genes involved in neuronal development, neurotransmission, and most recently the mechanical basis for neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), often referred to as Lou Gehrig's disease.

o Dr. Benjamin Arenkiel, NRI faculty member, was awarded a Klingenstein-Simons Fellowship in Neuroscience, the nation’s oldest and most illustrious fellowships for young investigators in neuroscience research. Aimed at advancing cutting-edge Investigations, the awards are presented to highly promising, early career Scientists. The fellowship provides $75,000 per year for three years.

o Dr. Huda Zoghbi, received the 2014 March of Dimes Prize in Developmental Biology, an annual award given to researchers whose career has profoundly advanced the scientific knowledge of birth defects. Although generally recognized for the discovery of the genetic cause of Rhett Syndrome, her many research accomplishments have provided insight into a broad spectrum of neurological disorders, including autism and other neuropsychiatric disorders. Zoghbi delivered the 19th Annual March of Dimes Lecture entitled, “Rhett Syndrome and MECP2 Disorders: From the Clinic to Genes and Neurobiology,” during the Pediatric Academy Societies annual meeting in Vancouver and received the prize in a special award ceremony held during the meeting.

o Dr. Benjamin Arenkiel was awarded a Klarman Family Foundation award of $400,000 over 2 years for a project entitled, “Dissecting Cholinergic Circuits in Feeding Behavior”. The Foundation supports translational research that will accelerate progress in developing effective treatments for anorexia nervosa, bulimia nervosa and binge eating disorder.  The Arenkiel Lab, using metabolic profiling, electrophysiological, and ontogenetic experimentation, aims to reveal previously unidentified components of feeding circuits and provide new insight into the convergent mechanisms of how cholinergic circuits intersect to influence body weight, metabolism, and mood control.

o Dr. Huda Zoghbi, was the recipient of an honorary Doctor of Medical Sciences degree at Yale University’s 2014 Commencement Ceremony on May 19. One of 12 individuals awarded honorary degrees for achieving distinction in their fields; she was recognized as a role model for conducting translational research and a leader in the scientific community.

o Dr. Joshua Shulman was selected as the recipient of the 2014 Grass Foundation – American Neurological Association (ANA) Award in Neuroscience, presented at the ANA annual meeting in Baltimore. The award recognizes outstanding young investigators conducting basic or clinical neuroscience research.
For more information about recent breakthroughs or to support the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, visit nri.texaschildrens.org.

Children’s Nutrition Research Center

The Children's Nutrition Research Center (CNRC) is a unique cooperative venture between Texas Children's Hospital, Baylor College of Medicine and the U.S. Department of Agriculture/Agricultural Research Service. As the first federal nutrition research center to investigate the nutritional needs of pregnant and nursing women, and children from conception through adolescence, the Children's Nutrition Research Center conducts research that helps improve the maternal, infant and child nutrition guidelines used by physicians, parents and others responsible for the care and feeding of children. CNRC research programs include:

• Absorption and Metabolism of Essential Mineral Nutrients in Children
• Clinical Nutrition in Childhood 
• Development and Prevention of Childhood Obesity 
• Molecular, Cellular, and Regulatory Aspects Of Nutritional Metabolism During Childhood Development 
• Molecular, Cellular, and Regulatory Aspects of Obesity Development in Childhood
• Center for Collaborative Research on WIC Nutrition Education Innovations 

The Clinical Research Center (CRC)

The Clinical Research Center (CRC) provides a clinical research infrastructure for investigators who want to conduct patient-oriented clinical research at Texas Children’s Hospital.   The facility includes:

• outpatient clinic research space
• 3 inpatient/swing research rooms
• room for patient interviews and consultations
• sample preparation laboratory
• blood draw room
• waiting area
• playroom
• kitchen

Staffed by 10 specially trained research nurses, the CRC supports more than 100 investigators and about 340 active research protocols. A research dietitian and dietary technicians provide specialized diets for research protocols that require these services.

The CRC conducts innovative research studies that cut across all disciplines. Many of the studies evaluate the effects of new therapies in children and are intensive in terms of obtaining blood and other biologic samples to learn as much as possible about these therapies.

The CRC admits adults as well as children and is staffed 24 hours a day. For specialized neonatal research studies, the CRC provides research nursing support in Texas Children’s Newborn Center. In addition, the CRC provides biostatistical review of all protocols and furnishes additional biostatistical support for active projects when requested.

To ensure that this highly regarded resource is optimally used, a scientific advisory committee meets monthly to review protocols, assess their scientific merit and allocate resources. Priority is given to NIH-funded studies, although investigators funded by other sources also are eligible to use the facilities. All studies receiving support from the CRC first must be approved by the Baylor College of Medicine Internal Review Board (IRB) and the CRC Scientific Advisory Committee.

In its 50-year history CRC has played host to a number of notable studies and breakthroughs, including:

• Significant improvements in HIV care, including the long-term monitoring of anti-retroviral side effects and prevention of mother to infant HIV transmission
• Characterization and treatment of numerous inherited diseases and the development of molecular genetic tools to diagnose these diseases
• Development of vaccines for Norwalk virus and other viral infections
• Understanding the nutritional needs of preterm and newborn infants
• Characterization of metabolic alterations due to chronic disease
• Use of sophisticated MRI techniques to study mother/infant attachment
• Determining the best antibiotic regimen post appendectomy
• Novel cell and gene therapy treatments for adult and pediatric cancers
• Development of many new drugs for the treatment of pediatric cancer
• The largest study of its kind to look at the impact of cytomegalovirus (CMV) from infancy to adulthood

Some of Texas Children’s Research Community Partners include:

Texas Children’s Affiliate and Academic Partner – Baylor College of Medicine

Alex’s Lemonade Stand

American Cancer Association

Beyond Batten Foundation

Bill and Melinda Gates Foundation

Braden’s Hope for Childhood Cancer

Chevron Corporation

City of Houston

Centers for Disease Control and Prevention (CDC)

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Howard Hughes Medical Institute

Houston Endowment

Huffington Foundation

Institute for Cell and Regenerative Medicine

James A. Baker III Institute for Public Policy at Rice University

Jeffery Modell Foundation

Juvenile Diabetes Foundation

Juvenile Diabetes Foundation, the Commonwealth of Pennsylvania (Center for Excellence in Regenerative Medicine)

Keck Foundation

MD Anderson Cancer Center

Methodist Hospital

National Cancer Institute, NIH

National Institute of Diabetes and Digestive and Kidney Diseases, NIH

National Institutes of Heath (NIH)

National Institute of General Medical Services, NIH

The National Institute of Neurological Disease and Stroke, NIH

Rice University

Robert and Janice McNair Foundation

St. Baldrick’s Foundation

The Sabin Institute Product Development Partnership (Sabin PDP)

Sidney Kimmel Foundation

Stand Up to Cancer (SU2C)

Texas Department of Health and Human Services

Thrasher Research Fund

U.S. Department of Agriculture