November 1, 2016

11216nribrain640A new study published in the journal Neuron found that taking a pill that prevents the accumulation of toxic molecules in the brain might someday help prevent or delay Alzheimer’s disease.

According to researchers at Texas Children’s Hospital, Baylor College of Medicine and Johns Hopkins University School of Medicine, the study took a three-pronged approach to help subdue early events that occur in the brain long before symptoms of Alzheimer’s disease are evident.

“Common diseases like Parkinson’s, Alzheimer’s and dementia are caused in part by abnormal accumulation of certain proteins in the brain,” said senior author Dr. Huda Zoghbi, director of the Jan and Duncan Neurological Research Institute at Texas Children’s. “Some proteins become toxic when they accumulate and they make the brain vulnerable to degeneration.”

Tau is one of those proteins involved in Alzheimer’s disease and dementia. When tau accumulates as the person ages, it increases the vulnerability of the brain to developing Alzheimer’s.

“Scientists in the field have been focusing mostly on the final stages of Alzheimer’s disease,” said first author Dr. Cristian Lasagna-Reeves, postdoctoral fellow in the Zoghbi lab. “Here we tried to find clues about what is happening at the very early stages of the illness, before clinical irreversible symptoms appear, with the intention of preventing or reducing those early events that lead to devastating changes in the brain decades later.”

To find out which enzymes affected tau accumulation, the scientists inhibited about 600 enzymes called kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of tau.

By confirming this discovery in three different experiments – in fruit flies, mice and human cells – the researchers said the next step is to develop drugs that will block the production of Nuak1.

“If we can find drugs that can keep tau at levels that are not toxic for the brain, we would be able to prevent or delay the development of Alzheimer’s and other diseases caused in part by toxic tau accumulation,” Zoghbi said.

Click here to read the joint Baylor and Texas Children’s news release for more details on this study.

11216cancercenterdocsinside640Texas Children’s Cancer Center Texas Children’s and Baylor College of Medicine will lead a statewide effort to understand the causes of childhood cancer through development of the Adolescent and Childhood Cancer Epidemiology and Susceptibility Service for Texas, or ACCESS-Texas, with support from a $6 million grant from the Cancer Prevention and Research Institute of Texas.

“Much progress has been made in the treatment of childhood cancer, but in most cases we still don’t know why children get cancer,” said Dr. Michael Scheurer, Texas Children’s Cancer Center and ACCESS-Texas director and associate professor of pediatrics – hematology/oncology at Baylor. “The vast majority occur with no recognizable cause.”

ACCESS-Texas will focus on identifying genetic risk factors and gene-environment interactions that may lead to susceptibility to cancer among children and adolescents. A diverse population of children newly diagnosed with cancer and their parents will be enrolled in the program at eight childhood cancer treatment centers across the state: Texas Children’s Hospital and Baylor, Children’s Hospital of San Antonio, UT Southwestern/Children’s Medical Center Dallas, Cook Children’s Medical Center in Fort Worth, Vannie Cook Children’s Cancer Clinic in McAllen and Texas Tech University children’s hospitals in Lubbock, Amarillo and El Paso.

“It is our mission to find a cure for all children with cancer, and ACCESS-Texas will help us understand why certain children get cancer, a critical step in finding cures,” said Dr. David Poplack, director of Texas Children’s Cancer Center, professor of pediatrics at Baylor, and deputy director of Baylor’s Dan L. Duncan Comprehensive Cancer Center.

The program will include data collection through a risk-factor questionnaire of patients and their parents focusing on sociodemographics, lifestyle, clinical risk factors, family history of cancer and other diseases, environmental and occupational exposures and maternal and infant diet. In addition, blood and saliva samples will be collected along with key clinical and follow-up data, including tumor pathology and staging and molecular characterization of the tumor, treatment summaries and treatment toxicities and late-effects. All of these data and the biospecimens will be banked in a central repository accessible to researchers conducting family-based studies of genetic risk factors for childhood cancer and gene-environmental interaction studies.

Recent research has identified genetic risk factors for common childhood cancers such as acute lymphoblastic leukemia (ALL) and neuroblastoma, but many other cancers have yet to be evaluated using a genome-wide approach. In addition, few gene-environment links that may lead to cancer susceptibility have been fully evaluated. A centralized facility that gives researchers access to the data to conduct large-scale research projects is a much needed resource in the state to advance current research, Scheurer said.

“The resources gathered through ACCESS-Texas would place Texas researchers in a better position to develop and lead international collaborations to explore novel risk factors for childhood cancers,” he said. “Once we more fully understand the causes of childhood cancers, we can then start to develop prevention strategies.”

“A major goal of our program is to understand the causes of childhood cancer, so we can detect the cancers earlier to make treatments more effective,” said Dr. James Amatruda, professor of pediatrics, internal medicine and molecular biology at UT Southwestern Medical Center. “We’re excited to be collaborating with colleagues across the state through ACCESS-Texas.”

Enrollment of Hispanic patients and families also is an important aspect of the program. “This is a highly vulnerable population,” Scheurer said. “Hispanics generally have higher rates of cancer and worse outcomes, and the opportunity to collect data and conduct research that may help us understand the reasons for this is very important.”

The Children’s Hospital of San Antonio is one site involved in the new program that cares for many Hispanic patients. “The Children’s Hospital of San Antonio is proud and excited to participate in this important statewide resource, the outcomes of which will greatly impact our understanding of children’s cancer,” said Dr. Vivienne Marshall, professor of pediatrics and director of clinical research at the Max and Minnie Tomerlin Voelcker Clinical Research Center at the Children’s Hospital of San Antonio. “We serve a unique population that is often under-represented in national studies, so this is a significant opportunity to further advance knowledge that will benefit our children.”

ACCESS-Texas is built on a similar but smaller-scale program already in place at Texas Children’s Cancer Center that has resulted in significant research findings, including the first genome-wide assessment of maternal genetic effects among pediatric ALL patients and a study evaluating the role of gene-nutrient interactions on ALL risk.

October 11, 2016

4115Drzoghbi640The Shaw Prize Foundation awarded the 2016 Shaw Prize in Life Science and Medicine to pioneering neuroscientist Dr. Huda Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Howard Hughes Medical Institute investigator and Dr. Ralph D. Feigin professor at Baylor College of Medicine.

The award was presented jointly to Zoghbi and Dr. Adrian P. Bird, Buchanan professor of Genetics at the University of Edinburgh, during a special ceremony on September 27 in Hong Kong for their groundbreaking discovery of the genes and the encoded proteins associated with Rett syndrome.

Considered the “Nobel Prize of the East,” the Shaw Prize is an international award established in 2002 designed to foster scientific research. Awarded annually, the prize honors individuals who have achieved significant breakthroughs in academic and scientific research or applications and whose work has resulted in a positive and profound impact on mankind.

“I am humbled to be honored by the esteemed Shaw Prize Foundation,” Zoghbi said. “We will use this support to continue the research into how Rett syndrome affects the brain with the hope that our research will impact future treatment options.”

Rett syndrome is the leading cause of intellectual disabilities in girls, affecting one in 10,000, and is particularly devastating as girls affected by the syndrome develop normally for the first few months of life before a catastrophic decline in neurological capabilities.

Zoghbi’s discovery that mutations in the MEPC2 gene cause this devastating neurological disorder paved the way for the development of a diagnostic genetic test for Rett syndrome.

The $1.2 million Shaw prize will be shared by Bird and Zoghbi to advance Rett syndrome research.

October 4, 2016

10516daisytran175The Clinical Research Center/Research Resources Office presented the Clinical Research Award for Third Quarter 2016 to Daisy Tran, lead food allergy program research coordinator, Texas Children’s Food Allergy Program.

This award was established by the Clinical Research Center in collaboration with the Research Resources Office to recognize and honor individual contributions to protecting the best interest of the research subjects and compliance with applicable rules and regulations.

Tran’s research activities in the CRC focus on food allergic disorders including peanut desensitization, diagnosing and treating eosinophilic esophagitis, and atopy patch testing.

September 13, 2016

91416biliaryatresia640Physicians at Texas Children’s Hospital and Baylor College of Medicine have found a way to detect biliary atresia and other neonatal liver diseases in newborns using a simple blood test. Infants with biliary atresia, a life-threatening and hard-to-detect disease of the liver and bile ducts, can now be diagnosed and treated earlier, which has the potential to reduce the number of infants needing liver transplantation.

“Biliary atresia is a particularly devastating disease and is the most common reason why children need a liver transplant,” said Dr. Sanjiv Harpavat, a pediatric gastroenterologist at Texas Children’s and assistant professor of pediatrics – gastroenterology, hepatology and nutrition at Baylor. “We know that diagnosing and treating biliary atresia earlier with an operation called the Kasai portoenterostomy could help children delay or even avoid transplant. However, we also know that biliary atresia is very challenging for clinicians to identify early.”

To address the problem of making an early diagnosis, Harpavat and his colleagues, including Dr. Benjamin Shneider, professor of pediatrics and George Peterkin Endowed Chair at Baylor and chief of the gastroenterology, hepatology and nutrition service at Texas Children’s, designed a study to test a simple way to screen infants for biliary atresia in the first 2 to 3 weeks of life. Their research appears in the August issue of the New England Journal of Medicine.

The population-screening study included all infants born in four hospitals around Houston during a 15-month period. The research now has been expanded to 10 hospitals in Houston and South Texas. The screening they developed is based on newborn direct or conjugated bilirubin measurements, a common test available in newborn nurseries. In previous research, Harpavat and colleagues showed that direct or conjugated bilirubin levels are elevated in all newborns with biliary atresia. This finding was somewhat unexpected as many believe the disease starts in the first few weeks of life.

All of the infants in the study were screened, and those identified as having bilirubin concentration exceeding the 95th percentile were rescreened at or before their first well-child visit. A total of 11 infants retested positive at the median age of 14 days.

“This new study presents preliminary data on a novel method for screening for biliary atresia in newborns, and shows that the test is very accurate,” Harpavat said. “If confirmed in larger studies, our screening method might be used to screen every infant born in the United States for biliary atresia, similar to the way newborns are routinely screened for other diseases.”

Biliary atresia accounted for about 60 percent of liver transplants in infants less than one year of age from 2005 to 2014, so developing a screening that can reduce the need for liver transplants in infants is a significant advancement, he said.

Researchers worked closely with primary care pediatricians throughout the city during the study, offering guidance and education when a patient tested positive initially, Harpavat said. Physicians have used the information and incorporated it into their own practice to identify infants with biliary atresia earlier who were not part of the screening protocol. “This was an unanticipated and very welcome benefit of the work. The landscape of biliary atresia in Houston has changed dramatically since these changes were instituted,” Shneider said.

Others who contributed to this work include Texas Children’s neonatologist Dr. Joseph A. Garcia-Prats, who also is a professor of pediatrics at Baylor College of Medicine. Research was supported by the Cade R. Alpard Foundation for Pediatric Liver Disease, the American Association for the Study of Liver Diseases Jan Albrecht Clinical and Translational Research Award and Baylor College of Medicine Junior Faculty Seed Award.

August 9, 2016

72716SusanKirk175Susan Kirk, a physician assistant at Texas Children’s Cancer Center, was recently honored with the Dr. Marilyn Hockenberry Advanced Practice Provider (APP) Award for Excellence in Clinical Practice, Education and Research.

Established in 2012, this internal award recognizes an advanced practice nurse (APN) and/or physician assistant (PA) who has made exemplary contributions to the education of clinical fellows, nurse practitioners, PAs or nurses, or has completed a clinical practice improvement project that has significantly impacted patient care in Texas Children’s Cancer Center and Hematology Service.

The hematology faculty at Texas Children’s nominated Kirk for her many contributions, particularly in the areas of hematology education and research.

While Kirk has taken the lead on the development and revision of Clinical Practice Guidelines for several areas in Immune Hematology, she is heavily involved in teaching. She is frequently requested to have trainees shadow her and is passionate about teaching both disease specific and operational aspects of daily practice. Kirk also teaches multiple courses in Immune Hematology to nursing staff and lectures PA students on hematology topics. This year, she has volunteered to precept a Baylor College of Medicine PA student.

In addition to clinical education, Kirk ensures staff in the hematology clinic are up to speed on the latest technology. She teaches her colleagues how to perform tasks in Epic on a daily basis and is an active member of the Beacon Committee for the development of an online chemotherapy ordering program.

Kirk has also made remarkable accomplishments in pediatric hematology research. She is part of the backbone of the immune hematology research program and is involved in the development and operation of multiple research studies, some of which have been published in Thrombosis Research. Kirk has also written abstracts that have been accepted for presentation at the International Society for Thrombosis and Hemostasis annual meeting. She recently presented an educational session on sickle cell disease at Texas Children’s 2016 APP Conference.

Kirk is a member of several professional organizations including the Texas Academy of Physician Assistants, a content expert for the National Commission on Certification for Physician Assistants and an abstract review committee member for the American Academy of Physician Assistants Annual Meeting.

72716Drchumpatazi175Dr. Bruno Chumpitazi, an assistant professor of pediatric gastroenterology at Baylor College of Medicine and clinical director of Texas Children’s Neurogastroenterology and Motility Program, recently received the Baylor College of Medicine Rising Star Clinician Award.

This annual award recognizes outstanding up and coming clinicians for their exemplary contributions to clinical excellence and expertise, consistent high level of patient care, commendable leadership skills and continuous exemplary service to the Baylor community.

Chumpitazi’s contributions to the field of pediatric gastroenterology, particularly in the area of gastrointestinal (GI) motility disorders, have received numerous accolades from his Texas Children’s and Baylor colleagues.

“As director of a cutting edge, productive, and nationally recognized clinical program, Dr. Chumpitazi has truly been a rising star within our department and within the College,” said Dr. Mark W. Kline, Texas Children’s physician-in-chief and chair of the Department of Pediatrics at Baylor. “He successfully introduced procedures such as anorectal manometry, colonic manometry, antroduodental manometry and esophageal manometry at Texas Children’s. He also introduced pH/impedance testing, the current gold standard of gastric esophageal reflux testing.”

Texas Children’s Neurogastroenterology and Motility Program is on the cutting edge of clinical care and research for children with gastrointestinal functional and motility disorders. Individuals within the program work with others throughout Baylor and Texas Children’s to offer several multidisciplinary programs (including an esophageal achalasia program, neurostimulation program, and rumination program); gastrointestinal motility evaluations (including wireless capsule manometry); and therapies (including guided imagery).

Chumpitazi has worked with child life specialists and multi-sensory distraction devices to make procedures as pediatric friendly as possible. In addition to the previously mentioned efforts, Chumpitazi has created a multidisciplinary program with our physical therapy colleagues for children with defecation disorders amenable to therapy. Each of these programs are highly specialized, were created to address a pressing clinical need, and are not available in the vast majority of pediatric gastroenterology programs throughout the country.

The Motility program’s success can be measured in part by the high volume of national, regional and local consultation requests for the program’s clinical expertise and the high volume of specialized procedures completed.

“I’m extremely humbled by this award and want to emphasize that I’m just one individual within a fantastic team environment,” Chumpitazi said. “It’s been a pleasure working with other like-minded individuals throughout Baylor and Texas Children’s to improve the health of the children that we see.”

“Dr. Chumpitazi is an excellent example of a rising star clinician,” said Dr. Benjamin Shneider, chief of Gastroenterology, Hepatology and Nutrition at Texas Children’s. “He is a true triple threat, with tremendous skills as a clinician, educator and investigator. I am certain he will continue to represent Baylor and Texas Children’s as a national leader within his field and I am grateful he is part of our team.”

Click here for more information about the Neurogastroenterology and Motility Program.