February 3, 2015

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People interested in participating in the sixth annual Edmond T. Gonzales, Jr. Surgical Research Day must submit an abstract by Monday, February 9. Anyone involved in surgery-related research is encouraged to participate.

Authors of top peer-reviewed abstracts will have the opportunity to present their research at the event, which will be from 7 a.m. to 1 p.m., Friday, May 8, in Texas Children’s Pavilion for Women fourth-floor conference center.

Authors who are not selected for an oral presentation will be invited to present their work as a poster, with a prize awarded to the top scoring one. The third annual Samuel Stal Research Award also will be presented at Surgical Research Day to recognize outstanding research by a resident or fellow in the Department of Surgery.

Hosted by the Department of Surgery and the Department of Research Administration, and started by Edmond T. Gonzales, Jr., a Texas Children’s urologist and the organization’s first surgeon-in-chief, Surgical Research Day includes invited lecturers, presentations and posters that showcase the academic efforts of the surgical faculty, post- graduate trainees, nursing personnel and operating room staff.

Have questions or need additional information? Please contact Stacey Staples at Ext 4-3366 or email Research Administration at resadmin@texaschildrens.org. To submit an abstract click here.

February 2, 2015

bench and beside Header

Bench and Bedside is a digest of the previous month’s stories about the clinical and academic activities of our physicians and scientists. We welcome your submissions and feedback.

 

January 2712815kidneydialysis640

Renal Center reaches milestone in delivery of high-volume patient care

In January, Texas Children’s Renal Center delivered more than 100 acute therapies in less than 10 days – a remarkable milestone that demonstrates the value of teamwork and our hospital’s commitment to putting patients’ needs first.

“This is an incredible accomplishment,” said Texas Children’s Chief of Renal Services Dr. Michael Braun. “As the demand for our services continues to grow, so has our collaborative spirit to ensure critically ill patients receive efficient, high quality care every time they walk through our doors.” Read more

 

January 21

Leung advances research and care for cystic fibrosis patients

Dr. Daniel Leung, medical director of the Viral Hepatitis Clinic at Texas Children’s, has devoted much of his research to improving the outcomes of children with cystic fibrosis and cystic fibrosis-associated liver diseases. To accelerate CF research and patient care at Texas Children’s, Leung received a $100,000 Developing Innovative Gastroenterology Specialty Training (DIGEST) grant last spring from the Cystic Fibrosis Foundation. This three-year grant is awarded to physicians across the country who demonstrate promise in changing the field of gastrointestinal care and research for CF patients. Read more

 

January 20

Call-to-action: Encourage your patients to sign up for MyChart

MyChart, the online patient portal that allows patients or their parents to access health information from Epic, recently underwent significant changes. The increased use of MyChart by Texas Children’s patient families will help providers stay connected to their patients, improve patient care and save time. Here’s how:

  • MyChart is an effective tool for patient engagement, leading to better outcomes. The more patient families are involved in their care, the better their outcomes.
  • MyChart allows easy login – whether on a computer or a smart phone – so patient families can see their health information and review comments from their physicians.
  • MyChart enhances how physicians communicate directly with their patients by allowing conversations to occur online and at times that are convenient for the physician and the patient. This direct communication helps patient families feel connected to their care providers.
  • MyChart improves the patient experience by allowing easier access to their health information, such as after-visit summaries, immunization histories and more.
  • MyChart promotes efficiency by decreasing the need for printing, mailing and faxing patient information.
  • Read more or Watch the video

 

January 2012115MataTwins640

Positioning team designs, builds swing to help conjoined twins sit up

Taking care of conjoined twins, Knatalye Hope and Adeline Faith Mata, is hard, even for the highly-trained medical staff charged with looking after the two 9-month-old girls. Diaper changes, baths, feedings, even moving the girls from one place to the other takes a lot of effort, thought and hands. So, when the team of surgeons assigned to the twins asked the girls’ primary nurses and physical therapist to figure out a way to help the twins sit up, Frank McCormick, Jennifer Pitlik and Jennifer McGinnis were stumped. Read more or Watch the video

 

January 20

2014 a record-breaking year for pediatric residency applicants

About 350 applicants visit the hospital campus between November and January. These students are hopeful they will be part of the elite group of 43 accepted to the highly competitive pediatric residency program. This academic year, the Department of Pediatrics had more than 990 residency applicants – the highest number of applicants in the program’s history. It’s about 100 more than last year, and it’s double the number of residents who applied just five years ago. “Recruiting residents is one of the most important things we do,” said Physician-in-Chief Dr. Mark W. Kline. “We’re ensuring the health of Houston’s children 10, 15, 20 years down the road.” Read more or Watch the video

 

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In memoriam: Lifelong teacher Dr. Edward B. Singleton passes away leaving rich legacy

A vase of flowers rests outside the office of Dr. Edward B. Singleton with the note, “we’ll miss you.” It’s a feeling shared by all who knew Singleton, Chief Emeritus of the Edward B. Singleton Department of Pediatric Radiology at Texas Children’s Hospital. Singleton passed away on January 10 at the age of 94. Read more or watch the video

 

January 13

Tissue engineering expert to speak at Cooley Lectureship

Renowned tissue engineering expert and Harvard Medical School John Homans Professor of Surgery Dr. Joseph Vacanti will be the featured speaker at this year’s Denton A. Cooley Lectureship in Surgical Innovation Tuesday, February 10. Beginning at 7:30 a.m. in the fourth-floor Conference Center at Texas Children’s Pavilion for Women, Vacanti will discuss “Tissue Engineering and the Care of Children,” a burgeoning area of research that has untapped potential for people who need new organs. Read more

 

January 13

Shneider named new chief of Gastroenterology, Hepatology and Nutrition

Texas Children’s recently announced the arrival of Dr. Benjamin Shneider, our new chief of Gastroenterology, Hepatology and Nutrition. Shneider was also appointed professor of pediatrics at Baylor College of Medicine. Shneider obtained his undergraduate education at Stanford University and earned his medical degree from the University of Chicago. He completed pediatric residency training at Boston Children’s Hospital and Harvard Medical School, as well as a subspecialty fellowship in pediatric gastroenterology at Yale University. Read more

 

January 13

Dietary intervention study underway to improve outcomes in IBS patients

Texas Children’s researchers have embarked on a five-year crossover dietary intervention study that could determine why certain children with Irritable Bowel Syndrome (IBS) develop symptoms when eating wheat. In collaboration with researchers at Baylor College of Medicine and funding from the National Institutes of Health (NIH), Texas Children’s Gastroenterologist Dr. Bruno Chumpitazi and his team are conducting a double-blind, randomized, placebo-controlled study to examine the effects of fructans – a natural sugar found in wheat – in 80 children with IBS. Read more

 

January 6

Texas Children’s welcomes new cardiovascular surgeon

Texas Children’s Heart Center recently welcomed Cardiovascular Surgeon Dr. Lauren Kane. Kane is also an assistant professor of surgery and pediatrics at Baylor College of Medicine. “We are thrilled to have Dr. Kane join our growing team as she brings with her a great array of clinical and research experience,” said Surgeon-in-Chief Dr. Charles D. Fraser Jr. “Not only will her addition to the team allow for more convenient access for children in need of cardiac surgery, but we’re confident her research will continue to advance the national prominence of our cardiovascular team.” Kane’s clinical and research interests include the full spectrum of congenital heart surgery, with a particular interest in neonatal palliation and outcomes-based research. Read more

 

January 6

Pilot program makes scheduling surgery from remote locations easier

Historically, it has been difficult to schedule surgery from Texas Children’s Hospital locations outside Main Campus. A pilot project launched a few months ago in Otolaryngology has overcome this challenge and made scheduling surgery from remote locations easier. Surgeons now can add an order in Epic at the time of a patient visit. Previously, when otolaryngologists traveled to see patients, they faxed or transported paper forms to Main Campus or called to schedule surgery. “Those methods of scheduling surgery from offsite locations were less efficient and rife with opportunities for missed communications,” said Dr. Carla Giannoni, the Texas Children’s otolaryngologist who spearheaded the project. Read more

 

Submissions for Bench and Bedside

Bench and Bedside is produced monthly by Texas Children’s Corporate Communications team to spotlight recent news about Texas Children’s physicians and scientists. The team welcomes submissions related to speaking engagements, staff awards/recognition, research, clinical work and academic activities. Send your questions or submissions to connectnews@texaschildrens.org.

January 14, 2015

Bench and Bedside is a digest of the previous month’s stories about the clinical and academic activities of our physicians and scientists. We welcome your submissions and feedback.

12/19/2014

Texas Children’s Medical Staff: Required Training for Fluroscopic Procedures

On May 1, 2013 the Texas Department of State Health Services (DSHS) made specific changes to its regulations of Texas Administrative Code §289.227 “Use of Radiation Machines in the Healing Arts.” This rule requires all physicians and midlevel providers to obtain additional radiation training prior to performing fluoroscopic procedures. This is not a Texas Children’s Hospital policy but a modification of state law goes into effect May 1, 2015. Read more

12/18/2014

Mata conjoined twins take first step toward separation with tissue expansion

Conjoined 8-month-old twin girls, Knatalye Hope and Adeline Faith Mata, underwent a five-hour surgery December 16 at Texas Children’s Hospital Main Campus to place custom-made tissue expanders into their chest and abdomen area. The tissue expanders will help stretch the babies’ skin in preparation for their separation surgery, which is expected to take place early next year. Dr. Alberto Hernandez with Interventional Radiology performed the examination. Chief of Plastic Surgery Dr. Larry Hollier and Dr. Ed Buchanan with the Division of Plastic and Reconstructive Surgery conducted the tissue expander placement surgery. Dr. Helana Karlberg led the anesthesia team and Audra Rushing led the surgical nursing team. Read more

12/18/2014

Tessier receives NASPGHAN Fellow Research Award for C. Difficile study

Dr. M. Elizabeth Tessier, a pediatric gastroenterology fellow at Texas Children’s, received the 2014 Fellow Research Award from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). Her award-winning study titled, “Bile acid signatures in children confer protection from clostridium difficile infection,” found that changes in the bile acid composition in the stool may predispose patients to Clostridium difficile (C.diff), a bacterial infection that causes intestinal inflammation and diarrhea. Read more

12/17/2014

Neurosurgery represents Texas Children’s at AANS Annual Meeting

The Texas Children’s Hospital Division of Neurosurgery was well represented at the recent American Association of Neurological Surgeons annual meeting in Amelia Island, Fla. The division had eight posters accepted for presentation. Of those eight, three were selected as “Top Posters.” In addition, Neurosurgery had four abstracts accepted for oral presentation. Read more

12/16/2014

Voice of Nursing blog: Physician-nurse partnership (By Dr. Tony Mott)

Trust, respect and a sense of humor. What do these things have in common? In my opinion, they’re the key ingredients for developing a successful nurse-physician partnership. As medical director, my partnership with Assistant Clinical Director Tarra Kerr is vital to the success of 15 West Tower. In fact, from our shared partnership, we have established a shared vision – a vision of what 15WT can be and the path to that end. Read more

12/16/2014

Department of Surgery unveils surgery preparation video

No parent ever wants to hear their child will need to have surgery – whether it’s a routine procedure that only takes minutes or it’s something more serious. That’s why the Department of Surgery goes out of its way to make the surgical experience at Texas Children’s a good one for patients as well as their families. The department’s most recent effort to ensure a positive surgical experience is had by all is a video for parents that talks about what to expect when their child has surgery at Texas Children’s. The video, available in English and Spanish, covers eating and drinking instructions, what to bring to the hospital and what parents will experience while their child is in surgery. “Our goal in the Department of Surgery is to have our patients and their families prepared as well as possible for the surgical experience,” Chief of Plastic Surgery Dr. Larry Hollier said. “Setting appropriate expectations is crucial to patient satisfaction.” Read more or Watch video

12/16/2014

The patient census and what it means for Texas Children’s

On any given day, hundreds of patients come through the hospital doors at Main Campus and West Campus. Whether they walk through our doors on their own, or are transferred from another hospital, these patients require the care of Texas Children’s Hospital specialists. In November, 101 patients had to be turned away from Texas Children’s Hospital. The patients were denied a transfer from another institution because we were above census. “We have to always remember that when people come to us, they are bringing their children who are ill for care,” said Surgeon-in-Chief Dr. Charles D. Fraser, Jr. “We have to put ourselves in their position, and respond.” Read more or Watch video

12/16/20146

Texas Children’s hosts second cardiac artery anomalies conference

Texas Children’s Hospital hosted its second national conference December 4 and 5, addressing a series of fatal conditions known as coronary artery anomalies. Coronary artery anomalies are a group of rare congenital heart defects that have been associated with coronary ischemia, myocardial infarction, and sudden death. It is the second most common cause of sudden death in young healthy athletes. Read more

12/16/20146

Texas Children’s Heart Transplant Program celebrates 30th anniversary

Texas Children’s Hospital recently celebrated the 30th anniversary of its heart transplant program. Since its inception in 1984, Texas Children’s Heart Center has performed more than 300 heart transplants, making the program one of the most active and largest in the nation. “The true results of our team’s exceptional work over the past 30 years can be seen in the hundreds of success stories of our patient families,” said Texas Children’s Heart Failure, Cardiomyopathy and Cardiac Transplantation Medical Director Dr. Jeff Dreyer. “As one of the largest programs in the nation, our experience in treating patients with heart failure is leading the way in positive outcomes.” Read more

12/09/2014

Kayyal to co-lead development of Neuro-NICU program

Dr. Simon Kayyal, an assistant professor of pediatrics and neurology at Baylor College of Medicine, recently joined Texas Children’s neurology team. He will develop and co-lead the Neuro-Neonatal Intensive Care Unit (Neuro-NICU) with Texas Children’s Neonatologist Dr. Jeffrey R. Kaiser, a professor of pediatrics, obstetrics and gynecology at Baylor College of Medicine. Read more

12/08/2014

Hand and Microvascular Surgery Clinic offers multidisciplinary team

Patients treated at the Texas Children’s Hospital Hand and Microvascular Surgery Clinic now benefit from not only two physicians whose focus is on hand and upper extremity care but also from a full-time certified hand therapist. Plastic and reconstructive surgeons Dr. Mitchel Seruya and Dr. Thomas Hunt III formed a multidisciplinary team with certified hand therapist Tara Haas. Seruya, Hunt and Haas work with registered nurses, occupational hand therapists and medical assistants to perform clinical evaluations, formulate diagnoses and provide treatment plans for patients. Read more

12/03/2014

Texas Children’s Pediatrics opens new practice, merges two others

Texas Children’s Pediatrics recently welcomed a new practice to the inner loop and merged two others in the Houston area. The new practice, Texas Children’s Pediatrics Green Park, opened November 18 and is located at 7505 S. Main St., Suite 450. Three new physicians – Dr. Michael Connelly, Dr. Shannon Hayes and Dr. Jackie Wanebo – are seeing patients at the location. Connelly, a Houston native, earned his medical degree from and completed his residency with the University of Texas Medical School in Houston. Connelly specializes in fitness, healthy eating, and infants and newborns. Hayes is from Katy and earned her medical degree from Baylor College of Medicine. Hayes completed her residency at Baylor as well, and trained at Texas Children’s Hospital. Wanebo came to Texas from Charlottesville, Va., earned her medical degree from the University of Virginia and completed her residency with the University of North Carolina Chapel Hill. She specializes in asthma, healthy eating, teenagers and children with special needs. Read more

 

Submissions for Bench and Bedside

Bench and Bedside will be produced monthly to spotlight recent news about Texas Children’s physicians and scientists. The Connect team welcomes submissions related to speaking engagements, staff awards/recognition, research, clinical work and academic activities. Send your questions or submissions to connectnews@texaschildrens.org.

December 18, 2014

Dr. M. Elizabeth Tessier, a pediatric gastroenterology fellow at Texas Children’s, received the 2014 Fellow Research Award from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).

Her award-winning study titled, “Bile acid signatures in children confer protection from clostridium difficile infection,” found that changes in the bile acid composition in the stool may predispose patients to Clostridium difficile (C.diff), a bacterial infection that causes intestinal inflammation and diarrhea.

In general, children are less susceptible to C.diff infection than adults and tend to have milder disease. However, Tessier says pediatric cases are on the rise, which may be attributed to a newer more toxigenic strain of C. diff called NAP1.

Antibiotics disrupt the bacterial communities in the colon which can alter bile acid compositions, creating favorable conditions for C.diff spores to germinate. Certain types of bile acids can activate or inhibit the growth of this bacterium.

In their study, Tessier and her colleagues in Tor Savidge’s lab in the Texas Children’s Microbiome Center, collected stool samples to examine the bile acid profiles of healthy children between the ages of 7 and 12, healthy adults, patients with antibiotic-induced diarrhea and C.diff patients.

The healthy control group had higher levels of chenodeoxycholic acid (CDCA) – which inhibits C.diff growth – compared to the other two groups. They found healthy children had more CDCA than healthy adults, which may contribute to children’s decreased susceptibility to C.diff infection.

In contrast, patients with antibiotic-induced diarrhea, who may be prone to C.diff infection, had elevated levels of the spore-germinating bile acid called taurocholate. While C. diff patients had lower levels of both bile acid types, they had high serum levels of fibroblast growth factor 19 (FGF-19), a hormone that regulates bile acid synthesis in the liver.

“Based on our findings, C.difficile toxins may alter bile acid profiles in the gut by inducing FGF-19 production,” said Tessier. “Further studies need to be done to determine if this hormone is a true marker of C.diff infection.”

Tessier’s study also examined the bile acid profiles of four patients who received liver transplants. High levels of taurocholate were found in their stool, which increased their risk of C.diff infection.

December 17, 2014
The Texas Children’s Hospital Division of Neurosurgery was well represented at the recent American Association of Neurological Surgeons annual meeting in Amelia Island, Fla. The division had eight posters accepted for presentation. Of those eight, three were selected as “Top Posters.” In addition, Neurosurgery had four abstracts accepted for oral presentation.
Top Poster Presentations
  • Comparison of Patient Populations and Utilization for Hypothalamic Hamartoma Treatment
    Dr. Sandi Lam, Dr. Daniel Curry, Dr. Thomas Luerssen, Iwen Elaine Pan, PhD
  • Use of a Formal Assessment Instrument of Evaluation of Resident Operative Skills in Pediatric Neurosurgery
    Caroline Hadley, Dr. Sandi Lam, Valentina Briceno Marmol, RN, Dr. Thomas Luerssen, Dr. Andrew Jea
  • Endonasal Endoscopic Resection of Pediatric Craniopharyngiomas
    Dr. Sohum Desai, Dr. William Whitehead
Poster Presentations
  • Endoscopic Third Ventriculostomy and Ventriculoperitoneal Shunting: A Comparative Effectiveness Study with MarketScan Administrative Data
    Dr. Sandi Lam, Dr. Dominic Harris, Dr. Thomas Luerssen, Iwen Elaine Pan, PhD
  • Cerebrospinal Fluid Shunt Placement in Children: A Model of Hospitalization Cost
    Dr. Sandi Lam, Dr. Visish Srinivasan, Dr. Thomas Luerssen, Iwen Elaine Pan, PhD
  • Using Pediatrics National Surgical Quality Improvement Program (NSQIP) Data to Examine 30-Day Outcomes of Craniosynostosis Surgery
    Dr. Jared Fridley, Dr. Sandi Lam, Dr. Thomas Luerssen, Iwen Elaine Pan, PhD
  • Using Pediatrics National Surgical Quality Improvement Program (NSQIP) Data to Examine 30-day Outcomes of Posterior Fossa Tumor Surgery
    Dr. Sandi Lam, Dr. Jared Fridley, Dr. Andrew Jea, Dr. Thomas Luerssen, Iwen Elaine Pan, PhD
  • The Safety and Efficacy of Use of Low Molecular Weight Heparin in Pediatric Neurosurgical Patients
    Dr. David Gonda, Dr. Jared Fridley, Sheila Ryan, JD, MPH, CCRP, Valentina Briceno Marmol, RN, Dr. Sandi Lam, Dr. Thomas Luerssen, Dr. Andrew Jea
Oral Presentations
  • Outcomes of Pediatric Autologous Cranioplasty after Decompressive Craniectomy: A Multicenter Study
    Dr. Sandi Lam, Pediatric Outcomes Workgroup
  • Streamlining Fetal Repair of Myelomeningoceles
    Dr. Jared Fridley, Dr.William Whitehead
  • The Efficacy of Routine Use of Recombinant Human Bone Morphogenetic Protein-2 in Occipitocervical and Atlantoaxial Fusions of the Pediatric Spine
    Dr. Christina Sayama, Caroline Hadley, Valentina Briceno Marmol, RN, Dr. Huy Dinh, Sheila Ryan, JD, MPH, CCRP, Dr. Daniel Fulkerson, Dr. Thomas Luerssen, Dr. Andrew Jea
  • Acute Implantatationo Reduced Graphene Oxide Scaffolds in Spinal Cord Injury in Rats
    Dr. Jared Fridley, Dr. Thomas Luerssen, Dr. Andrew Jea
November 18, 2014

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Dr. Susan Blaney, executive vice chair of Research in the Department of Pediatrics, recently announced the winners of the 2014 Pediatric Pilot Awards Research Grant Program. Twelve research applications were chosen by review committee members to receive grant funding in the amount of up to $50,000 for their projects.

The purpose of the Pediatric Pilot Awards Research Grant Program is to provide initial start-up “seed funding” for research projects. This grant program provides opportunities for new or less established researchers as well as experienced researchers who desire to expand their area of research. The grant projects are awarded based upon their scientific merit and the potential to generate the initial data necessary for a successful grant application submission to the NIH or other external, peer-reviewed funding mechanisms.

The pilot award program is a collaborative effort between Texas Children’s Hospital and its academic partner, Baylor College of Medicine.

Congratulations to the following 2014 pilot grant awardees. Click on the name below to learn more about the research project being funded.

Ronald Bernardi, M.D., Ph.D.
Assistant Professor, Pediatrics – Hematology/Oncology
Combinatorial tyrosine kinase inhibition as a novel therapeutic strategy in PTPN12-deficient pediatric cancers

Jennifer Foster, M.D.
Instructor, Pediatrics – Hematology/Oncology
Pre-clinical evaluation of ML4924, a novel NEDD-8 activating enzyme inhibitor in pediatric malignancies

Andras Heczey, M.D.
Assistant Professor, Pediatrics – Hematology/Oncology
Glypican-3 specific T cells to cure pediatric liver disease

Marisa Hilliard, Ph.D.
Assistant Professor, Pediatrics – Psychology
Promoting resilience in youth with type 1 diabetes: Pilot of a strengths-based family intervention to improve diabetes outcomes

Jimmy Holder, M.D.
Assistant Professor, Pediatrics – Neurology
Identifying post-translational regulators of SHANK3 – toward developing targeted therapeutics for neuropsychiatric disorders in children

Dongfang Liu, Ph.D.
Assistant Professor, Pediatrics – Immunology, Allergy and Rheumatology
Super-resolution imaging of HIV-specific CTL immunological synapse

Silke Paust, Ph.D.
Assistant Professor, Pediatrics – Immunology, Allergy and Rheumatology
Pollen grains as trojan horses for child-friendly oral vaccination

Elaine Seto, M.D., Ph.D.
Assistant Professor, Pediatrics – Neurology and Development Neuroscience
Investigating the role of dopamine in neurocognitive function

Amy Sims, M.D.
Assistant Professor, Pediatrics – Cardiology
Clinical-Officer led screening for rheumatic heart disease in Malawi, Africa

Bernard Suter, M.D.
Assistant Professor, Pediatrics – Neurology and Development Neuroscience
In vivo analysis of motor cortex function in the MECP2 duplication mouse

Scott Wenderfer,M.D., Ph.D.
Assistant Professor, Pediatrics – Renal
Novel Auto-antibody Markers of Lupus Nephritis

Janice Zawaski, Ph.D.
Assistant Professor, Pediatrics – Hematology/Oncology
The role of bone marrow in glioma radiotherapy response

 

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Ronald Bernardi, M.D., Ph.D.
Assistant Professor – Hematology/Oncology
Combinatorial tyrosine kinase inhibition as a novel therapeutic strategy in PTPN12-deficient pediatric cancers

Some cancers are driven primarily by increased activity of a single proliferation signal. Frequently, this abnormal stimulatory signal comes from an overactive tyrosine kinase, a class of enzymes that regulate cellular proliferation by adding phosphate groups to substrate proteins.

In this setting, specific tyrosine kinase inhibitors can limit the progression of the disease and even cause tumor regression. The development of such agents has improved outcomes dramatically for some cancers. However, for the vast majority of pediatric malignancies, the situation is not so straightforward. Thus, current options for therapy for many pediatric cancer patients remain limited in that they either have serious side effects or are ineffective.

We propose an approach that may broaden the use of tyrosine kinase inhibitors. Tyrosine phosphatases are a class of proteins that normally function to counteract the activity of tyrosine kinases. As tyrosine phosphatases typically have several substrates, loss of a tyrosine phosphatase may aberrantly activate multiple tyrosine kinases, which can act in concert to promote tumor progression.

We previously identified PTPN12 as a tyrosine phosphatase that is frequently deficient in breast cancer, leading to the activation of a number of tyrosine kinases. Combinatorial inhibition of these activated tyrosine kinases reduced proliferation of PTN12-deficient models that are resistant to single agents. We also have preliminary evidence that diminished PTPN12 expression correlates with poor prognosis in pediatric cancers. In this pilot project, we aim to more thoroughly assess the spectrum of loss of PTPN12 in pediatric cancers and to assess the functional role of PTPN12 and identify the tyrosine kinases that it regulates in this setting. Further, we plan to test the combined inhibition of PTPN12 regulated tyrosine kinases for the ability to inhibit the growth of pediatric cancers that have diminished PTPN12.

Our results will be critical for designing clinical trials of drug combinations that are tailored to the genetic alterations and susceptibilities of each individual tumor.

Jennifer Foster, M.D.
Instructor – Hematology/Oncology
Pre-clinical evaluation of ML4924, a novel NEDD-8 activating enzyme inhibitor in pediatric malignancies

Neuroblastoma is a devastating form of cancer that develops from immature nerve cells. Only half of children diagnosed with high-risk neuroblastoma survive beyond childhood. New treatments are needed to improve their survival.

In our proposed study, we will examine a novel chemotherapeutic agent, MLN4924. MLN4924 kills neuroblastoma cells differently than standard chemotherapy. The traditional way to kill neuroblastoma tumor cells has been to attack their DNA. However, in this proposal, we will test another mechanism which involves killing neuroblastoma cells by preventing protein breakdown. Blocking protein breakdown with a new drug, MLN4924, will result in “proteotoxic stress” that can kill the cancer cells following standard chemotherapy, improving our ability to kill tumor cells.

MLN4924 is currently undergoing testing in adults with various forms of cancer and has yielded promising results. Adults with relapsed or difficult to cure cancer treated with MLN4924 experience improved survival with minimal side effects. Our goal is to improve clinical outcomes in neuroblastoma by adding MLN4924 to standard chemotherapy regimens. Our preliminary data shows that MLN4924 is effective at killing neuroblastoma cells.

This research will provide the pre-clinical data necessary to successfully incorporate MLN4924 into pediatric clinical trials and is being conducted in conjunction with a proposed Phase 1 clinical trial run by the National Cancer Institute (NCI)-sponsored Children’s Oncology Group (COG). In this proposal we will determine 1) with what chemotherapies MLN4924 works best in conjunction to kill neuroblastoma cells and 2) how neuroblastoma cells are dying after treatment with MLN4924. This information is crucial in optimally designing future clinical trials for patients with neuroblastoma which will combine MLN4924 with standard anti-cancer agents. The addition of novel anti-cancer drugs, such as MLN4924, to the treatment regimen of children with neuroblastoma is crucial in improving their survival.

Andras Heczey, M.D.
Assistant Professor – Hematology/Oncology
Glypican-3 specific T cells to cure pediatric liver disease

Hepatoblastoma and hepatocellular carcinoma are the most common forms of liver cancer in children. Despite severe side effects, current medical therapies have limited effectiveness in patients whose tumors cannot be surgically removed completely.

In our study, we propose to collect and genetically modify special immune cells from the blood to destroy liver cancer cells in the laboratory. Our long-term goal is to develop a new immunotherapy method by genetically engineering the patient’s own immune system to eliminate liver cancer without the toxicity of current therapies.

Marisa Hilliard, Ph.D.
Assistant Professor of Pediatrics – Psychology
Promoting resilience in youth with type 1 diabetes: Pilot of a strengths-based family intervention to improve diabetes outcomes

Type 1 diabetes is a common chronic condition characterized by the body’s inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas.

The daily management requirements of type 1 diabetes are complex and demanding. Adolescence is a particularly difficult period as teens begin to assume responsibility for their own diabetes management and worsening glycemic control is common during this time.

Complex issues that make diabetes even more challenging to manage for adolescents include family disagreements about diabetes, depression, and “diabetes burnout.” Family factors that help teens and families manage diabetes more easily include being good problem-solvers, ongoing parent support, and coping with diabetes challenges in an optimistic way.

Psychologists and physicians have developed intervention programs to promote good diabetes outcomes and most have focused on minimizing the impact of diabetes challenges. However, there are fewer programs designed to promote good diabetes outcomes by building on teens’ and families’ existing strengths.

Thus, the purpose of this study is to pilot test an intervention program that will recognize specific actions teens with diabetes and their families do well for their diabetes management (such as talking to friends about diabetes and asking parents for help when needed) in order to strengthen those positive diabetes behaviors.

As part of the intervention, teens and their parents will complete a web-survey before attending two routine visits with their diabetes care provider. The web-survey will include a questionnaire about positive diabetes behaviors and one about how often the teen and family complete various diabetes management tasks (such as checking blood glucose values or giving insulin). At the diabetes clinic visits, the diabetes care provider will receive a print-out of the family’s “Diabetes Strengths Profile” and will be trained to talk with the teen and family about their strengths and successes with diabetes management during the clinical encounter, rather than focusing on what is not going well.

We hope this strengths-based family approach will help patients and families feel more satisfied with diabetes care, feel less burdened by diabetes management demands, and feel empowered to use more positive diabetes behaviors. Ultimately, we expect these improvements will translate to better quality of life and better glycemic control for adolescents with type 1 diabetes.

Jimmy Holder, M.D.
Neurology & Development Neuroscience
Identifying post-translational regulators of SHANK3 – toward developing targeted therapeutics for neuropsychiatric disorders I children

Autism is a common neurodevelopmental disorder affecting more than one in 100 children. Currently, there are no effective therapies to treat the primary symptoms of autism which include abnormal language development, socialization and restricted interests. This is largely due to our incomplete understanding of the neurobiological basis of autism.

Mutations of a gene called SHANK3 are one of the more common genetic causes of autism. In addition to the core symptoms of autism, children with mutations in SHANK3 have moderate to severe intellectual disability and often intractable epilepsy.

Through this pilot award, we will attempt to identify regulators of SHANK3 protein stability. Identifying these regulators will serve as therapeutic entry points for treating the symptoms of autism due to mutations in SHANK3 as well as potentially providing insight into the neurobiological of autism.

Dongfang Liu, Ph.D.
Assistant Professor – Immunology, Allergy and Rheumatology
Super-resolution imaging of HIV-specific CTL immunological synapse

How do some patients infected with HIV control virus levels in their blood to an undetected level without HIV medications? Why do HIV medications require a life-long commitment for patients? Can we control the virus to an undetected level without lifetime treatment?

My study will use multiple innovative, super-resolution imaging approaches in live, single cells – at the single-molecule level – to answer these critical questions and explain how one population of white blood cells fights HIV during chronic infection.

HIV is a virus that attacks the immune system in our bodies. HIV is different from other viruses because the body’s immune system never fully gets rid of it. Over time, HIV destroys the body’s ability to fight infection and disease. When that occurs, HIV infection can lead to Acquired Immune Deficiency Syndrome, or AIDS.

Cytotoxic T lymphocytes (CTLs) is one type of white blood cell that recognizes and kills HIV-infected cells in the body. However, the CTLs fail to function normally and do not prevent progression of disease in most people during chronic HIV infection. The mechanism responsible for CTLs dysfunction remains unclear.

A major gap in our current knowledge of CTLs dysfunction is the lack of understanding of the CTLs-virally infected target cell interface called immunological synapses (IS). Formation of a functional interface is required for effective CTLs responses to occur, which is essential for eradicating HIV.

HIV medications inhibit HIV but do not eradicate HIV. The virus rebounds after cessation of HIV medications. Neither eradication of the virus nor restoration of effective CTLs function can be achieved by HIV medications. Therefore, it is crucial to understand the interface between CTLs and virally infected target cells during HIV infection and to train CTLs in the body to fight HIV. Traditional biochemical and cell biological approaches do not reveal the critical spatiotemporal parameters of intracellular signal transduction cascades and dynamics of interface between CTLs and HIV-infected target cells.

My study will use high-resolution imaging at the single-molecule level to address important questions about CTLs and HIV-infected target cell’s interface. They include dynamics of interface formation (how CTLs recognize a virally infected target cell) and the critical factors determining the outcome of interface. By looking at the interface between CTLs and target cells using high-resolution imaging at the single-molecule level, we will determine the mechanism of CTLs dysfunction during chronic HIV infection. This knowledge will provide an excellent framework for designing specific protein inhibitors or antagonists to restore CTLs functions during chronic HIV infection.

Silke Paust, Ph.D.
Assistant Professor – Immunology, Allery and Rheumatology
Pollen grains as trojan horses for child-friendly oral vaccination

With the absence of a preventive or therapeutic HIV vaccine, 2.7 million new HIV infections occur annually, and over 34 million people are infected worldwide. As differences in infection levels are most pronounced among young people aged 15-24 years, a preventive HIV vaccine will need to be administered to children.

We propose to evaluate an inexpensive, child-friendly, self-administrable HIV vaccine for simple translation to the clinics. My collaborator at Texas Tech University, Dr. Gill, has developed a vaccine formulation based on pollen grains, which are cleaned to remove their allergenic compounds and refilled by vacuum with HIV protein antigens and vaccine adjuvants. Pollen-based formulations are administered orally (they are eaten), thus offering the advantages of a painless, needle-free, child-friendly, easy vaccination approach.

This pilot project is to assess the effectiveness of this novel HIV vaccine when it is administered orally to mice that have been given a human immune system. By vaccination and HIV challenge of this animal model, we can assess the quality of the human immune response upon HIV pollen vaccination and assess whether this vaccine formulation protects against HIV infection.

If successful, this project will aid in the development of an inexpensive, easy-to-transport and administer HIV vaccine that is suitable for adults and children.

Elaine Seto, M.D., Ph.D.
Assistant Professor – Neurology and Development Neuroscience
Investigating the role of dopamine in neurocognitive function

Cells of the nervous system, known as nerve cells or neurons, function through the regulated release of chemical messengers known as neurotransmitters. The human brain utilizes many different neurotransmitters to relay information from neurons to downstream cells. One neurotransmitter that has garnered significant attention is dopamine. During adulthood, misregulation of dopamine is thought to underlie the movement abnormalities seen in patients with Parkinson’s disease.

Interestingly, dopamine can be detected early in fetal brain development and misregulation in the developing brain may likely contribute to neuropsychiatric conditions such as attention deficit hyperactivity disorder (ADHD).

In a screen for modifiers of dopamine in fruit flies, we have isolated genes implicated in several neurodevelopmental conditions such as autism and intellectual disability. By altering these genes specifically in dopamine-expressing neurons, we can determine how these genes affect dopamine transmission and if these changes result in altered cognition.

My study will provide further insight into the role dopamine plays in pediatric neurocognitive disorders. This work may also lead to novel therapeutic options since medications that modulate dopamine transmission are already being utilized for other medical diagnoses.

Amy Sims, M.D.
Assistant Professor – Cardiology
Clinical-Officer Led Screening for Rheumatic Heart Disease in Malawi, Africa

While almost eradicated in the U.S., rheumatic heart disease (RHD) is the leading cause of cardiac morbidity and death among children in impoverished nations around the world, like Malawi, Africa.

RHD is a chronic heart condition caused by acute rheumatic fever which can result in severe heart valve damage. Secondary prevention consists of monthly penicillin injections for RHD patients, which prevents progression of heart valve disease. The 2012 guidelines issued by the World Heart Federation provides consensus for RHD diagnosis by echocardiography. RHD screening programs that use echocardiography to produce images of the heart’s valves and chambers are sensitive to detecting early signs of the disease. Early detection and effective secondary prevention dramatically reduces morbidity and mortality.

We conducted a study last year which was the first to establish the prevalence of RHD in Malawi. Our preliminarily findings suggest that Malawi may have one of the highest prevalences of RHD in the world. Thus, expanding the capacity to screen for RHD and enroll affected children in secondary prophylaxis programs can drastically reduce the sequaelae of this disease.

With 0.19 physicians per 1000 people in Malawi and no in-country pediatric cardiologist, it is not feasible for RHD screening to be led by physicians. Task-shifting to Clinical Officer (CO)-led RHD screening is a more sustainable option. Computer-based modules describing screening for RHD aimed at non-physicians have been developed and validated.

This pilot award project aims to train nine Malawian CO’s in echocardiographic screening for RHD. After didactic and computer-based training, each CO will accompany a pediatric cardiologist to a local Malawian school and learn to screen for RHD first hand. We expect to screen over 1000 children for RHD. Each CO will be evaluated in their ability to screen for RHD.

This study will be a step towards eradicating RHD, the leading cause of cardiac death in children worldwide.

Bernard Suter, M.D.
Assistant Professor, Neurology and Development Neuroscience
In vivo analysis of motor cortex function in the MECP2 duplication mouse

Boys born with higher levels of a specific gene called MECP2 have autism spectrum disorder. Common symptoms include severe verbal and communication problems, as well as impaired motor function Specifically, their ability to walk is perturbed and over time becomes unstable. To date, we don’t know how the control of gait is disturbed in these individuals. In the mouse model of this disease, the way the mice walk worsens over time.

My study will examine part of the mouse brain that controls movements and gait called the primary motor cortex. Our brain works by the electrical firing signals of its principal cells, the neurons. In the primary motor cortex of MeCP2-duplication mice, I look at many neurons at the same time and observe what pattern of firing they exhibit during walking and running, and compare this to the patterns observed in normal mice.
By understanding how control of gait is disrupted, we can identify methods to modify and improve gait in humans with autism spectrum disorders.

Scott Wenderfer,M.D., Ph.D.
Assistant Professor – Renal
Novel Auto-antibody Markers of Lupus Nephritis

This project will assess a novel diagnostic tool for monitoring kidney involvement in children with systemic lupus erythematosus (SLE), a chronic inflammatory condition that occurs when the body’s immune system attacks tissues and organs.

Kidney involvement in SLE often drives the therapy decisions due to its enormous impact on patient outcomes and kidney function. To date, there are no reliable non-invasive diagnostic or prognostic markers for kidney involvement in these patients. Prior research by the applicant, assessing auto-antibodies against basement membrane material, found that severe kidney disease commonly develops in children with SLE, which can change the concentration in their bloodover time, and can discriminate between subsets of SLE patients.

In this study, the ability of this novel biomarker from blood to predict kidney involvement will be tested using a collection of subjects enrolled in the Midwest Pediatric Nephrology Consortium (MWPNC), a group of over 40 pediatric centers including Baylor College of Medicine. We will correlate findings with results of the more invasive kidney biopsy test. We will also explore relationships between anti-basement membrane antibodies and current clinical measures of kidney involvement in SLE.

The results will guide the applicant’s development of future studies to examine the value of this novel diagnostic tool among pediatric lupus patients and ultimately translate these findings to clinical practice.

Janice Zawaski, Ph.D.
Assistant Professor – Hematology/Oncology
The role of bone marrow in glioma radiotherapy response

Bone marrow derived cells (BMDCs) contribute to tumor growth and are associated with a worse clinical prognosis. Upon tumor initiation, the exact pathway/mechanism by which these BMDCs are recruited, migrate, and retained in the tumor are not well understood. However, low tumor oxygenation, as a result of radiotherapy, increases the influx of BMDCs.

The goal of this research is to create and characterize a mouse brain tumor model in which the bone marrow is fluorescent (GFP+) to study the contribution of BMDCs to tumor growth. As a result of the bone marrow being fluorescent it allows us to measure the magnitude and kinetics of the influx of BMDCs into the tumor pre- and post-radiotherapy using imaging techniques (microscopy, fluorescence imaging). In addition, translational imaging (PET and MRI) techniques, similar to clinical imaging currently performed on patients, will be used to study the effect of tumor oxygenation on the recruitment of BMDCs into the tumor pre- and post-radiotherapy.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

November 11, 2014

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When you think about our outstanding neurology team at Texas Children’s Epilepsy Center – one of the largest Level 4 epilepsy centers in the nation – one particular attribute comes to mind: their passion for innovation.

“Our focus has always been to discover new and innovative ways to treat and cure children with various forms of epilepsy,” said Dr. Angus Wilfong, a Texas Children’s neurologist who is leading the hospital’s first worldwide clinical trial of a cannabis-derived experimental drug to treat pediatric Dravet Syndrome.

The syndrome, which occurs in about one in every 30,000 births, is a rare and catastrophic form of intractable epilepsy that causes patients to experience dozens or even hundreds of seizures a day. If left untreated, children struggle with developmental delays, serious health complications and death.

That’s the grim reality 6-year-old Izaiah Ruiz faces daily. His grandmother, Lori Fountain, says Ruiz’s epilepsy is so severe that despite taking numerous seizure medications, nothing seems to produce long-term relief. Ruiz’s first seizure occurred when he was 2 months old, and since then, he’s almost lost his life twice. “I want him to be a normal little boy without having to worry about a seizure every time he goes to the playground or when he gets a runny nose,” said Fountain.

Ruiz is one of 30 patients worldwide enrolled in Texas Children’s study to examine the safety and efficacy of Epidiolex®, a highly purified cannabis extract that contains pure Cannobidiol (CBD). Although it is derived from the cannibas plant, Epidiolex contains no tetrahydrocannabional (THC), the psychoactive chemical in marijuana. GW Pharmaceuticals, who will fund the trial, is the only company in the world that produces pure plant-derived CBD, which is believed to help control seizures in children. The CBD medication is administered orally as a suspension or via feeding tube.

Wilfong, who is the study’s lead investigator and the first physician to administer Epidiolex in Texas, says the trial will be conducted in two stages. The first phase will determine the ideal dosage for children with Dravet Syndrome and the second phase will evaluate the drug’s safety and efficacy in this patient population.

“We are hopeful that in the next year, the results of this trial will show this drug has a positive impact on enrolled patients and that it will have implications for patients with other forms of intractable epilepsy,” said Dr. Gary Clark, chief of Neurology and Developmental Neuroscience at Texas Children’s.

Texas Children’s first began using Epidiolex in April of this year under a compassionate use protocol approved by the Food and Drug Administration for patients with catastrophic forms of epilepsy who were not responsive to seizure medications.

Wilfong said, “Initial trials of Epidiolex demonstrate promising signs of efficacy in children with treatment-resistant epilepsy. We are excited to partner with GW Pharmaceuticals in the first worldwide trial for this group of patients with such a catastrophoic form of epilepsy.”

Fountain hopes her grandson receives the experimental CBD medication rather than a placebo, but she knows that if he doesn’t, he’ll get the drug soon thereafter.

“If this drug could reduce Izaiah’s seizures and give him any semblance of a normal life, I can’t tell you how ecstatic I’ll be,” said Fountain.

Currently, Texas Children’s Epidiolex trial is accepting only pediatric patients with confirmed Dravet Syndrome. To learn more, click here or call Christina Tally, BS, CCRP, at Ext. 2-1276.

Click the link for more information about Texas Children’s Epilepsy Center.