November 18, 2014

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On Thursday, Texas Children’s President and CEO Mark A. Wallace shared exciting news: Texas Children’s Board of Trustees has enthusiastically approved our plans for CareFirst.

Wallace and the leadership team launched CareFirst in January to reinvest in the programs our most critically ill patients need – primarily in the Critical Care units, operating rooms, Heart Center, Emergency Center and many of our Diagnostic and Therapeutic Services.

“These programs are at the core of our mission to create a healthier future for children throughout our broad community,” Wallace said.

The CareFirst plan includes adding 19 floors to the existing building base next to Texas Children’s Pavilion for Women. For now, this new tower is named “Pediatric Tower E.” The 25-floor tower is slated to come online in 2018 and will house a 130-bed intensive care unit, new operating rooms with the latest technology and Texas Children’s Heart Center, including the cardiovascular operating rooms and the cardiovascular intensive care unit. The CareFirst plan also includes renovation of the Emergency Center and other areas in the West Tower that will become available once Pediatric Tower E is completed. Diagnostic and Therapeutic Services will be located throughout the new spaces so that care can be delivered close to where patients are.

“This is cause for celebration,” Wallace said. “A considerable number of people, including board members, medical staff, managers and employees, have invested countless hours in this work, and together, we conducted a comprehensive study of our challenges, needs and aspirations, and a thorough assessment of the most effective solutions. The result is CareFirst.”

The expansion of the hospital’s facilities and programs in the Texas Medical Center will create access and allow us to provide the best quality care for the children who need us the most.

“CareFirst will ensure the best possible outcomes for some of the nation’s sickest children,” Wallace said. “And it will help us deliver on our promise to make Texas Children’s the best possible place to give and receive care.”

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Each year more than two million people in the United States get infections that are resistant to antibiotics and at least 23,000 people die as a result.

Dr. Debra Palazzi, a pediatric infectious diseases specialist and medical director of Texas Children’s Hospital’s Antimicrobial Stewardship Program, said the hospital has a good history of keeping antibiotic resistance at bay, but that the organization isn’t immune to the worldwide problem and has seen an increase in such cases during the past few years.

“We now see children with complicated diseases for whom we have limited or no effective antimicrobial therapy,” Palazzi said. “This is a growing problem in our pediatric population and results in increased morbidity and mortality.”

To help raise awareness of antibiotic resistance and the importance of appropriate antibiotic prescribing and use, Texas Children’s Hospital is joining more than 20 children’s hospitals across the country this week to promote the Center for Disease Control and Prevention’s Get Smart About Antibiotics Week. The goals of the annual event are to raise awareness of antibiotic resistance and to educate health care providers and the public about the appropriate and safe use of antimicrobial therapy.

Palazzi and Ruston Taylor, the clinical pharmacy specialist for the Antimicrobial Stewardship Program, have been working hard to achieve both of those goals and formed earlier this year a multidisciplinary Antimicrobial Stewardship Program aimed at optimizing the selection, dose, duration and route of therapy given to patients at Texas Children’s Hospital. Since then, a member of the program’s team has reviewed microbiology reports daily to assist healthcare providers in prescribing the appropriate antimicrobial therapy.

In some cases, the stewardship team – which is composed of people from multiple departments including Pharmacy, Infection Control, Infectious Diseases, Microbiology, and Quality and Safety – makes a recommendation to improve a patient’s antimicrobial treatment plan. The recommendation might be to de-escalate therapy, use an alternative therapy or stop therapy altogether.

“When most people think of antimicrobial stewardship, they say ‘antibiotic police’,” Taylor said. “We’ve actually called providers to START a drug that’s active against a reported bacterial pathogen rather than calling for discontinuation of agents.”

Another tool the team uses to help optimize a patient’s treatment plan is a rapid diagnostic test that can identify the presence of certain antibiotic-resistant strains of bacteria in a few hours instead of days. Before the availability of the test, physicians had to wait on culture-dependent methods for identification, which could take two to three days. Now, results can be determined in about an hour, allowing physicians to prescribe more appropriate treatment sooner rather than later.

Another intervention developed by the Antimicrobial Stewardship Program team started in the Pediatric Intensive Care Unit (PICU) and has quickly spread to other parts of the hospital. This summer, members of the stewardship team began rounding with all PICU teams to introduce a care bundle for antimicrobial prescribing to their daily provider progress notes. The bundle addresses the infectious disease the team is trying to treat, the antimicrobial agents the patient is on, microbiology data obtained, and the plan for antimicrobial therapy.

“The appropriate use of antimicrobials is something that affects all of us,” Taylor said. “The choices we make today may have consequences for generations to come.”

For more information on Get Smart About Antibiotics Week and how you can help, visit http://www.cdc.gov/getsmart/week/.

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If you have been thinking about quitting smoking or using nicotine, you are not alone.

Texas Children’s is here to support your efforts to quit, especially in light of the Great American Smokeout, an annual event that occurs the third Thursday of November and challenges smokers across the nation to make a plan to stop smoking.

Tobacco consumption remains the largest preventable cause of disease and premature death in the Unites States, and it is estimated that about 43.8 million Americans still smoke cigarettes, which is almost one in every five adults.

Secondhand and thirdhand smoke also present health risks to those who smoke and to those around them. Research shows that secondhand smoke can seep into hair, clothing, dust, and other surfaces, and that it creates thirdhand smoke or particles that are left on surfaces after the visible smoke is gone. These particles can become airborne and can be picked up by people – especially babies and small children – who touch the surfaces and get the particles on their hands and bodies.

The best way to prevent all such risks is to stop smoking, a step the Acting U.S. Surgeon General Boris Lushniak said is the “single most important step that smokers can take to enhance the length and quality of their lives.”

Here at Texas Children’s, we value your total well-being and are committed to providing education and resources that optimize your health and wellness. That’s why employees covered under the Texas Children’s medical plan can receive free tobacco cessation medications and over-the-counter treatments. As of September 1, these tools are covered at 100 percent for Texas Children medical plan participants with a prescription.

Before you go out and get these medications and treatments, however, it’s best to set a date for when you want to quit smoking and devise a plan on how to do it. Here are some tips on how you can kick the habit:

  1. Set a Quit Date
    First things first – pick your quit date. By having a day you’re working toward, you’ll be able to prepare mentally and physically to quit smoking. Avoid choosing a day where you know you will be busy, stressed, or tempted to smoke.
  2. Tell Family and Friends You Plan to Quit
    Quitting smoking is easier when the people in your life support you. Let them know you are planning to quit and ask for their support in staying accountable.
  3. Anticipate and Plan for Challenges While Quitting
    Quitting smoking is hardest during the first few weeks. You will deal with uncomfortable feelings, temptations to smoke, withdrawal symptoms, and cigarette cravings. Just remember that they are temporary, no matter how powerful they feel at the time.
  4. Remove Cigarettes and Other Tobacco from Your Home‚ Car‚ and Work
    Don’t be tempted to smoke during your quit. Stay strong. You can do it! Removing cigarettes and things that remind you of smoking will get you ready to stop.
  5. Talk to Your Medical Provider about Quit Options
    It is difficult to quit smoking on your own, but quitting “cold turkey” is not your only choice. Smoking cessation medications can dramatically increase your likelihood of successfully quitting. Texas Children’s medical plans covers prescription medication and over-the-counter treatments at 100 percent with a prescription.

Your well-being contributes to making Texas Children’s the best possible place to work and receive care. Good luck and thank you for continuing to optimize your health and wellness.

For more information or additional guidance, please call the Employee Medical Clinic at Ext. 4-2150 or visit the Wellness Website on Connect.

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Texas Children’s Health Plan opened its second location of The Center for Children and Women on November 11. The approximately 65,000-square-foot facility, which is located at 9700 Bissonnet Street in the Southwest Corporate Center, provides comprehensive medical care for Texas Children’s Health Plan members in the Southwest area of Houston.

Through a partnership with Baylor College of Medicine, the patient- and family-centered medical home includes pediatricians, advanced nurse practitioners, OB/GYNs, certified nurse midwives, optometrists, imaging specialists, speech therapists, a laboratory, and an onsite pharmacy. There are also plans to add dentistry services. Having all these services under one roof makes it possible for members to have their medical needs met on the same day and in the same location.

“Texas Children’s Health Plan is very proud to expand The Center for Children and Women to another location in Houston,” said Christopher Born, Texas Children’s Health Plan president. “The Center for Children and Women model has exceeded our expectations at our Greenspoint location and we look forward to the same success at the Southwest location.”

The new facility is the second Texas Children’s Health Plan – The Center for Children and Women to open in the past year and a half. The first facility opened in the Greenspoint area in August of 2013 and has made a great impact on the surrounding community. Within its first year of operation, The Center for Children and Women in Greenspoint completed more than 27,000 appointments, delivered more than 260 births, and hosted breastfeeding, car seat safety, and new parent classes to help educate the community. The facility also received National Committee for Quality Assurance recognition and was selected by Texas Health and Human Services for a national pregnancy medical home pilot program.

“Our goal is to ensure that Texas Children’s Health Plan members receive the same level of care as those with commercial health insurance,” stated Tangula Taylor, director of operations at The Center for Children and Women. “We are very proud of what we have accomplished in the time that the Greenspoint location has been open and we are uniquely positioned to serve the Medicaid and CHIP populations in Southwest Houston with the same commitment.”

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What is supposed to be a joyous occasion – the birth of your baby – suddenly gives way to anxiety. While you know the next few months are critical to your premature infant’s survival, you never expect to hear this dreaded diagnosis: “Your baby has necrotizing enterocolitis.”

Texas Children’s Neonatologist Dr. Amy Hair is on a crusade to protect fragile and premature infants from necrotizing enterocolitis (NEC), a life-threatening neonatal condition that causes inflammation and death of intestinal tissue. In the worst cases of NEC, perforations develop in the intestine which may require portions of the intestine to be surgically removed.

Since the internal organs of premature infants are not fully developed, they are more susceptible to NEC, which claims the lives of 500 premature infants each year in the United States. Jennifer Canvasser, a mother whose infant son died of NEC, knows this reality all too well. “My son Micah was critically ill when I first heard about NEC. In a matter of hours, Micah went from being a beautiful five-pound baby to being critically ill and intubated with cords, wires and tubes on each of his extremities.”

Micah’s tragic outcome and one from Hair’s earlier years in residency – she treated a baby who died of NEC – motivated Hair to protect premature infants from this deadly disease by encouraging nursing mothers to donate the lifesaving gift of breast milk.

“Breast milk donors are lifesavers,” said Hair. “Unlike formula derived from cow protein – which is known to increase the risk of NEC – breast milk contains antibodies and anti-inflammatory factors that protect babies against NEC and a host of bacterial infections.”

Hair says the most effective way to reduce the rate of NEC is by feeding infants a human milk diet, which supports the guidelines issued by the American Academy of Pediatrics. This diet consists of mother’s own milk, pasteurized donor breast milk and protein fortifiers that add calories and nutrients to human milk to help critically-ill infants grow and thrive.

Since Texas Children’s implemented its exclusive human milk feeding protocol in 2009, NEC rates in our NICU have dropped significantly from the national average of 10 -12 percent to 2 percent. Hair attributes this remarkable decline to the generous mothers who donate their breast milk to Texas Children’s Mother’s Milk Bank, many of whom are Texas Children’s employees.

“Every ounce of donor breast milk improves neonatal outcomes in our NICU,” said Hair. “If more mothers donate their excess supply to our Milk Bank, we can ensure our tiniest, most vulnerable patients receive a constant supply of nourishment and protection to stay healthy.”

As the associate medical director of neonatal nutrition at Texas Children’s, Hair has devoted her entire research to neonatal nutrition and delivers numerous presentations each year touting the lifesaving benefits of human milk at pediatric research conferences wordwide.

She also serves as a scientific advisor to the NEC Society, a non-profit organization that was established by Canvasser to honor her son, Micah, increase awareness about the lifesaving power of human milk, and encourage more mothers to donate their breast milk to protect babies from NEC.

Dr. Hair’s call-to-action is simple: Donate breast milk and save a baby’s life.

Click Texas Children’s Mother’s Milk Bank to learn more about our donor breast milk program.

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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.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Texas Children’s was well represented this month at the Periwinkle Foundation Kickball Classic, an event that raises money for an organization that provides healing programs and camps to children, young adults and families who are challenged by cancer and other life-threatening illnesses.

Employees from across the hospital organized 23 of the 36 teams that participated in the November 8 event at the Houston Sportsplex. Kicks R 4 Kids, the team that represented Texas Children’s Hospital’s Pediatric Radiology Department, took home the second-place title.

First place went to Lamar Squad, a team representing Lamar High School, and third place went to Kick Ballers, a team representing Bellaire High School.

More than 700 people turned out to watch the tournament, which raised $32,000 for the Periwinkle Foundation’s inaugural Kickball Classic.

The Kickball Classic involves teams of at least 10 people rallying together to raise funds while kicking to improve the lives of those affected by cancer. Each team is guaranteed three games in the round robin tournament and individuals are welcome to attend as well.

For more information about the Periwinkle Foundation, visit the organization’s website at http://periwinklefoundation.org/.