First batch of awardees announced for new Chief Scientific Officer small grant program

When Dr. Terence Sanger started at CHOC in January 2020 as its first vice president for research and chief scientific officer, one of his priorities was to “Go Beyond” by making the CHOC Research Institute more robust.

One example of how he’s going about that is a new small grant program he’s funding that is open to all CHOC associates, staff, and faculty with principal investigator (PI) status.

The first batch of awardees in the CSO Small Grant Program, which launched in the third quarter of the current fiscal year, has been announced. Research projects of the winning applicants – 12 of 23 were awarded funding – range from virtual reality training for autism caregivers to racial and ethnic influences in adolescent obesity to the use of artificial intelligence to predict COVID-19 and related diseases.

The amount of all grants totaled $589,365, with recipients receiving up to $75,000 each, says Aprille Tongol, CSO Small Grants Program administrator. In the coming fiscal year, Dr. Sanger, a physician, engineer, and computational neuroscientist who also is vice chair of research for pediatrics at the UCI School of Medicine, will award a total of $1 million in CSO grants, Tongol says.

The CSO Small Grant Program aims to develop promising new research, expand current research activities, and encourage collaboration internally and externally with CHOC research partners. The program promotes and supports CHOC researchers who aspire to leverage research to improve the quality of care, patient outcomes, and well-being for children.

Virtual reality training and autism

Casey Clay, PhD,director of the Behavior Program at the Thompson Autism Center (TAC), was awarded a grant for a project that will examine if a newly developed virtual reality (VR) simulation using behavioral skills training (BST) is effective for training parents of children with autism who exhibit challenging behavior.

Clay says VR simulation is an improvement to typical training because it may increase skills of trainees without exposing them, or individuals with Autism Spectrum Disorder (ASD), to risk such as aggression, property destruction, etc.

Clay’s project builds off previous research he did at the University of Missouri, where he worked before joining CHOC in January 2020. That prior project involved training pre-clinical students to work with kids with autism. Clay’s CHOC project will do the same for parents or caregivers of children with ASD.

“Using the simulation, parents will follow training methods to engage with a virtual avatar and try to say and do the right things and arrange the environment in the right way,” Clay explains. “The idea is to work collaboratively with parents to build their skills at increasing appropriate behavior, and modifying the environment to decrease challenging behavior.”

Clay’s one-year project will begin in August 2021. He plans to sign up 16 teams of parents/children and measure pre- and post-skill levels of the participants, as well as assess parents’ acquired skills with live children during intervention sessions.

“This VR simulation will give parents the opportunity to practice and get immediate feedback from a clinician,” Clay says. “And it’s the practice that makes behavioral intervention effective over time.”

Clay praised the launch of the CSO Small Grants Program.

“It’s a great opportunity to jump start a lot of research,” he says.

Adolescent obesity study

Dr. Uma Rao, director of education and research in psychiatry at CHOC, was awarded a grant to study obesity in adolescents in the African-American, Hispanic/Latina, and Non-Hispanic White female population. The goal of the study is to reduce racial/ethnic health disparities and morbidity and mortality in this population, says Rao, also a professor and vice chair for child and adolescent psychiatry, psychiatry, and human behavior at the UCI School of Medicine.

Adolescence is a critical period for the development and life-long persistence of obesity, a public health epidemic with a range of short- and long-term medical and psychosocial problems and earlier death, Dr. Rao notes.

Her CSO grant is supplemental to a parent grant funded by the National Institutes of Health (NIH). That study, which Rao began in 2018, is assessing biobehavioral processes and social/environmental factors associated with obesity risk from a multi-dimensional perspective in the African-American, Hispanic/Latina, and Non-Hispanic White female population.

The aim of the CSO grant is to identify early stages of liver fibrosis and type 2 diabetes in these samples and assess whether inflammatory biomarkers serve as risk mechanisms for these two obesity-related disease outcomes. 

Knowledge regarding the underlying mechanisms of obesity-related disease burden among high-risk groups will be helpful in early detection and developing effective personalized interventions, thereby reducing racial/ethnic health disparities, morbidity and mortality associated with the obesity epidemic, Dr. Rao says.

Ultimately, she says, the goal is to enroll 300 participants in the study – 100 from each of the three ethnic groups. Participants will range in age from 13 to 17.

“We hope this research ultimately leads to the development of more personalized interventions for these groups to reduce disparities, which cause real havoc,” Dr. Rao says.

List of grant awardees

The second group of awardees of CSO grants was notified on Monday, June 21, 2021.

Here are the 12 recipients of the first round of CSO grants with a brief description of their projects:

Lisa Murdock, RN — Evaluation of a Nurse-Administered Screening Tool to Identify Victims of Child Trafficking in Patients with High-Risk Chief Complaints in a Pediatric Emergency Department

Dr. Autumn Ivy — Identifying Targetable Epigenetic Mechanisms of Early-Life Seizures and Exercise Intervention

Dr. Van Huynh — Utility of Antifungal Prophylaxis to Prevent Invasive Fungal Disease in Pediatric and Adolescent Patients with Hematologic Malignancy

Michelle Fortier, PhD — Opioid Prescribing Patterns in Pediatric and Young Adult Cancer Patients

Dr. Diane Nugent – COVID Antibody Response in Children: Protection and Risk for MIS-C and Late Effects

Dr. Suresh Magge — School-age Outcomes in Patients with Single Suture Craniosynostosis After Endoscopic-assisted Strip Craniectomy and Orthotic Therapy

Dr. Lilibeth Torno — Monitoring of Plasma Cell Free DNA BRAF V600E+ Mutations in Patients with Langerhans Cell Histiocytosis

Casey Clay, PhD — Virtual Reality Training for Autism Caregivers

Alexander Stover, MS — Derivation and Characterization of an NDUFAF5 Mouse Model for the Study of Mitochondrial Complex I Disorders

Louis Ehwerhemuepha, PhD — Artificial Intelligence for Prediction of COVID-19, MIS-C, and Juvenile Dermatomyositis

Dr. Theodore Heyming — Identification of Social and Environmental Determinants of Pediatric Health in an Emergency Setting and Referral Utilization

Dr. Uma Rao — Racial/Ethnic Influences in Adolescent Obesity: Risk Mechanisms for Disease Burden

Pandemic has provided lessons on continuing research during a crisis

COVID-19 has been a tragic wrecking ball on several fronts, but something that isn’t mentioned much is clinical research.

Long a linchpin at CHOC and, moving forward, poised to become even more central as CHOC evolves into a leading pediatric health system, clinical research has had to quickly readjust under the strain of the pandemic.

But out of these dark days have emerged several lessons on not only how to continue research during a crisis, but how to keep it thriving.

That was a key message delivered by Phuong Dao, director of Research Operations at CHOC, during a recent webinar beamed around the country.

Phuong Dao, director of research operations at CHOC

“There’s a renewed sense of energy and purpose to use science to solve problems that are important to our patients and the public,” Phuong said during a panel discussion that was part of a two-week summit on rare diseases hosted by Global Genes, an Aliso Viejo-based non-profit that advocates for the rare disease community.

“I think we can really harness and leverage this shared renewed energy and translate that to the conducting of rare-disease trials,” Phuong said.

The panel, speaking on “Proactive Planning for Continuity of Research During a Crisis,” also featured moderator Nina Wachsman, founder and president of Augur Health, a New York-based clinical research recruitment firm, and Gerald Mosely, founder and principal of CP&P Development, a Sacramento-based specialty consulting firm focused on pharmaceutical sales and operations.

Wachsman laid out some realities hospitals face during COVID-19:

  • Less access to doctors and inpatient visits
  • Less interest in research into rare diseases
  • An explosion in telehealth visits
  • E-signatures for informed consent
  • Nurse home visits
  • Lab tests done remotely

As for clinical research, Wachsman said, challenges include a lack of available capital, a lack of access to enough clinical trial participants and the ability to retain them, and getting the attention of the FDA at a time when COVID-related studies dominate.

And in a world of virtual meetings, Mosely noted, effective teamwork can be a challenge.

“The people aspect is what can make or break things,” Mosely said. “Successful outcomes can be affected more by interpersonal than technical skills.”

But bright spots abound, Phuong said.

COVID-19 studies can serve as a template for clinical research well beyond the end of the pandemic. “We have seen study teams form quickly and multi-disciplinary teams mobilize,” she said.

The contracting and budgeting processes for COVID-19 studies have accelerated and teams involved in “master trial protocol” studies involving multiple hospitals have readily shared resources, when in the past there were more hurdles.

“This focus on leaner and faster clinical trials can be leveraged in the rare disease space as well,” Phuong said.

Other positive changes introduced during the pandemic that can affect all clinical trials moving forward include:

  • Fast tracking by the Institutional Review Board (IRB)
  • The acceptability, and patient popularity, of telehealth
  • Home-based testing and monitoring technologies
  • Curbside/courier pick-up and delivery of participant samples and investigational products
  • Digital data collecting tools
  • Remote Site Initiation Visits (SIVs) and monitoring
  • Less reliance of participants having to be on site

Phuong noted that clinical trials involving kids impact entire families, one of the things that makes pediatric research different from studies involving adults.

The consenting process is unique, she added, and some teenagers who still are minors sometimes have a different opinion from their parents when it comes to treatment plans.

Moving forward with telehealth, Phuong said, clinicians need to think about how to engage with study participants in the languages they understand best.

And there are other questions that need to be addressed, including:

  • How research should be structured to adapt to new realities
  • How to keep motivation high to conduct clinical studies into rare diseases
  • How virtual meetings and healthcare visits affect productivity

“I hope that we sustain the gains we have made to move toward more efficiently and that we are able to approach clinical research in ways that are more streamlined and modernized,” Phuong said.

To learn more about CHOC’s Research Institute, click here.

Wired for hope: deep brain stimulation for dystonia

Every morning when she awakes, Sydney Amato begins her daily battle with her body.

If she’s lucky, the 16-year-old will have gotten a handful of hours of uninterrupted sleep – dreaming, perhaps, of doing what most healthy kids her age take for granted:

Hanging out with friends. Going to school. Learning to drive.

Because of a neurological condition called dystonia, Sydney, who is in excellent cognitive health but speaks and walks with some difficulty, suffers from involuntary and near-constant contraction of muscles in her neck, arms, legs and trunk.

Sydney with her father, Louis

Her mind is unable to control the painful jerking that makes most of her body twist and go rigid, her muscles moving out of normal sequence.

Born a right-hander, she can feed herself with some struggle using her left hand. She wants to dress and put on makeup herself, but those normally simple tasks become lengthy ordeals.

“My body fights me all the time,” says Sydney, trying to distract herself in her hospital bed by watching an old episode of “Keeping Up with the Kardashians.” Listening to her favorite music – Ariana Grande, Lauren Daigle, Drake – can only temporarily transport Sydney away from her debilitating condition.

“She knows what she wants to do,” says her father, Louis. “But her body won’t let her.”

Specialists at CHOC are working hard to change that.

A first for CHOC

On Aug. 14, 2020, a team led by Dr. Terence Sanger, a physician, engineer, and computational neuroscientist who joined CHOC in January 2020 as its first chief scientific officer, and Dr. Joffre E. Olaya, CHOC’s functional restorative neurosurgeon, implanted several temporary electrodes into Sydney’s brain.

Dr. Terence Sanger, a physician, engineer, and computational neuroscientist and CHOC’s chief scientific officer

The surgery marked the first time a patient with a movement disorder at CHOC underwent a procedure called deep brain stimulation (DBS).

Working in perfect harmony as a team, Dr. Sanger and Dr. Olaya performed the first stage of a three-stage surgery on Sydney. As the surgeon, Dr. Olaya placed the leads following advice from Dr. Sanger, the neurologist, where they should go.

In the procedure, millimeter-thick electrodes were precisely positioned into the basal ganglia region of Sydney’s brain – about three inches deep. The surgery involved the use of the ROSA Robot, the same tool that has been used during brain surgery on epilepsy patients at CHOC since 2015.

Dr. Joffre E. Olaya, CHOC pediatric neurosurgeon

Considered one of the most advanced robotized surgical assistants, ROSA includes a computer system and a robotic arm. It’s a minimally invasive surgical tool that improves accuracy and significantly reduces surgery/anesthesia time.

The ROSA Robot helped with implanting and targeting the electrodes, and a portable operating-room CT scanner confirmed their position.

Turning down the volume

DBS is designed to ease Sydney’s condition by sending electrical currents to jam her malfunctioning brain signals.

Think of turning down the volume on your car radio.

“Nobody really understands the cause of dystonia,” Dr. Sanger explains, “but there’s probably too much electrical stimulation going on in the motor areas of the brain. We’re trying to calm down that extra noise.”

Although DBS dates to the 1960s, it wasn’t until the 1980s that the modern era of using it to treat adult patients with tremor and Parkinson’s disease began.

In 2000, Dr. Sanger, working with engineers, data scientists, neurosurgeons, and others, began implanting electrodes in pediatric patients.

Instead of the established method of placing the leads at predetermined sites and hoping they worked, Sanger and his team, just as they did in Sydney’s case, placed temporary leads to best assess where they should go permanently based on patient response.

In 2016, Dr. Sanger began honing DBS to treat children with dystonia. Before the surgery on Sydney, Dr. Sanger had performed DBS on 26 children using the same three-stage technique. He says 80 percent of those children have seen successful results.

Early signs

Sydney began showing symptoms of dystonia – tremors in her hands — when she was 5 ½ years old.

A year later, she was using a wheelchair. She had her first brain surgery at age 7.

Since then, “she’s been all over the U.S.” seeking the right treatment for her condition after several setbacks, says her father.

But her condition was not improving.

Early this year, a neurologist in Kansas City, Mo., recommended that Sydney see Dr. Sanger.

“I asked him, ‘If Sydney was your kid, where would you go?’ Louis Amato recalls. “He said, ‘Hands down, Dr. Sanger.’”

The COVID-19 pandemic pushed Sydney’s surgery to mid-August.

Sydney already had two electrodes in her brain that were only partially working when she came to CHOC in early August for surgery.

After two extensive run-throughs with their team, Dr. Sanger and Dr. Olaya, in a six-hour procedure that at one point had nearly 20 people in the operating room, implanted more electrodes to give her a total of nine.

On Thursday, Aug. 20, six days after Sydney’s surgery, Dr. Sanger stopped by her room at CHOC Hospital. The room was decorated in purple, Sydney’s favorite color.

Dr. Sanger greeted her as CHOC staff members, joined by members of Sanger Lab, which conducts research in pediatric movement disorders, prepared to have Sydney walk back and forth down a hallway while connected to electrical equipment programmed to record signals in her brain and muscles.

A thick coil of multicolored wires snaked from under a large white bandage covering Sydney’s head. Extending about 6 feet, the wires were plugged into specialized recording equipment controlled by Jennifer MacLean, a pediatric nurse practitioner whose job was to manipulate the strength of electrical charges affecting the four points of contact on each electrode.

The goal: determine which charges worked best and on which electrodes.

“It could have turned out that the DBS procedure made no difference,” Dr. Sanger says. “But we’ve seen a very good response in Sydney.”

For example, her once mostly useless right hand was working much better.

“It gives you goosebumps,” Louis Amato says.

After taking a bite of a veggie burger and sipping some water, Sydney started to walk.

Following her were seven CHOC and Sanger Lab specialists.

“Go nice and slowly,” Jennifer told Sydney. “You’re going too fast for us!”

Perhaps Sydney was anxious to get back to riding Tigger, a quarter horse, in her hometown of Carthage, Mo. She has been riding him for six months.

Sydney is eager to get back to riding her favorite horse, Tigger.

“Her balance isn’t bad on the horse,” says Louis Amato.

Sydney also loves to tan by her pool and swim.

What she wants most, however, is to be freed from her body so she can return to school and do what most teens enjoy.

“It’s stressful,” says her mother, Angie. “She has a lot of friends her age, but she can’t do a lot of the things they do. She has her days when she can get really upset.”

Now, however, working with Dr. Sanger, Dr. Olaya and the entire team at CHOC, the Amatos are more optimistic than ever.

“We’re hopeful that this is going to be a big life-changer for her,” Angie Amato says. “That would be the best thing that could ever happen – better than winning the lottery.”

‘The A Team’

After crunching numbers for a week to assess which of the nine electrodes proved to be the most effective based on how Sydney responded to varying degrees of electrical currents, Dr. Sanger and his team settled on four electrodes that were permanently used to treat her condition – three new ones, and one existing one.

The team performed this second surgery on Sydney in late August.

In the third and final surgery, successfully completed in early September, a rechargeable generator that powers the DBS leads was implanted in Sydney’s chest.

“As we get better and better at this,” says Dr. Sanger, “and as the technology progresses, we’ll be able to do this on kids who are less sick than Sydney.”

Dr. Sanger and Dr. Olaya are poised to dramatically improve the lives of many more patients like Sydney at CHOC.

“I’m really excited that we will be doing more of these procedures to help pediatric patients with movement disorders and significantly improve their quality of life,” says Dr. Olaya. “I look forward to continuing to provide this type of personalized care.”

Angie and Louis Amato say Sydney has never gotten this much special attention during her 11-year-plus medical journey.

“Here at CHOC,” Louis Amato says, “we feel like we’re with the A Team.”

Says Sydney: “I’ve never felt this much confidence and this good about treatment before.”

Learn more about deep brain stimulation (DBS) surgery at CHOC.

How COVID-19 survivors can support others through plasma donation

For Steve Emfinger, donating his blood plasma at CHOC was fast, painless and a way to give meaning to his battle with COVID-19.

“It was very simple,” he said. “And to know it’s helping kids is very cool.”

Man donates plasma to help COVID-19 patients
Steve with his COVID-19 convalescent plasma donation at CHOC Blood Bank.

Registered with the U.S. Food and Drug Administration, the CHOC Blood Bank is available to collect and process blood plasma donations from COVID-19 survivors. These donations are being used to help patients at CHOC and throughout the community.

“We’re still learning about COVID-19, but it’s possible that those who have recovered from the disease have produced antibodies to protect them from the infection,” says Dr. Antonio Arrieta, a pediatric infectious disease specialist who is studying the use of convalescent COVID-19 plasma at CHOC. “If so, their blood plasma would contain these antibodies and may be helpful in the treatment of COVID-19 disease in others.”

Since CHOC began collecting and processing blood plasma donations from recovered COVID-19 patients this spring, more than a dozen CHOC patients have benefited.

And as COVID-19 diagnoses continue to mount in Orange County and fall approaches, the need for blood plasma donations will only grow at CHOC, Dr. Arrieta says.

A surprising diagnosis

Typically, an early riser with boundless energy, Steve just felt zapped in late winter. Attributing the lethargy to two back-to-back trips he’d just taken, Steve decided to work from home. 

Though his symptoms – including a slight cough and dizziness – were minor, Steve’s energy shift was so atypical that he ultimately decided to go to a local hospital. There, he was tested for the flu and strep throat and had a chest scan, which all came back negative.

Steve had one more test – for COVID-19. A couple days later, he got word the test was positive.

Steve hunkered down at home, and notified any friends, family and neighbors he’d been in contact within the weeks before his diagnosis. Some days he felt good – able to work remotely and cook meals – and others were much more challenging.

All in all, though, Steve felt fortunate to have mild symptoms, never experiencing a fever, body aches or significant respiratory problems, despite a lifelong mild case of asthma.

“I think I’m blessed to know that I had minor symptoms and was able to get through it and my family didn’t get sick,” he says.

As Steve’s diagnosis came early into the pandemic’s spread in Southern California, he was initially reluctant to share his story with a broader network of friends, family and colleagues. But as he got more comfortable, Steve’s decision to tell others proved fortuitous.

A friend who worked at CHOC told Steve about the COVID-19 convalescent plasma program and how badly donations were needed.

“I had heard that blood plasma was needed, but I didn’t know where to find a donor center,” he said. “I called CHOC the next day to make an appointment.”

The process to donate plasma to support COVID-19 patients
Steve has already donated plasma twice at CHOC to help support others fighting COVID-19.

Steps to donate

Potential donors must meet some criteria to be eligible:

  1. Donors must show laboratory test proof of their COVID-19 diagnosis either through a diagnostic test (nasopharyngeal swab) at the time they were sick, or a positive serological test for SARS-CoV-2 antibodies after they recovered.
  2. Donors must have been symptom-free for at least 14 days before they donate.
  3. They must meet all other health requirements for blood donors.
  4. Though donors may be male or female, female donors will need to meet some additional requirements that the Blood Bank team will help explain further.

Confirming these requirements takes about a week. Once donors are confirmed and at the Blood Bank, the simple donation process takes about two hours. Donors can return every 28 days to donate again.

Steve is already on his second donation at CHOC and plans to continue in the future – in addition to donating blood and platelets.

“To help someone else makes it all worth it,” he says.

To schedule an appointment or learn more, call the CHOC Blood Bank at 714-509-8339.

Rapid genome testing for infants saves lives, costs

Its name conjures up images of a familiar fairy tale, but Project Baby Bear has produced some very impressive real-world results that could save the lives of thousands of seriously ill infants.

The recently completed two-year pilot program at five clinical sites in California – including CHOC – helped doctors target a baby’s specific genetic disease in a matter of days, instead of the four to six weeks required for standard genetic tests.

That means quicker diagnoses leading to quicker treatments, less time in the hospital and more answers for anxious parents.

“It can be a real game changer,” said Dr. Jason Knight, a pediatric critical care physician and medical director of CHOC’s pediatric intensive care unit and one of the physician leads on the project. “It’s a tool we didn’t have a few years ago.”

Changing the game

By employing rapid whole genome sequencing (rWGS), doctors could gather vital information that changed the decisions families and clinicians made, and ultimately saved lives and resources. The procedure has historically been used only as a last resort.

By pinpointing the cause of rare disease with rWGS, physicians can customize treatment. And having a genetic diagnosis can eliminate the need for further tests, improve outcomes, reduce hospital stay length and improve the experience of care for families – all while also reducing costs.

In addition, substantial reductions in healthcare spending — $2.5 million — accrued largely because rWGS permitted doctors to discharge babies sooner and reduce the number of procedures that may have been performed in the absence of a precise diagnosis.

Avoided procedures included 11 major surgeries and 16 fewer diagnostic tests such as  open muscle, liver and other biopsies that are performed under general anesthesia.

Success story

In one case, a newborn baby girl with a life-threatening irregular heartbeat was admitted to CHOC Hospital. Instead of undergoing an arduous battery of tests, the child was diagnosed within two days with Timothy Syndrome, an extremely rare cardiac condition that put her at risk for sudden death.

With the genetic diagnosis in hand, CHOC physicians were able to treat the infant with the appropriate medication  for her condition. Her heartbeat was restored to normal, significantly reducing the risk of sudden cardiac death. Her physicians, secure in her diagnosis, implanted a pacemaker, dramatically improving her chances for a happy and healthy childhood.

She recently celebrated her first birthday.

“Without the results of her rapid whole genome sequence, she would have gone home on a different medication and been at a much higher risk for sudden death,” Dr. Knight said. “She got the right diagnosis and we gave her a pacemaker so her risk of sudden death went to zero.”

In all, Project Baby Bear provided diagnoses for 76 of the 178 babies who completed rWGS. This led to a change in the care of 66 babies. It diagnosed 35 rare conditions that occur in less than one in 1 million births. About 150,000 children could benefit from rWGS.

Turning every stone

Even if the test doesn’t diagnose a problem, it can help comfort families, Dr. Knight said.

“Even a negative test can be helpful for some families to know we’re not missing something,” he said. “It gives them assurance that we’ve turned over every stone.”

With the success of the study, Dr. Knight hopes to see the service expand to reach more patients.

“Should we be doing this with all newborns?” he asked. “Based on our experience with Project Baby Bear, it would seem feasible that for newborns and children in intensive care units without clear diagnoses, this should be part of our diagnostic process and the earlier the better.”

Multidisciplinary, multi-site effort

CHOC’s role in Project Baby Bear is a collaborative, multi-disciplinary effort involving many clinicians and staff, including research coordinators Cathy Flores, Erum Naeem and Ofelia Vargas-Shiraishi, and physician leads Drs. John Cleary, Juliette Hunt, Adam Schwarz and Neda Zadeh, in addition to Dr. Knight.

Led by Rady Children’s Hospital-San Diego, Project Baby Bear helps infants who are undergoing intensive care and covered by Medi-Cal. The other participating hospitals include UCSF Benioff Children’s Hospital Oakland, UC Davis Children’s Hospital in Sacramento, and Valley Children’s Healthcare in Madera.

The $2 million Project Baby Bear was funded by the State of California. In-kind contributions of $400,000 from Rady Children’s Hospital ensured more than 90 percent of the state funds were used to support the care and management of critically ill babies.

Learn more about the CHOC Research Institute.