Danielle Guez Barber, MD, PhD,
Wins Philip R. Dodge
Young Investigator Award

Danielle Guez Barber, MD, PhD, a neonatal neurologist at Children's Hospital Colorado, received this year's Philip R. Dodge Young Investigator Award from the Child Neurology Society. Her work, shaped by her daughter’s early days in the neonatal intensive care unit, is transforming the field of neonatal neurology.

Researching hypoxic ischemic encephalopathy

Dr. Guez Barber studies perinatal hypoxic ischemic encephalopathy (HIE), a brain injury caused by lack of oxygen or blood flow before, during or shortly after birth. HIE affects between 1 and 4 per 1,000 live births in the United States and can cause epilepsy, cerebral palsy, autism, learning and attention problems, and more. Currently, therapeutic hypothermia is the only treatment, and the clock starts ticking at birth. Clinicians have just six hours to identify a newborn with HIE and begin cooling therapy

"Cooling slows down brain metabolism and the injury process that HIE sets in motion," Dr. Guez Barber says.

But often, cooling is not enough, and it doesn't work on babies born prematurely. Dr. Guez Barber is hoping to find a better treatment. Through her lab at the University of Colorado School of Medicine, she's exploring ways to target therapies later in the injury process. By targeting the body's immune response, it gives doctors what they don't have now — time.

To accomplish this, the research team is focused on macrophages, sometimes thought of as the clean-up crew. These specialized cells are best known for finding and destroying harmful dead cells and pathogens. But if they’re too active, they can worsen inflammation and damage tissue on the edge of the injury, making the overall injury worse. In the healthy brain, resident macrophages are known as microglia. During HIE, microglia mount a fierce immune response, clearing dead cells and producing cytokines that impact neighboring cells. Monocyte-derived macrophages (MDMs) also become active during HIE, crossing from the blood into the brain.

"For both microglia and MDMs, it's still not clear whether they are making things better or making them worse," Dr. Guez Barber says. "In a preclinical study, we found that when we deplete microglia using a drug, it makes the injury worse in females but better in males.”

These findings suggest that microglia play a protective role in females by helping limit injury. In males, however, the balance between microglia and the MDMs appears to be different.

To explore this further, Dr. Guez Barber and her team are using a genetic approach. Through transgenic mouse models and selective depletion of microglia or MDMs, the team is investigating how these cells influence brain injury after HIE. They hope to understand which cells make injury better or worse, why the response differs between males and females, and whether sex chromosomes or hormones drive those differences.

"My lab focuses on the inflammatory process that happens after the injury to try to figure out what treatments will help more babies than we can help now," Dr. Guez Barber says. When we understand the principles of what these cells are doing, we will be able to manipulate them to get new treatments that should help all babies after HIE.

How personal experience shapes her work as a clinician, researcher and advocate

Dr. Guez Barber has always been fascinated by the brain. But in 2011, the science became intertwined with her own life. During medical school, her daughter was born prematurely and diagnosed with HIE. As a first-time mom, she watched her daughter spend 23 days in the neonatal intensive care unit. Every physician, every conversation shaped her into the physician, researcher and patient advocate she is today.

"It stays with you for a long time," Dr. Guez Barber says. "It changes the way I counsel families both in the NICU and after they leave the acute setting. Uncertainty is hard. Sometimes the uncertainty about a prognosis can be the hardest part, but it also leaves room for hope."

That hope is part of her ethos not just in her medical practice but also in her advocacy work — extending her expertise to support patients and families across the world. Dr. Guez Barber serves on the board of directors and the medical advisory board for Hope for HIE, the leading patient advocacy organization for HIE that serves more than ten thousand families worldwide.

Building infrastructure to help families now and in the future

Through a partnership with Hope for HIE and the Cerebral Palsy Research Network, Dr. Guez Barber leads a team of researchers to build a registry to record long-term outcomes for babies with HIE. Most research only records data from birth to 2 years old. As a result, it can miss important aspects of a child's development and may not always reflect what families are experiencing at home. The registry addresses that gap by combining clinical data with caregiver-reported outcomes to provide a more complete picture.

"We're really trying to get the outcome measures that families most care about," Dr. Guez Barber says. "What we're focusing on is so much more than an MRI. Is the family's understanding the same as the doctor's understanding or different?"

The registry has grown into a multicenter collaboration. What started three years ago with four researchers now includes 20 investigators across 14 institutions.

That commitment to bridging science and lived experience has become a hallmark of Dr. Guez Barber's work. By centering the voices of the HIE community alongside clinical data, she's helping redefine how researchers study, understand, and ultimately treat HIE.

As Betsy Pilon, executive director of Hope for HIE, puts it, Dr. Guez Barber is unique, like a triple-word score in Scrabble — a lab researcher, a clinical researcher and a parent-advocate. Winning the Phil Dodge Young Investigator Award is only the beginning.

"It's a remarkable honor,” Dr. Guez Barber says. “I'm mostly grateful that it means HIE will have a larger platform and that I can help elevate this work."