SET Center Pilot Grant

The SET Center awards an annual Pilot Grant to junior University of Chicago faculty members. The grant program was intentionally designed to invite new researchers to study biological development who need funding to start a novel line of questioning. Projects can examine any organ system or biologic process using any model as long as the results can be applied to human development. We have funded three projects since 2023.

2025 Awardee – Fetal cerebral cortex development depends on thyroxine

Thyroid hormones are vital for the development of an infant’s brain, especially the region called the cerebral cortex. The hormone called thyroxine (T4), which comes from the mother, is crucial for the infant’s neurodevelopment, although science does not yet understand why this is the case. In premature infants, low levels of T4 are common due to the underdeveloped thyroid system and can lead to delayed neurodevelopment. Scientists hypothesize that T4 needs to be changed into another hormone (T3) to work properly in brain cells. An enzyme called DIO2 helps this change happen and is found in neural precursor cells (NPCs), which are early-stage brain cells that eventually become neurons. However, we don’t know exactly how T4 affects these NPCs or even more fundamentally, which stages of brain development are impacted by low T4 levels.

In order to understand these processes, the SET Center has awarded its 2025 Pilot Grant to Federico Salas-Lucia, PhD, a junior investigator in the Section of Endocrinology. Dr. Salas-Lucia’s previous research has used cortical organoids, or lab-grown brain tissue, from patients with a condition called MCT8-deficiency, which affects the body’s ability to absorb thyroid hormones, to show that these patients have trouble transporting thyroid hormones into brain cells, affecting NPC growth.

With the SET Center’s support, Dr. Salas-Lucia will continue this line of questioning to discover if T4 changes NPC gene activity and how low T4 levels affect neurodevelopment. Using new mouse models and advanced cell study techniques, this study will advance our understanding of how T4 helps brain formation, and more specifically why low T4 in premature infants affects their neurodevelopment. These results can also provide insights into the challenges faced by patients with MCT8-deficiency, potentially leading to better treatments for all patients.

2024 Awardee – Epigenomes in the Neonatal Brain

When compared to their peers who are born full-term, infants born preterm have impaired brain development over time. Even at 10 years of age, scientists have found a correlation between brain volume and the gestational age at birth. Children and adults who were born premature are more likely to have neurodevelopmental delays and psychiatric disorders than people born full-term. What is happening in the brain during the final weeks of pregnancy that does not happen for preterm infants in our NICU? The development in the infant brain in the third trimester and in the first weeks of life impact the health and well-being of our patients for the rest of their lives. But this development is not currently understood.

The brain is comprised of incalculable numbers of diverse cell types, anatomical structures, and neural circuits. Each of these have specific epigenomes, or combinations of regulatory information associated with the genome that can turn on and off specific genes in different cells. The postnatal brain possesses uniquely dynamic epigenomes that can shift and evolve as the neural pathways are set. This provides us an opportunity to optimize the development, in particular for vulnerable patients such as premature infants. The challenge lies in the fact that the brain is complex, and would require the study of epigenomic regulation for each cell type, brain region, and neural circuits. The epigenome of the developing neonatal brain is uncharted and can offer fundamental knowledge of brain plasticity and critical insights into various brain disorders.

The SET Center is excited to award its second Pilot Grant to Zhuzhu Zhang, PhD, from the Department of Human Genetics. Dr. Zhang will use her expertise to study the role of epigenetic regulation in postnatal brain development. The knowledge gained from her research will enable us to better understand what is happening in the brains of newborns, and eventually could lead to treatments that support optimal neurodevelopment.

2023 Awardee – Artificial Skin-to-Skin Contact

While infants are hospitalized in NICUs, they can struggle to adjust to life outside the womb and may face several health challenges due to their underdevelopment. Many preterm infants have challenges regulating their body temperature, maintaining appropriate sleep-wake cycles, and fighting infections. They also typically have higher cortisol levels, indicating they have higher stress.

Skin-to-Skin Contact (SSC) is one intervention that has been shown to increase survival and decrease morbidity when implemented. Also called Kangaroo Mother Care (KMC), SSC is the practice of placing an infant directly on a parent or caregiver’s bare chest in an upright position. To name just a few benefits, SSC in several studies has been shown to decrease pain, improve an infant’s body temperature regulation, lowered the risks of infections, and lowered cortisol levels. One study even demonstrated that infants who received SSC scored higher on neurodevelopmental assessments at 6 months, and at 10 years old, had better stress responses, improved cognitive control, and slept better.

What happens when families are not able to be present in the NICU to provide the kangaroo care that we know offers so many advantages for long-term development? Often when infants are born prematurely, the birthing parent is hospitalized for their own health concerns and frequently they have undergone a caesarean section. Socioeconomic factors often stand in the way. As the only high-income country that does not offer paid parental leave, the majority of parents must return to work shortly after giving birth. We have also found that parents with other children in the home are less able to visit the NICU while they are caring for older siblings. Travel to and from the hospital can also hinder parents’ ability to provide SSC. Our patient population on the South Side of Chicago is at even higher risk of these barriers due to historic disinvestment in the local communities and neighborhoods.

To solve this complicated problem, the SET Center awarded its inaugural Pilot Grant to the team of Leah Fox, MD and Bozhi Tian, PhD, a neonatologist and chemist respectively, who are developing an artificial skin-to-skin tool that mimic’s the physiologic features of SSC that can be implemented in the NICU. This new care regimen would provide innumerable advancements to infants’ development during their hospitalization and long into the future.