Priyanka Karmokar, PhD

Hepatoblastoma Fund for the Cure Postdoctoral Research Fellowship Award
$25,000 over one year

St. Jude Children's Research Hospital

Neonatal Intermittent Hypoxia in Normal Liver Development and Pediatric Hepatoblastoma

Mentor: Liqin Zhu, PhD

Hepatoblastoma (HB) is the most common liver cancer in children. It is the only cancer that is significantly more common in babies born prematurely. These babies are also more frequently affected by worse HB subtypes that often metastasize and kill. What biology links prematurity and HB remains unclear.

Intermittent hypoxia (IH), the fluctuation of oxygen levels in the body, is one of the most common complications in preterm infants due to their underdeveloped lung. Adults with breathing difficulties can also experience IH and adult IH has been found to be a strong inducer of inflammation in the liver. Since inflammation is a known risk factor in many cancers, we ask - does neonatal IH also induce inflammation in the liver and promote HB? Answering this question is not an attempt to merely repeat adult findings in neonates. In fact, recent studies, including one from our group, have revealed that the biology of the neonatal liver is drastically different to that of the adult liver. One of the most noticeable differences is their nearly inverted immune systems, with a large amount of innate immune cells in neonates and the adaptive immune cells taking over in adults. Innate immune cells are the initiator of inflammation. Indeed, we found IH induced rapid and potent inflammatory responses in the neonatal liver and accelerated HB in our models. Thus, our central hypothesis that IH-induced inflammation in the neonatal liver is a key mechanistic link between prematurity and HB. We aim to define the systemic crosstalk between the immune and liver cells in the normal and IH-stressed neonatal liver, and pinpoint the specific molecular mechanisms underlying neonatal IH-accelerated HB development.

Pediatric cancer is not small adult cancer. Our data suggest that the unique biology of the neonatal liver can be a strong promoter of HB. The success of this project will, for the first time, explain the higher HB incidence in preterm babies and identify new therapeutic targets.