Embryo within its yolk sac (magenta) during early brain development with blood cells (green) in the yolk sac before they invade the embryo.
rOLE OF MICRO rnas in embryonic development
Birth defects are the leading cause of death in children. We are interested in understanding how miRNAs control early embryonic development and how their misregulation contributes to central and peripheral nervous system birth defects. Some of this microRNAs include MIR290, MIR302 and MIRLet7.
Mouse craniums showing enlarged ventricles in the Mir302 mutant compared to Wiltype
Role of mir302 in embryonic development
The loss of the MIR302 microRNA (miRNA) family is associated with a range of congenital birth defects, including neural tube defects, craniofacial abnormalities, and defects of the eye and the heart—some of the most prevalent congenital conditions in humans. The MIR302 family comprises four members: MIR302a, MIR302b, MIR302c, and MIR302d. Notably, approximately 98% of the total MIR302 miRNAs are derived from the 3p strand, which all share an identical seed sequence. Typically, miRNAs with the same seed sequence are thought to have similar roles in mRNA repression. However, variations in the accumulation levels and the presence of isomiRs with non-canonical seed sequences among MIR302 miRNAs may lead to divergent regulatory outcomes despite their shared canonical seed sequence. Our goal is to elucidate the distinct regulatory functions of MIR302 members during embryonic development.
E13.5 mouse embryos: normal embryo inside its yolk sac and placenta in the side (right) same embryo expressing epsilon globin
rOLE OF EXTRAEMBRYONIC TISSUES IN NEURAL TUBE CLOSURE
Neural tube defects (NTDs) arise from the failure of proper neural tube closure during embryonic development. Despite ongoing research, NTDs continue to occur, and there are no effective prevention strategies. The risk of NTDs increases with poor maternal health during pregnancy, particularly hyperglycemia, which affects both the embryo and the extraembryonic tissues such as the yolk sac and placenta. These tissues are vital for the transport of essential nutrients and metabolites from the mother to the embryo, and any disruption in their function can impair developmental processes. However, it remains unclear how these interconnected mechanisms contribute to the increased incidence of NTDs in hyperglycemic conditions.
hIAPP protofibrils (yellow) accumulate and form plaques (green) in diabetic mouse pancreatic islets (white outline), leading to macrophage (magenta) recruitment and exacerbating disease progression.
Protein misfolding in Type 2 Diabetes
In Type 2 diabetes, islet amyloid polypeptide (IAPP) can misfold and form toxic aggregates in the pancreas, promoting cell death and exacerbating T2D progression. We have developed a monoclonal antibody that targets the early soluble and cytotoxic form of misfolded IAPP, allowing T2D treatment and tracking the spread of toxic oligomers throughout the disease. We are interested in further exploring the effects of toxic misfolded IAPP peptides on different organs in T2D, especially how they impact the brain and may increase Alzheimer's disease risk.
Example of tumors generated by somatic tissue engineering. Blue labels nuclei, and red labels tumor cells.
PANCREATIC CANCER
Pancreatic cancer is the most lethal type of cancer. More than 95% of patients carry mutations in oncogene KRAS. We are interested in studying the mechanisms of how oncogenic KRAS alters post-transcriptional regulation and promotes tumor progression. We are also building flexible mouse models via somatic tissue engineering to study pancreatic cancer.