Dr. Huppert’s commitment to cell signaling and liver biology spans almost twenty years. Her work, demonstrating that proper cell fate decisions stem from Notch signaling imparting feedback regulation of ligand and receptor asymmetric expression, continues to be a central concept in canonical Notch signaling. Currently, her research program investigates hepatic epithelial cell plasticity and commitment – the cellular contribution and molecular factors required for differentiation, maturation and formation of the three-dimensional hepatic architecture during development, homeostasis and regeneration. The work has established a three-dimensional blueprint for the formation of intrahepatic bile duct architecture. The combination of hepatic three-dimensional knowledge with molecular and cellular lineage information allows generation of fundamental blueprints and hypotheses for powerful mechanistic studies to be performed in experimental mouse models and human induced pluripotent stem cell generated liver organoid models.
As part of the multidisciplinary CCHMC Pediatric Cell Atlas initiative to build a detailed molecular reference map of all cell populations in human organs, she lead the liver group with Dr. Takanori Takebe with goals to 1) define known and novel cell populations, 2) develop three-dimensional imaging cell maps, and 3) build better multicellular liver organoid models. Their complimentary in vivo mouse models, human liver organoid culture systems and single cell multiome analyses allow many clinically relevant and technically challenging questions to be addressed.
She established an independent research program at Vanderbilt University Medical Center in the Department of Cell and Developmental Biology as the first recruit to the Vanderbilt Center for Stem Cell Biology. In 2012, upon moving her research program to the Cincinnati Children’s Hospital Medical Center (CCHMC) in the Division of Gastroenterology, Hepatology & Nutrition, she benefitted from a rich environment where she interacts and collaborates with colleagues in the Digestive Health Center (NIH NIDDK funded Silvio O. Conte Digestive Diseases Research Core Center) and CCHMC clinical realm to address questions that are timely and clinically relevant to understand, diagnose and treat patients with hepatobiliary disease.
In addition to her research program, she is dedicated to the teaching and career development of future scientists. Since 2014, she has served on the Schmidlapp Undergraduate Program Committee at CCHMC, dedicated to the career development and assurance of the next generation women scientists. From 2014-2017, she was the Associate Program Director of the Medical Scientist Summer Research Program (MSSRP) at the University of Cincinnati. From 2014-2016, she was invited and devoted a week each year to lecture and provide hands on laboratory training at the international Cold Spring Harbor Laboratory Mouse Development, Stem Cells & Cancer Course. She was invited to run the Cold Spring Harbor Laboratory course starting in 2017 but decided to pursue more local contributions by becoming the Co-Director and Curriculum Director of the Molecular and Developmental Biology graduate program from 2017-2019. In 2019, she stepped down to become the IACUC chair, overseeing the animal care and use program of CCHMC. In addition to training and education, she is invested in the international liver and developmental biology research communities organizing international meetings. In June 2019, she had the privilege of working with the Alagille Syndrome Alliance to organize an international scientific meeting centered around Alagille Syndrome, “Connecting the Pieces”. This meeting was attended by scientists, clinicians, patients and families from around the world. She will be co-organizing a second in-person scientific meeting centered around Alagille Syndrome in 2022. For 2020, she was selected by her peers to organize a FASEB Summer Research Conference, “Liver Biology: Fundamental Mechanisms & Translational Applications” (re-scheduled for abbreviated virtual meeting 2021 and in-person meeting 2022), and a Keystone Symposia, “Tissue Plasticity: Preservation and Alternation of Cellular Identity” held virtually 2021.