Kristen Kroll, Breaking New Ground in Understanding Brain Development
(Photo : Kristen Kroll, Breaking New Ground in Understanding Brain Development)

Neurodevelopmental disorders (NDDs) are a complex set of diseases that significantly impact the human population. A few examples of NDDs include attention deficit disorder, hyperactivity disorder, and autism spectrum disorder  (ASD). The Centers for Disease Control and Prevention report that 1 in 54 children in the United States was identified with ASD in 2016. Further research suggests that the prevalence of NDD cases is rising worldwide. The World Health Organization has identified NDDs as a grave concern for global health. Despite the prevalence of NDDs, the causes of these disorders are complex and remain largely unknown. The research focus of Washington University School of Medicine's Dr. Kristen Kroll is understanding the mechanisms that underlie the development of the human brain and how their dysregulation can lead to NDDs. 

Hailing from Wisconsin, Kroll completed her early education at Wilmot High School in 1984. She then obtained a bachelor's degree with highest honors in Molecular and Cell Biology from Northwestern University in 1988. While working as an undergraduate researcher in the laboratory of Dr. Robert Holmgren, Ph.D., Kroll developed an interest in a career in developmental biology. Her research in the Holmgren laboratory involved cloning the segment polarity gene Cubitus Interruptus, a Drosophila homolog of the Gli transcription factor that mediates Hedgehog signaling in the developing embryo. 

Breakthroughs in Understanding Brain Development

After completing her BA, Kroll performed her graduate studies at the University of California, Berkeley, obtaining a Ph.D. in Biochemistry, Molecular, and Cell Biology. Her doctoral research in John Gerhart's laboratory and in collaboration with Dr. Enrique Amaya was focused on developing nuclear transplantation-based approaches for transgenesis in embryos of the frog Xenopus laevis. Since its inception, transgenesis in Xenopus has been used extensively by other researchers to analyze the roles of genes in embryonic development and organ function. After her Ph.D. research, Kroll completed her postdoctoral studies at Harvard Medical School in the laboratory of Dr. Marc Kirschner, supported by a fellowship from the Damon Runyon-Walter Winchell Foundation Cancer Research Fund. In this work, she identified several genes involved in patterning the early embryo. These included the nuclear protein Geminin (Gmnn), which plays several roles in regulating the development of the central nervous system.

After completing her postdoctoral research, Kroll joined the Department of Developmental Biology (previously the Department of Molecular Biology and Pharmacology) at Washington School of Medicine (WUSM) in 2000. Her research focuses on understanding the roles of transcriptional and epigenetic regulation in controlling the development of the central nervous system. Kroll and the members of her laboratory discovered that Gmnn interacts with several chromatins modifying complexes to control various aspects of this process, with Gmnn playing a role in promoting a hyperacetylated chromatin state to promote neural gene transcription during the specification of early embryonic cells as neuron precursors.

Currently, Kroll and her team use stem cell-based approaches to model aspects of human brain development. They use human pluripotent stem cell models (hPSCs) to identify the processes by which the development of different types of neurons is disrupted in the developing brain to contribute to NDDs. Cortical interneurons (cINs) are one such neuronal cell type. These inhibitory nerve cells regulate the activity of excitatory neurons in the brain. Excitatory and inhibitory activities in the cortex must work in equilibrium for normal brain function. Therefore, disruption of the development or function of cINs can contribute to causing NDDs. A majority of cINs develop in a fetal brain structure below the cortex called the medial ganglionic eminence (MGE). cINs born in the MGE region migrate upward into the cortex to form connections with excitatory neurons. These aspects of brain development are critical for normal brain function. Kroll modified extant methods to stimulate the production of MGE-like neural progenitors from hPSCs to study cIN development.  

Kroll currently leads research at WUSM to characterize how pathogenic gene variants lead to intellectual and developmental disabilities in hPSC-derived models. She heads the Cellular Models Program for the institution's Intellectual and Developmental Disabilities Research Center. She has been a recipient of multiple honors and awards since she began her academic journey. After she graduated from Wilmot High School, Kroll was inducted into the school's Alumni Hall of Fame in 2003. During her graduate work at the University of California, Berkeley, she received the Outstanding Graduate Student Instructor and Teaching Effectiveness Awards. During her time at Washington University, Kroll has also received research awards, including the Basil O'Connor Scholar Award from the March of Dimes, Howard Hughes Medical Institute Faculty Development Research Award, and Research Scholar and Hope Awards from the American Cancer Society. She currently has over 50 publications in the field of developmental biology and serves as an inspiring mentor to the next generation of developmental and stem cell biologists at WUSM.