Dr. Loftus' research is conducted within the Mouse Embryology Section, led by Dr. William Pavan. Her work focuses on the genetic and cellular processes that control mammalian development, with the goals of understanding both inborn errors of embryonic development as well as diseases that strike later in life. Although finding the gene(s) responsible for such conditions does not automatically lead to a cure, research findings can give important clues about anomalies at the cellular level, both during development and during maintenance of mature cell functions.
Dr. Loftus is analyzing the molecular and genetic basis of neural crest development. Neural crest cells, which appear along the dorsal surface of the neural tube in early embryos, are pluripotent (i.e., able to differentiate into many cell types). They migrate through the body and develop into a variety of tissues, including cells of the peripheral nervous system, melanocytes, cartilage, and bone. The Mouse Embryology Section is particularly interested in understanding the role that neural crest cell-expressed genes play in regulating a migrating cell's fate to either continue migration to another location, or to stop migrating, proliferate, and proceed with differentiation into distinct cell types. Disruption of these genes during neural crest cell development can lead to a variety of congenital disorders such as albinism and neurocristopathies, while disruption at later stages can contribute to cancers such as melanoma.
One example of a neurocristopathy is Waardenburg syndrome, a congenital peripheral nervous system disorder that can cause facial abnormalities, lack of pigment in several regions, and deafness. Patients with Waardenburg syndrome may lack peripheral nervous system innervation of the gut. Several years ago, Dr. Pavan's laboratory found that mutations in the transcription factor SOX10 disrupt neural crest development in mice and are responsible for neural crest defects in some individuals with Waardenburg syndrome. Dr. Loftus has been developing technologies to clarify the relationship between SOX10 and an additional transcription factor, MITF, both of which are altered in Waardenburg syndrome and melanoma tumors.
In order to identify downstream targets of these transcription factors, Dr. Loftus uses DNA microarray analysis to study gene expression differences in neural crest-derived cell lines. Using this information, she seeks to identify genes or combinations of genes that govern neural crest cell development and are involved in both developmental disorders and cancer progression. She is specifically interested in finding the genes that start neural crest cell migration through the embryo, and ascertaining the role these same genes play in causing primary melanoma tumor cells to proliferate, invade surrounding tissues and metastasize to other locations in the body. She is also investigating how to mark and distinguish the individual cells undergoing this process in vivo.
In addition, Dr. Loftus uses mouse disease models to identify and understand the underlying defects in similar genetic disorders in humans. For example, in earlier work, Dr. Loftus used a mouse model to clone both the mouse and human gene responsible for Niemann-Pick C disease, a rare lipid storage disorder that severely damages the liver, spleen, and nervous system and is fatal to most patients by their teens. She continues to study the molecular and genetic defects responsible for this condition.
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Last Reviewed: June 25, 2013