HomeResearchIntramural ResearchResearch Branches at NHGRIGenetic Disease Research Branch Loftus Lab

Stacie Loftus, Ph.D. Associate Investigator Genetic Disease Research Branch B.S. California State University, 1990 Ph.D. University of California, Irvine, 1996 (301) 594-1752 (301) 402-2170 sloftus@mail.nih.gov Building 49, Room 4A51 49 Convent Dr, MSC 4472 Bethesda, MD 20892-4472 Selected Publications

Dr. Loftus' research focuses on the genetic and cellular processes that control mammalian development, with the goal of developing a better understanding of inborn errors of embryonic development. Although finding the gene(s) responsible for such conditions does not automatically lead to a cure, such findings can give important clues about what is going wrong at the cellular level, and animal models carrying these genetic alterations can provide researchers with useful ways to test potential therapies.

As part of the Mouse Embryology Section, led by Dr. William Pavan, Dr. Loftus is analyzing the molecular and genetic basis of neural crest development. Neural crest cells, which appear at the top 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. Errors in neural crest cell development, thus, can lead to a wide array of human diseases, such as albinism, melanoma, and neurocristopathies.

The Mouse Embryology Section is particularly interested in 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 also may lack peripheral nervous system innervation of the gut. Several years ago, Dr. Pavan's laboratory found that mutations in a 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 interrelationship between SOX10 and two other transcription factors that are altered in Waardenburg syndrome (MITF and PAX3), identify their downstream target genes, and specify the effects those gene products have on normal neural crest cell development.

As a way 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 at each stage of the development process. She is specifically interested in finding the genes that encode the molecular signals that start neural crest cells migrating through the embryo, ascertaining whether the same genes determine the type of cell a neural crest cell ultimately becomes, and finding the contributing factors intrinsic to each cell in determining whether it becomes a glial cell, a melanocyte, or part of the jaw. She is also investigating how the extracellular environment, through which neural crest cells must pass, contributes to their development.

Dr. Loftus has developed a strain of transgenic mice that is useful for studying neural crest cells in vivo in normal and gene-defective disease states. In addition, she studies other mouse disease models to identify an understand the underlying defects in seemingly 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 underlying defects in this condition. In addition, she is studying acinar cell apoptosis, or programmed cell death of the pancreatic cells that secrete digestive enzymes. This defect in mice leads to malnutrition, growth inhibition, and a compromised immune system. Using this mouse model, Dr. Loftus is working to identify the responsible gene and to determine whether a homologous gene in humans is responsible for a subset of Shwachman-Diamond syndrome patients, who exhibit a similar clinical phenotype.

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Last Reviewed: August 5, 2008