Lee A. Niswander (University of Colorado, Denver)

Lee A. Niswander (University of Colorado, Denver)

Butler Seminar Series

Event Date/Location

December 14, 2016 - 12:00 pm
Thomas Laboratory 003

Speaker

  • Photo of Dr. Lee Niswander

    Lee Niswander

    Professor and Section Head of Developmental Biology
    University of Colorado School of Medicine

    The Niswander lab investigates novel mouse models of embryonic development with the overarching goal of providing insights into fundamental developmental processes, major human birth defects and potential clinical therapies. We examine the interplay among genes, environment, and epigenetic mechanisms. Our studies over the past 15 years have provided a unique perspective on the molecular mechanisms that control the formation of the central and peripheral nervous system, as well as lung, limb, and neuromuscular development. Our particular focus is on the common and severe birth defect wherein the neural tube (NT) fails to close resulting in neural tube defects (NTDs, such as spina bifida).

    To provide a more comprehensive understanding of the genetic basis of NTDs and other birth defects, and to reflect better the allelic variation in humans, we used unbiased forward genetic screens in the mouse. With respect to NTDs, we identified and cloned >25 genes not previously implicated in NT closure and developed assays to define the processes disrupted by these mutations. Moreover, using a combination of molecular, biochemical and cell biological assays we determined their mechanisms of action. Because the inability to visualize the cellular dynamics of NT closure in the living mouse embryo has been a handicap, we developed innovative methods for time-lapse imaging that allow us to couple our molecular insights to the regulation of cell behaviors that drive NT closure. Although environmental factors clearly influence human NTD risk, only a small subset of mouse mutants had been tested for their responsiveness to dietary factors. Therefore, we are using our mouse models to explore gene-environment interactions that influence NTD risk, including iron and zinc homeostasis and folic acid fortification. We also study the developmental defects associated with mutations in epigenetic regulators and have defined the impact of mutations in epigenetic modifiers (chromatin modifiers and histone acetyltransferases), as well as how folic acid pathway as the universal methyl donor in the cells may impact the epigenome using methods that include transcriptional profiling, whole-genome DNA methylation analyses, and ChIP-Seq.

    I have extensive experience and success in administering research projects, in mentoring and training, leading collaborative projects, and an excellent track record in significant scientific achievements. I am firmly committed to mentoring and to graduate education.  I am very proud that 100% of my former trainees (11 graduate students and 13 postdoctoral trainees and 2 clinical fellows) have remained in scientific careers. Moreover, of my 32 former and current trainees, 65% of them are women. I have also taken the lead numerous times in graduate education. Briefly, I served as the joint Director of the six-week Embryology Course for 5 summers, as well as lecturer and faculty head of the chick/mouse lab module since 1997 at the Marine Biological Labs at Woods Hole, MA.  I served as the Director of the Graduate Program in Molecular Biology at Cornell University/Sloan-Kettering Institute, which through my leadership transitioned to a joint graduate program in Cell Biology & Genetics and Molecular Biology (2001-2004).  At the University of Colorado, I served as the Associate Director of the campus-wide Graduate Program in the Biomedical Sciences Program (2007-2012). I am the Section Head of the Developmental Biology Section within Pediatrics and the Research Leader in the Emphasis Area of Developmental Origins of Health and Disease, as well as Chair of the Advisory Committee for the Colorado K12 Child Health Research Career Development training grant program. I also serve on a number of external Boards of Scientific Advisors, including two of KOMP2 international projects.

Topic

Visualizing neural tube closure and uncovering the causes of neural tube defects

The Niswander lab focuses on the neural tube, which forms the embryonic brain and spinal cord, and on the common and severe birth defect when the neural tube fails to close called neural tube defects. We approach this from the viewpoint of genetics, epigenetics, and environmental factors and how these converge to affect phenotypic expression. We are using the mouse embryo as a model of human development to ask what are the genes that regulate NT closure and how do these novel genes function. Time-lapse imaging is expanding our understanding of the normal cell behaviors that drive NT closure. This imaging platform then allows us to determine the link between novel molecular regulators and cell behaviors and how these molecular/cellular changes affect the highly coordinated process of neural tube closure.

Audience

Free and open to the university community and the public.

Host

Rebecca Burdine, Department of Molecular Biology