Kristine S. Vogel, Ph.D., Assistant Professor
University of Oregon
1988

(210) 567-0259
VOGELK@UTHSCSA.EDU

I'm a graduate of Rice University (BA Biology, BA Anthropology), and I did my PhD research and dissertation, on avian neural crest cell differentiation, in the laboratory of Dr. Jim Weston at the University of Oregon. By training, I am a developmental neurobiologist, but I became interested in peripheral nerve tumorigenesis while working on developmental aspects of the Nf1 knockout mouse as a postdoc. I'm also very involved in graduate neurobiology/developmental biology teaching and medical education at UTHSCSA, and serve on both the Medical School PreClinical Promotions and Admissions Selection Committees.

Currently, I teach in the Medical Gross Anatomy and Embryology course, and will be teaching in the Medical Neuroscience course in Spring 2007; I also give many of the lectures on developmental neurobiology in the interdepartmental graduate neuroscience course. I'm especially interested in adapting both innovative technologies and Dr. Edward Tufte's principles of information design, to enhance medical education in the basic sciences. My current project uses a unique resource, UTHSCSA Virtual, to provide first-year medical students with additional images and tutorials for learning human embryology.

UTHSCSA Virtual for Medical Embryology Teaching Slideshow Presentation

Model of a human embryo at neurula stage
(21-22 days post-fertilization),
created with Sculpey polymer clay. Dorsal view.

Neurofibromatosis Type 1 and Genomic Instability
Neurofibromatosis Type 1 (NF1) is a common genetic cancer syndrome that primarily affects derivatives of the neural crest, including Schwann cells and melanocytes; other tissues, such as bone and the CNS, are also involved in some patients. The expressivity, progression, and prognosis for NF1 can be highly variable, even among family members with the same germline mutation in the NF1 gene. Currently, my laboratory uses a mouse model for peripheral nerve sheath tumors (PNST), which I generated as a postdoctoral fellow in Dr. Luis Parada's laboratory, to examine the contributions of genomic instability to NF1 disease progression.

Two ongoing collaborations with other C&SB faculty focus on spontaneous mutagenesis in PNST, and on DNA repair mechanisms in PNST cell lines. With Dr. Chris Walter, we have characterized the spontaneous mutant frequency in tumors and normal tissues in our PNST mouse model (cisNf1+/-;p53+/-). We plan to continue this project with an emphasis on tumor characteristics (apoptosis, proliferation, DNA repair capacity) that may contribute to the heterogeneity in mutant frequency, and on genomic instability that may arise during development in Nf1-deficient animals. With Drs. Olivia Perreira-Smith and Kaoru Tominaga, we are examining contributions of the chromodomain protein-encoding gene Mrg15 in tumorigenesis for our mouse PNST model. Recently, we've used the comet assay to show that Mrg15 deficiency slows the DNA repair process in PNST cell lines exposed to ionizing radiation.

Spontaneous mutant frequencies, measured in tumors and brains isolated from cisNf1;p53 mice, using the lacI transgene.

A pilot project award from the Nathan Shock Center will allow us to compare DNA damage sensitivity and DNA repair capacity in Schwann cells (the cell-of-origin for PNST) isolated from Nf1+/- and Nf1+/+ mice, throughout the lifespan.

Nf1 Gene Expression and Apoptosis during Embryonic Development
Using a targeted null mutation in the Nf1 gene, generated over 10 years ago by Dr. Cami Brannan, I've been able to demonstrate that the neurofibromin protein plays an important role in modulating the survival response to neurotrophins in embryonic neurons. A collaboration with Dr. Patricia Dahia, focusing on the Egln3 gene, continues this research interest in the context of the sympathoadrenal lineage.

Dr. Carolina Livi, a computational and molecular developmental biologist, and I are collaborating to identify cis-regulatory regions that control expression of the Nf1 gene in different cell lineages.

Research Techniques:
Mouse models for peripheral nerve sheath tumors (PNST)
Spontaneous mutagenesis in PNST and NF1 mouse models (Big Blue lacI assay)
DNA damage sensitivity and DNA repair in PNST cell lines and Schwann cells (comet assay)
Neuronal apoptosis during development (primary neuron cultures, neurotrophin biology)
Nf1 gene expression during development (qPCR, computational biology)

The Children's Tumor Foundation
International Consortium
on the Molecular Biology
of NF1, NF2, and Schwannomatosis
is held annually in beautiful
Aspen, Colorado-just down the hill from Independence Pass.

 

PUBLICATIONS:
Garza R, Hudson RA, McMahan CA, Walter CA, and Vogel KS A mild mutator phenotype arises in a mouse model for malignancies associated with neurofibromatosis type 1. Mutation Research (accepted, pending revisions)

Ling BC, Wu J, Miller SJ, Monk KR, Shamekh R, Rizvi TA, Decourten-Myers G, Vogel KS, DeClue JE, Ratner N. (2005) Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis. Cancer Cell. Jan;7(1):65-75.

Miller SJ, Li H, Rizvi TA, Huang Y, Johansson G, Bowersock J, Sidani A, Vitullo J, Vogel K, Parysek LM, DeClue JE, Ratner N. (2003) Brain lipid binding protein in axon-Schwann cell interactions and peripheral nerve tumorigenesis. Mol Cell Biol. Mar;23(6):2213-24.

Vogel KS, El-Afandi M, Parada LF. (2000) Neurofibromin negatively regulates neurotrophin signaling through p21ras in embryonic sensory neurons. Mol Cell Neurosci. Apr;15(4):398-407.

Vogel KS, Klesse LJ, Velasco-Miguel S, Meyers K, Rushing EJ, Parada LF. (1999) Mouse tumor model for neurofibromatosis type 1. Science. Dec 10;286(5447):2176-9.