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Peter Lwigale Assistant Professor Assistant Professor of Biochemistry and Cell Biology e-mail:[email protected] Senior Research Fellow (2007-2008) California Institute of Technology Postdoctoral Fellow (2002 -2007) California Institute of Technology B.S. Biology (1994) University of Northern Iowa M.S. Cell & Developmental Biology (1997) University of Northern Iowa Ph.D. Cell & Developmental Biology (2001) Kansas State University Primary Department Department of Biochemistry and Cell Biology Department Affiliations Institute of Biosciences and Bioengineering Other Affiliations Baylor College of Medicine Websites Lwigale Lab Web Page Research Areas Molecular regulation of cell migration during eye development and cornea regeneration Research Statement I am interested in events that regulate the differentiation of the multipotent neural crest cells during corneal development and neural crest-derived stromal keratocytes during cornea regeneration. The cornea is a highly specialized transparent tissue located at the anteriormost surface of the eye. An embryonic cell population known as neural crest cells gives rise to majority of the cells in the cornea, including: stromal keratocytes, corneal endothelium, and sensory nerves. Development and regeneration of the cornea are both multi-step processes that involve coordinated migration and differentiation of neural crest cells and keratocytes, respectively, as well as the intricate patterning of sensory nerves. Using the chick as a model organism and a combination of molecular, microsurgical, and tissue culture approaches, we have shown that: 1) only a subpopulation of neural crest cells can properly contribute to the cornea, 2) corneal keratocytes retain the stem cell-like properties of their neural crest progenitors when challenged in an embryonic environment, and 3) the lensderived axon guidance molecule, Semaphorin3A, regulates sensory innervation of the cornea. Currently, our research is aimed at further elucidating the role of guidance molecules during cornea development. Since cornea regeneration recapitulates development, we will extrapolate our studies to cornea wound healing. In addition to the chick, these studies will involve the mouse as a genetic model organism to further our understanding of the genes that are involved in these processes. We are also studying the stem cell potential of keratocytes and their characteristics in the embryonic environment. Ultimately, the goal of our research is to provide an insight into how guidance molecules are disrupted in congenital eye disorders and cornea wound healing, which may lead to discoveries of remedies or cures to these ocular problems. Selected Publications Abstracts Griswold, S and Lwigale, P. "Optic Neural Crest Migratory Stream Consists Of Two Rostrocaudal Subpopulations Recruited Toward Ventral Midline." , 53 (March 26, 2012) : 4931. Kwiatkowski, S., Nupur, J., Munjaal R.P., and Lwigale, P. "Expression of angiogenic factors during development of the anterior eye." , 53 (March 26, 2012) McKenna, C. and Lwigale, P. "Sema3A/Npn1 signaling is required to maintain corneal avascularity during development." , 53 (March 26, 2012) : 4739. Ojeda, A., Munjaal R.P., and Lwigale, P. "Expression of Chemokines During Ocular Development and in the Adult Cornea." , 53 (March 26, 2012) : 4743. Schwend, T., Lwigale, P., and Conrad, G. "Robo-slit signaling regulates avian cornea innervation." (May 2011) : 1975. Spurlin, J. and Lwigale, P. "Characterization of the Wound Healing Response and Scar Free Regeneration of the Embryonic Cornea." , 53 (March 26, 2012) : 3547. McKenna, C., Munjal R.P., and Lwigale, P. "Sema3A/Npn1 Signaling Is Required For Proper Innervation Of The Mouse Cornea During Development." Invest Ophthalmol Vis Sci. Meeting Abstract: 2090 (May 2011) Refereed articles Chao, J., Bronner, M., and Lwigale, P. "Human Corneal Keratocytes have Multipotent Characteristics in the Developing Avian Embryo." Stem Cells and Development. Under review. (2013) Griswold, S. and Lwigale, P. "Analysis of neural crest migration and differentiation by crossspecies transplantation." J. Vis. Exp. , 7 (60) (2012) : 3622. Kwiatkowski, S., Munjaal, R., Lee, T., and Lwigale, P "Expression of Pro- and Anti-angiogenic Factors in the Anterior Eye during Development of the Chick Cornea and Periocular Vasculature." Dev Dyn. Under review. (2012) McKenna, C. and Lwigale, P. "Semaphorin3A/neuropilin-1 signaling inhibits angioblast migration and vascularization of the embryonic cornea." in preparation (2012) McKenna, C., Munjaal, R., and Lwigale, P. "Distinct roles for Neuropilin1 and Neuropilin2 during mouse corneal innervation." PLoS ONE, 7 (5) (2012) : e37175. Ojeda A., Munjaal, R. and Lwigale, P. "Chemokine expression during development and in adult ocular tissues." in preparation (2012) Schwend, T., Lwigale, P., and Conrad, G. "Nerve repulsion by the lens and cornea during cornea innervation is dependent on Robo-Slit signaling and diminishes with neuron age." Dev. Biol. , 363 (2012) : 115-127. Spurlin, J. and Lwigale, P. "A Technique to Increase Accessibility to Late-stage Chick Embryos for In Ovo Manipulations." Dev Dyn., DOI 10.1002/dvdy.23907 (2012) McKenna, C. and Lwigale, P. "Innervation of the mouse cornea during development." Invest Ophthalmol Vis Sci., 52 (2011) : 30-35. Lwigale, P.Y. and Bronner-Fraser, M. "Semaphorin3A/neuropilin-1 signaling acts as a molecular switch regulating neural crest migration during cornea development." Dev Biol, 336 (2009) : 257-265. Shiau, C.E., Lwigale, P.Y., Raman, M.D., Wilson, S.A., and Bronner-Fraser, M. "Robo2-Slit1 dependent cell-cell interactions mediate assembly of the trigeminal ganglion." Nature Neuroscience, 11 (2008) : 269-276. Lwigale, P.Y., and Marianne Bronner-Fraser "Lens-derived Semaphorine3A regulates cornea innervation." Dev Biol., 306 (2007) : 750-759. Lwigale, P.Y., Cressy, P. A., and Bronner-Fraser, M. "Corneal keratocytes retain neural crest progenitor cell properties." Dev Biol, 288 (2005) : 284-293. Cerny, R, Lwigale, P., Ericsson, R, Meulemans, D., Epperlein, H. and Bronner-Fraser, M. "Mandibular arch morphogenesis and the origin of jaws: new interpretation of "maxillary" and "mandibular"." Dev BioI, 276 (2004) : 225-236. Lwigale, P.Y., Gary W. Conrad, and Marianne Bronner-Fraser "Graded potential of neural crest to form cornea, sensory neurons and cartilage along the rostrocaudal axis." Development, 131 (2004) : 1979-1991. Lwigale, P.Y., and Marianne Bronner-Fraser "Embryonic origin of avian corneal sensory nerves." Dev BioI, 239 (2001) : 323-337. Riley, N. C., Lwigale, P., and Conrad, G. "Specificity of corneal nerve positions during embryogenesis." Mol. Vis., 7 (2001) : 297-304. Lwigale, P.Y., Thurmond, 1. E., Norton, W. N.; Spooner, B. S. and Wiens, D. 1. "Simulated microgravity and hypergravity attenuate heart tissue development in explant culture." Cells Tissues Organs, 167 (2000) : 171-183. Lwigale, P.Y. "Nuclear morphologies of bovine corneal cells as visualized by confocal microscopy." Cells Tissues Organs, 165 (1999) : 104-112. Book chapters Lee, V.M. and Lwigale, P.Y. "Neural Crest, Sensory Neuron and Muscle Cultures." Methods Cell Biology, 87 (2008) : 115-133. Lwigale, P.Y. and Schneider, R.A. "Other Chimeras: Quail-Duck and Mouse-Chick." Methods Cell Biology, 87 (2008) : 59-74. Presentations Invited talks "Cellular and Molecular Mechanisms of Ocular Surface Morphogenesis." Development and Diseases session, International Society of Eye Research (ISER), Berlin. (2012) "Invited speaker, Pediatric Keratoplasty Association gathering." ARVO, (2012) "Multicellular Self-Organization Meeting." John S. Dunn-BRC Collaborative Research Event, (2012) "Molecular regulation of cornea Development." TERMIS-North America Bioengineering Conference, Houston, TX. "Molecular regulation of cornea Development." Department of Genetics, UT MD Anderson Cancer Center, Houston, TX. "Neural Crest in Ocular development: Turning Points in Development and Disease." Annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), Fort Lauderdale, FL. "Contribution and molecular regulation of neural crest cells during eye development." Department of Biochemistry & Cell Biology Annual Retreat, Rice University. (October 13, 2008) Lectures "Fundamentals Issues in Vision Research." (FIVR course), Marine Biological Labs, Woods Hole. (2012) "Eye Development." Developmental Biology, California Institute of Technology, Pasadena, CA. (2008) Posters "The Cornea of the Chouse: Understanding Neural Crest Cell Differentiation in the Cornea Using a Chick-Mouse Chimeric Technique." Rice IBB symposium, Houston, TX. With Chou, D. and Spurlin J. "VEGF Expression in the Developing Cornea." Rice IBB symposium, Houston, TX. With Paulsen, S., Munjaal, R., McKenna, C., Kwiatkowski, S. and Ojeda, A. "Corneal plasticity: Characterization of the multipotentiality of human keratocytes." Association for Research in Vision and Ophthalmology, Annual Meeting, With Chao, J.R., Bronner-Fraser, M., and Lwigale, P.Y. "Semaphorin3A regulates neural crest migration during ocular development." Society of Developmental Biology, 67th Annual Meeting, (2008) With Lwigale, P. and Bronner-Fraser, M. "Semaphorin3A regulates neural crest migration into the eyes during cornea development." Association for Research in Vision and Ophthalmology, Annual Meeting, With Lwigale, P. and Bronner-Fraser, M. Seminar speaker "Contribution and molecular regulation of neural crest cells during eye development." Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA. (January 21, 2008) "Contribution and molecular regulation of neural crest cells during eye development." Department of Biochemistry & Cell Biology, Rice University, Houston, Texas. (February 18, 2008) "Molecular regulation of neural crest cell migration during eye development." Department of Ophthalmology and Visual Science, University of Texas Medical School. (October 10, 2008) "Molecular regulation of neural crest cells during eye development." Department of Biology, California State University, Northridge. (May 9, 2008) "Research proposal/Chalk talk, Contribution and molecular regulation of neural crest cells during eye development." Dept. of Pharmacological Sciences, State University of New York, Stony Brook. (January 30, 2008) "Research proposal/Chalk talk, Contribution and molecular regulation of neural crest cells during eye development." Dept. of Pediatrics, Division of Human Molecular Embryology, Medical College of Wisconsin, Milwaukee. (Febfruary 11, 2008) Supervised Theses & Dissertations Cody Gregory, MA Investigation of the role of Wee2 in the zebrafish midblastula transition. (2010) (Committee Member) Derek L. Shenefelt, MA FGFR4 and β-Klotho in Metastatic Prostate Cancer. (2012) (Committee Member) Chelsea McKenna, Ph.D. The Role of Semaphorin/Neuropilin Signaling in the Development of Innervation and Avascularization of the Cornea. (2012) (Thesis or Dissertation Director)