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Peter Lwigale Associate Professor Associate Professor of BioSciences 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 BioSciences Department Affiliations Institute of Biosciences and Bioengineering Other Affiliations Baylor College of Medicine Websites Lwigale Lab Web Page Research Areas Molecular regulation of cornea development and regeneration. • Neural crest cell migration and differentiation • Trigeminal Sensory innervation • Ocular vasculogenesis and cornea avascularity • Cornea wound healing/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 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 lens-derived axon guidance molecule, Semaphorin3A, regulates sensory innervation of the cornea, neural crest cell migration, and vascular patterning in the anterior eye. 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 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. Teaching Areas BIOC 310, BIOC 412, BIOC 443, BIOC 544, BIOC 588, Selected Publications Abstracts Ojeda, A., and Lwigale, P. "Chemokine signaling is required for proper neuropatterning during ocular development." ISER Meeting Abstract (September 2016) Ojeda, A., and Lwigale, P. "The chemokine CXCL14 regulates neurovascular patterning during corneal development." ARVO Meeting Abstract #6154 (May 2016) Kwiatkowski, SC and Lwigale PY (2015) "PlexinD1 is required for Vascular Patterning in the periocular region and Establishment of Corneal Avascularity." Investigative Ophthalmology & Visual Science, 56: 3531. Spurlin, JW and Lwigale, PY. (2015) BMP-3 is a novel antagonist to TGF beta-2 mediated myofibroblast differentiation in embryonic keratocytes. Investigative Ophthalmology & Visual Science 56(7): 1301 Ojeda, A., Traweek, R., and Lwigale, P. (2014). Functional implication of CXCL14 chemokine during cornea development. Invest Ophthalmol Vis Sci. ARVO Meeting E-Abstract #5507. May 2014. Kwiatkowski, S., Munjaal R.P., and Lwigale, P. Expression patterns of angiogenic factors correlate with vascular patterning of the developing anterior eye. Invest Ophthalmol Vis Sci. ARVO Meeting Abstracts May 2013.305:4720. McKenna, C. and Lwigale, P. Lens-derived Sema3A inhibits angioblast migration and vascularization of the developing cornea. Invest Ophthalmol Vis Sci. ARVO Meeting Abstracts May 2013.117:1286. McKenna, C. and Lwigale, P. Angioblast migration and vascularization of the embryonic cornea are inhibited by lens-derived Semaphorin3A signaling (2013). SDB Meeting Abstract #54 JUL, 2013. Spurlin, J. and Lwigale, P. Innervation of embryonic corneas during regeneration. Invest Ophthalmol Vis Sci. ARVO Meeting Abstracts May 2013. 256:3901 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 Kwiatkowski SC, Ojeda AF, Lwigale PY. PlexinD1 is required for proper patterning of the periocular vascular network and for the establishment of corneal avascularity during avian ocular development. Dev Biol. pii: S0012-1606(15)30142-1 [Epub ahead of print] PubMed PMID: 26783882. Ojeda, A.*, Munjaal, R., and Lwigale, P. "CXCL14 knockdown disrupts neurovascular patterning during ocular development." Developmental BiologyIn Progress Agrawal SJ and Lwigale PY. Quail-chick chimeras and eye development. Methods Mol Biol. (2015) 1189:255-263 Ojeda, A., and Lwigale, P. CXCL14 knockdown disrupts neurovascular patterning during ocular development. Manuscript in progress. McKenna, C., Ojeda, A., Spurlin, J., Kwiatkowski, S., and Lwigale, P. (2014). Sema3A maintains corneal avascularity during development by inhibiting Vegf induced angioblast migration. Dev Biol. 391, 241-250. Featured on cover of journal issue Chao, J., Bronner, M., and Lwigale P. "Human Fetal Keratocytes Have Multipotent Characteristics in the Developing Avian Embryo." Stem Cells Dev. , 22 (15) (2013) : 2186-95. Kwiatkowski, S., Munjaal, R., Lee, T., and Lwigale, P. "Expression of pro- and anti-angiogenic factors during the formation of the periocular vasculature and development of the avian cornea." Dev Dyn. , 242 (6) (2013) : 738-751. Ojeda A., Munjaal, R. and Lwigale, P. "Expression of CXCL12 and CXCL14 during eye development in chick and mouse." Gene Expression Patterns, 13, (2013) : 303-310. Spurlin, J. and Lwigale, P. "A Technique to Increase Accessibility to Late-stage Chick Embryos for In Ovo Manipulations." Dev Dyn. , 242 (2) (2013) : 148-154. Recommended by Faculty of 1000. Spurlin, J. and Lwigale, P. "Wounded Embryonic Corneas Exhibit Nonfibrotic Regeneration and Complete Innervation." Invest. Ophthalmol. Vis. Sci. , 54, (2013) : 6334-6344. Griswold, S. and Lwigale, P. "Analysis of neural crest migration and differentiation by crossspecies transplantation." J. Vis. Exp. , 7 (60) (2012) : 3622. McKenna, C., Munjaal, R., and Lwigale, P. "Distinct roles for Neuropilin1 and Neuropilin2 during mouse corneal innervation." PLoS ONE, 7 (5) (2012) : e37175. 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. 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. "Embryonic origin of avian corneal sensory nerves." Dev BioI, 239 (2001) : 323337. 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 Agrawal, S. and Lwigale, P. (2015) Quail-chick chimeras and eye development In "Tissue Morphogenesis: Methods and Protocols", Volume 1189 of the series Methods in Molecular Biology. Nelson, CM ed. pp 255-263 Lwigale, PY. (2015) Corneal Development: Different Cells from a Common Progenitor. In "Molecular Biology of Eye Disease" Volume 134 of Progress in Molecular Biology and Translational Science. Hejtmancik, JF and Nickerson, JM eds. 134:43-59 Agrawal, S. and Lwigale, P. (2014). “Quail-chick chimeras and eye development” Tissue Morphogenesis: Methods and Protocols, Methods in Molecular Biology, vol. 1189. 255-263. Agrawal, S. and Lwigale, P. (2014). “Neural crest cells in eye development”. Neural Crest Cells: Evolution, Development and Disease. Ed. Paul Trainor. Elsevier. 189-203. Agrawal, S. and Lwigale, P. “Quail-Chick chimera Techniques in Studying Ocular Development” Methods in Molecular Biology- Tissue Morphogenesis. 2013. In Press. Agrawal, S. and Lwigale, P. “Neural Crest Cells in Eye Development”. Neural Crest Cells: Evolution, Development and Disease. Ed. Paul Trainor. Elsevier. (2013). 189-203. 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 "Novel functions of CXCL14 in regulating neurovascular patterning during corneal development”. Gordon Conference: Pathobiology of the Cornea. 02/2016. “Anterior eye during development and new insights from embryonic corneal regeneration”. Department of Molecular Physiology and Biophysics, University of Iowa. 2016. “Eyeing the neural crest”. Stem Cells, Gene regulatory networks and Evolution of Vertebrates symposium. Caltech. 01/2016. "Invited Talk-International Society of Developmental Biology." (July 2013) "Seminar Speaker-Molecular, Cell, and Developmental Biology Department, UT Austin." (2013) "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 "Lecture: Molecular and Developmental Biology of Vision Research Course." Baylor College of Medicine. (2013) "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 "Invited Talk-Annual meeting of the Association for Research in Vision and Ophthalmology." (2013) "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) James Spurlin, Ph.D. A novel paradigm for non-fibrotic regeneration of the cornea: The role of TGFβ superfamily during embryonic cornea regeneration. (2015) (Thesis or Dissertation Director) Sam Kwaitkowski, Ph.D. Role of Pro- and Anti-Angiogenic Factors during Formation of the Periocular Vasculature and Establishment of Corneal Avascularity. (2015) (Thesis or Dissertation Director) Ana Ojeda Cardenas, PhD Regulation of the neurovascular patterning by growth factors and cytokines during anterior ocular development. (2015) (Thesis or Dissertation Director) Micaela Morgado, Ph.D. MUC16/CA125 Regulation by the Proinflamatory Cytokines TNFα and IFNγ and the PPARγ Agonist Rosiglitazone in Breast and Ovarian cancers. (2016) (Committee Member) Ruda Cui, TBD. (2019) (Thesis or Dissertation Director) Anna Babushkina, Ph.D. TBD. (2020) (Thesis or Dissertation Director) Lian Bi, Ph.D. TBD. (2020) (Thesis or Dissertation Director) Justin Ma, Ph.D. TBD. (2020) (Thesis or Dissertation Director) Jennifer Petsche Connell, Amniotic fluid-derived stem cell isolation, maintenance, and differentiation for cardiac tissue engineering. (Committee Member) Renee Edlund, Foxi3 is required for patterning in the first branchial arch and for craniofacial development.. (Committee Member) Positions Held Member, Association for Research in Vision and Ophthalmology (ARVO) . (2014 - 2015) Member, Society of Developmental Biologists (SDB) . (2014 - 2015) Member, American Society for Cell Biology (ASCB). (2014 - 2015) Member, International Society for Eye Research (ISER). (2014 - 2015) Member, American Society for Gravitational and Space Biology (ASGSB). (2014 - 2015) Member, International Society for Developmental Biology (ISDB). (2014 - 2015)