B.S., University of Rochester, Molecular Genetics, Rochester, NY (1991)
Ph.D., Ohio State University- Molecular Genetics, Columbus, OH (1998)
Postdoctoral Fellow, University of Pennsylvania, Department of Medicine, Philadelphia, PA (2003)
- BY350 Comparative Anatomy
- BY352 Vertebrate Anatomy Lab
- BY310/510 Developmental Biology
- BY300/622 Advances in Biology Research
- BY405 Undergraduate Research
- BY482/682 Molecular Genetics
My research focuses on migration and differentiation of neurons that populate the intestine as well as development of smooth muscle, which is responsible for mixing and propulsive activity. I use zebrafish, which is an excellent model research organism. Transparent zebrafish embryos develop externally over the course of five days. At the end of embryogenesis there is a similar arrangement of digestive organs and cell types when compared to humans. Zebrafish embryos also have extensive similarities to the genetics and physiology of human organ development with broad implications for human development and disease states.
Development of the vertebrate enteric nervous system
I have been concentrating on 1.) understanding how the enteric neural system develops; 2.) determining the role of genes involved in differentiating enteric neurons, smooth muscle, and enteroendocrine cells within the intestinal epithelium. I am concentrating on four interrelated topics in my research.
Characterization of enteric precursor migration, proliferation, and differentiation.
The objective of this research is to define and characterize the major events that occur during enteric neural development. This is important because knowledge of normal development is required in order to understand defects generated by genetic manipulation of the system.
In zebrafish, enteric neural precursors migrate from the neural crest into the anterior digestive system to migrate to the posterior. We show that enteric precursors differentiate into neurons beginning at 54 hours in embryogenesis in an anterior to posterior direction. Differentiation of neurons occurs in groups rather than an even gradient. Proliferation among the precursors is even and decreases throughout development except for a short anterior region during the second day of embryogenesis. The anterior proliferation rate likely contributes to lower anterior neuron numbers.
We find that major events in smooth muscle differentiation correspond to large increases in the numbers of enteric neurons. This suggests that differentiation of smooth muscle is necessary to differentiate enteric neurons. One of our short-term goals is to identify how the loss of smooth muscle affects enteric neural differentiation. A long-term goal is to define the signals shared between differentiating smooth muscle and enteric neurons.
FKBP9 is necessary for differentiation of intestinal smooth muscle. FKBP9 is a member of the FK506 binding proteins. We have found that the zebrafish homologue has a role in intestinal smooth muscle differentiation.
Enteric neural and smooth muscle defects in flotte latte (flo) and slim jim (slj) mutations. Previously, I determined that flo and slj develop lower numbers of enteric neurons and predominately longitudinal smooth muscle by the end of embryogenesis. The objective is to determine how these mutants arrive at this point.
Development and manipulation of the serotonin signaling system within the intestine.
Mechanical and chemical stimulation of intestinal epithelial cells generates a serotonin signal from epithelial endocrine cells. Serotonin binds to receptors on nearby enteric neurons to induce luminal chloride release and as a result secretion of fluids. Intestinal motility is also altered. The objective is to determine how this system develops and operates in zebrafish embryos.
To investigate these topics, I am using mutant analysis, molecular biology techniques, histology, immunohistochemistry, RNA in situ hybridization, and antisense technology to knock down gene function in developing embryos. Each of these techniques is a powerful tool to identify molecular pathways involved in enteric neural development and function.
Publications (last 5 years)
(* denotes undergraduate co-author)
Wallace, K.N., Akhter, S., Smith, E.M., Lorent, K., and Pack, M. (2005) Intestinal growth and differentiation in zebrafish. Mechanisms of Development 122: 157-173.
Wallace, K.N., Dolan, A.C., Seiler, C., Smith, E.M., Yusuff S., Chaille-Arnold L., Judson B., Yengo C., Sweeney H.L., Pack, M. (2005) Mutation of smooth muscle Myosin causes epithelial invasion and cystic expansion of the zebrafish intestine. Developmental Cell. 8(5): 717-726.
Chen, X., Moorman, S.J., Wallace, K.N., Pack, M., and Haendel, M.A. (2007) ZFIN Anatomy Working Group: Digestive System. Manually curated data.
Wallace, KN, Olden*, T, Beckman, SA*. "Zebrafish enteric neuron formation corresponds to smooth muscle development."First Pan American Conference in Developmental Biology, Cancun, Mexico, 2007. Abstract published in Developmental Biology (2007) 306 (1): 420.
Olden, T.*, Akhtar, T., Beckman, S.A.*, and Wallace, K.N. (2008) Differentiation of the zebrafish enteric nervous system and intestinal smooth muscle. Genesis. 46(9): 484-498.
Wallace KN, Akhtar, T., Yerry, R*. "Zebrafish homologue of FKBP65 plays a role in intestinal smooth muscle differentiation." Society of Developmental Biology. 67th Annual meeting, Philadelphia, PA, 2008 Abstract published in Developmental Biology (2008) 319 (2): 608.
Ispas, C., Wallace, KN, and Andreescu, S., "Cytotoxicty studies of metal and metal oxide nanoparticles using zebrafish embryos as model toxicological target." 236 National Meeting of the American Chemical Society, Philadelphia, PA, 2008. Abstract published in Papers of the American Chemical Society (2008) 236.
Ispas, C, Andreescu, D., Patel, A.*, Goia, D.V., Andreescu, ES, Wallace K.N. (2009) Toxicity and developmental defects of different sizes and shape nickel nanoparticles in zebrafish. Environmental Science and Technology, 43(16): 6349-6356.
Akhtar, T., Li, J., Olden, T.*, and Wallace, K.N. (2009) Use of Phospholipase A2 for antigen retrieval in zebrafish whole mount immunohistochemistry. Zebrafish, 6(3): 223-227.
Njagi, J, Ball, M.*, Best, M.*, Wallace, K.N., and Andreescu, E.S. Electrochemical quantification of serotonin in the embryonic zebrafish intestine. Analytical Chemistry, 82(5): 1822-1830.
Wallace, K.N. Fish digestive development. (2010) Fish Physiology. Eds. Farrell, T and Stevens, D., Elsevier. In Press.