Kenneth D. Poss, Ph.D.

(Biology, Massachusetts Institute of Technology)

Assistant Professor, Cell Biology

Duke University Program in Genetics
Cell and Molecular Biology Program
Developmental Biology Training Program

The zebrafish model system. The zebrafish has proved to be a valuable model system for understanding how vertebrate organisms acquire their form. Experimental advantages of this teleost include rapid development, embryonic transparency, ease of rearing and maintenance, and above all, amenability to genetic manipulation. In fact, hundreds of genes essential for zebrafish development have been isolated from chemical and insertional mutagenesis screens. The significance of zebrafish as a laboratory model will continue to grow as sequencing of its 1.7 billion base pair genome moves toward completion.

Adult zebrafish are highly regenerative. Zebrafish organs carry out the same basic functions as mammalian organs, and are subject to similar disorders. Accordingly, human disease can be modeled in the zebrafish. Research groups have already begun using zebrafish to understand human hematological disorders, cancer and skeletal defects. Many diseases are linked by a common theme - tissue damage. For instance, Alzheimer's disease, heart failure, spinal cord injury, and diabetes are all caused by irreparable organ damage. While most human organs have an extremely limited ability to regenerate, zebrafish organs possess an elevated regenerative capacity, facilitating renewal of spinal cord, retina, appendages (fins), heart muscle, and potentially other tissues. Thus, zebrafish are susceptible to diseases found in humans, but also maintain a unique defense mechanism, regeneration. Our lab currently focuses on appendage and heart regeneration.

Fin regeneration. We will continue to apply forward and reverse genetic approaches to find new genes essential for perfect regeneration of the zebrafish tail fin. Fin regeneration is a very rapid process (~10-14 days) that replaces bone, epidermis, blood vessels, nerves, and connective tissue. To date, pilot screens and positional cloning strategies have revealed 4 genes essential for formation and function of the regeneration blastema, a proliferative structure crucial for fin regeneration in zebrafish and limb regeneration in certain amphibians. I expect that expanded screening efforts and candidate gene testing will uncover genes responsible for induction, proliferation, patterning, and completion of regeneration. Also, we have used inducible transgenic technology to detail how positional information in the appendage sets a defined level of Fgf signaling, and in doing so controls how fast new structures are replaced. We are further dissecting functions of Fgfs during fin regeneration, and have also branched out to investigate the roles of other developmental programs and regulatory mechanisms.

Heart regeneration. Recent discoveries of cardiac progenitor cells in mammals have exciting implications for cardiac biology and disease. Yet, it is unclear why they fail to support natural regeneration after myocardial infarction, an extremely common cause of human mortality and morbidity. Recently, we discovered that, by contrast with mammals, adult zebrafish regenerate heart muscle after major injury. Currently, we are investigating how progenitor cells for this new muscle arise and are coaxed toward successful regeneration. We are also defining the developmental response of non-myocardial cell types to injury, and their importance in heart regeneration.

Email
K.Poss@cellbio.duke.edu

349 Nanaline Duke Building, Box 3709
Duke University Medical Center
Durham, NC 27710

Telephone 919-681-8457
Fax 919-684-5481


Poss Lab Website

Selected Recent Publications
Yin, V., Thompson, J. M., Thummel, R., Hyde, D., Hammond, S., and Poss, K. D.  (2008).  Fgf dependent depletion of microRNA-133 promotes zebrafish appendage regeneration. Genes and Development 22, 728-733. -PDF-

Wills, A.A, Holdway, J.E., Major, R.J., Poss, K.D. (2008). Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish. Development 135, 183-192. Epub 2007 Nov 28. -PDF-

Shin, D., Shin, C.H., Tucker, J., Ober, E., Rentzsch, F., Poss, K.D., Hammerschmidt, M., Mullins, M.C., and Stainier, D.Y.R. (2007). Bmp and Fgf signaling are essential for liver specification in zebrafish. Development 134, 2041-2050. -PDF-

Nechiporuk, A., Linbo, T., Poss, K.D., and Raible, D.W. (2007). Specification of epibranchial placodes in zebrafish. Development 134, 611-623. -PDF-

Poss, K.D. (2006). Getting to the heart of regeneration in zebrafish. Seminars in Cell and Developmental Biology 18, 36-45. -PDF-

Lepilina, A., Coon, A. N., Kikuchi, K., Holdway, J. E., Roberts, R. W., Burns, C. G., and Poss, K. D.  (2006). A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration.  Cell 127, 607-619.

Lee, Y., Grill, S., Sanchez, A., Murphy-Ryan, M., and Poss, K. D. (2005). Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration. Development 132, 5173-5183.

Poss KD. A zebrafish model of germ cell aneuploidy. Cell Cycle. 2004 Oct;3(10):1225-6. Epub 2004 Oct 13.

Poss, K. D., Nechiporuk, A., Stringer, K. F., Lee, C., and Keating, M. T. (2004). Germ cell aneuploidy in zebrafish with mutations in the mitotic checkpoint gene mps1. Genes and Development 18, 1527-1532.

Traver, D., Paw, B. H., Poss, K. D., Penberthy, W. T., Lin, S., and Zon, L. I. (2003). Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants. Nature Immunology 4, 1238-1246.

Poss, K. D., Keating, M. T., and Nechiporuk, A. (2003). Tales of regeneration in zebrafish. Developmental Dynamics 226, 202-210.

Nechiporuk, A., Poss, K. D., Johnson, S. L., and Keating, M. T. (2003). Positional cloning of a temperature-sensitive mutant emmental reveals a role for Sly1 during cell proliferation in zebrafish fin regeneration. Developmental Biology 258, 291-306.

Poss, K. D., Wilson, L. G., and Keating, M. T. Heart regeneration in zebrafish. (2002). Science 298, 2188-2190.

Poss, K. D., Nechiporuk, A., Hillam, A. M., Johnson, S. L., and Keating, M. T. (2002). Mps1 defines a proximal blastemal proliferative compartment essential for zebrafish fin regeneration. Development 129, 5141-5149.

Lab personnel
Junelle Bumgardner (research tech)
Jennifer Holdway (research tech)
Alexandra Lepilina (MD, research tech)
Greg Egnaczyk (Cardiology fellow)
Yi Fang (postdoctoral fellow)
Kazu Kikuchi (postdoctoral fellow)
Robert Major (postdoctoral fellow)
Jinhu Wang (postdoctoral fellow)
Viravuth Yin (postdoctoral fellow)
Yoonsung Lee (graduate student)
Greg Nachtrab (graduate student)
Airon Wills (graduate student)
David Chi (undergraduate student)
Christian Parobek (undergraduate student)