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Michael
W. Kingmiking
@ iupui.edu

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Molecular and Developmental Biology
Studies of Gene Function in Regeneration,
Early Development and Cancer
Executive Member, IU Center for Regenerative Biology
and Medicine
Professor of Biochemistry and Molecular Biology, IU School Medicine
Professor of Biology, Indiana State University
Research Professor of Applied Biology and Biomedical
Engineering, Rose-Hulman Institute of Technology
Ph.D. Biochemistry, University of California at Riverside, 1984
Research being
conducted in my laboratory centers on the isolation and
characterization of novel factors involved in tissue regeneration. Frogs
represent a useful animal model with which to study molecular mechanisms that
drive regeneration and, conversely, which repress gene activity that could lead
to inhibition of the regenerative capacity in higher vertebrates. In these
species limbs and spinal cords regenerate well during larval stages, but
gradually lose this ability as the animal approaches metamorphosis. Adult frogs
do not regenerate and the response of these structures to surgical transection
is normally similar to that of higher vertebrates. This stage difference in
regenerative ability can be used to advantage experimentally to discover, by
differential gene screening, the molecules and molecular pathways that drive
regeneration or inhibit regeneration within the same species. This project is
being carried out with a consortium of researchers at Indiana
University, Bloomington,
IUPUI Indianapolis and Eli Lilly and Co., Indianapolis
Treatment of axlotl limbs (which can regenerate throughout
the life of this urodele) with beryllium sulfate after
amputation abolishes the ability of the limbs to regenerate. It is known
that beryllium augments inflammatory responses and thus, its ability to
interfere with regeneration may be related to this immune system response.
We treated stage 53 Xenopus laevis hindlimbs (regeneration capable stage)
with beryllium sulfate immediately after amputation and then collected limb
blastema tissue samples at various times for RNA extraction and RT-PCR
analysis of gene expression levels. We examined the expression of genes
involved in the inflammatory response, tissue reprogramming and pluripotency
as well as genes involved in patterning the blastema during regeneration.
These data show that beryllium does indeed increase the immune gene
expression while simultaneously inhibiting blastema patterning with little
or no effect on reprogramming gene expression.
Selected Publications from Last Five Years
Research
Wilson, JM, Martinez-De Luna,RI, El Hodiri, HM, Smith, R,
King, MW, Mescher, AL,
Neff, AW and Belecky-Adams, TL.
2010 RNA helicase Ddx39 is expressed in the
developing central nervous system, limb, otic vesicle, branchial arches and
facial mesenchyme of
Xenopus laevis Gene Expression Patterns 10(1):44-52
Rao, N, Jhamb, D, Milner, DJ, Li, B, Song, F, Wang, M, Voss, SR, Palakal, M,
King, MW, Saranjami, B,
Nye, HLD, Cameron, JA, and Stocum, DL
2009 Proteomic analysis of blastema
formation in regenerating axolotl limbs.
BMC Biology 7:83
Malloch, E, Perry, KJ, Fukui, L, Johnson, V, Cheng, M, Wever, J, Beck, CW,
King, MW, and Henry, JJ.
2009
Gene Expression Profiles of Lens Regeneration and Development in
Xenopus laevis.
Developmental Dynamics
238:2340-2356
King, MW, Neff, AW and Mescher, AL
2009 Proteomics
analysis of regenerating amphibian limbs: changes during the onset of regeneration.
International Journal of Developmental Biology
53(7):955-969
Million Passe, CM, White, CR,
King, MW, Quirk, PL, Iovanna, JL and Quirk, CC
2008
Loss of the protein NUPR1 (p8) leads to delayed LHb expression, delayed ovarian maturation, and testicular development of a Sertoli-cell-only syndrome-like phenotype.
Biology of Reproduction 79:598-607
Werner, SR, Mescher, AL,
Neff, AW,
King, MW, Harty, MW, Smith,
RC.
2007 Neural MMP-28 expression precedes myelination
during development and peripheral nerve repair.
Developmental Dynamics
236:2852-2864
Brannon, KM, Million Passe, CM, White, CR,
A Bade, N.,
King, MW, Quirk, CC
2007 Expression of the high mobility group A family member p8
is essential to maintaining tumorigenic potential by promoting cell cycle
dysregulation in LβT2 cells.
Cancer Letters 254:146-155
Alshaibi, N,
King, MW, Duong, T, and Ghosh, SK
2007 DP58, an
inducible myeloid protein, is constitutively expressed in murine neuronal
nuclei.
Frontiers of Bioscience 12:2947-2956
Grow, MW,
Neff, AW, Mescher,
AL and
King,
MW 2006 Global analysis of gene
expression in
Xenopus hindlimbs
during stage-dependent complete and incomplete regeneration.
Developmental Dynamics 235:2667-2685
Neff,
A.W.,
King, MW, Harty, M.W., Nguyen, T., Calley, J., Smith, R.C. and
Mescher, A.L.
2005 Expression of
Xenopus XlSALL4 during limb
development and regeneration.
Developmental Dynamics 233: 356-367
Education Publications
Textbook Editor:
Lange
Q&A USMLE Step 1, 6
th edition,
2008.
McGraw-Hill, NY
Lange
Q&A USMLE Step 1, 5
th edition,
2005. McGraw-Hill, NY
Appleton
& Lange’s Review for the USMLE Step 1, 4
th edition,
2002.
McGraw-Hill,
NY
Textbooks:
Biochemistry: Examination and Board Review, Balcavage,
WX and
King, MW 1995.
Appleton and Lange, Stamford, CT.
Textbook Book Chapters in Last Three Years:
King,
MW 2008 2008 Chapter 3:
Biochemistry, and Practice Tests (Chapter 8 - 14) in:
Lange Q&A USMLE
Step I, 6
th ed. McGraw-Hill, NY, NY.
King, MW 2007 Chapter 7, pp 177-207: Genetic
Mechanisms in
Cell and Molecular Biology for Engineers, ed. Waite and
Waite, McGraw-Hill,
NY, NY.
King, MW 2007 Chapter 9, pp 233-253: Cellular
Development in
Cell and Molecular Biology for Engineers, ed. Waite and
Waite, McGraw-Hill, NY, NY.