Download STEM CELL BIOLOGY RESEARCH GROUP

STEM CELL BIOLOGY
RESEARCH GROUP
Objectives
 Putting stem cells to work in the service of medicine.
 Repairing and/or regenerating tissues damaged by genetic, developmental,
or acquired disease processes, cancer or aging.
 Training of medical, allied health, graduate, undergraduate, high school and
M.D./Ph.D. students in the health sciences.
Current Projects and Collaborations
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Biology of breast cancer stem cells,
microenvironmental effects and metastasis.
Investigators: JG Sharp, Ph.D., B O’Kane,
Ph.D., A Kessinger, M.D., E Reed, M.D., P
Mukhopadhyay, Ph.D., and T Farrell, B.S.
Breast cancer cells in bone marrow grow
as epithelial “domes” in vitro
References: Murphy BO, et al. A murine model of bone marrow micrometastasis in breast cancer. Clin
Exp Metastasis. 2002;19(7):561-9; Mukhopadhyay P, et al. Murine Cl66 orthotopic breast cancer cells
with stem cell phenotypes exhibit heterogeneity of in vitro agar colony and tumorsphere formation, and in
vivo tumor growth (Abstract presentation at Cold Springs Harbor Symposium on Mechanisms and Models
of Cancer, 2012)
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Lymphoma stem cells and their survival in
stem cell niches.
Investigators: JG Sharp, Ph.D., and SS
Joshi, Ph.D. Former student (now postdoc
at Hopkin’s) Abby Hielscher, Ph.D.
Cobblestone areas formed by lymphoma
cells growing on stroma resemble hematopoietic stem
cell cobblestone areas.
Reference: Sharp JG, Jackson JD. Hematopoietic stem cells and cytokines. Atlas of Clinical
Hematology. JO Armitage, editor. Philadelphia: Current Medicine; 2008. Chapter 7
For translational studies that are leading to a new clinical trial, see: Hegde GV, et al. Novel therapy
for therapy-resistant mantle cell lymphoma: Multipronged approach with targeting of hedgehog
signaling. Int J Cancer. 2012 Apr 17.
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a)
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b)
Physical activity/exercise as a counter to
inflammation, obesity and cardiovascular
disease as well as promoting vascular
health and immunity in cancer survivors.
Investigators: L Bilek, Ph.D., T McGuire,
D.Pharm., M Lang, B.S., T Farrell, B.S.
Endothelial cells (CD31+,
a), their precursors
(CD34+, b), and stem cells
(CD133+/VEGFR-2+, c)
all decrease significantly as
body mass index increases.
c)
References: McGuire TR, et al. Inflammation associated with obesity: relationship with blood and bone marrow
endothelial cells. Obesity(Silver Spring). 2011 Nov;19(11):2130-6; Wardyn GG, et al. Effects of exercise on
hematological parameters, circulating side population cells, and cytokines. Exp Hematol. 2008 Feb;36(2):216-23.
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a)
b)
Non-reprogrammed (a) and reprogrammed (b) CD34+
mouse bone marrow cells
Reprogramming of bone marrow cells for
tissue repair or regeneration in the elderly.
Investigators: JG Sharp, Ph.D., P
Mukhopadhyay, Ph.D., I Ahmad, Ph.D., T
Farrell, B.S.
Recently completed Nebraska Department of Health LB606 grant. For an update on iPSC see: Parameswaran
S, et al. Nucleic acid and non-nucleic acid-based reprogramming of adult limbal progenitors to pluripotency
(PLos ONE) in press 2012
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(c)
OMA-AD cells on (a) uncoated glass which
appear unhealthy and (b) on IBAD deposited
nano-structured transparent pure cubic ZrO2 film
which look healthy, confluent and associated with
each other. (c) OMA-AD grown and stained with
Alazarin red indicates osteoblast (bone cell)
differentiation
Stromal cells, stem cells, proteins
and nanoscale metal/oxide substrates
for prosthesis integration.
Lead Investigator: F Namavar,
Ph.D., with JG Sharp, Ph.D., and G
Thiele, Ph.D., R Miralami, B.S.
Reference: Namavar, et al. Nano-engineering
Biocompatibility of Implant Surfaces for Enhanced
Biointegration. [Abstract] APS March Meeting 2010
Volume 55, Number 2
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In an analysis of lung repair employing a GFP parabiotic donor
as the source of cells, elastase administered to the cell recipient
induced emphysema (Fig 1) in the recipient, but also the cell
donor, i.e. “action at a distance” by producing apoptosis [Fig 3
(no fig 2)]. The mediator of this effect appears to be T cells
(Fig 4).
Is emphysema an autoimmune
process?
Investigators: S Rennard, M.D., M
Liu, M.D., S Kawasaki, M.D.
(fellow, now faculty, U. Tokyo,
Japan), JG Sharp, Ph.D., T Farrell,
B.S., A Nelson, B.S., J Michalski,
Ph.D., X Wang, M.D.
This project is funded by a current LB506 grant