Jiro Nagatomi, Ph.D.
Assistant Professor of Bioengineering
B.S. (Cum laude) Biomedical Engineering (Mech. Concentration),
1994 Rensselaer Polytechnic Institute
Ph.D. Biomedical Engineering (Cellular Bioengineering), 2002
Rensselaer Polytechnic Institute
Postdoctorate Bioengineering, 2005 University of Pittsburg
1994 Rensselaer Polytechnic InstitutePh.D. Biomedical Engineering (Cellular Bioengineering), 2002
Rensselaer Polytechnic InstitutePostdoctorate Bioengineering, 2005 University of Pittsburg
Research Interests
Mechanobiology
Biomechanics
Functional Tissue Engineering
Biomechanics
Functional Tissue Engineering
Email:
Office: 313-2 Rhodes Research Center
Phone: 864.656.5193
Office: 313-2 Rhodes Research Center
Phone: 864.656.5193
Honors, Awards, and Professional Activities
Yamada Scholarship Award, Rensselaer Polytechnic Institute (1994)Paul Daitch Travel Award, Rensselaer Polytechnic Institute (1997)Sigma Xi Research Society (1998)Travel Award, Society for Basic Urologic Research Meeting (2002)Certificate of Merit, the US National Committee on Biomechanics (2003)2nd Place, Annual CURE-SCI Poster Competition, University of Pittsburgh (2003) Society Memberships:
Biomedical Engineering Society, BMES Society For Biomaterials, SFBSigma Xi Research Society American Society of Mechanical Engineers, ASMECurrent Research
Investigation
of Mechanically-induced
Tissue Remodeling
It
has been reported
in the clinical literature
of Urology that majority
of patients with outlet
obstruction and other
forms of lower urinary
tract dysfunctions
due to spinal cord
injury develop so-called “non-compliant” bladder.
Since one of the main
functions of the urinary
bladder is to store
urine at a relatively
low pressure for long
periods of time, high
compliance is a very
important mechanical
characteristic of the
bladder wall tissue,
and the loss of compliance
can lead to increased
intravesical pressure
and put the upper urinary
tract at risk. Our
current hypothesis
is that these tissue
remodeling events result
from the cellular/molecular
responses of the bladder
cells (urothelial and
smooth muscle cells)
to the abnormal mechanical
environments caused
by the urinary tract
dysfunctions (obstruction,
spastic bladder, etc.).
We are currently developing
in-vitro experimental
systems to expose cultured
bladder cells to controlled
mechanical force stimuli
such as cyclic hydrostatic
pressure and biaxial
stretch and to examine
the long-term cellular/molecular
responses of the bladder
cells to these stimuli.
Discovery and
Identification of
Mechano-Sensitive
Molecules
The
goal of this research
is to elucidate how
mammalian cells can
actually sense mechanical
stimuli, especially
hydrostatic pressure
and turn them into
biochemical signals.
We are interested
in both the immediate
mechano-sensing events
(in the order of milliseconds
to seconds) and down-stream
signal transduction
events (in the order
of minutes to hours).
We are currently developing
experimental systems
to investigate the
mechanotransduction
events at the single-cell
level using an electrophysiological
approach and at the
multi-cell level response
using a proteomics
approach. Identification
of the pressure sensors
in various cells will
help guide the development
of new pharmacological
agents for numerous
applications from peripheral
organs to the central
nervous system.
Application of
Mechanobiology to
Functional Tissue
Engineering
Attempts
to engineer tissues
in vitro have been
successful in addressing
the biomaterial aspects
(such as material
composition, architecture,
biocompatibility, etc.)
as well as the cellular
aspects (through advancement
of techniques for culturing
pertinent cell types).
The researchers of
Tissue Engineering
are becoming increasingly
aware that in order
for the cultured cells
to develop functional
tissues in vitro, it
is necessary to have
not only the biochemical
cues but mechanical
environments similar
to those of the in-vivo
conditions. A growing
number of literature
reports in Tissue Engineering
of bone, cartilage,
blood vessels, and
heart valve, support
this idea and provide
a promise for the emergence
of a new and important
field of research.
For this research,
specifically, we design,
build and calibrate
novel bioreactors which
will condition cultured
cells and tissue engineering
constructs under mechanical
stimuli necessary to
guide growth and development.
These studies will
provide a new methodology
in Tissue Engineering
to generate and to
characterize fully
functional, implantable
tissue constructs.
Studying the Role
of the Extracellular
Matrix Proteins on
the Mechanical Behavior
of Native Engineered
Tissues
Although in-vitro
engineered tissue constructs
currently being developed
such as bone, cartilage,
blood vessels, heart
valves, bladders, etc.
to date certainly have
the cellular and extracellular
compositions that match
those of the native
tissues, their mechanical
performances are not
nearly satisfactory.
This is partially due
to lack of understanding
of mechanical behaviors,
detailed architecture,
and the structure-strength
relationships of native
tissues. For this reason,
we are interested in
mechanical and histomorphometrical
characterization of
tissues such as bladder
wall. More specifically,
multi-axial mechanical
testing is utilized
to determine the three-dimensional
constitutive relationships
of tissues. Furthermore,
the tissue architecture
and composition information
are determined via
quantitative histomorphometry
and molecular biology
techniques and will
eventually be used
to develop structure-based
constitutive models.
These models will then
allow computer simulation
of mechanical behavior
of both native and
engineered tissues,
of which the direct
measurements of in-vivo
stresses are extremely
difficult.
Recent Publications
Nagatomi, J., Arulanandam, B.P., Metzger, D.W., Meunier, A., and Bizios, R. Effects of Cyclic Pressure on Bone Marrow Cell Cultures. Journal of Biomechanical Engineering 124: 308 - 314 (2002).
Nagatomi, J., Gloeckner, D.C., Chancellor, M.B., deGroat, W.C., and Sacks, M.S. Changes in the Biaxial Viscoelastic Response of the Urinary Bladder following Spinal Cord Injury. Annals of Biomedical Engineering 32: 1409 - 1419 (2004).
Nagatomi, J., Toosi, K.K., Grashow, J.S., Chancellor, M.B., and Sacks, M.S. Quantification of Bladder Wall Smooth Muscle Cell Orientation in Normal and Spinal Cord Injured Rats. Annals of Biomedical Engineering 33: 1078 - 1089 (2005)
Nagatomi, J., Demiguel, F., Torimoto, K., Chancellor, M.B., Getzenberg, R.H., and Sacks, M.S. Early Molecular-Level Changes in Rat Bladder Wall following Spinal Cord Injury. Biochemical and Biophysical Research Communications 34:1159-1164 (2005)
Long, R.A., Nagatomi, J., Chancellor, M.B., Huard, J., and Sacks, M.S. MMP-I Up-Regulation is a Potential Mechanism for Increased Compliance in Muscle Derived Stem Cell-Seeded SIS. Biomaterials 27:2398-2404 (2006)
