Directory > Faculty
Laura R. McCabe, Ph.D.
 |
Professor
Departments of Physiology and Radiology
2201 Biomedical Physical Science
Department of Physiology
Michigan State University
East Lansing, MI 48824-1225
Phone: 517-355-6475 x1156
Fax: 517-355-5125
E-mail: mccabel@msu.edu
Education
B.S., Ph.D., University of Chicago
|
Biomedical
Imaging Research Center
Areas
of Research Interest [PDF]
Research Interests:
Over 34 million Americans have decreased bone mass and an additional
10 million are classified as osteoporotic (severe bone loss).
Aging, disuse and disease contribute to decreased bone density
and its associated increase in fracture risk. In the elderly,
a bone fracture is strongly associated with depression and morbidity.
Most therapies prevent bone resorption, while few are able to
enhance bone formation. By taking an integrative approach to examine
bone adaptation to diseases (such as diabetes and inflammatory
bowel disease), my lab is working toward identifying
mechanisms regulating bone formation by osteoblasts. Approaches
include examination of transcription factor activity, intracellular
signaling pathway activation, stem cell lineage selection, apoptosis,
metabolism and immune system contributions utilizing cell culture
systems, animal models and human imaging. We are also developing
therapeutics to target our identified mechanisms/pathways to increase
bone formation.
Type I (T1)-Diabetes: Improved glucose monitoring
and insulin delivery methods allow T1-diabetic patients to live
longer lives but increase the risk of complications from extended
exposure to diabetic conditions. Bone loss is an overlooked complication
that is evident in T1-diabetes and may affect more than 50% of
males and females with this disease, and more than 20% of patients
age 20-56 meet the criteria for being termed osteoporotic (having
significantly low bone density). This means that T1-diabetic women
and men are entering menopause and old-age with already reduced
bone density and an increased risk of fractures, which can be
associated with depression, dependency and decreased lifespan.
Our studies have determined that in addition to bone loss there
is an increase in bone marrow fat in streptozotocin induced T1-diabetic
animal models (Botolin et al., 2005), which is also evident in
spontaneously diabetic mouse models (Botolin and McCabe, 2007).
This may be the result of bone marrow stem cells (which can become
osteoblasts or adipocytes or other cell types) maturing into adipocytes
at the expense of osteoblasts. We have shown that males and females
exhibit the bone loss and it is evident in all bones including
the skull (Martin et al., 2007). We also demonstrated that inhibition
of PPAR (a transcription factor important in adipocyte differentiation)
does not prevent T1-diabetic bone loss but does prevent induced
marrow adiposity (Botolin et al. 2006). The use of insulin receptor
knockout and selective knockin mice indicates that a lack of insulin
receptor signaling cannot completely account for T1-diabetic bone
loss (Irwin et al., 2006). Current and future studies are directed
at cell culture, animal model, and human study approaches to identify
the altered signaling pathways involved in T1-diabetic bone loss
so that we can restore normal function and prevent bone loss.
This would allow T1-diabetic patients to live long lives with
strong healthy bones; thereby improving both the quality and length
of life.
Inflammatory Bowel Disease: Inflammatory bowel
disease (IBD) affects as many as 1.4 million people in the United
States and is the most common chronic gastrointestinal illness
in children and adolescents. IBD is a risk factor for bone loss
and can reduce bone growth (critical functions needed early in
life to attain maximum bone strength and height). To develop and/or
choose optimal treatments, the mechanisms that contribute to IBD
bone pathology in children must be identified. Studies in humans
are confounded by interfering actions of steroids and other therapies
used to treat IBD and by the lack of bone histology and architecture
studies needed to accurately assess osteoblast, chondrocyte, osteoclast
and trabecular versus cortical bone pathologic-adaptation. To
address this need, my lab is examining the mechanisms of IBD (by
pharmacologic and bacterial approaches) induced bone loss. Results
will determine contributing factors to and potential therapies
for IBD induced bone loss.
Development of Potential Therapeutics: Hip and
knee joint implants are used in more than 1,500,000 operations
each year. In collaboration with faculty from Chemistry and Engineering,
my lab is applying our basic knowledge about anabolic pathways
to enhance bone fracture and implant healing. We are examining
surface responses, manipulation of surface structures and effects
of growth factors on the success of implant integration. In addition,
we are testing therapies for bone loss under conditions of disease.
Publications
This will open a new browser window and connect you in
to the NIH Entrez search engine. Please, close the new window
to come back to this page.
