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 Assistant
Professor, Immunology and Microbiology
Indiana University School of Medicine- South
Bend
Adjunct Assistant Professor, Biology
University of Notre Dame
email:
bohlson.2@nd.edu
Ph.D.,
University of Notre Dame
Postdoctoral,
University of California, Irvine
Research
Interests
Specific
cells in the body are designed to ingest dangerous
particles, such as invading bacteria. These
professional eating cells, or phagocytes, also eat
dead or dying cells. This process of clearance of
dead or dying cells is necessary to allow for the
repair of damaged tissue, and to maintain normal
tissue. When this process of cellular ingestion
(phagocytosis) is dysregulated, the body becomes
susceptible to chronic infections and
autoimmunity. My laboratory focuses on phagocyte
recognition and clearance events with the goal of
developing therapies that strengthen the body's
ability to ingest and kill infectious particles or
dead/dying cells.
Billions
of cells die in the body every day by normal
processes (apoptosis). These dead cells need to be
recognized by phagocytes and cleared rapidly. CD93
is a protein that regulates phagocytosis of dead
cells. It is found on phagocytes and other cell
types involved in controlling inflammation. We
recently demonstrated that CD93 is released from
the surface of cells in response to inflammatory
signals. This shed or "soluble" form of
CD93 is found in human blood. Soluble CD93 may be
used by the body to modulate the response to
injury and to decrease the damage associated with
inflammation. We are testing soluble CD93 for its
ability to regulate these events. These studies
may help develop novel therapeutics to fight
inflammatory and autoimmune diseases such as
atherosclerosis, rheumatoid arthritis and lupus.
In
addition to our work with CD93, my lab
investigates the host response to infection with
pathogenic mycobacteria. Infection with M.
tuberculosis, the causative agent of TB, is
the second leading cause of death due to an
infectious microorganism and is responsible for
approximately 2 million deaths annually. In order
to survive within the host, mycobacteria reside in
human phagocytes. To gain access to this
intracellular space, mycobacteria utilize a
variety of host factors including blood proteins
called complement and a family of molecules called
defense collagens. We investigate the interaction
of complement proteins and defense collagens with
pathogenic mycobacteria, and how these
interactions regulate phagocyte activation.
Defense collagens bind both microorganisms and
dead cells via their globular head regions and
activate host immune functions (e.g. phagocytosis)
via their collagen-like tails. We are
investigating the mechanisms driving enhanced
phagocytosis in these systems, and how cell
signaling pathways are altered in response to
clearance of dead cells (anti-inflammatory) versus
clearance of pathogenic mycobacteria
(inflammatory).
Phagocytic
cells must functionally sum the signals received
from the particles being detected via their
diverse pattern recognition receptors to direct a
gene expression program that dictates an
appropriate immune response (inflammatory or
anti-inflammatory). TF, transcription factor; TLR,
Toll like receptor, PSR; phosphatidyl serine
receptor; C1qR, C1q/MLB receptor. Artwork by
Cheryl Cotman. Reproduced from Bohlson et al.,
2006, Molecular Immunology
(http://www.elsevier.com/locate/molimm).
A
new direction for our lab and the medical school
stems from a recent partnership with the
University of Notre Dame Ford Program in
Development Studies and Solidarity
(http://kellogg.nd.edu/fordprogram/index.shtml).
We will provide medical outreach and biomedical
research expertise in Nnindye parish (Mpigi
District, Uganda). Working closely with our
partners at University of Notre Dame, Nnindye
parish, and Uganda Martyrs University, our initial
projects involve assessing the current burden of
prevalent infectious diseases, namely HIV,
tuberculosis and malaria. Efforts will be
undertaken to expand health care services in
Nnindye and improve prevention for common tropical
diseases. Previous studies have linked
polymorphisms in defense collagens to
susceptibility to mycobacteria infections, and we
are initiating field studies in Nnindye to assess
the evolution of defense collagen polymorphisms in
TB endemic regions.
Our Lab
Top
left to right; Ana Kozmar (visiting
scholar), David Johnson (graduate rotation
student), Suzie Bohlson (P.I.), Mike Kuelbs
(graduate student), Jonah Smith (Research
Assistant). Bottom left to right: Mallary
Greenlee (graduate student), Sarah Sullivan
(undergraduate research assistant), Jessica Morris
(undergraduate research assistant).
Publications
Roach,
T.I.A., Slater, S.E., Koval, M.,
White, L., Cahir McFarland, E., Okumura, M.,
Thomas, M., and Brown, E.J. CD45 Regulates Src
Family Kinase Activity associated with Macrophage
Integrin-mediated Adhesion. Current Biology,
7(6):408-417, 1997.
Blystone,
S.D., Williams, M.P., Slater, S.E.,
and Brown, E.J.: Requirement of Integrin β3
Tyrosine 747 for β3 Tyrosine
Phosphorylation and Regulation of αvβ3
Avididty. Journal of Biological Chemistry,
272 (45): 28757-28761, 1997.
Roach,
T.I.A., Slater, S.E., White, L.,
Zhang, X., Majerus, P.W., Brown, E.J., and Thomas,
M.L.: The Protein Tyrosine Phosphatase SHP-1
Regulates Integrin-mediated Adhesion of
Macrophages. Current Biology,
8(18):1035-1038, 1998
Blystone,
S.D., Slater, S.E., Williams,
M.P., Crow, M.T. and Brown, E.J.: A Molecular
Mechanism of Integrin Crosstalk: αvβ3
Supression of Calcium/Calmodulin-Dependent
Protein Kinase II Regulates α5β1
Function. Journal of Cell Biology,
145 (4):889-897, 1999
Bohlson,
S.S., Strasser, J.A., Bower, J.J and
Schorey J.S.: The Role of Complement in M.
avium Pathogenesis: In vitro and in
vivo analysis of the Host Response in the
Absence of Complement Component C3. Infection
and Immunity, 2001, 69 (12) 7729-35.
Bohlson,
S.S, Zhang, M., Ortiz, C.E., and Tenner,
A.J. CD93 interacts with the PDZ domain containing
protein GIPC: Implications in the modulation of
phagocytosis. Journal of Leukocyte Biology,
2005, 77(1):80-9.
Zhang,
M., Bohlson, S.S., Dy, M., and
Tenner, A.J. Modulated interaction of the ERM
protein, moesin, with CD93. Immunology,
2005, 115:63-73.
Bohlson,
S.S., Silva, R. Fonseca, M.I. and Tenner,
A.J. CD93 is rapidly shed from the surface
of human myeloid cells in response to a variety of
stimuli and the soluble form is detected in human
plasma. Journal of Immunology, 2005,
175: 1239-1247.
Fraser
D., Bohlson, S.S., Jasinskiene,
N., Rawal, N., Palmerini, G., Ruiz, S., Rochford,
R., and Tenner, A. C1q and MBL, components of the
innate immune system, modulate monocyte cytokine
expression. Journal of Leukocyte Biology,
2006, Jul;80(1):107-16
Bohlson,
S.S., Fraser, D., Tenner, A.J.
Complement Proteins C1q and MBL are PAttern
Recognition Molecules that Signal Immediate and
Long Term Protective Immune Functions. Review.
Molecular Immunology, 2007
Jan;44(1-3):33-43.
Fraser
D., Arora, M, Bohlson, S.S,
Lozano, E., and Tenner, A.J. Generation of
Inhibitory NFkB Complexes and pCREB Correlates
with the Anti-inflammatory Activity of Complement
Protein C1q inHuman Monocytes. J Biol
Chem, 2007 Mar 9;288(10):7360-7.
Greenlee,
M.C., Sullivan, S.A., and Bohlson, S.S.,
CD93 and Related Family Members: Their Role
in Innate Immunity. Review. Current
Drug Targets. 2008, Feb:9(2):130-8.
Lillis,
A., Greenlee, M., Mikhailenko, I., Pizzo, S.,
Tenner, A., Strickland, D., and Bohlson,
S. Murine LRP is required for
phagocytosis of targets bearing LRP ligands but is
not required for C1 q-triggered enhancement of
phagocytosis. Journal of
Immunology. 2008, Jul 1;181(1):364-73.
Greenlee,
M.C., and Bohlson, S.S.
CD93 is shed under inflammatory conditions in vivo
and the soluble form regulates phagocytosis of
apoptotic cells. Submitted.
Editorials:
Bohlson,
S.S. Modulators of the innate
immune response. Editorial. Current
Drug Targets. 2008, Feb:9(2):101.
Bohlson,
S.S. and Tenner, A.J., Defense
Collagen receptors on phagocytes: just the
beginning. Editorial. Focus on
Complement. 2008, June (1):8.
Book
chapter:
Thomas,
M.L., Roach, T.I.A., Slater, S.E.,
White, L., Okumura, M., and Brown, E.J.: The
Protein Tyrosine Phosphatase, CD45, in Adhesion
and Signal Transduction. Kinases and Phosphatases
in Lymphocyte and Neuronal Signaling. New York:
Springer-Verlag, 1997
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