Assistant Professor, Immunology and Microbiology
Indiana University School of Medicine- South Bend
Adjunct Assistant Professor, Biology
University of Notre Dame
email: sbohlson@iupui.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 Developmental 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
