Angelika Antoni, Ph.D.
Assistant Professor, Biology Department
Education, Courses Taught, Research Interests, Projects, Publications
Postdoc - 1998-2004, University of Chicago, Immunology
PhD - 1998, University of Montana, Biochemistry & Microbiology
MS - 1990, Missouri State University, Molecular Biology
BS - 1988, Missouri State University, Biology
Courses Taught at KU
BIO 224/225 Applied and Environmental Microbiology Lab
BIO 470 Special Topics: Molecular Biology of Cancer
BIO 336/337 Medical Microbiology with Lab
BIO 447 Immunology
Autoimmune diseases such as
Systemic Lupus Erythematosus, (Lupus) and Juvenile Diabetes (Type-I Diabetes)
can be devastating. The nature of these diseases is that the immune system
attacks self proteins or cells as if they were invading organisms. The few
available treatments for most autoimmune diseases involve immunosuppression and
lifestyle changes. If not managed properly, these diseases can lead to kidney
failure and death. It is extremely important that the scientific community
understand the causes of autoimmune diseases. It is known that they have both
an inherited component and an environmental trigger; however, no clear
understanding of the mechanism of disease initiation has been elucidated.
In order to understand how the diseases begin, it is important to study the cells of animals that will develop autoimmunity but donít already have it. To that end, I and my collaborators study the cells of mice from inbred strains that are known to develop either Lupus or Type-I Diabetes. Cells from these mice have already provided great insights. We traced a functional defect in the macrophages of autoimmune-prone mice to at least one major signaling molecule: RhoA (Longacre et al., 2004). Signaling molecules allow cells to communicate with other cells and control their function. The finding with RhoA was tested in other mice and the same defect in signaling was identified in all autoimmune-prone mouse strains tested: five different strains that develop Lupus and the one Type-I Diabetes strain. Importantly, none of the seven normal mouse strains tested had the defective macrophage signaling (Fan et al., 2006).
The defect in macrophages of autoimmune-prone mice is significant because macrophages are key cell types that present antigens (proteins) to other cells of the immune system and activate them. These other cells are the ones that, in the case of autoimmune diseases, attack the self. The defect in RhoA signaling affects many functions of the macrophage. RhoA is a key regulator of the cytoskeleton, the component of cells that gives them structure and allows them to move or stay put. Improper signaling through RhoA results in profound abnormalities of adhesion (cell stickiness) and cytoskeletal organization. These defects in turn can alter the function of the macrophages so that they respond to self proteins by activating an immune response against them, instead of ignoring them.
We propose that autoimmune disease in susceptible animals is due to improper signaling through RhoA, but since RhoA signaling is completely normal in the macrophages unless they are exposed to apoptotic cells or serum lipids, it is likely that RhoA itself is not defective. Instead, we propose that a molecule responsible for controlling RhoA signaling is defective and only triggered by apoptotic cells or serum lipids. It is our goal to characterize the signaling abnormality and identify the defective molecule(s).
Ongoing Research Projects
Collaboration with Dr. Cristen Rosch: Analysis of Signaling and Structural Defects in Cells of Autoimmune-prone Mice
We aim to characterize the defect in signaling and cell structure in
autoimmune-prone macrophages and identify the critical control mechanisms of
the RhoA signaling pathway in order to identify the exact genetic abnormality
that leads to their defective function. Specific Objectives:
Collaboration with Jerry Levine at the University of
Illinois at Chicago:
Selective hybridization to clone genes differentially expressed by two
different but related cell lines in the hopes of identifying the apoptotic
cell binding receptor or important signaling molecules triggered by
apoptotic cell binding.
Collaboration with Joyce Rauch at McGill University in Montreal, Canada:
Use genetic engineering to construct various iterations of protein
molecules that will be used to stimulate an immune response against
self-molecules in mice. The hope is to understand whether binding of
molecules to apoptotic cells is sufficient to trigger an immune response
against those molecules, and second, whether binding is necessary.
Research and Teaching Grants since 2005
PICEH-AEAB Curriculum Development Grant
Childrenís Environmental Health Issues in Biology for Non-majors.
Funded: July 1, 2009 Ė Jan 31, 2009
PASSHE Faculty Professional Development Council Grant
Joint proposal, Angelika Antoni, PI and Cristen Rosch
Analysis of Signaling and Structural Defects in Cells of Autoimmune-prone Mice
Funded: May 1, 2009 - Oct 31, 2009
Students Supervised in Research and Their Accomplishments:
Fall 2009 Kyle Bowman
Kyle will quantitate and partially identify bacterial species existing on fruits purchased from various sources available to the public.
Fall 2009 Christopher Ballard
Christopher will quantitate and partially identify bacterial species existing on fruits purchased from various sources available to the public, after attempting to clean them using readily available methods.
Spring 2009 Taryn Dick
Taryn performed selective hybridization to clone genes differentially expressed by two different but related cell lines in the hopes of identifying the apoptotic cell binding receptor or important signaling molecules triggered by apoptotic cell binding.
v Taryn was awarded a KU Undergraduate Student Research Grant, KU Foundation, $500
v Taryn was awarded a KU Biology Dept. Undergraduate Student Research Grant, $150
Spring 2009 Stasia Hydock
Stasia performed genetic engineering to construct various iterations of protein molecules that will be used to stimulate an immune response against self-molecules in mice. The hope is to understand whether binding of molecules to apoptotic cells is sufficient to trigger an immune response against those molecules, and second, whether binding is necessary.
v Stasia was awarded a KU Undergraduate Student Research Grant, KU Foundation, $500
Stasia presented her work, Itís
amost OVA: the production of ovalbumin constructs, to the
KU Biology Department as partial fulfillment of the requirements for BIO 370.
Spring 2008 Lee Graham
Lee performed selective hybridization and cloned four genes whose expression was repressed in human kidney tumor tissue compared to normal kidney tissue from the same donor. Lee also assisted in identifying and elucidating the significance of genes related to the development of autoimmunity, from previous research results.
v Lee was awarded a KU Undergraduate Student Research Grant, KU Foundation, $500
v Lee was awarded a KU Biology Dept. Undergraduate Student Research Grant, $150
v Lee presented his work, Graham, L. and A. Antoni. 2008. RNA Comparisons in Disease Research, Identification of Genetic Damage in a Derived Cell Line That Responds Abnormally to Apoptotic Cells, at the 9th Annual Undergraduate Research and Creativity Conference, Kutztown University of PA.
v Some of Leeís work was included in two separate manuscripts, one is in publication, the other is being rewritten.
Publications and Manuscripts Submitted or in Preparation, since 2005
9) Antoni, A., D. Spiegel, and J.S. Levine (in preparation) Comparative Analysis Using DNA Microarrays: Maximization of Number of Linearly Independent Measurements through use of a Strategy of Recurrence.
8) Antoni, A., V.A. Patel, H. Fan, D.J. Lee, L.H. Graham*, D. Spiegel, J. Rauch, and J.S. Levine. (in preparation) Macrophages from Lupus-Prone MRL Mice Have a Conditional Signaling Defect That Leads to Dysregulated Expression of Multiple Genes. *KU studentís work included in manuscript
7) Patel, V.A., D.J. Lee, L. Feng, A. Antoni, W. Lieberthal, J.H. Schwartz, J. Rauch, D.S. Ucker, and J.S. Levine. (submitted to the Journal of Biological Chemistry) Recognition of apoptotic cells by epithelial cells: conserved versus tissue-specific signaling responses.
6) Antoni, A., L.H. Graham*, J. Rauch, and J.S. Levine (2009) Altered cell-cell and cell-matrix interactions in the development of systemic autoimmunity. Autoimmunity, 42:278-281. *KU studentís work included in manuscript
5) Patel, V.A., D.J. Lee, A. Longacre-Antoni, L. Feng, W. Lieberthal, J. Rauch, D.S. Ucker, and J.S. Levine (2009) Apoptotic and necrotic cells as sentinels of local tissue stress and inflammation: Response pathways initiated in nearby viable cells. Autoimmunity, 42:317-321.
4) Patel, V.A., A. Longacre-Antoni, M. Cvetanovic, D.J. Lee, L. Feng, H. Fan, J. Rauch, D.S. Ucker, and J.S. Levine (2007) The Affirmative Response of the Innate Immune System to Apoptotic Cells. Autoimmunity, 40:274-280.
3) Patel, V.A., A. Longacre, K. Hsaio, H. Fan, F. Meng, J.E. Mitchell, J. Rauch, D.S. Ucker, and J.S. Levine (2006) Apoptotic cells, at all stages of the death process, trigger characteristic signaling events that are divergent from and dominant to those triggered by necrotic cells: Implications for the Delayed Clearance Model of Autoimmunity. J. Biol. Chem., 281:4663-4670.
2) Fan, H., V.A. Patel, A. Longacre, and J.S. Levine. (2006) Abnormal regulation of the cytoskeletal regulator Rho typifies macrophages of the major murine models of spontaneous autoimmunity. J Leukoc Biol., 79:155-165.
1) Longacre, A., L.R. Scott, and J.S. Levine (2005) Linear Independence of Pair-Wise Comparisons of DNA Microarray Data. J. Bioinformatics & Computational Biology, 3:1243-1262.