I am investigating the role of C1q in the activation profile of phagocytic cells upon ingestion of apoptotic cells. We use whole genome microarray to study gene expression and thus identify molecular pathways and signaling cascade stimulated by C1q in monocytes, macrophages and dendritic cells.
I am also studying the role of complement and inflammation in the pathogenesis of Alzheimer’s Disease (AD). We showed that C1q enhances neuronal survival and prevents neuronal cell death induced by amyloid-beta, a pathologic peptide that accumulates in the brain during AD. I use microarray approach to identify the C1q neuroprotective pathways and investigating the role of C1q-modulated genes that are associated with survival in rat and mouse neurons.
Staff Research Associate
I am investigating the role of complement activation and subsequent inflammation in Alzheimer’s Disease by using in vivo models, such as triple transgenic and Tg2576 mouse models. I utilize sectioning of brain tissues, immunostaining of sections, and data analysis to study the pathology of transgenic mice. Also I participate in animal husbandry, breeding, and mouse colony maintanence and genotype transgenic mice by PCR and QPCR for breeding.
Graduate Student (Mol. Bio. & Biochemistry)
Many autoimmune and other chronic diseases are characterized by the presence of chronic inflammation. Targeting this inflammation at the molecular level may be one way to therapeutically intervene in the pathology of these diseases. To this end, I am studying the immuno-regulatory role of complement protein C1q on inflammatory signaling and gene expression during the phagocytosis and degradation of dying cells and how these C1q-mediated changes in macrophage polarization may modulate T-cell activation under these conditions. Since the C1q-polarized state appears similar to that in tumor associated macrophages (TAM), I am also interested in the potential for reversal/inhibition of these pathways that may be useful in reprogramming TAM to provide more anti-tumor activity.
|Marisa Fonseca Ph.D.
Research Associate Specialist
I am studying the role of complement and inflammation in the pathogenesis of Alzheimer’s Disease (AD). Using a mouse model of AD that is deficient in complement C1q we have demonstrated a detrimental effect of complement activation on the neuropathology of the disease. We have also investigated the effect of an inhibitor of complement C5a-C5a receptor interaction on the neuropathology and behavior of mouse models of AD. At present, we continue studying the role of the complement C5a in new transgenic models of AD using pharmacologic and genetic manipulations of the C5a-C5aR interaction.
Graduate Student (Pathology and Laboratory Medicine)
I am studying the role of distinct activation states of microglia in the progression of Alzheimer’s Disease in mouse models like Tg2576, 3XTg, and Arctic. I am also interested in how complement influences microglial activation states in ageing murine brain and AD mouse models.
3205 McGaugh Hall
University of California, Irvine
Irvine, CA 92697-3900
Tel: (949) 824-3268
Fax: (949) 824-8551