User:Erik Lillehoj

I am a cell biologist with interest in elucidating the interactions of microbial pathogens with the respiratory and gastrointestinal mucosal surfaces. Two model systems are currently being explored: (1) expression, structure, and function of MUC1 mucin by respiratory epithelial cells, and (2) intestinal immunity against coccidiosis. In addition, a third project is investigating the role of human endogenous retroviruses (HERVs) in the pathogenesis of acute onset schizophrenia and bipolar disease.

Expression, structure, and function of MUC1 mucin by respiratory epithelial cells. MUC1 belongs to a family of mucin gene products that are divided into secreted and membrane-bound forms. MUC1 is a membrane mucin expressed by mucosal epithelial cells, and overexpressed by most carcinomas. Unlike other membrane mucins, the cytoplasmic region of MUC1 contains multiple sites of serine and tyrosine phosphorylation that are associated with a wide array of cellular processes, including the host response to pathogenic microorganisms, cell growth, cell differentiation, intercellular adhesion, and apoptosis. In collaboration with scientists at the Temple University School of Medicine and the University of Maryland School of Medicine, we are currently investigating the role of MUC1 in (1) Pseudomonas aeruginosa lung infection, (2) intracellular signal transduction, (3) cell-cell adhesion, and (4) lung injury, repair, and restitution. Through these studies, we hope to glean new information relevant to understanding the pathogenesis of cystic fibrosis and lung damage due to inhalation of deleterious toxicants.

Intestinal immunity against coccidiosis. Coccidiosis is an intestinal disease caused by protozoa belonging to the genus Eimeria that impairs the feed utilization and growth of commercial poultry. Anti-coccidial antibiotics are currently used to control outbreaks of infection, but parasite drug resistance and regulatory restrictions on antibiotic use in livestock have spawned an interest in alternative strategies for disease control. In collaboration with scientists at the USDA Agricultural Research Service, our laboratories are identifying immunogenic components of Eimeria with the goal of developing coccidiosis vaccines. We have identified Eimeria profilin, an actin binding protein, as an agonist for chicken TLR21 that holds promise as a coccidiosis vaccine antigen. In addition, we are isolating and characterizing chicken cytokines and chemokines as vaccine adjuvants. Our recent results have identified two important mediators of innate immunity in the chicken intestine, NK-lysin and lipopolysaccharide-induced TNF-α factor (LITAF), that play critical roles in regulating the anti-coccidiosis host response.

HERVs in the pathogenesis of acute onset schizophrenia and bipolar disease. Retroviruses constitute a group of phylogenetically conserved genetic elements  that exist as either independent infectious units alternating between proviral and cell-free states (exogenous retroviruses) or permanently integrated into the germ-line of the host (endogenous retroviruses). Previous studies have provided evidence that endogenous retroviruses, such as HERVs, may contribute to the etiology of some cases of schizophrenia and bipolar disorder. In particular, activation of both class I (e.g. HERV-W, ERV9) and class II (e.g. HERV-K10) endogenous viruses has been identified at significantly greater frequency in schizophrenia patients compared with unaffected controls. Our own studies have revealed that antibodies to exogenous non-human primate retroviruses are present at significantly greater incidence in patients with acute onset schizophrenia vs. controls. Simian retrovirus antibodies in patient's sera are likely the result of cross-reaction between the highly conserved exogenous and endogenous viruses. In collaboration with scientists at the Johns Hopkins University School of Medicine, we are currently attempting to isolate transcriptionally active HERVs that are differentially expressed in patients with schizophrenia or bipolar disorder.