Dr. Mor's Lab
Immunology of PregnancyResearch Summary
The objectives of the laboratory are to understand the communication between the maternal and fetal components of pregnancy and how pathogens contribute to the disruption of this crosstalk leading to preterm labor. Research in our laboratory includes the following areas:Trophoblast Biology. Trophoblast response and regulation to inflammatory responses.
Our previous work has demonstrated the expression of Toll-like receptors on trophoblast cells and ligation of these receptors produce a cytokine/chemokine network in response to either endogenous or exogenous stimuli at the maternal fetal interface. Therefore trophoblast cells serve as sensors for the recognition and response to the environment throughout implantation and gestation, suggesting that the trophoblast itself might act as an innate immune cell by recognizing microbial products. We currently are investigating the tight regulation of TLR function and signaling in trophoblast and how this contributes to their immunological role.
Immune cells regulation and function at the maternal/fetal interface. Maternal/fetal macrophages role in tolerance to bacterial infections, and response to persistent viral infections.
In recognizing and responding to the uterine microenvironment trophoblast may recruit immune cells, such as macrophages, and regulate their distribution and function. We are currently investigating how trophoblast cells induce differentiation of macrophages into a pregnancy-supporting phenotype and how this phenotype is associated with a tolerant response to bacteria to prevent an inflammatory response.
Infection in Pregnancy. Mechanisms of immune, placental, and decidual responses to pathogens leading to preterm labor. In vivo model of preterm in polymicrobial diseaseDr. Mor’s laboratory is actively investigating how viral infection may disrupt the fetal-maternal interaction by modifying the function of TLRs Our studies have shown that a viral infection of the placenta and decidua will lead to a disruption in immune cell distribution and function and consequently preterm labor. To further understand the role of infection in pregnancy we have developed an in vivo model looking at the mechanisms in polymicrobial disease at the maternal/fetal interface and preterm labor.
Ovarian Cancer ProgramResearch Summary
The objectives of the laboratory are to understand the role of ovarian cancer stem cells in the process of tumor formation, recurrence and chemoresitance. Research in our laboratory includes the following areas
Origin of Ovarian Cancer. Identifying the signals originating from the ovaries that have the capacity to attract malignant tumor initiating cells
We are currently investigating the origin of ovarian cancer. Studies in the laboratory have shown that tumor initiating cells are attracted to the ovaries following ovulation and once the malignant cells reach the ovaries, the ovaries are able to provide a “fertile soil” that can support tumor initiation. These findings have open the opportunity for the development of new venues to prevent ovarian cancer by inhibiting the factors associated with the recruitment of transformed cells towards the ovaries. Furthermore it has provided the identification of new makers for early detection.
We have developed a unique in vivo model for Stage I and II ovarian cancer.
Recurrence and chemoresistance. Identifying cancer stem cells as the source of chemoresistance and recurrence.
Another pressing question in the field of ovarian cancer research is why recurrent ovarian cancer does not respond to the therapy that was initially successful in inducing remission in the primary disease. Previous work in our laboratory has identified and characterized two types of ovarian cancer cells comprising a heterogeneous tumor, and these two cell types respond differently to chemotherapies. We have identified a subgroup of cancer stem cells that promote the development of chemoresistance and metastasis during the process of ovarian cancer recurrence. On-going research is directed to develop therapeutic modalities aiming to reverse this resistance.
In vivo model of recurrence. We have developed an intra-peritoneal (i.p.) recurrent ovarian cancer animal model that mimics the clinical profile observed in patients with EOC.This animal model has allowed the identification of key factors involved in the promotion of metastasis and chemoresistance. Using this model we have identified specific chemotherapy-induced tumor modifications that contribute to the development of metastasis and chemoresistance. The Mor Lab has established an active drug screening system for the identification of novel compounds that can prevent recurrence and target chemoresistant recurrent disease. In addition, our model has allowed identification of markers for predicting chemoresponse and therefore can aid in therapy selection or Personalized Medicine, which is a major objective of Dr. Mor’s laboratory.
This animal model is currently being used to develop a novel drug delivery system that specifically target tumor blood vessels and not normal blood vessels
Tumor Immune Interactions. We have established the differential interaction of ovarian cancer cells with immune cells.
Our studies have shown that ovarian cancer stem cells modulate macrophage differentiation and function through the expression of unique modulatory cytokines while ovarian cancer cells promote Treg recruitment and function. These findings reveled a complex tumor immune interaction based on cancer cell type specific signals.