Helen Kaipe

Infection with Rift Valley fever virus (RVFV) is associated with miscarriage in humans and cause mass abortions in livestock. The candidate RVFV vaccine strains MP12 and clone 13, both with a non-functional virulence RVFV NSs-gene, still have teratogenic effects. Virus infection pathways in the fetus and host protective mechanisms, e.g. by the innate immune system, are poorly understood. Thus, there is a major gap in the field in understanding how viruses in general, and RVFV, are transmitted from mother to fetus. We will determine RVFV tropism and the inflammatory response in human placental cells for wild-type and NSs deleted RVFV. Both in early-stage and late-stage human placental cells, we will study the infection process, antiviral and cytokine response, as well as gene expression by single cell RNA sequencing. In addition, we will use our assays to study other vertically transmitted mosquito-borne viruses. RVFV infection during pregnancy will also be characterized in a mouse model. In preliminary studies, we have established 2D and 3D-human stem cell cultures, and we show that trophoblast cell lines and human placental stem cells are infected by RVFV ,and cause a pro-inflammatory cytokine response. Our research will provide novel information on pathogenesis of vertically transmitted RVFV and add to the general understanding of fetal infections for other viruses. RVFV is a prioritized disease listed by WHO for urgent research and development of counteraction.

Pancreatic cancer is one of the most aggressive types of cancer. The high mortality is partly due to the fact that the tumor is often resistant to chemotherapy, which leads to metastasis. Around the tumor, a thick layer of connective tissue cells, fibroblasts, is formed, which can prevent chemotherapy and own immune cells from reaching out to kill the tumor cells. Researchers have studied how fibroblasts interact with tumor cells, which have shown that they can support tumor cell growth. Less is known about how fibroblasts in tumors affect immune cells, such as T cells and mucosal associated invariate T (MAIT) cells, and how their activity is regulated. The body's own immune system has the potential to kill cancer cells, but the environment in the tumor can inhibit the function of the immune cells. We study how the functions of T cells and MAIT cells are affected by fibroblasts in pancreatic tumors. We investigate the expression of the receptors on T cells that so-called checkpoint inhibitors bind to, and how fibroblasts affect T cells and the ability of MAIT cells to migrate. Vitamin D and A metabolites can suppress the activation of cancer fibroblasts, which could inhibit tumor growth, and we study how these substances regulate immune cells. We also investigate how MAIT cells are reconstituted after an allogeneic stem cell transplant. Immunotherapy treatment has proven effective in some types of cancer, but so far, few advances have been made in pancreatic cancer. Reprogramming of fibroblasts' activation with vitamin D metabolites has proven effective in animal models, but is still little known about how they interact with human immune cells. An increased understanding of how fibroblasts in the tumor regulate immune cells could lead to new immunotherapies being developed in the long term.

Allogeneic stem cell transplantation is an established treatment for leukemia, but despite major advances, many patients suffer from severe complications. One of the most common causes of these problems is that the patient's tissues are perceived as foreign to the new immune system, which can lead to the body's own cells being attacked, a so-called graft-versus-host (GvH) reaction. This condition can be life-threatening. We want to cure GvH and other severe complications after stem cell transplantation, and study whether placental and fetal cells from a fully-fledged pregnancy can inhibit this type of inflammation. In the fetus, there are immune-suppressing cells, decidual stromal cells, which prevent the mother's immune system from repelling the child. Fetal membranes have been used for burns, indicating that they also have a healing ability. In the laboratory, we investigate how decidual stromal cells affect the immune system's cells and try to identify the properties that the cells use to suppress inflammation, and how we can best utilize this phenomenon. We treat stem cell transplanted patients who are affected by GvH or other lesions with decidual stromal cells, and map the effects of cell therapy on the immune system and injury counts. We have so far treated about 50 patients with decidula stromal cells, most of them for GvH, but also for bleeding and lung damage. Many patients have responded well to the treatment and have been wholly or partially cured from these conditions. We hope that our research will lead to a better understanding of how the cells' capacity can be optimized for treatment in transplant-related complications and inflammation. By extension, it would lead to improved survival and quality of life for patients with leukemia, but also for patients with other types of cancer who suffered from treatment-related problems, such as radiation injuries.

Allogeneic stem cell transplantation is an established treatment for leukemia, but despite major advances, many patients suffer from severe complications. One of the most common causes of these problems is that the patient's tissues are perceived as foreign to the new immune system, which can lead to the body's own cells being attacked, a so-called graft-versus-host (GvH) reaction. This condition can be life-threatening. We want to cure GvH and other severe complications after stem cell transplantation, and study whether placental and fetal cells from a fully-fledged pregnancy can inhibit this type of inflammation. In the fetus, there are immune-suppressing cells, decidual stromal cells, which prevent the mother's immune system from repelling the child. Fetal membranes have been used for burns, indicating that they also have a healing ability. In the laboratory, we investigate how decidual stromal cells affect the immune system's cells and try to identify the properties that the cells use to suppress inflammation, and how we can best utilize this phenomenon. We treat stem cell transplanted patients who are affected by GvH or other lesions with decidual stromal cells, and map the effects of cell therapy on the immune system and injury counts. We have so far treated about 50 patients with decidula stromal cells, most of them for GvH, but also for bleeding and lung damage. Many patients have responded well to the treatment and have been wholly or partially cured from these conditions. We hope that our research will lead to a better understanding of how the cells' capacity can be optimized for treatment in transplant-related complications and inflammation. By extension, it would lead to improved survival and quality of life for patients with leukemia, but also for patients with other types of cancer who suffered from treatment-related problems, such as radiation injuries.

Allogeneic stem cell transplantation is an established treatment for leukemia, but despite major advances, many patients suffer from severe complications. One of the most common causes of these problems is that the patient's tissues are perceived as foreign to the new immune system, which can lead to the body's own cells being attacked, a so-called graft-versus-host (GvH) reaction. This condition can be life-threatening. We want to cure GvH and other severe complications after stem cell transplantation, and study whether placental and fetal cells from a fully-fledged pregnancy can inhibit this type of inflammation. In the fetus, there are immune-suppressing cells, decidual stromal cells, which prevent the mother's immune system from repelling the child. Fetal membranes have been used for burns, indicating that they also have a healing ability. In the laboratory, we investigate how decidual stromal cells affect the immune system's cells and try to identify the properties that the cells use to suppress inflammation, and how we can best utilize this phenomenon. We treat stem cell transplanted patients who are affected by GvH or other lesions with decidual stromal cells, and map the effects of cell therapy on the immune system and injury counts. We have so far treated about 50 patients with decidula stromal cells, most of them for GvH, but also for bleeding and lung damage. Many patients have responded well to the treatment and have been wholly or partially cured from these conditions. We hope that our research will lead to a better understanding of how the cells' capacity can be optimized for treatment in transplant-related complications and inflammation. By extension, it would lead to improved survival and quality of life for patients with leukemia, but also for patients with other types of cancer who suffered from treatment-related problems, such as radiation injuries.