 Hi, my name is Marvin Karimi. I am an assistant professor at the Department of Microbiology and Immunology, the Upstate Medical University at Syracuse, New York. Research in my lab is focused on the cell transduction pathway. That includes T cells, V cells, and NK cells, ILCs. More specifically, we are interested in modulating signal transduction pathway downstream, and the lead out of this we presented as a disease model could be graph versus host disease, graph versus tumor, and also our immune models, and you can apply to many, many different things. So we work as a upside down parameter. We look at the phenotype on the animal models, and then step down, we look at the cell function, and we're looking at the transcription factors, and we're looking at specific genes, and we can target to specific genes, and then see these genes are responsible for this phenotype. So we would like to think that the paper that we submitted for uncle Target and that we are very happy with them, and we are surprised by many aspects of them, because when we modulate the chemokine receptors and the migration pathway, and we want to look at how this T cells will migrate to the inflamed tissues. For example, in a normal circumstances, this T cells might not migrate from one area to another if you modulate some of the chemokine receptors. So in this manuscript, we looked at three different genes. One was CRK1 as a part of CT10 regulatory kinase pathway, and also we look at CRK1 knockout, CRK double knockout, which means that CRK and the ligand for CRK is also knocked out, and we also specifically look for ligand. What happened if you knock out the ligand? So we saw in the in vitro and in vivo, we saw a little bit difference in the migration, but that did not give us full satisfaction because we wanted to test this in this disease models. So in this manuscript, what we did is we took a ball, see and irradiate, give them full body irradiations, and then did a major mismatch transplantation from B6 mice, which they're genetically they are different. What happened is that the wild type cells were able to migrate from secondary lymphoid organs to liver and small intestine and skin, which are the GVHD target organs, but the mice with the CRK double knockout and CRK ligand knockout were unable to migrate to GVHD target organ. What happened is when we irradiate mice, malci mice, and those mice produce cytokines and they're inflamed tissue. So the donor T cells will come and they will migrate to those inflamed tissue and they generate severe damage. And trafficking is now, donor T cells trafficking is now one of the hallmark of GVHD. So we were so surprised that we did a hollow mismatch allogenic T cells, they were unable to travel to the GVHD target organ. And we can only see up to we quantify those and quantification data suggested only 10% of the cells will be able to migrate versus in the wild type they were like 90%, 80%. So that was significant for us. So when we checked with this mice we'll develop graph versus host disease. Since the migration was defective significantly the host mice did not develop graph versus host disease. And then we checked with a clear tumor. So the next experiment we did is we give them, we irradiate them, we establish the hollow mismatch transplant model and we also give them B cell leukemia. And we were so surprised that this donor T cells either from the wild type or from the knockout they were both able to clear the tumor in the periphery but they did not cause GVHD. So we wanted to see what will be the limitation of this model. So the limitation of this model is to check is when we establish GVHD but instead of giving them IV tumor we give them IP tumor under the skin and see if the donor cells can migrate under the skin and can clear the tumor. So in a wild type models the donor T cells were able to go to second order them for organs, go to liver, small intestine, also to tumor under the skin and they were able to clear the, clear it. But when we look at the crack knockout and crack L knockout or the double knockout that they were unable to go to the tumor where you put it under the skin. So in the hematological malignancies and since everything takes place in the periphery so it will be a good model to use but for the solid tumor this might not be a useful tool. So we looked at both whether it can be applied to hematological malignancy or whether it can be applied to solid tumors. So in our lab we wanted to research, to look at all aspect of the models. We wanted to look at the limitation of it. How much we can push this to make it a better model and this data show that in hematological malignancy donor T cells have a defect in the migrations and they cannot go to GVHD target organ but they can clear the tumor in the periphery and they do not cause GVHD. So as far as graphosis host disease it will be a great models. Our collaborators and other people are working to make this as a small molecule and they can inhibit this and hopefully we can start soon in the clinical model to move it from the bench side to the bed. And we will also check this and see what specific pathway is disrupted in the mice and what specific other pathway is disrupted in the human as well. So at this point we are satisfied with our and we will mice model but we wanted to test this also in the human models and see if there is any similar effect that we see in the migration. And if that's a true hopefully the small molecule would be an ideal candidate for hematological malignancy and also for graphosis host disease because graphosis host disease is one of the disease but there are many disease involved that cause outer immunity, primarily by T cells and if you can inhibit T cells migrations to inflame tissue that might be used for other diseases like arthritis, other outer immune models. And so really excited about this and we are hoping that we can move this forward as far as we can get. So other projects in my lab is we studied ITK signaling. We have recently developed a small inhibitors and when we looked at an mouse models that if you inhibit ITK signaling and upregulate some of the molecules that are responsible for the cytotoxic function but it inhibit cytokine productions and chemokine receptor upregulation. So in the lab recently we are moving this to how that will affect patient samples that patients who develop GVHD or have outer immune disease where their T cells are inflamed. How can we find out how which one will be a better models and second model that we are using this ITK models for is there are a lot of drugs available to inhibit the BTK but BTK drugs are not specific. So we made it a very specific inhibitors and we can use both the ITK and BTK inhibitors simultaneously. And one hand you can inhibit tumor growth and another one you can proliferate or expand T cells that will produce less cytokine and will be less exhausted and can be more effective. So we are really excited about this work since we published our paper in the uncle target we have two other papers coming out one in frontier immunology and science immunology and we hope we can grow it and make it a much better successful models. With this I would like to thank again the people in uncle target and anybody who wants to collaborate with us wants to look at this work please contact us. Please let us know that your opinion whether it's negative positive and we as scientists we are open to any criticism any positive impacts that we can improve the life of people. With that thank you very much.