Erik Ranheim: Research Projects

My laboratory is interested in really 2 primary areas, and both of which have to do a certain kind of lymphoma, small lymphocytical lymphoma, also know as chronic lymphocytic leukemia or CLL, but this is applicable to many kinds of b-cell lymphomas. The first area is, what are the signals that are altered or deranged in lymphoma cells that perhaps they’ve taken from their normal life as a b-cell and now have become deranged in the lymphoma cell that allows the lymphoma cells either to grow in an uncontrolled way or to stay alive when they should be dying. The pathway we are particularly interested in has rather a funny name it is Wendt-Frizzled pathway, and it involves an important protein called beta-catenin. This pathway is normally involved in stem cells and different organs, be it the bone marrow, the skin, the intestine, and it allows the stem cells to maintain themselves throughout the life of the person or the animal, and this pathway we know is activated in an inappropriate way in a number of cancers, most notably colon cancer but also it is coming to light this is true in b-cell lymphomas as well. We have been working with a very nice mouse model of CLL, and we can show that this pathway is up regulated as the cells progress from normal to pre-leukemia or lymphoma to frank lymphoma cells, and it seems to have something to do with their biology. We know that this pathway also is activated in the human version of this disease and may be involved in other b-cell Lymphomas as well, which we currently are examining with patients cells. The purpose of this work really is to identify specifically which proteins of the many that are involved in this pathway might be abnormally increased and whether we can find specific therapeutic drugs that could target those pathways without disrupting this very important pathway in the rest of the patient’s body. The other area that we are really interested in is and this is particularly relevant to lymphoma since it is a cancer of immune cells, is can we redirect the immune system to kill the patients lymphoma cells. My work as a graduate student involved how different proteins are regulated on the surface of tumor b-cells to make them more attractive to immune, killing by t-cells or other immune cells. That work has resulted in an on-going clinical trial, that’s proceeding right now at the University of CA-San Diego, and other centers. In our own lab right now we are asking whether some of the cells in what we call the innate immune system, sort of the crude immune system that gobbles up bacteria and protects us sort of a frontline defense, might be involved in anti-tumor immunity, in fact we can show that if we activate that system through drugs and anti-bodies that are already in clinical trials and in people, that we can in fact activate those cells to kill cancer cells specifically, and we are trying to work out how those cells know their cancer cells vs. normal, and whether this could be translated from what looks very effective in mice to humans first in a sub-cultured dish and then later in clinical trials. We’ve developed a really excellent website in collaboration with our partners and that’s at www.forwardlymphoma.org.