Alexandre Chigaev, PhD
Research Associate Professor
Center for Molecular Discovery
Cancer Therapeutics: Technology, Discovery and Targeted Delivery
The goal of the proposed research is to validate and prioritize repurposed drugs exhibiting activity as Inhibitors of Cyclic AMP Efflux (ICE) to be novel therapeutic agents for AML in a murine xenograft model. The current proposal is based on a novel hypothesis that in certain leukemias the removal of the second messenger (cAMP) from a leukemic cell represents a secondary oncogenic event that protects cancer cells from oncogenic stress and apoptosis. We proposed that this mechanism can be targeted using small molecules. To target this process we developed and validated a novel assay and screened two libraries consisting of FDA approved drugs and bioactives totaling ~2100 compounds . We identified several drugs that triggered appropriate signaling pathways and elicited activities predicted by our hypothesis (US patent #9,314,460  and ). We also collected a set of data using a murine xenograft leukemia model and primary bone marrow patient samples that supports our hypothesis. Thus, the current proposal is unique and innovative since it is based on a new hypothesis that identifies a novel target in hematological space. If successful, this project will lead to the development of a novel class of anticancer therapeutics.
I have vast experience in leukocyte biology, immunology and signaling (18 years), membrane transport and biophysics (10 years), authored > 50 publications (~ 42 of those in English), have several US patents, and mentored 8 graduate trainees at the level of students and postdocs. I started my scientific career at the Department of Biophysics at Moscow State University, the top university of Russia and continued at the famous Weizmann Institute of Science in Israel. There was an interruption of my academic career track due to my immigration to the USA. It took a decade to become a US citizen; part of that time (2003-2006), I was employed as a Senior Research Scientist. Presently, in my capacity as Associate Professor in the UNM Pathology Department, the UNM Comprehensive Cancer Center and the Center for Molecular Discovery (UNMCMD), in close collaboration with the current UNMCMD Director and my long-term colleague Dr. Sklar, I lead and participate in several projects that are focused on leukocyte biology and hematological malignancies. Being trained in the highest-ranking institutions around the world, and having a broad background in biochemistry, biophysics, and immunology, I have the expertise and the motivation necessary to lead the proposed work. I am very enthusiastic about the current application, which builds on my prior expertise and my record of successful projects in the field of leukocyte physiology.