New Vision Research Focus - Cristian Lasagna-Reeves
March 1st, 2017, was one of the most important days of my scientific career: I officially opened my laboratory at Indiana University School of Medicine. On March 2nd, I flew to Charleston, South Carolina, to participate in the 5th annual CCAD, my first meeting as an independent investigator. I was extremely excited to present my new ideas at this unique meeting intended to support highly innovative projects that push the frontiers of Alzheimer’s disease (AD) research.
At the CCAD, I proposed to develop a strategy to identify proteins that interact with tau in a tau conformation–dependent manner. The overarching hypothesis of my proposal was that specific interactors, not merely tau oligomeric structures, drive disease propagation. The main goal of the project was to clarify the elusive role of protein interactors in tau-seed formation, stabilization, and toxicity in AD and other tauopathies. This approach would ultimately be useful for designing and selecting therapeutic agents that disrupt interactions between tau and related proteins, preventing AD and other related disorders. This project, which has become the center of my research program, was equally inspired by my PhD work focused on the relevance of tau oligomers in the pathogenesis of AD under the mentorship of Dr. Rakez Kayed at UTMB and my postdoctoral work with Dr. Huda Zoghbi at Baylor College, where I studied the role of Ataxin-1 oligomers and their relation to known Ataxin-1 interactors in Spinocerebellar Ataxia Type 1.
At the CCAD, I received insightful recommendations from my colleagues and mentors on how to improve my proposed project. I still remember the suggestions provided by Dr. Peter Davies to better characterize the tau seed. When I returned to my newly formed laboratory, I immediately started working on the suggestions to improve my project. I received tremendous support from my mentor committee at IUSM and Dr. Davies, who provided me with all his tau antibodies. In a certain way, I can say that Dr. Peter Davies was the first official collaborator of the Lasagna-Reeves Laboratory. After years of hard work and with the unconditional support of a spectacular and diverse team of trainees, the project that I originally designed as an application for CCAD has allowed us to obtain multiple lines of funding from governmental and private institutions, such as the National Institute of Health, Department of Defense, and Alzheimer’s Association. Undoubtedly, the project’s focus on identifying proteins that interact with neurotoxic tau seeds has become one of the foundations of my laboratory at Indiana University.
Five years after I presented my proposal at the 5th annual CCAD, I attended the 10th annual CCAD in Hawaii. During this tenth-anniversary meeting that served as an alum reunion, I presented the results from my 2017 application. It was extremely rewarding to have the opportunity to show for the first time the finalized project at the very same meeting where everything started. The data presented in Hawaii was recently published in Nature Neuroscience. Through this study, entitled “Bassoon contributes to tau-seed propagation and neurotoxicity,” I was recently selected to receive the Inge Grundke-Iqbal Award for Alzheimer’s Research at the Alzheimer’s Association International Conference (AAIC). This award was developed to recognize the senior author of the most impactful study on the biology of AD and related conditions published during the two calendar years preceding the AAIC.
Not only was the CCAD the spark that initiated my research program, but it also gave me the opportunity to meet new collaborators with whom I continue to work on this project and others. I wish to express thanks for the opportunity to share my experiences and emphasize how important it is to have an environment of supportive mentors, a diverse team of trainees, and wonderful collaborators to build a successful research program.