Joshua Jacobs - US grants

The University of Chicago (UChicago) Institute for Translational Medicine (ITM) was created in 2007 to assemble, integrate, and create the intellectual, administrative, and physical resources required to catalyze research and research training in Clinical and Translational Science. We have trained university scientists and health care providers to work together with stakeholders in all concerned communities to determine the molecular, genetic, pathophysiologic, and social determinants of disease; to develop and test interventions directed toward those mechanisms; and to achieve these goals in a way that is rigorous, efficient, ethical, respectful of, and responsive to our community?s needs and values. In its first 9 years, the ITM has capitalized on outstanding intellectual and physical resources throughout UChicago and at ITM affiliate institutions ? Rush University Medical Center (Rush), NorthShore University HealthSystem (NorthShore), and Illinois Institute of Technology (IIT) ? to build the infrastructure for a transformative, energized, and self-improving home for clinical and translational research. Now, we pursue a bold guiding vision for ?ITM 2.0? ? that health outcomes will be improved throughout Chicagoland by mitigating disease risk, morbidity and mortality through collaborative, multidisciplinary team science. We will work toward this vision by assembling scientific, institutional, and community stakeholders, and together focusing on the highest value propositions to improve mutually defined health concerns, leveraging synergies that accelerate progress across the translational spectrum. Our core conviction is that participating in health research is a matter of shared self-interest and social justice, a ?new normal? prevailing viewpoint toward which we will strive together over the next 20 years. ITM 2.0 will work hand-in-hand with health stakeholders throughout Chicagoland and throughout the nation, conceptualizing, developing and deploying innovative processes and practices to achieve our common goal. Preparing for this ambitious challenge, we broadened the scope of institutional and community stakeholders. Rush now joins UChicago as an ITM lead institution, and Loyola University Medical Center and Advocate Health Care join as ITM affiliates. We partner with esteemed institutions ? the Chicago Community Trust, the Illinois Biotechnology Industry Organization, and the Chicago and Illinois Departments of Public Health ? and inclusively leverage strong collaborations with the other two Chicago CTSAs, with the Chicago-wide PCORnet CDRN CAPriCORN, and with the recently awarded Illinois Precision Medicine Consortium. In ITM 2.0, we will together develop innovative and sometimes disruptive approaches to advance the science and practice of clinical and translational research by rigorously determining which approaches work and then disseminating the results of both successes and failures. We expect that this approach will improve the conduct of and training for clinical and translational research for the benefit of Chicago, the CTSA Consortium, and the nation.

Project Summary Spatial navigation and memory are critical aspects of life for animals and humans. To identify how the brain supports these processes, our experiments examine how specific types of spatial and non-spatial knowledge are represented by the activity of single neurons and neuronal populations in the human medial temporal lobe. Previously, we and others showed that spatial knowledge is supported by networks of ?place? and ?grid cells,? each of which represent a person?s location in an environment by activating at individual locations and groups of locations, respectively. Though the human medial temporal lobe is also believed to be critical for memory, imagination, prediction, and planning, whether and how spatial cell types also support these complex forms of cognition is unknown. Here we will test the hypothesis that place- and grid-like firing patterns, as well as other cell types in the hippocampal system, support the neuronal representation of more complex spatial and non-spatial information beyond the neural coding of location for these diverse, inter-related aspects of human cognition. We examine this issue by conducting direct recordings of the human hippocampal and entorhinal network from neurosurgical epilepsy patients performing computerized virtual-reality tasks. In Aim 1 of our project we will examine whether medial temporal lobe neuronal firing patterns, including place- and grid-like firing, go beyond encoding spatial information to represent a ?cognitive map? of each environment that represents which sets of locations and paths are connected and how they are rewarded. In Aim 2, we examine the role of place and grid cells in representing multiscale information, including large-scale geography. In Aim 3, we probe whether the activity of human place cells represent imagined and viewed locations in a manner similar to the activity present during active navigation. Finally, in Aim 4 we measure human ?time cells? and test whether the activity of time cells in episodic memory are similar to the properties of place and grid cells during navigation. Our proposed studies are likely to create fundamental insights into the core neuronal responses and computational mechanisms that underlie both spatial and non-spatial memory and cognition.