We analyzed student persistence across our introductory science and math series to determine where students either fail or pass but then decide to leave STEM, while attending to differences in outcomes for URM and non-URM students. To combat this attrition, we will develop transformed introductory courses in biology, chemistry, and physics that have online lectures, freeing class time for active learning and inquiry-based experiences. Evidence is mounting that active learning and inquiry-based experiences increase student performance and persistence in the sciences. Our goal is to mount course offerings that will reach 25% of the students seeking degrees in biological or environmental sciences by the end of the award. To offer these courses, we will renovate and equip existing space to create a 125-seat active-learning classroom. We will train the STEM educational community in effective teaching methods. We will launch an undergraduate Learning Assistants Program and train graduate students in active- and inquiry-learning via workshops offered by the Institute for Science and Engineering Educators (ISEE). We will hire 3 postdoctoral fellows who will couple specific disciplinary backgrounds with in-depth knowledge about science education and evidence-based approaches to educational improvement. These fellows will work with faculty and ISEE-trained graduate students to catalyze course transformations and together they will build a community of practice around curricular innovation. ISEE will be the administrative center of our HHMI program, and ultimately we hope to transform it into the campus center for programs and teaching approaches that increase student learning and persistence in STEM fields, especially for URM students. Finally, we will evaluate the effectiveness of our new courses at achieving desired learning outcomes, the impact of the HHMI program on our two primary goals, the factors among our program that do (or do not) affect student learning and persistence, and if we are effectively changing the way that we teach. ISEE will oversee program assessment and evaluation.