Education and Advanced Professional Training
BS, Biology: University of Pennsylvania
MD and PhD (Genetics): University of Pennsylvania, NIH-funded Medical Scientist Training Program (MSTP)
Medical Internship: Morristown Memorial Hospital, Morristown, NJ
Neurology Residency: Harvard-Longwood Training Program, Boston, MA
Research Postdoctoral Fellowship (developmental neurogenetics): Brandeis University, Waltham, MA, NIH-funded Clinical Investigator Development Award
Interests:
Drug discovery
Genetics
Molecular medicine
Neuroscience
Precision medicine
Selected Publications
Restifo LL (2022). Unraveling the Gordian knot: genetics and the troubled road to effective therapeutics for Alzheimer’s disease. GENETICS 220(1):iyab185.
Andrew DR, Moe ME, Chen D, Tello JA, Doser RL, Conner WE, Ghuman JK, and LL Restifo (2021). Spontaneous motor-behavior abnormalities in two Drosophila models of neurodevelopmental disorders. J Neurogenetics 35:1-22.
Kraft R, A Kahn, JL Medina-Franco, M Orlowski, C Baynes, F Lopez-Vallejo, K Barnard, GM Maggiora, and LL Restifo (2013). A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions. Disease Models & Mechanisms 6:217-235.
Restifo LL and GR Phelan (2011). The cultural divide: exploring communication barriers between scientists and clinicians. Disease Models & Mechanisms 4:423-426.
Restifo LL (2005). Mental retardation genes in Drosophila: new approaches to understanding and treating developmental brain disorders. Ment Retard Dev Disabilities Res Rev 11:286-294.
Biography:
Linda L. Restifo, MD, PhD, has a lifelong passion to understand the genetics of brain disorders. Currently Professor of Neurology, Neuroscience, and Cellular & Molecular Medicine at the University of Arizona (UAz), she launched her research program with an initial basic-science emphasis and gradually moved toward translational medicine. Her team demonstrated the extraordinary similarity of genes essential for normal brain development in humans and fruit flies, and the utility of primary cultured mutant neurons as a cellular bioassay for drug discovery. In collaboration with medical geneticists, she participated in gene identification for early-onset epilepsy and other severe disorders using whole-exome sequence data. Other innovative collaborations led to software development for 2D neuron-image analysis and a microfluidic system for dissociation of neural tissues. Her research funding has come from NINDS, NICHD, John Merck Fund, Muscular Dystrophy Association, Autism Speaks, Jerome Lejeune Foundation, and TechLaunch Arizona. In 2019-20, Dr. Restifo was a Visiting Scientist at Tucson-based Critical Path Institute’s Consortium for Parkinson’s Disease, to share her genetics expertise and to learn about clinical trial design and analysis. As an educator, Dr. Restifo starts with the principle that “the molecule is not the disease,” emphasizing the importance of clinical diagnosis and disease classification alongside studies of cellular and molecular pathogenesis. She has supervised the research projects of graduate students in Neuroscience, Insect Science, and Genetic Counseling, as well as many undergraduates.
Innovative Teaching
CMM/NRSC/GENE/PSIO/MCB/BIOC 695D (3 units)
Advanced Analysis of Human Genetic Disease: from chief complaint to drug discovery
This course teaches an approach to thinking about any disease, using these themes:
(i) different degrees of genetic causation;
(ii) the clues from differential diagnosis, natural history, and histopathology;
(iii) evolving insights about disease classification.
Together, these strategies promote the critical analysis of research on molecular pathogenesis and the development of safe and effective therapeutics.
Each year, we focus on four exemplar diseases, moving from simple Mendelian genetic with well-understood pathophysiology to more complex and mysterious disorders with substantial environmental influence. Students in the class participate in the selection of disease topics for that semester.