Robert G. Thorne, PhD

Dr. Robert G. Thorne has served as an Affiliate Faculty member in the Department of Pharmaceutics at the University of Minnesota since February 2019. He is currently a full-time Denali Fellow with Denali Therapeutics (September 2018 to present). He previously worked for over 10 years on the faculty at New York University School of Medicine and the University of Wisconsin-Madison, where he was most recently an Assistant Professor in Pharmaceutical Sciences, a faculty member of the Institute for Clinical and Translational Research, and a Trainer in the Neuroscience, Cellular and Molecular Pathology, and Clinical Neuroengineering Training Programs. Dr. Thorne has a BS in Chemical Engineering from the University of Washington and a PhD in Pharmaceutics (collateral field in Neuroscience) from the University of Minnesota.

The focus of Dr. Thorne’s research has been to develop a mechanistic understanding of drug delivery to the brain. One of his main interests has been the study of diffusive and convective transport within the extracellular and perivascular spaces of the central nervous system – his group’s work has aimed to leverage knowledge of physiology, CNS structure, and the blood-brain and blood-cerebrospinal fluid barriers with a variety of methods in order to identify how best to deliver antibodies, oligonucleotides, and gene therapy vectors to the brain following intraparenchymal, intrathecal, or intranasal administration. Dr. Thorne’s work with Denali Therapeutics is now focused on a variety of engineering approaches for the treatment of neurodegenerative diseases, including novel blood-brain barrier transport vehicles allowing disease-modifying antibody or enzyme delivery and adeno-associated virus-based vectors for CNS gene therapy. The ultimate aim of this new work is to enable new first-in-class treatments informed by genetics, biology, and biomarker-based approaches.

Dr. Thorne’s scientific achievements include pioneering measurements of extracellular diffusion in the brain to determine the width of brain extracellular spaces and CNS binding interactions in vivo, elucidation of physiologic determinants governing perivascular space access and transport from the CSF, and the identification of transport pathways allowing large molecule entry into the brain from the nasal passages. Dr. Thorne has taught systems neuroscience, neuroanatomy, drug delivery, pharmacokinetics, research ethics, and science communication to graduate, professional and undergraduate students at a variety of academic institutions, including the University of Wisconsin-Madison, New York University School of Medicine, the University of Washington, and Stanford. Robert previously chaired the 2016 ‘Barriers of the CNS’ Gordon Research Conference and co-edited the 2014 book ‘Drug Delivery to the Brain: Physiological Concepts, Methodologies and Approaches’ with Margareta Hammarlund-Udenaes and Elizabeth de Lange. Working with Reina Bendayan and Per-Ola Freskgard, Dr. Thorne has been responsible for establishing and co-chairing a new AAPS-IBBS Workshop on ‘Novel Approaches Targeting Brain Barriers for Effective Delivery of Therapeutics’, to be held for the first time in 2019. He is currently a member of the editorial boards of both Fluids and Barriers of the CNS and the Journal of Cerebral Blood Flow and Metabolism and was elected in 2017 to serve as the Vice President (President-elect) of the International Brain Barriers Society, a global organization responsible for leadership and directing worldwide initiatives related to the CNS barriers and drug delivery fields.

• Vice President (President-Elect), International Brain Barriers Society (IBBS)
• American Association of Pharmaceutical Scientists
• Society for Neuroscience

• Neuroscience
• Drug delivery to the brain

• Imaging
• Electron microscopy
• Radiolabel- and fluorescence-based methods
• In vivo preparations
• Cranial windows

• Systems neuroscienceeuroanatomy
• Drug delivery
• Pharmacokinetics
• Research ethics
• Science communication

• In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space. Thorne & Nicholson, (2006) PNAS 103:5567-5572.
• In vivo diffusion of lactoferrin in brain extracellular space is regulated by interactions with heparan sulfate. Thorne et al., (2008) PNAS 105:8416-8421.
• Diffusion of Macromolecules in the Brain: Implications for Drug Delivery. Wolak & Thorne, (2013) Molecular Pharmaceutics 10:1492-504.
• Probing the extracellular diffusion of antibodies in brain using in vivo integrative optical imaging and ex vivo fluorescence imaging. Wolak et al., (2015) Journal of Controlled Release 197:78-86.
• Intrathecal antibody distribution in the rat brain: surface diffusion, perivascular transport and osmotic enhancement of delivery. Pizzo et al., (2018) Journal of Physiology 596:445-475.
• Molecular characterization of perivascular drainage pathways in the murine brain. Hannocks et al., (2018) Journal of Cerebral Blood Flow and Metabolism 38:669-686.
• The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system? Abbott et al., (2018) Acta Neuropathologica 135:387-407.
• Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Thorne et al., (2004) Neuroscience 127:481-96.
• Delivery of interferon-β to the monkey nervous system following intranasal administration. Thorne et al., (2008) Neuroscience 152:785-97.
• Intranasal delivery of biologics to the central nervous system. Lochhead & Thorne, (2012) Advanced Drug Delivery Reviews 64:614-628.
• Rapid Transport within Cerebral Perivascular Spaces Underlies Widespread Tracer Distribution in the Brain after Intranasal Administration. Lochhead et al., (2015) Journal of Cerebral Blood Flow & Metabolism 35:371-381.
• Delivery of immunoglobulin G antibodies to the rat nervous system following intranasal administration: Distribution, dose-response, and mechanisms of delivery. Kumar et al., (2018) Journal of Controlled Release 286:467-484.

WN@TL - Research Ethics, Higher Purposes, and Challenges Facing Science, Robert Thorne - September 19, 2018