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Northwestern University Feinberg School of Medicine

Faculty Profile: Jay Gottfried, MD, PhD, Professor of Neurology

Jay Gottfried, MD, PhD

Jay Gottfried, MD, PhD, professor of Neurology, studies the human sense of smell. Understanding the neural mechanisms of the olfactory system, which is impaired in many neurodegenerative and neuropsychiatric disorders – often prior to the onset of overt symptoms and signs – may open up new translational research directions for disease modification.

He joined the Feinberg faculty in 2004 and has a secondary appointment in Psychology at the Weinberg College of Arts and Sciences.


What are your research interests?
My research focuses on how the brain perceives and interprets information about different smells, such as the aroma of mint, peanut butter or wet dog. For a variety of reasons, smell is often regarded as the trivial “fifth” sense, but this sentiment is incorrect: Evidence increasingly shows that the human sense of smell is highly refined. Our noses can discriminate odor molecules with subtle differences in molecular structure, distinguish hundreds of thousands of unique smells, transport us back in time to reactivate distant memories and detect certain odors with greater sensitivity than observed in other animals. Additionally, the olfactory system (in humans and other vertebrates) is an increasingly attractive and powerful model for studying neural circuit function under normal and pathological conditions. Because almost nothing is known about the basic neuroscience of the human olfactory system, it’s exciting to explore this “final frontier” of the senses.

What is the ultimate goal of your work?
To leverage the unique features of the olfactory system as a hub around which to span the human condition from molecule to mind, and from health to disease. Broadly, a better understanding of the molecular, cellular, systems and behavioral foundations of olfaction will uncover basic principles of molecular recognition that apply across biological systems. To this end, my research program is thematically organized into three broad components ranging from the microscopic to the macroscopic: cellular, molecular and genetic analysis of human olfactory tissue; in vivo electrophysiological analysis using intracranial electroencephalographic (EEG) recordings in patients with temporal lobe epilepsy; and systems-level analysis using fMRI and olfactory psychophysical techniques in human subjects. 

How did you become interested in this area of research?
My reason for studying human olfaction is three-fold. First, the unique anatomical organization of the olfactory system – including its relative simplicity and its intimate overlap with limbic networks – means that odor stimuli can be effectively used to explore the interface between sensory perception, emotion, memory and behavior. Second, when it comes to animal model systems, the human animal holds a distinct advantage: the gift of speech. The ability of human subjects to verbalize their perceptual experiences and provide behavioral ratings offers a highly tractable method to relate perception directly to brain states. Third, impairments in the sense of smell are commonly reported in Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders, often before the emergence of cognitive and neurological deficits. The implication is that a comprehensive understanding of the human olfactory system may guide future development of translational applications for pre-clinical diagnosis and monitoring, and perhaps even for establishing how these disorders first take hold in the brain.

What collaborations are you engaged in across campus and beyond?
I closely collaborate with Tom Bozza, PhD, in Neurobiology, who has considerable expertise in mouse olfactory genetics and behavior. Together we have devised an interdepartmental research project that exploits next generation sequencing, genetic “trans vivo” approaches, physiological recordings and immunohistochemical techniques to uncover the cellular and anatomical organization of the human olfactory pathway. 

Recent NIH funding from the National Institute on Deafness and Other Communication Disorders (NIDCD) has been essential for getting our study underway. This project includes other critical collaborators (Eileen Bigio, MD, professor of Pathology; Changiz Geula, PhD, research professor in the Cognitive Neurology and Alzheimer’s Disease Center; William Kath, PhD, in Engineering Sciences and Applied Mathematics; Bruce Tan, MD, ’10 GME, assistant professor of Otolaryngology), enabling us to gain a comprehensive characterization of the human olfactory system at multiple levels of analysis. 

I am also working closely with the Comprehensive Epilepsy Center and Surgical Epilepsy Program at Northwestern to investigate odor-evoked patterns of EEG activity directly from the human brain in patients with medically refractory epilepsy. This patient-based research project relies on a large team of investigators in Neurology and Neurological Surgery (Stephan Schuele, MD, MPH, Josh Rosenow, MD, Marc Slutzky, MD, PhD), whose combined expertise in clinical neurology, epilepsy, functional neurosurgery and extraoperative recording and stimulation of the human brain is difficult to rival at other institutions. This research will open a unique window to the physiological underpinnings of the olfactory system with unparalleled temporal and spatial resolution. In bringing a more comprehensive basic research understanding of human olfaction in patients with epilepsy, our project may help optimize the development of olfactory diagnostic tests that will improve prediction of epilepsy surgery outcomes.

Who are your mentors?
Jack Kessler, MD, has been instrumental in guiding my career development, especially when I was an assistant professor trying to navigate the treacherous waters of the tenure track process. Marsel Mesulam, MD, was scientific mentor on my NIH K08 training grant, and has served as an inspiring role model of a consummate physician-scientist who can seamlessly integrate basic neuroscience and behavioral neurology. Aryeh Routtenberg, PhD, whose scientific enthusiasm and spiritual patronage gave me an extra boost of confidence early in my career. His loss has been felt by many Northwestern and beyond. I also draw inspiration and creativity from many non-scientific sources, including vintage comic books, John Updike, Vosne-Romanée and the smell of fresh shiso leaf, all of which filter indirectly into my research.