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David John Irwin, MD

Assistant Professor of Neurology
Member , Penn Institute for Translational Medicine and Therapeutics
Associate Fellow, Penn Institute on Aging
Advisory Board Member, Penn Institute on Aging Internal Advisory Board
Director, Penn Frontotemporal Degeneration Center
co-PI, Penn Cure PSP Center of Excellence for Progressive Supranuclear Palsy
Department: Neurology

Contact information
Hospital of the University of Pennsylvania
Department of Neurology
3400 Spruce Street, 3 W Gates
Philadelphia, Pa 19104
Graduate Group Affiliations
Drew University, 2001.
Drexel University College of Medicine, 2006.
University of Pennsylvania Perelman School of Medicine, 2015.
Post-Graduate Training
Intern in Medicine, Hahnemann Hospital, Philadelphia, 2006-2007.
Resident in Neurology, Hahnemann Hospital, Philadelphia, 2007-2010.
Chief Resident in Neurology, Hahnemann Hospital, Philadelphia, 2009-2010.
Fellowship in Cognitive Neurology/Neurodegenerative Disease, Hospital of the University of Pennsylvania, Philadelphia, 2010-2014.
American Board of Psychiatry and Neurology, 2010.
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Description of Clinical Expertise

My clinical focus is on cognitive neurology and neurodegenerative disease including frontotemporal dementia, primary progressive aphasia, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy. I have a particular interest in young-onset dementia and the behavioral variant of frontotemporal dementia.

Description of Other Expertise

Research Interests: Neuropathology and Biomarkers of Neurodegenerative Disease.

Keywords: Neuropathology, Digital Pathology, Biomarkers, Frontotemporal degeneration, Primary progressive aphasia, Amyotrophic lateral sclerosis, Lewy body disorders, Parkinson's disease, Alzheimer's disease, tau, amyloid-beta, alpha-synuclein, TDP-43.

Research Details: In the Penn Digital Neuropathology Lab (DNPL), we use a multidisciplinary approach merging techniques in "wet-lab" based histopathology of human brain tissue with "dry-lab" based image analysis and bioinformatics tools with the overarching goal of improving our understanding of brain-behavior relationships and the antemortem diagnosis of neurodegenerative disease.

Currently, the diagnostic standard is neuropathological examination at autopsy, which is a major obstacle for clinical trials in neurodegenerative disease. To address this problem our approach is to "work backwards" to study human brain tissue and measure neuropathology objectively using novel open-source digital image analysis tools; We use a "tissue-guided biomarker discovery” method to translate our findings with the ultimate goal to develop new laboratory and imaging tests to detect pathology in living patients.

Rotation projects: Quantification of neuron loss and gliosis in neurodegenerative disease, Distribution of TDP-43 pathology across the spectrum of ALS and FTLD-TDP, Distribution of tau and amyloid-beta in non-amnestic Alzheimer's disease patients.

Lab Personnel: Claire Peterson- research assistant, Emily Xie- research assistant, Rebecca Lobrovich- research assistant, Lucia Giannini- visiting scholar, Daniel T Ohm- Postodctoral fellow, Sanaz Arezoumandan- Postdoctoral Fellow, Alejandra Bahena- Penn PURM researcher, Emily Kopp- Penn ITMAT Translational Research Program Intern \.

Description of Research Expertise

The overall mission of my translational research program is to improve the diagnosis and treatment for young-onset and atypical neurodegenerative dementias. A major limitation for therapeutic trials in these disorders is that the gold-standard for diagnosis is neuropathological examination at autopsy. To address this problem, my lab (Penn Digital Neuropathology Lab) develops novel open-source digital image analysis tools to study gold-standard histopathology in an objective and reproducible manner with rigorous validation. My lab utilizes both innovative “wet-lab” human brain histology techniques and novel “dry-lab” digital image analysis methods and bioinformatics to integrate fine-grained measures of postmortem neuropathology with antemortem clincial data. My goal is to identify diagnostic and prognostic markers of disease progression that can serve as endpoints in treatment trials. The approach of my lab represents the blending of my training in two separate but complementary specialties of cognitive neurology and neuropathology.

Selected Publications

Irwin David J*, Lleó Alberto, Xie Sharon X, McMillan Corey T, Wolk David A, Lee Edward B, Van Deerlin Viviana M, Shaw Leslie M, Trojanowski John Q, Grossman Murray: Ante mortem cerebrospinal fluid tau levels correlate with postmortem tau pathology in frontotemporal lobar degeneration. Annals of neurology 82(2): 247-258, Aug 2017 Notes: *Corresponding author.

Irwin David J*, Grossman Murray, Weintraub Daniel, Hurtig Howard I, Duda John E, Xie Sharon X, Lee Edward B, Van Deerlin Vivianna M, Lopez Oscar L, Kofler Julia K, Nelson Peter T, Jicha Gregory A, Woltjer Randy, Quinn Joseph F, Kaye Jeffery, Leverenz James B, Tsuang Debby, Longfellow Katelan, Yearout Dora, Kukull Walter, Keene C Dirk, Montine Thomas J, Zabetian Cyrus P, Trojanowski John Q: Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis. The Lancet. Neurology 16(1): 55-65, Jan 2017 Notes: *Corresponding author.

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Last updated: 06/26/2022
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