A new lab, the Penn Digital Neuropathology Lab, has recently been established within the Penn Frontotemporal Degeneration Center! Congratulations to lab Principal Investigator, Dr. David Irwin, and all others involved, on its grand opening. Here, special guest writer and DNPL member Claire Peterson introduces us to the work done at the DNPL. Read on to learn more!

The Penn Digital Neuropathology Lab (DNPL) uses a multidisciplinary approach merging “wet-lab” based histopathology of human brain tissue with “dry-lab” based image analysis tools, in the hopes of improving the antemortem diagnosis of neurodegenerative diseases, including Frontotemporal dementia, Lewy body disorders and Alzheimer’s disease. Rapid and accurate diagnosis of underlying neuropathology in living patients is critical for the development of effective disease-modifying therapies. Currently, the diagnostic standard is neuropathological examination at autopsy, which is a major obstacle for clinical trials. Our approach is to “work backwards”: examining human brain tissue with objective measures of neuropathology using novel and freely available digital image analysis tools. Thus, we use a “tissue-based biomarker” discovery method to translate our findings into new laboratory and imaging tests to detect pathology in living patients.

Members:

David Irwin, MD, MSTR – Primary Investigator

dave_irwinDavid is a cognitive neurologist at the Penn FTDC and PI of the Penn Digital Neuropathology Laboratory. He previously trained as a postdoctoral fellow at both the Penn FTDC under Dr. Murray Grossman and the Penn Center for Neurodegenerative Disease research under Dr. John Trojanowski where he had dual training in cognitive neurology and neuropathology/biomarkers in neurodegenerative disease. These blend of experiences in cognitive neurology and neuropathology led to the unique translational approach of the Penn DNPL. David continues to evaluate and treat patients at the Penn FTDC. David enjoys time with his wife and two small children who have taught him birding and gardening and loves to go fishing at the Schuylkill River each spring.

Daniel Ohm, PhD – Post-Doctoral Fellow

Screen Shot 2019-05-24 at 1.37.59 PMDan, our newest addition to the lab, joined in April 2019 after recently completing his PhD in Neuroscience at Northwestern University. In an effort to better understand mechanisms of disease and improving diagnoses and treatments for patients, Dan is interested in investigating the vulnerability of select regions and cell types to tau or TDP proteinopathies, and how patterns of disease in the brain relate to in vivo biomarkers that can be obtained during life, such as MRI and cognitive measures. When not in lab, Dan enjoys being outdoors and finding new mountains to hike with his friends and family.

David Coughlin, MD, MSTR – Fellow

coughlin-david-headshot.0.0.1800.2122.150.177.cDavid is a Movement Disorders fellow at the University of Pennsylvania where he is also completing a masters in translational research. His research interests center around the neuropathology of movement disorders. David uses novel digital imaging techniques in autopsied tissue to better understand the patterns of neuropathology in Parkinson’s disease, dementia with Lewy bodies and how these patterns relate to in vivo biomarkers including cognitive performance, CSF analytes, and PET imaging. He completed his residency at the University of Pennsylvania and graduated from medical school at Columbia University College of Physicians and Surgeons. He obtained his undergraduate degree from Brown University where he majored in neuroscience and was captain of the crew team. David will be joining the faculty at UCSD this summer where he will establish his own laboratory. Congratulations and best of luck, David!

Claire Peterson – Research Assistant

claireClaire joined the Penn FTDC and DNPL in May 2018 after graduating from Northeastern University in Boston, MA with a degree in behavioral neuroscience. Since joining, Claire has enjoyed learning more about how to use digital image analysis methods to further quantify neuropathological features. When not in the lab, Claire enjoys exploring Philadelphia with her friends and classmates.

Rebecca Lobrovich – Research Assistant

beckyRebecca joined the lab in September 2018 after completing her M.S. at the University of Helsinki. Rebecca has been a pivotal with maintaining organization in our growing library of data. Since joining, Rebecca has enjoyed the multitude of opportunities to learn and grow from working with collaborators overseas to attending weekly seminars to further her neuroscience knowledge. When not in the lab, Rebecca can be found playing with her adorable dog, Izzy.

Lucia Giannini – Visiting Scholar

lucia-giannini-photo-cropped.0.104.762.896.150.177.cLucia A.A. Giannini is a visiting scholar from the University of Groningen, the Netherlands. She earned her Bachelor’s degree in Medicine and Philosophy at the University of Groningen, and she is now pursuing her clinical training to become a doctor. She visited the Penn Digital Neuropathology Lab in 2017 and she has been collaborating with the lab ever since. Her research focuses on clinicopathological correlations in primary progressive aphasia (PPA). Lucia has also been helping the lab develop statistical methods to optimize digital pathology quantification. Following medical school, Lucia would love to become a cognitive neurologist and continue her research work as a clinician-scientist. Lucia is an avid coffee drinker and she indulges in a Starbucks now and then to recall the lovely time spent in Philadelphia.


The work of the DNPL is made possible through the analysis of patient data from the Center for Neurodegenerative Research (CNDR) Brain Bank. For more information on participation in the Brain Bank program, please contact:

  • Kevin Davies at the Center for Neurodegenerative Disease Research by telephone at 215-662-4474 or by email at daviesk@upenn.edu 
  • Gabriela (Gabby) Bustamante, RN, BSN, at the Penn FTD Center by telephone at 215-662-3361

 


Want to learn more about the work done at the DNPL? Check out these recent publications!

Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders

Coughlin, D., Xie, S., Liang, M., Williams, A., Peterson, C., Weintraub, D., McMillan, C., Wolk, D., Akhtar, R., Hurtig, H., Coslett, H., Hamilton, R., Siderowf, A., Duda, J., Rascovsky, K., Lee, E., Lee, V., Grossman, M., Trojanowski, J. and Irwin, D. Annals of Neurology 2019;85:259–271.

This paper is the first detailed comparison of digital histology measures of tau, amyloid and alpha-synuclein pathologies with traditional neuropathological staging in LBD and finds that tau pathology in LBD associates with specific cognitive impairments during life and is in a distribution in the brain that diverges from AD. Click here to read more!

Divergent patterns of TDP-43 and tau pathologies in primary progressive aphasia.

Giannini LAA, Xie SX, McMillan CT, Liang M, Williams A, Jester C, Rascovsky K, Wolk DA, Ash S, Lee EB, Trojanowski JQ, Grossman M, Irwin DJ.

Ann Neurol. 2019 May;85(5):630-643. doi: 10.1002/ana.25465. Epub 2019 Mar 28.

This paper is the first comparative study of distinct Tau and TDP-43 pathologies across hemispheres in patients with primary progressive aphasia (PPA). We find that Tau and TDP-43 have different regional patterns of pathology in the brain despite being associated with clinical PPA and that these distinct patterns relate to anteortem MRI and specific features of language disturbance. This data suggests that clinical and anatomical patters of disease during life may help differentiate Tau and TDP-43 pathologies in PPA patients. Click here to read more!


The DNPL would like to thank all the patients their families for their willingness to participate in research and the incredibly meaningful contribution to the brain donation program– this work would not be possible without your generous donations! We look forward to your continued support as we strive to uncover novel biomarkers and methods for detecting disease-related pathology earlier during life.

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