Project Team

Peter Novak MD, PhD, Inaugural Chief of the Autonomic Neurology Division, Harvard Medical School

Christopher Dupont, PhD, Associate Professor in Genomic Medicine, Environment & Sustainability, and Synthetic Biology, the J. Craig Venter Institute

Richard Scheuermann, PhD, Director of Informatics and La Jolla Campus Director, J. Craig Venter Institute; Adjunct Professor of Pathology, University of California San Diego

Michael VanElzakker, PhD, Assistant Professor in the Division of Neurotherapeutics, Harvard Medical School

Amy Proal, PhD, President/Research Director, PolyBio Research Foundation

Project Summary:

Project advisor Dr. Richard Scheuermann

A project to determine if pathogen persistence, immune dysregulation, and blood vessel dysfunction or microclotting contribute to small fiber neuropathy in patients with Long COVID, ME/CFS and Post Treatment Lyme disease (PTLDS). Skin punch biopsy tissue samples containing peripheral nerves are being collected from Long COVID, ME/CFS and PTLDS patients with a diagnosis of small fiber neuropathy by Dr. Peter Novak at Harvard Medical School. The project team is using advanced sequencing and spatial transcriptomics to identify the potential loss of nerve or other types of cells in samples, and to characterize the infectious, genetic and immune landscape of the tissue. A stain will be used to see if blood vessels in the tissue samples contain fibrinaloid microclots.

Project Background: 

Several research studies have shown that some LongCOVID, ME/CFS, and PTLDS patients develop small fiber neuropathy. This occurs when the small fibers of the peripheral nervous system that regulate autonomic functions such as heart rate and breathing are damaged or diminished. Symptoms of small fiber neuropathy include chronic pain, sensory impairment, gastrointestinal dysmotility, and autonomic dysfunction. While small fiber neuropathy can be diagnosed in LongCOVID and related infection-associated chronic illness patients via a punch biopsy procedure, the molecular mechanisms underlying small fiber neuropathy development remain to be characterized. This project is workingto identify these molecular mechanisms using advanced genomic and digital spatial profiling methods.

(Image from Narasimhaiah & Mahadevan 2022)