Primary Mentor:  

Maria C. Naskou DVM, PhD, Dipl.ACVP (Clinical Pathology), Assistant Professor of Clinical Pathology [email protected]

Mentor Team:

Maria Naskou DVM, PhD, Dipl. ACVP (Clinical Pathology)

Douglas R. Martin. PhD

Ioanna Skountzou, MD, PhD

Tom Jukier, DVM, MS, DACVIM (Neurology)      

Description of Potential Research Project(s):

Neuroinflammation complicates the clinical progression of many neurodegenerative diseases and is mainly characterized by reactive astrocytosis and microgliosis, which further exacerbate the severity of neurological disorders via the release of pro-inflammatory mediators and neurotoxic factors. Stem cell derived Extracellular Vesicles (SC-EVs) are heterogenous populations of plasma membrane-shed microvesicles  that derive from the endocytic pathway and have been shown to alleviate neuroinflammation by exhibiting an anti-inflammatory effect via suppression of astrogliosis and microgliosis and release of inflammatory mediators. Feline Sandhoff disease (SD) is a lysosomal storage disease caused by mutations of N-acetyl-β-hexosaminidase and is characterized by inflammatory features typical of all neurodegenerative diseases such as astrogliosis and microgliosis. Using a well-characterized single-gene disorder in a controlled research setting will allow us to demonstrate efficacy of SC-EVs, which is an important first step towards broader application in other diseases in which the causes are multi-factorial or not fully known. Our aim is to first evaluate the effect of SC-EVs in vitro on astrocytes and microglia that derive from SD cats. Subsequently, we will test in vivo a range of doses of SC-EVs and evaluate their effect against neuroinflammation compared to standard anti-inflammatory agents in SD cats, both short and long-term. Conclusions will provide insights for the potential use of SC-EVs as anti-inflammatory agents for a variety of diseases in which inflammation is part of the pathology and enable us to generate innovative therapeutic strategies for various neurodegenerative diseases.

Veterinary specialists appropriate as fellows for this research opportunity 

American College of Veterinary Pathologists 

American College of Veterinary Internal Medicine (Neurology)

Additional Training Opportunities:

The COHA fellow will receive advanced training in Extracellular Vesicle biology, molecular neuroscience, inflammation and immunology, and lysosomal storage diseases. He/she also will have additional career development opportunities via attendance of conferences, platforms presentations at conferences, attendance of formal courses and workshops, and grant preparation. Specifically, the COHA fellow will be encouraged to attend and present at the annual conference of the American Society of Gene & Cell therapy, the annual meeting of the American College of Veterinary Pathologists, the WORLD Symposium of Lysosomal Diseases and the International Society of Stem Cell Research. The fellow will be encouraged to attend formal coursework related to neuroscience, immunology (DRDD 7280 Neuroscience Methods, VBMS 7500 Cellular and Molecular Immunology), grant writing workshops offered by Auburn University, the ACVIM Neuroscience Course workshop (https://www.acvim.org/continuing-education/live-education---ace-courses/acvim-north-american-neurosience-course-(brain-camp), as well as the NIH R01 Boot camp. The fellow will be an active member of the “Auburn University Center for Neuroscience Initiative” that offers opportunities for networking while fostering collaborations between scientists from various research backgrounds. The fellow will participate in a journal club organized on topics of immunology and inflammation (Immunology Interest Group) as well as the neuroscience journal club organized by the Neurology service. The COHA fellow will participate in grant writing and will be encouraged to prepare a K08 application during the fellowship period under the direct guidance of members of the mentoring team that have extensive experience with such funding mechanisms. Career guidance and mentoring will be provided via weekly in-person meetings with the primary mentor while additional formal meetings with the rest of the mentoring team will occur every 4-6 months and informal meetings with individual mentors as needed.