Jessica Fortin
Assistant Professor of Pathobiology and Diagnostic Investigation | Michigan State University
East Lansing, MI, UNITED STATES
Dr. Jessica S. Fortin is a board-certified veterinary anatomic pathologist and holds both chemistry and pharmacy licenses from Quebec.
Biography
Dr. Jessica S. Fortin joined the Department of Pathobiology and Diagnostic Investigation and the Veterinary Diagnostic Laboratory as an assistant professor at Michigan State University in August 2018. She has several years of experience in medicinal chemistry and molecular pharmacology academic research. Her research program focused on drug discovery. Fortin’s long-time research interests are in the areas of design and development of anti-amyloid agents for the treatment of Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes. Her academic interests are in DNA secondary structures, protein folding disorders, neuropathology, and neurotoxicology.
Fortin is originally from Quebec, Canada. She is a board-certified veterinary anatomic pathologist and holds both chemistry and pharmacy licenses from Quebec. She received a combined DVM-PhD (pathology) degree in 2015 from the University of Montreal and a MSc with honors in medicinal chemistry (2008) from Laval University. In June 2018, she completed a veterinary anatomic pathology residency training program at the University of Missouri.
Areas of Expertise (5)
Toxicology
Molecular Pharmacology
Pharmacy
Medicinal Chemistry
Pathology
Accomplishments (2)
ACVP Harold W. Casey Memorial Scholarship (professional)
2018
Diplomate of the American Board of Toxicology (DABT) (professional)
2019
Education (5)
Université de Montréal: PhD, Veterinary Science, Pathology 2016
Université de Montréal: DVM, Veterinary Medicine 2015
Université Laval: MSc, Pharmacy (Medicinal Chemistry) 2008
With Honors
Université Laval: BSc, Chemistry
Université Laval: BPharm
Links (3)
News (1)
College PDI Trainees and New Faculty at the American College of Veterinary Pathologists Annual Meeting
CVM News
Veterinary students Anna Gates, Amber Olson, and Ashleigh Shoemaker as well as third-year resident, Dr. Wallaya (Lek) Manatchaiworakul, presented posters. Dr. Leah Stein presented not one, but two Mystery Slide cases (neuropathology and neuromuscular pathology) as well as a platform talk. Dr. Steven Hsu had one Mystery Slide case and Dr. Raisa Glabman made a platform presentation. Dr. Erica Corda provided a case for the ASVCP Mystery slide session. Dr. Colleen Monahan won this year’s CL Davis-Thompson trainee award for MSU. One of our newest PDI faculty members, Dr. Jessica Fortin, was the 2018 winner of the ACVP Casey Award, intended to recognize and reward outstanding individuals training in pathology and striving to achieve ACVP certification.
Journal Articles (5)
Methods Optimization for Routine Sciatic Nerve Processing in General Toxicity Studies
Toxicologic PathologyJessica S. Fortin, Elizabeth A. Chlipala, Daniel P. Shaw, Brad Bolon
2019 Recent “best practice” recommendations for peripheral nervous system sampling and processing provide guidance regarding nerve preparation for animal toxicity studies. This study explored the impact of delayed fixation, type of fixative, processing cycle times, starting ethanol concentration, and water bath temperature to improve nerve preservation in routinely prepared (paraffin-embedded, hematoxylin and eosin [H&E]-stained) sections. Sciatic nerves from adult Wistar rats (diameter, 1.04 ± 0.1 mm) and young domestic pigs (diameter 5.9 ± 1.2 mm) fixed at necropsy (“0” hours) or 3, 6, 12, or 24 hours after death were immersed in neutral-buffered 10% formalin containing 1.2% methanol (NBF) or methanol-free 4% formaldehyde (MFF) at room temperature. After fixation for 24 hours (rat) or 48 hours (pig), specimens were processed into paraffin, and ∼5-μm-thick sections were flattened on water baths set at 35°C, 40°C, or 45°C before H&E staining. Large-diameter nerves (pig) required longer processing cycles to ensure sufficient paraffin infiltration. For both small-diameter (rat) and large-diameter nerves, structural integrity was optimal if fixation by NBF or MFF occurred within 3 hours and the initial ethanol concentration for tissue processing was lowered to 50%. At all time points, structural preservation of nerve fibers was acceptable using NBF but was better with MFF. Use of a water bath at 35°C reduced processing-related nerve fiber separation within sections.
Discovery of ethyl urea derivatives as inhibitors of islet amyloid polypeptide fibrillization and cytotoxicity
Canadian Journal of Physiology and PharmacologyJessica S. Fortin, Marie-Odile Benoit-Biancamano, René C.-Gaudreault
2015 Islet amyloid polypeptide (IAPP) has been shown to form amyloid deposits in pancreatic islets, thereby furthering type 2 diabetes disease progression. Further discovery of new molecules is needed to create a diverse set of molecules that impede pancreatic amyloidosis. We have recently designed and synthesized N-phenyl-N′-(2-ethyl)ureas (EU) that are non-cytotoxic small molecules, to evaluate the role of the aryl-substituted moiety on the inhibition of hIAPP fibrillization. Several EUs were tested in vitro for their anti-amyloidogenic activity using the fluorometric ThT assay, the photo-induced cross-linking (PIUCP) assay, and cell survival assay in pancreatic MIN-6 cells. EU-362 and EU-418 were able to significantly inhibit the formation of hIAPP fibrils and protected cells from amyloid cytotoxic effects. Our results suggest that increasing the nucleophilic potency of the aryl moiety significantly enhances the anti-amyloidogenic activity of the molecules.
Wildlife sequences of islet amyloid polypeptide (IAPP) identify critical species variants for fibrillization
AmyloidJessica S. Fortin & Marie-Odile Benoit-Biancamano
2015 Amyloid can be detected in the islets of Langerhans in a majority of type 2 diabetic patients. These deposits have been associated with β-cell death, thereby furthering diabetes progression. Islet amyloid polypeptide (IAPP) amyloidogenicity is quite variable among animal species, and studying this variability could further our understanding of the mechanisms involved in the aggregation process. Thus, the general aim of this study was to identify IAPP isoforms in different animal species and characterize their propensity to form fibrillar aggregates. A library of 23 peptides (fragment 8–32) was designed to study the amyloid formation using in silico analysis and in vitro assays. Amyloid formation was impeded when the NFLVH motif found in segment 8–20 was substituted by DFLGR or KFLIR segments. A 29P, 14K and 18R substitution were often present in non-amyloidogenic sequences. Non-amyloidogenic sequences were obtained from Leontopithecus rosalia, Tursiops truncatus and Vicugna pacos. Fragment peptides from 34 species were amyloidogenic. To conclude, this project advances our knowledge on the comparative pathogenesis of amyloidosis in type II diabetes. It is conceivable that the additional information gained may help point towards new therapeutic strategies for diabetes patients.
Characterization of a pancreatic islet cell tumor in a polar bear (Ursus maritimus)
ZoobiologyJessica S. Fortin, Marie-Odile Benoit-Biancamano
2014 Herein, we report a 25‐year‐old male polar bear suffering from a pancreatic islet cell tumor. The aim of this report is to present a case of this rare tumor in a captive polar bear. The implication of potential risk factors such as high carbohydrate diet or the presence of amyloid fibril deposits was assessed. Necropsy examination revealed several other changes, including nodules observed in the liver, spleen, pancreas, intestine, and thyroid glands that were submitted for histopathologic analysis. Interestingly, the multiple neoplastic nodules were unrelated and included a pancreatic islet cell tumor. Immunohistochemistry of the pancreas confirmed the presence of insulin and islet amyloid polypeptide (IAPP) within the pancreatic islet cells. The IAPP gene was extracted from the paraffin‐embedded liver tissue and sequenced. IAPP cDNA from the polar bear exhibits some differences as compared to the sequence published for several other species. Different factors responsible for neoplasms in bears such as diet, infectious agents, and industrial chemical exposure are reviewed. This case report raised several issues that further studies may address by evaluating the prevalence of cancers in captive or wild animals.
Cycloalkyl-substituted aryl chloroethylureas inhibiting cell cycle progression in G0/G1 phase and thioredoxin-1 nuclear translocation
Bioorganic and Medicinal Chemistry LettersJessica S. Fortin, Marie-France Côté, Jacques Lacroix, Alexandre Patenaude, ÉricPetitclerc, RenéC.-Gaudreault
2008 1-(2-Chloroethyl)-3-(4-cyclohexylphenyl)urea (cHCEU) has been shown to abrogate the presence of thioredoxin-1 into the nucleus through its selective covalent alkylation. In the present letter we have evaluated the structure–activity relationships of the substituents at positions 3 and 4 of the phenyl ring of cHCEU derivatives on cell cycle progression and thioredoxin-1 nuclear translocation. Active CEU derivatives exhibited GI50 ranging from 1.9 to 49 μM on breast carcinoma MCF-7, skin melanoma M21, and colon carcinoma HT-29 cells. On one hand, compounds 1, 2, 9c, 10c, 13, and 14 arrested the cell cycle in G2/M phase while CEUs 3, 4, 5c, 6c, 11c, and 12c blocked the cell division in G0/G1 phase. On the other hand, CEUs 2–4, 5c, 7c, 8c, 11c, and 12c abrogated the translocation of thioredoxin-1 while the other CEU derivatives were inactive in that respect. Our results suggest that CEU substituted on the phenyl ring at position 3 or 4 by lower cycloalkyl or cycloalkoxy groups arrest cell progression in G0/G1 phase through mechanism of action different from their antimicrotubule counterparts, presumably via thioredoxin-1 alkylation and modulation of its activity. The mechanism of action of these new molecules is still undetermined. However, the significant accumulation of cells in G0/G1 phase suggests that these molecules may act similarly to known chemopreventive agents against cancers. In addition, the inhibition of Trx-1 nuclear localization also suggests the abrogation of an important chemoresistance mechanism towards a variety of chemotherapeutic agents.
