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Kenneth Simpson, BVM&S, PhD

Kenny Simpson

I am a clinician-scientist, with clinical specialization in Small Animal Internal Medicine and Gastroenterology, and research training in gastrointestinal and pancreatic physiology (PhD), host-pathogen response and molecular microbiology (K08-mentored clinical scientist). I teach veterinary students and train Interns and Residents in the Cornell University Hospital for Animals, and supervise undergraduate and post-graduate researchers in my laboratory.

My interest in gastrointestinal physiology and pathophysiology across species is long-standing, and has evolved from studying pancreatic function and dysfunction and cobalamin absorption in dogs and cats, to a sustained emphasis on interactions between the enteric microenvironment (microbial, dietary, and chemical) and the GI tract in health and disease (inflammation and IBD), and the application of culture-independent methods to detect bacteria in clinical samples.

Advances in science have created molecular microbiology and “-omics” methodologies that enable un-solved problems to be tackled with new approaches. This facilitated the discovery of the causal association of E. coli and granulomatous colitis in Boxer dogs and French Bulldogs with genetic susceptibility encoded by the CD48/SLAM family of genes on CFA38, linked to IBD in people. By combining comparative genomics, the ability of E. coli to utilize chemicals associated with intestinal inflammation (identified by metabolomics), and in vivo colonization of IBD susceptible murine models we are beginning to identify mucosal metabolites and metabolic pathways and virulence traits in E.coli that underpin their ability to grow in the inflamed intestine and to induce inflammation and cancer in a genetically susceptible host. Recent work has established interplay between bacterial microcompartments in AIEC that metabolize  propanediol (pdu) and ethanolamine (eut), mucosal substrates, Th17 immune responses and intestinal inflammation. These exciting results, connecting virulence and metabolic capacity of enteric bacteria, immunity and tumorigenesis, have uncovered unique opportunities to combat dysbiosis and intestinal inflammation across species e.g. the identification of small molecules with selective antimicrobial activity against E.coli and enteropathogens (Patent, PCT/US2020/054557) and E. coli LpfA antigen for prevention and treatment of infectious diseases (Patent, US9119802B2).

 

Our research related to AMR is focused on three areas:

1. E.coli associated granulomatous colitis in dogs and Crohn’s ileitis in people: 
 
Escherichia coli‐associated granulomatous colitis in dogs treated according to antimicrobial susceptibility profiling

AC Manchester, B Dogan, Y Guo, KW Simpson
Journal of veterinary internal medicine 35 (1), 150-161
S Zhang, X Morgan, B Dogan, FP Martin, S Strickler, A Oka, J Herzog, …
JCI insight 7 (10)
 
B Dogan, E Scherl, B Bosworth, R Yantiss, C Altier, PL McDonough, …
Inflammatory bowel diseases

V Kothary, EJ Scherl, B Bosworth, ZD Jiang, HL DuPont, J Harel, …
Antimicrobial agents and chemotherapy 57 (2), 811-817
 
2. Novel strategies to combat MDR enteropathogens:
 
Antimicrobial and antiviral effects of c2-c7 alkyl boronic acids

KW Simpson, S Zhang, M Fischbach
US Patent App. 17/767,119
Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn’s disease

G Chevalier, A Laveissière, G Desachy, N Barnich, A Sivignon, …
Microbiome 9 (1), 1-16
Short Chain Fatty Acids Modulate the Growth and Virulence of Pathosymbiont Escherichia coli and Host Response

S Zhang, B Dogan, C Guo, D Herlekar, K Stewart, EJ Scherl, KW Simpson
Antibiotics 9 (8), 462
 
S Zhang, J Fu, B Dogan, EJ Scherl, KW Simpson
The Journal of antibiotics 71 (11), 950-961
 
3. Rapid determination of antimicrobial susceptibility:
 
Diffusion–convection hybrid microfluidic platform for rapid antibiotic susceptibility testing

AV Nguyen, M Azizi, M Yaghoobi, B Dogan, S Zhang, KW Simpson, …
Analytical Chemistry 93 (14), 5789-5796
Gradient-Based Microfluidic Platform for One Single Rapid Antimicrobial Susceptibility Testing

M Azizi, B Davaji, AV Nguyen, S Zhang, B Dogan, KW Simpson, …
ACS sensors 6 (4), 1560-1571
Nanoliter-sized microchamber/microarray microfluidic platform for antibiotic susceptibility testing

M Azizi, M Zaferani, B Dogan, S Zhang, KW Simpson, A Abbaspourrad
Analytical chemistry 90 (24), 14137-14144
Title: Professor