Reese Hitchings

BWF PUP program: Albert Einstein College of Medicine of Yeshiva University "Education Connecting Laboratory Investigation and Population Science at Einstein (eCLIPSE)"

Email: rhitchin@mail.einstein.yu.edu

Phone: (719)761-8176 (o)

Personal/Professional Website

Research interests: The way the microbiome interacts with medication as a major influence on the pharmacokinetics of drugs.

Current projects: Sulfasalazine (SSZ) is a prodrug used to treat rheumatoid arthritis and inflammatory bowel disease (IBD) that relies entirely on bacterial azoreductases in the gut for activation and efficacy in patients. Although poorly investigated, the superfamily of azoreductase proteins in bacteria is known to be highly diverse and variable between individuals. We hypothesize that the diversity of azoreductases in a patient’s gut microbiome will predict the kinetics of SSZ activation. To test this hypothesis, we are combining novel protein sequence analysis pipelines with an ex-vivo SSZ turnover assay to identify the metagenomic signatures most predictive of SSZ activation. To identify the diversity of azoreductases in the gut microbiome, we are analyzing whole-community DNA metagenomic sequencing (WCMGS) data from healthy individuals in the Bronx and public data to build sequence similarity networks. These networks identified conserved sequence motifs in metagenomic azoreductases, and revealed that the current crystal structures poorly represent the diversity of azoreductases in the human gut. To identify clinically relevant azoreductases, we have developed an HPLC-MS method detect SSZ turnover. We have collected fecal samples from healthy volunteers and begun profiling their azoreduction rates in context with their WCMGS data. This work represents the first step toward individual patient-based precision dosing of SSZ.

System of Study: