Postdoctoral Fellow - Gastroenterology Research

Overview

A postdoctoral fellow position is available in the department of Gastroenterology. Developing Non-Invasive Strategies for Colorectal Cancer Surveillance in Lynch Syndrome. The Postdoctoral fellow position centers on addressing a critical gap in Lynch syndrome (LS) care: the incomplete prevention of colorectal cancer (CRC) by colonoscopy alone, particularly in carriers of MLH1 and MSH2 variants whose tumors may arise through accelerated, non-adenomatous pathways.

The program aims to move LS surveillance from a one-size-fits-all colonoscopy-based model toward a precision prevention strategy that leverages non-invasive biomarkers tailored to each patient's genetic and clinical profile.

All duties and responsibilities are carried out in compliance with institutional policies, ethical research standards, and applicable federal and state regulations.

Learning objectives

Primary Objective

To develop, validate, and clinically evaluate novel non-invasive biomarker-based strategies for colorectal cancer surveillance in individuals with Lynch syndrome, with the goal of improving early detection, reducing unnecessary invasive procedures, and enabling gene-specific, personalized surveillance protocols.

Specific Objectives

• Optimize stool-based biomarker strategies for LS surveillance
• Assess the performance of quantitative fecal immunochemical testing (FIT) at low positivity thresholds (=4.1 µg Hb/g feces) as a triage tool to safely extend colonoscopy intervals in FIT-negative LS carriers.
• Explore fecal tumor DNA markers (e.g., BAT-26, methylated gene panels), fecal microRNA, and gut microbiome composition (e.g., Desulfovibrio enrichment) as complementary or standalone surveillance biomarkers.
• Conduct prospective validation studies with gene variant-specific outcome reporting.
• Characterize and validate blood-based liquid biopsy approaches for LS-associated CRC detection
• Investigate circulating cell-free DNA (cfDNA) assays, including frame shift mutation panels targeting coding mononucleotide repeats characteristic of MMR-deficient tumors, cfDNA methylation profiling (e.g., methylated SEPTIN9 and genome-wide methylation signatures), and chromosomal copy number variation analysis.
• Determine the sensitivity, specificity, and positive/negative predictive values of these assays for detecting early-stage CRC and advanced adenomas in LS carriers, stratified by MMR gene variant.
• Develop integrated multi-omics risk stratification models
• Combine blood-based and stool-based biomarker data with clinical and genetic risk factors (MMR gene, age, sex, adenoma history, family history) into predictive models for individualized cancer risk assessment.
• Apply bioinformatics and machine learning approaches to integrate multi-omics layers (genomics, epigenomics, transcriptomics, metabolomics) for improved cancer prediction accuracy.
• Validate models in independent, prospective LS cohorts with longitudinal follow-up.
• Design and conduct prospective clinical studies
• Establish or leverage existing LS registries and biobanks to recruit well-characterized cohorts of MMR gene variant carriers under active surveillance.
• Design studies that compare non-invasive biomarker-guided surveillance strategies against standard colonoscopy-based protocols, with endpoints including CRC incidence, stage at detection, interval cancer rate, colonoscopy burden reduction, patient adherence, quality of life, and cost-effectiveness.
• Ensure gene-stratified analyses to account for the distinct cancer biology and risk profiles of MLH1, MSH2, MSH6, and PMS2 carriers.
• Translate findings toward clinical implementation
• Develop standardized assay protocols suitable for clinical laboratory adoption.
• Generate evidence to support regulatory evaluation and potential integration into clinical practice guidelines.
• Collaborate with multidisciplinary teams (gastroenterology, genetics, oncology, pathology, bioinformatics) and patient advocacy groups to ensure clinical relevance and patient-centered design.

Eligibility Requirements

PhD

Expected Outcomes and Impact

This postdoctoral research program aims to produce validated, non-invasive…