Postdoctoral Research Fellowship in Esophagus Imaging
Wang Laboratory, University of Michigan, Ann Arbor, MI, United States
Employer Description:
PI: Thomas D Wang, MD,PhD, University of Michigan
Project goal is to develop of state-of-the-art methods that combine imaging with biomarkers to develop a targeted in vivo imaging strategy for early detection of esophageal cancer.
Post-doctoral research opportunities are available in the Wang Lab at the University of Michigan to join a highly collaborative, multi-disciplinary team to accelerate clinical translation of an integrated imaging strategy for early detection of esophageal adenocarcinoma in patients with Barrett’s esophagus undergoing surveillance endoscopy. Target identification will be performed using single cell RNA sequencing and spatial transcriptomics analysis of human specimens from an existing clinical database. Peptide monomers that bind specifically to tissue targets expressed uniquely by high-grade dysplasia will be identified using phage display methods. The candidate monomer sequences will be optimized with structural models using Hex docking software. Optimized monomers will be combined in a multimer configuration and labeled with a near-infrared fluorophore for fluorescence detection. The dimensions of PEG and amino hexanoic acid linkers will be tuned to prevent steric hindrance from peptide binding interactions. Binding interactions, including specificity, kinetics, and contrast, will be validated using a flexible fiber endoscopic imaging accessory. In vivo imaging will be performed in pre-clinical models using implanted patient-derived organoids. The validated peptide multimer will be clinically translated in the Medical Procedures Unit at Michigan Medicine to detect pre-malignant lesions that have potential to transform into adenocarcinoma and would otherwise be missed.
Requirements: Candidates with a Ph.D. in biochemistry, protein chemistry, medicinal chemistry, organic chemistry, physical chemistry, molecular biology, cell biology, structural biology, or a related discipline with hands-on experience in wet lab chemistry, peptide synthesis, and organ culture are invited to apply. Hands-on experience with small animal imaging is desirable. International investigators are welcome. Research skills to be mastered in this project include the following:
· Identify promising tissue targets using scRNAseq analysis and spatial transcriptomics
· Select peptide monomers using phage display methods
· Arrange peptide monomers in multimer configuration
· Analyze peptide binding interactions using structural models
· Optimize linker dimensions and configurations
· Develop patient-derived organoids
· Characterize peptide multimer pharmacokinetics and biodistribution.
· Assess peptide multimer stability in serum.
· Perform in vivo imaging in small animal models.
· Develop scientific independence, organizational, and communication skills.
Research environment: The University of Michigan is committed to diversity and equality in education and employment, and is an ideal training ground for postdocs who want to further develop their skills in pursuit of a career in academia or industry. Salary will be commensurate with the applicant’s experience and in compliance with NIH guidelines.
The Wang Laboratory is located in the Biomedical Science Research Building (BSRB) on the University of Michigan medical campus. The wet lab space is ~2000 sq. ft., and includes 16 wet benches, desks, and computers. The laboratory is equipped with 4oC refrigerators, -20oC and -80oC freezers, water baths, top loading and analytical balances, orbital shakers, microcentrifuge, high speed refrigerated centrifuge, pH meter, brightfield and fluorescence microscopes, and cell culture facility equipped with two sterile laminar flow hoods and dual chamber CO2 incubators. The lab is also equipped with a HPLC (Dual injector 2489 Waters breeze system), automatic peptide synthesizer (Protein Technologies), and lyophilizer (Freezone 4.5, Lab Conco Corp.). Core facilities in the BSRB include a tissue laboratory (800 sq. ft.) that is available for processing tissue specimens (microtome) and performing histology. There is also an imaging laboratory (~250 sq. ft) that has an inverted confocal microscope (Zeiss LSM 510) with 3 laser excitation lines (488, 514, and 633 nm), and an automated imaging system for capturing and archiving tissue microarray experiments. A freezer room with automated alarm and self-dialing emergency system is located next to the core lab. It is equipped with 4 Fisher scientific upright -80oC freezers for the storage of serum and tissue samples. The Center for Molecular Imaging is a state-of-the-art small animal imaging center that provides systems, instruments, and services for performing molecular imaging research.
Candidates should submit CV and contact information by email:
Thomas D. Wang, M.D.,Ph.D.
Professor of Medicine, Biomedical Engineering, and Mechanical Engineering
H. Marvin Pollard Collegiate Professor of Endoscopy Research
University of Michigan
109 Zina Pitcher Pl. BSRB 1522
Ann Arbor, MI 48109-2200
Email: tdwangmd@gmail.com