Structural and Mechanistic Studies of Glypicans

The research group of Dr. Mitchell Ho at the National Cancer Institute (NCI) is seeking a postdoctoral fellow to conduct structural and functional studies on cell surface heparan sulfate proteoglycans, in particular glypicans. Our goal is to better understand the role of cell surface glypicans so we can develop more effective antibody-based cancer therapies (https://ccr.cancer.gov/Laboratory-of-Molecular-Biology/mitchell-ho). We are combining structural techniques such as macromolecular crystallography and cryo-EM with biochemical and molecular methods to investigate the structure and function of glypicans and their associated proteins including Wnt/Frizzled molecules. We have developed antibodies that can recognize the functional sites of glypicans (Feng et al. PNAS, 2013 PMID: 23471984; Gao et al. Hepatology 2014 PMID: 24492943; Gao et al. Nature Communications, 2015 PMID: 25758784) and used them as tools to study the structure and function of glypicans. We have been collaborating with both structural biologists and computational biologists to complement our studies.

For this position, we are looking for a candidate who will carry out both structural studies and biochemical experiments on glypicans (e.g. GPC3) that interact with Wnt/Frizzled molecules using nanobodies as tools. Here are our recent papers relevant to this project:

• Li N, Gao W, Zhang YF, Ho M. Glypicans as Cancer Therapeutic Targets. Trends Cancer. 2018 Nov;4(11):741-754. doi: 10.1016/j.trecan.2018.09.004. Epub 2018 Sep 28. Review. PMID: 30352677
• Li N, Wei L, Liu X, Bai H, Ye Y, Li D, Li N, Baxa U, Wang Q, Lv L, Chen Y, Feng M, Lee B, Gao W, Ho M. A Frizzled-Like Cysteine-Rich Domain in Glypican-3 Mediates Wnt Binding and Regulates Hepatocellular Carcinoma Tumor Growth in Mice. Hepatology. 2019 Apr 9. doi: 10.1002/hep.30646. [Epub ahead of print] PMID: 30963603

The candidates should hold a Ph.D. degree with a strong background in structural biology and biochemistry and have  at least one first author publication in structural biology. Experience with molecular biology, protein expression, purification and biochemical characterization are required. Prior experience in any one or more of structural biology, membrane protein biochemistry, mammalian expression systems or computational modeling is highly desired.

It is absolutely essential that the candidate be highly motivated. The postdoctoral fellow will be working with colleagues and collaborators with diverse expertise in cancer biology and protein engineering.

Interested candidates can send an email to homimail.nih.gov containing a CV and a summary of previous research experience and future interests.

The NIH is an equal opportunity employer. The NIH is dedicated to building a diverse community in its training and employment programs.