Johns Hopkins Biomedical Engineering primary faculty
Kevin J. Yarema, PhD
Office: Smith 5029
Lab: Laboratory of Cell and Carbohydrate Engineering
Walla Walla College, B.S. (1988), Biology/Bioengineering
M.I.T., Ph.D. (1994), Biological Chemistry
Biotechnology and Clinical Aspects of Carbohydrate Engineering
The surface of a mammalian cell is covered with a layer of complex carbohydrates that are biosynthetically assembled by the glycosylation pathways of the cell. Monosaccharides, the basic “building blocks” used by these pathways, are typically obtained by the cell from external sources such as the diet. In certain cases the glycosylation pathways will also accept novel, abiotic monosaccharide analogs as substrates; the metabolic incorporation of the unnatural analogs into structural carbohydrates endows the cell surface with novel physical and chemical properties (1; see publications list below).
Two projects areas based on this “metabolic oligosaccharide engineering” (aka “metabolic glycoengineering”) technology are underway in our laboratory. In one, the surfaces are mammalian cells are being endowed with unique chemical properties that are complementary to the growth substrate (for example, thiols can be installed in surface sugars, which form high affinity interactions with gold-coated growth substrates (2)).
In ongoing work, the ability of an engineered binding interface to control stem cell fate is being investigated. In a second project, the sugar analogs used in metabolic glycoengineering are proving to have interesting anti-cancer properties, for example they reduce the invasive properties if metastatic breast cancer cells (3). In ongoing work, based on emerging evidence that the hexosamine template provides an attractive scaffold for drug discovery (4), we are investigating the use of this novel class of drug candidates in various aspects of regenerative medicine.
In a final glycosylation-related project, being pursued in collaboration with the Krambeck and Betenbaugh groups (JHU ChemBE), we are also developing bioinformatics and computational tools for the characterization of glycans (5). In addition, we have a project underway to study the effects of magnetic fields on human cells (6).
Sampathkumar, S.-G., Li, A., Jones, M.B., & Yarema, K.J. (2006) Metabolic installation of thiols into sialic acid modulates adhesion and stem cell biology Nature Chemical Biology, 2, 149–152.
Elmouelhi, N., Aich, U., Paruchuri, V.D.P., Meledeo, M.A., Campbell, C.T., Wang, J.J., Srinivas, R., Khanna, H.S., & Yarema, K.J. (2009) A platform for modulating gene expression and for sugar-based drug discovery. Journal of Medicinal Chemistry, 52, 2515–2530.
Du, J., Meledeo, M.A., Wang, Z., Khanna, H.S., & Yarema, K.J. (2009) Metabolic glycoengineering: Sialic acid and beyond. Glycobiology 19, 1382–1401.
Almaraz, R.T., Tian, Y, Bhattarcharya, R., Tan, E., Chen, L., Zhang, Z., Zhang., H., Konstantopoulos, K., & Yarema, K.J. (2012) Metabolic flux increases sialylation: Implications for cell adhesion and cancer metastasis. Molecular & Cellular Proteomics. 11, M112.017558.
Bennun, S.V., Yarema, K.J., Betenbaugh, M.J., & Krambeck, F.J (2013) Integration of the transcriptome and glycome for identification of glycan cell signatures. PLoS Computational Biology, 9, e1002813.
Mathew, M.P., Tan, E., Saeui, C.T., Bovonratwet, P., Liu, L., Bhattacharya, R., & Yarema, K.J. (2015) Metabolic glycoengineering sensitizes drug-resistant pancreatic cancer cells to tyrosine kinase inhibitors erlotinib and gefitinib. Bioorganic and Medicinal Chemistry Letters, 25, 1223–1227
Badr, H.A., AlSadek, D.M.M., Mathew, M.P., Li, C.-Z., Djansugurova, L.B., Yarema, K.J., & Ahmed, H. (2015) Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell surface glycosylation. Biomaterials, 70, 23–36.