JHU biomedical engineering primary faculty
Kevin J. Yarema, PhD
Associate Professor of Biomedical Engineering
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).
1. Campbell CT, Sampathkumar S-G, Weier C, & Yarema KJ. Metabolic oligosaccharide engineering: perspectives, applications, and future directions. Mol Biosyst. 2007; 3:187-194.
2. Sampathkumar S-G, Li AV, Jones MB, Sun Z, & Yarema KJ. Metabolic installation of thiols into sialic acid modulates adhesion and stem cell biology. Nat Chem Biol. 2006; 2:149-152.
3. Campbell CT, Aich U, Weier CA, Wang JJ, Choi SS, Wen MM, Maisel K, Sampathkumar S-G, & Yarema KJ. Targeting pro-invasive oncogenes with short chain fatty acid-hexosamine analogs inhibits the mobility of metastatic MDA-MB-231 breast cancer cell. J Med Chem. 2008; 51:8135–8147.
4. Elmouelhi N, Aich U, Paruchuri VDP, Meledeo MA, Campbell CT, Wang JJ, Srinivas R, Khanna HS, & Yarema KJ. Hexosamine template. A platform for modulating gene expression and for sugar-based drug discovery. J Med Chem. 2009; 52:2515-2530.
5. Krambeck FJ, Bennun SV, Narang S, Choi SS, Yarema KJ, & Betenbaugh MJ. A mathematical model to derive N-glycan structures and cellular enzyme activities from mass spectrometric data. Glycobiology. 2009 19:1163-1175.
6. Wang Z, Sarje A, Che P-L, & Yarema KJ. Moderate strength (0.23-0.28 T) static magnetic fields (SMF) modulate signaling and differentiation in human embryonic cells. BMC Genomics. 2009; 10:356.