Assistant Professor of Biomedical Engineering and Adjunct Assistant Professor of Pharmaceutics and Pharmaceutical Chemistry
Polymer Chemistry, Protein Engineering, Bioconjugation Techniques
Synthetic polypeptides are uniquely poised to harness the structure and function of native proteins with the synthetic advantages of chemically produced polymers. We synthesize polypeptides, which are applied in the following areas:
Synthesis of Biomimetic Materials:
The Kramer Lab is developing methods to synthesize mimics of the unique structural and signaling molecules found in nature. We are particularly fascinated by glycoproteins, which are proteins with sugars attached. Natural glycoproteins play roles in almost every area of biology and have diverse therapeutic applications. Many important classes of glycoproteins are produced by cells as heterogenous mixtures with small structure variations. The Kramer lab is developing methods to prepare structurally defined glycoproteins to enable structure-functions studies and to tune bioactivity.
The surface of every cell is covered with an array of glycoproteins, glycolipids, and polysaccharides that collectively form the glycocalyx. The glycocalyx is a heterogenous structure and biological methods to modulate the molecules within are currently extremely limited. The Kramer Lab synthesizes precisely defined glycoproteins and displays them on live cell surfaces in a glycocalyx engineering strategy. Our ability to systematically alter the glycocalyx structure is now allowing structure-function studies to shed light on fundamental biology, disease states, and therapeutic development.
The cancer glycocalyx: Cancer cells have a strikingly altered glycocalyx, but the causes and effects are poorly understood. The Kramer lab is developing tools and methods for systematic studies of the surface of cancerous and pre-cancerous cells and how this environment affects cell fate. This knowledge will guide new diagnostics, therapeutics, and vaccines for diverse cancers.
Synthetic human mucus for epithelial tissue models:
Mucosal coatings on epithelial tissues are our first point of contact with the outside world. Mucus acts as lubricating barriers that mediate absorption of gases, nutrients, drugs, and pathogens, and host the microbiome. Despite these diverse and essential roles in life, current research relies mainly on poorly-defined, unreproducible mucins extracted from farm animal tissues. The Kramer lab is developing fully synthetic human mucus to be used in defined and reproducible models of epithelial tissues.
Coronaviruses and mucins: Mucins are the first materials a coronavirus encounters as it makes its way toward the cell surface. These viruses have evolved to bind to mucins as part of their survival strategy. Further, each time a person sneezes or coughs they expel virus coated in mucus droplets. We are studying how mucins affect the ability of coronaviruses to both enter cells and survive when dried on surfaces after a cough or sneeze.
- , , , , , , , , , , , and The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins.
- MN Zhou, CS Delaveris, Jessica R Kramer, JA Kenkel, EG Engleman, CR Bertozzi. N-Carboxyanhydride Polymerization of Glycopolypeptides That Activate Antigen-Presenting Cells through Dectin-1 and Dectin-2. Angew Chem Int Ed Engl. Doi: 10.1002/anie.201713075 (2018)
- Jessica R. Kramer, Bibiana Onoa, Carlos Bustamante, Carolyn R. Bertozzi. Chemically tunable mucin chimeras assembled on living cells. PNAS. doi: 10.1073/pnas.1516127112 (2015).
- Jessica R. Kramer,* Rosine Petitdemange,* Laure Bataille, Katell Bathany, Anne-Laure Wirotius, Bertrand Garbay, Timothy J. Deming, Elisabeth Garanger, and Sébastien Lecommandoux. Quantitative side-chain modifications of methionine-containing elastin-like polypeptides. ACS Macro Lett., 4, 1283–1286 (2015).
- Jessica R. Kramer,* Nathan W. Schmidt,* Kristine M. Mayle, Daniel T. Kamei, Gerard C. L. Wong, and Timothy J. Deming, Reinventing cell penetrating peptides using glycosylated methionine sulfonium ion sequences. ACS Cent. Sci., 2, 83–88 (2015).
- Jessica R. Kramer, and Timothy J. Deming. Deming. Recent advances in glycopolypeptide synthesis. Polym. Chem. 5, 671-682 (2014).
- Jessica R. Kramer, and Timothy J. Deming. Multimodal switching of conformation and solubility in homocysteine derived polypeptides. J. Am. Chem. Soc. 136, 5547–5550 (2014).
- April R. Rodriguez, Jessica R. Kramer, and Timothy J. Deming. Enzyme-triggered cargo release from methionine sulfoxide containing copolypeptide vesicles. Biomacromolecules 14, 3610–3614 (2013).
- Jessica R. Kramer, and Timothy J. Deming. Reversible Chemoselective tagging and functionalization of methionine containing peptides. Chem. Comm. 49, 5144–5146 (2013).
- Jessica R. Kramer,* April R. Rodriguez,* Uh-Joe Choe, Daniel T. Kamei, and Timothy J. Deming. Glycopolypeptide conformations in block copolymer assemblies influence both nanoscale morphology and ligand binding properties. Soft Matter 9, 3389–3395 (2013).
- Jessica R. Kramer, and Timothy J. Deming. Preparation of multifunctional and multireactive polypeptides via methionine alkylation. Biomacromolecules 13, 1719–1723 (2012).
- Jessica Kramer, Souren Soukiazian, Sky Mahoney, and Jocelyn Hicks-Garner. Microbial fuel cell biofilm characterization with thermogravimetric analysis on bare and polyethyleneimine surface modified carbon foam anodes. J. Power Sources 210, 122–128 (2012).
- Jessica R. Kramer and Timothy J. Deming. Glycopolypeptides with a redox-triggered helix-to-Coil Transition. J. Am. Chem. Soc. 134, 4112–4115 (2012).
- Jessica R. Kramer and Timothy J. Deming. General method for purification of α-amino acid-N-carboxyanhydrides using flash chromatography. Biomacromolecules 11, 3668–3672 (2010).
- Jessica R. Kramer and Timothy J. Deming. Glycopolypeptides via living polymerization of glycosylated-L-lysine N-carboxyanhydrides. J. Am. Chem. Soc. 132, 15068–15071 (2010).