- Postdoctoral Fellow, Boston Children’s Hospital and Harvard Medical School, 2017
- Postdoctoral Fellow, Whitehead Institute for Biomedical Research and Massachusetts Institute for Technology, 2015
- Ph.D., University of Wisconsin-Madison, 2015
My research aims to develop new methods and tools applied to the study of biomolecules of interest, with a focus on designing new compounds for targeting cell surface receptors. My lab is particularly interested in the preparation of conjugates that consist of synthetic molecules and proteins. Towards this end, we develop new methods of protein preparation and conjugation, undertake medicinal chemistry campaigns, and perform pharmacological assays. These approaches focus on the pharmacology of G protein-coupled receptors, a family of proteins which constitute the target of over a quarter of approved therapeutics, with a specific emphasis on receptors relevant for the treatment of osteoporosis, diabetes, and inflammation. Findings from these studies will guide the rational design of therapeutics with improved properties.
- Improved GPCR ligands from nanobody tethering.
- Cheloha RW, Fischer FA, Woodham AW, Daley E, Suminski N, Gardella TJ, Ploegh HL.
- Nat Commun (2020 Apr 29) 11:2087. Abstract/Full Text
- Exploring cellular biochemistry with nanobodies.
- Cheloha RW, Harmand TJ, Wijne C, Schwartz TU, Ploegh HL.
- J Biol Chem (2020 Nov 6) 295:15307-15327. Abstract/Full Text
Research in Plain Language
Disease is often caused by the cells in our body responding inappropriately to signals sent by neighboring cells. As such many diseases can be treated by correcting these signaling problems. Chemistry can provide new molecules to understand these signaling problems and to correct them for the treatment of disease. My lab makes new compounds through linking molecules provided by biology (proteins) to those provided by chemistry. These compounds combine the useful properties of both to enable the study of processes related to human disease and to highlight the path towards making better therapeutics.
We use proteins uniquely found in the immune systems of camels, alpacas, and llamas called nanobodies. We can develop nanobodies that interact with any type of cell from within our body. We also work with chemicals known to turn on biological responses by interacting with receptors found on the outside surface of cells. Because of the special properties of nanobodies we can link them to biologically active chemicals to provide linked compounds that cause biological responses only in the type of cells bound by the nanobodies. This approach may allow us to develop linked compounds that induce desirable biological responses, such as treatments for diseases, without causing undesirable responses (side-effects). These efforts require that we use the tools of chemistry, biology, and the study of cell signaling. Success might allow for new treatments for osteoporosis, diabetes, and inflammation.