Section: Rotations

Postdoctoral Position Available

Stephen Miller, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Biochemistry and Molecular Pharmacology

Rotation Projects

Work in our lab focuses on chemical approaches to the study of living cells. This multi-disciplinary approach brings together the areas of synthetic organic chemistry, molecular biology, biochemistry and cell biology.

1) Spatio-temporal control of GTPases: GTPases act as molecular switches to control a wide variety of dynamic cellular processes. Key to their proper function is the location and timing of their activation (and inactivation). Unfortunately, there are currently no reagents that can allow the rapid control of GTPase function necessary to fully dissect their roles in cellular function. We will employ a variety of approaches to allow the rapid activation and inactivation of these proteins in living cells, including synthesis of potential inhibitors and direct chemical modification of specific GTPases. With these tools in hand, we will study the essential roles of localization and timing in the proper transduction of biological signals.

2) Genetically-targetable small molecules: Fluorescent tagging of proteins with GFP has been widely used to study protein localization in living cells. However, the large size of GFP can often prove disruptive to protein function and/or localization. The recent report of a fluorescent small molecule, FlAsH, that can be selectively targeted to a small genetically-encodable peptide tag suggests a potentially less invasive route to the study of proteins in vivo. Toward this end, we will develop and use small molecules that can selectively bind short peptide tags within a protein. With these molecules in hand, we aim to elucidate the dynamic cellular localization and interactions of specific proteins (primarily GTPases) in living cells.

3) Identification of post-translationally modified proteins: Post-translational modification of many proteins with lipids is critical for their proper localization and function. However, surprisingly little is known about which proteins are so modified, what the molecular consequences are, or how these modifications are regulated. The nature, number, and dynamics of these lipid modifications can serve as an important level of control for proper protein localization. To study these modifications in a cellular context, we will synthesize lipids that bear uniquely reactive chemical functionality. We will use this approach to identify proteins that are modified in living cells, and assess their dynamics, cellular localization, and interactions.

Office: LRB 805
Phone: 508-856-8865
Fax: 508-856-2003
E-mail: Stephen.Miller@umassmed.edu
Keywords: Cell Biology, Biochemistry, Imaging and Microscopy, Chemical Biology, Drug Design

More on Stephen Miller's Research Research | Rotations View All Sections on One Page

Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Experience in synthetic organic chemistry is preferred. Contact Dr. Miller for additional details.