Protein function

Protein inhibition

Membrane model development

Membrane protein interaction probes

Drug development

Education

• Postdoctoral Fellow/Research Associate, University of Pennsylvania, 2013-2019
• Ph.D., Chemistry/Biochemistry, University of California, San Diego, 2013
• B.S., Biochemistry, Oklahoma State University, 2007

Research Interests

The membranes of a cell are hotspots of biological activity. In turn, many diseases proceed through action near or within cellular membranes. Members of the peripheral membrane class of proteins are cytosolic until targeted to the membrane, either through covalent or non-covalent means. We are interested in understanding these proteins at atomic resolution. This information helps us gain a deeper understanding of these proteins and is used to inform rational inhibitor design efforts. The ultimate goal of the Fuglestad Lab is to inhibit peripheral membrane proteins for chemical biology investigations and to develop drug candidates to treat diseases such as cancer and cardiovascular disorders.

Protein/membrane interactions: Understanding the interactions between peripheral membrane proteins and lipids is of paramount importance in strategizing therapeutics. We use a number of models of biological membranes to probe the interactions between proteins and cellular membranes. Of particular interest in the Fuglestad Lab is leveraging reverse micelles as membrane mimics, which has several advantages over other more commonly used membrane models. We employ a multitude of techniques to study protein/membrane interactions including protein nuclear magnetic resonance (NMR) spectroscopy, fluorescence methods, and small-angle scattering, among others.

Fragment screening and inhibitor design: Rational design of inhibitors uses information about the structure and function of the protein target of interest. Fragment-based approaches have recently come to prominence in inhibitor design. This involves screening proteins for small inhibitor building blocks rather than larger drug-like molecules. Despite its tremendous promise, one instance where fragment screening generally fails is in the detection of inhibitor building blocks for ‘smooth’ proteins lacking natural ligand-binding pockets. We employ a recently developed technology that takes advantage of nanoscale confinement of proteins within reverse micelles to allow detection of fragment binding to smooth proteins. The information gained from these screens is used in highly collaborative efforts in inhibitor development for the ultimate goal of obtaining chemical biology tools and drug leads.

Select Publications

Stackhouse CI, Pierson KN, Labrecque CL, Mawson C, Berg J, Fuglestad B, Nucci NV. (2024) Characterization of 10MAG/LDAO reverse micelles: Understanding versatility for protein encapsulation. Biophysical Chemistry, 311, 107269.

Develin AM, Fuglestad B. (2024) Inositol Hexaphosphate as an Inhibitor and Potential Regulator of p47phox Membrane Anchoring. Biochemistry. 63(9):1097-1106. (Featured on the front cover)

Walters SH, Castillo AJ, Develin AM, Labrecque CL, Qu Y, Fuglestad B. (2023) Investigating protein‐membrane interactions using native reverse micelles constructed from naturally sourced lipids. Protein Science, e4786. (Featured on the front cover)

Labrecque CL, Nolan AL, Develin AM, Castillo AJ, Offenbacher, AR, Fuglestad B. (2022) Membrane-mimicking reverse micelles for high-resolution interfacial study of proteins and membranes. Langmuir, 38(12), 3676-3686. (Featured on the front cover)

Labrecque CL, Fuglestad B. (2021) Electrostatic drivers of GPx4 interactions with membrane, lipids, and DNA. Biochemistry, 60(37), 2761-2772.

Courses

• CHEM 403 - Biochemistry I
• CHEB 601 - Chemical Biology I