Structural Biology Faculty

The research of the primary and secondary faculty that use structural biology techniques are listed below along with a short description of their work.

Karen Anderson Structural  and functional studies on proteins that are molecular targets for antiviral, antimicrobial, antiparasitic therapies. Our lab is interested in mechanistic and structural studies of HIV-1 reverse transcriptase, an important target for the design of novel therapies to treat AIDS. We are also studying a class of bifunctional proteins having two different catalytic activities that are unique to parasitic protozoa. These protozoal pathogens are responsible for life-threatening opportunistic infections in AIDS patients as well as malaria which is a serious world health problem.
Titus Boggon Structural biology of signaling proteins. We focus on understanding how signal transduction pathways function at the atomic level, and the mechanisms by which these pathways become altered in disease. Major topics of interest: Regulation of cytokine signaling by the Janus kinases, intermolecular interactions of proteins involved in integrin signaling pathways, signal transduction in polycystic kidney disease.
David Calderwood Signaling through integrin adhesion receptors. Dynamic, and tightly regulated, adhesion of cells to the extracellular matrix that surrounds them is essential for development, wound healing, the immune response, hemostasis and cell migration. Disruption of normal adhesion and adhesion signaling contributes to inflammatory, auto-immune and cardiovascular diseases and tumor metastasis, making these promising pathways for therapeutic intervention. We combine the tools of structural biology, biochemistry and cell biology to investigate how intracellular signals regulate integrin cell adhesion receptors and how integrin-mediated signaling and linkage to the cytoskeleton control cell adhesion, migration, morphology, and mechanosensing.
Barbara Ehrlich  Structure-function of intracellular calcium channels. We study how structural features can be used to predict the function of the channels that release calcium from intracellular stores, In particular, we are interested in how calcium binding can regulate the shape and activity of the intracellular channels, polycystin 2 and the InsP3R, and how structure and function are altered in disease
Ya Ha  Intramembrane proteases. We use x-ray crystallography to solve structures of these membrane proteins with the hope that the structural knowledge will shed light on their mechanism of action, explain mutations that cause human disease, and help drug development.
Michael Hodsdon We are focused on the relationship between the biophysical properties of proteins and the molecular mechanisms of human disease. NMR spectroscopy is a central tool in our research program, which we use to determine the tertiary structures of proteins and monitor their biophysical behavior under physiologic conditions. In solution, proteins exist as interchanging ensembles of conformational states. Many protein functions are regulated by or derived from a thermodynamically-driven redistribution of these structural states. We have sought to identify biomedically-important proteins whose regulation by these dynamic equilibria are altered in disease. We have explored a number of protein systems, including members of the hematopoietic cytokine superfamily, a polymorphic drug-metabolizing enzyme, and proteins involved in vesicular transport.
James Howe  Structure-function of glutamate receptors. Ionotropic glutamate receptors are oligomeric transmembrane proteins that mediate excitatory synaptic transmission in the central nervous system. There are many high-resolution x-ray structures of individual protein domains of the receptors and recently an x-ray structure of the full-length receptor was published. Using these structures as a guide, we are attempting to understand the sequence of conformational changes that translates glutamate binding into receptor-mediated transmembrane currents. Our primary tool is patch-clamp electrophysiology, but we also have active collaborations that combine our functional measurements with structural information from crystallographic and spectroscopic studies.
Elias Lolis  Inflammatory proteins. Our focus is in (1) chemokines and their interactions with glycosaminoglycans and G-protein coupled receptors, and (2) macrophage migration inhibitory factor (MIF) and its interaction with small molecules and its receptors. Besides inflammation, these proteins are involved in cancer, HIV-1 infection, autoimmune disorders, and genetic diseases (e.g., WHIM syndrome). Our goal is to use structural biology (X-ray crystallography and NMR) to develop a better understanding of the mechanism of action of these proteins for the developing of therapeutics.
Gary Rudnick  Mechanism of membrane transport. The availability of X-ray crystal structures of membrane transport proteins has opened a window of insight into their function. We are particularly interested in neurotransmitter transporters and the conformational changes that accompany transmitter translocation and inhibitor binding. These transporters are targets for antidepressant drugs and psychostimulants such as amphetamines and cocaine. A combination of structural, biochemical and computational analysis has provided new insight into the mechanism of transport.
Joseph Schlessinger  Our laboratory is using x-ray crystallography and other biochemical and biophysical  approaches including electron microscopy to explore the mechanism of action of receptor tyrosine kinases (RTK),  cytoplasmic protein kinases and proteins involved in mediating their intercellular signaling pathways. Our goal is to obtain a a detailed molecular view of how RTKs are activated and how their cellular selectivity is controlled normally, in cancer and in other diseases.
Ben Turk We are interested in understanding how protein kinases target specific protein substrates, thus ensuring proper transmission of intracellular signals. Solving this problem requires elucidating the structural basis of kinase-substrate interactions, which we accomplish using a combination of structural biology, combinatorial library screening, and biochemistry. These approaches enable us to probe the consequences of disrupting these interactions as a means to unravel the molecular mechanisms of signal transduction in living cells.