Department of Biochemistry

Patrick J. Loll, Ph.D.
Associate Professor of Biochemistry

Telephone:215-762-7706
Pat.Loll@Drexel.edu

Education:
Ph.D. (1989) Biophysics,
Johns Hopkins University School of Medicine

Research Program:
Research in my lab revolves around molecular structure. The underlying goal for all our projects is to understand biologically important processes at the molecular level. Our principal tool is X-ray crystallography; we also devote much energy to protein expression, protein biochemistry, spectroscopy, and enzymology to support the structural efforts. Specific areas of interest include:

* The structural biology of membrane proteins. Many of the most fascinating and crucial processes which occur in living cells are modulated by integral membrane proteins. Our lab is studying a number of different membrane-bound enzymes, receptors, and transport proteins; in addition, a substantial effort focuses on the development of crystallization methodologies for these molecules.

* The molecular mechanism of polyglutamine disease. Focusing on ataxin-3, the causative agent of the neurodegenerative Machado-Joseph disease, we are applying structural, ultrastructural, biochemical, and biophysical methods to understand how expansion of polyglutamine tracts leads to protein misfolding, fibril formation, and, ultimately, neuronal toxicity.

* Structure-based drug design. In collaboration with Paul Axelsen's lab at Penn, we are applying structural and computational methods to deepen our understanding of how the antibiotic vancomycin functions, and to design novel drugs to combat antibiotic resistance.

* Structural studies of biochemically important proteins. In addition to the areas listed above, we are studying a diverse panel of other molecules, all of which are of significant medical interest. Projects include complexes of interleukin-5 and its cell surface receptor; viral kinases; proteins involved in lipid remodeling and endocytosis; and potential new targets for antibiotics.

Selected references:

Hitscherich, C. Jr., Kaplan, J., Allaman, M., Wiencek, J., & Loll, P. J.(2000) "Static light scattering studies of OmpF porin: Implications for integral membrane protein crystallization." Protein Science, 9: 1559-1566.

Loll, P. J. & Axelsen, P. H. (2000) "The structural biology of molecular recognition by vancomycin." Ann. Rev. Biophys. Biomolecular Struct. 29:265-289.

Selinsky, B. S., Kupta, K., Sharkey, C. T., & Loll, P. J. (2001) "Structural analysis of NSAID binding by prostaglandin H2 synthase: Time-dependent and time-independent inhibitors elicit identical enzyme conformations." Biochemistry, 40: 5172-5180.

Bevivino, A. E. & Loll, P. J. (2001) "An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel beta fibrils." PNAS USA 98:11955-11960.

Loll, P. J, Hitscherich, C. Jr., Allaman, M.,& Weincek, J. (2002) "Assessing micellar interaction and growth in detergent solutions used to cyrstallize integral membrane proteins." Cryst. Growth Design 2:533-539.

Loll, P. J (2003) "Membrane protein structural biology: The high throughput challenge." J. Struct. Biol. 142:144-153.

Gupta, K., Kaub, C. J., Carey, K. N., Casillas, E. G., Selinsky, B. S., & Loll, P. J (2004) "The 2.0 Angstrom resolution crystal structure of prostaglandin H2 synthase-1: Structural insights into an unusual peroxidase." J. Mol. Biol. 335:503-518.