Associate Professor of Biochemistry & Molecular Biology
Telephone:215-762-7706
Patrick.Loll@Drexelmed.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:

• Large natural product antibiotics. We are applying structural, computational, and biophysical methods to deepen our understanding of how antibiotics like vancomycin, ramoplanin, tyrocidine, and bacitracin function. We hope to use this information to design novel drugs to combat antibiotic resistance.
  
• The structural basis of drug action. We are interested in probing the interactions between drugs and their protein targets at the structural level. Currently, we are examining the binding of general anesthetics to model protein targets, with an eye toward elucidating the structural determinants that control anesthetic recognition.
  
• Deubiquitylation by Josephin proteins. Ataxin-3 and other Josephin proteins catalyze the degradation of poly-ubiquitin chains, modulating signals controlling protein breakdown and trafficking. We are using structural and biochemical approaches to study the function of these enzymes.
  
• The molecular mechanism of polyglutamine disease. We are studying ataxin-3, the causative agent of the neurodegenerative Machado-Joseph disease, using structural, ultrastructural, biochemical, and biophysical methods to understand how expansion of polyglutamine tracts leads to protein misfolding, fibril formation, and neuronal death.
  
• 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.

Selected References

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

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. (2003) “Membrane protein crystallization:  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)  “Manipulation of kinetic profiles in 2-aryl propionic acid cyclooxygenase inhibitors.”  Bioorg. Med. Chem. Lett., 14: 667-671

Liu, R., Loll, P. J., & Eckenhoff, R. G.  (2005) “Structural basis for high affinity volatile anesthetic binding in a natural 4-helix bundle protein.  FASEB J.,19: 567-576.

Gupta, K., Selinsky,  B. S. & Loll. P. J.  (2006)  “2.0 Å crystal structure of prostaglandin H2 synthase-1 reconstituted with a manganese porphyrin cofactor.” Acta Crystallogr. D62: 151-156.

Xi, J., Liu, R., Rossi, M. J., Yang, J., Loll, P. J., Dailey, W. P., & Eckenhoff, R. G. (2006) “High resolution features from low affinity interactions:  Photoactive analogs of the haloether anesthetics.” ACS Chem. Biol. 1: 377-384.

Weeks, S. D., Drinker, M., Loll, P. J. (2007) “Ligation independent cloning vectors for expression of SUMO fusions.” Prot. Expr. Purif. 53: 40-50.