Uncovering what underlies neurodegenerative disease

Senile plaques are built up deposits of amino acid-based peptides, called amyloid beta, in the grey matter of the brain. These deposits are associated with aging; however, a large buildup is associated with more serious neurodegenerative conditions, like Alzheimer’s. While scientists have begun to uncover the interactions between amyloid beta peptides and disease, a great deal remains unknown. Dr. Paul Cremer, Professor of Chemistry, Biochemistry, and Molecular Biology at Pennsylvania State University, studies the basic chemistry of ion-cell membrane interactions in order to elucidate why senile plaques form on these surfaces, and furthermore, how plaques are linked to neurodegenerative diseases. His studies are helping to understand the molecular behavior at the biointerface. In other words, how do ions, peptides, small molecules, and proteins all interact at the barrier to entrance into the cell? By answering these challenging questions, Dr. Cremer is developing a fundamental understanding of the basic chemistry that occurs at the biomembrane while providing insights into diseases that serves as the first step in finding cures.

Perhaps most unique about Dr. Cremer’s approach is the multidisciplinary nature of his research and team. By combining chemistry, engineering, medicine, spectroscopy, microfluidics, and nanotechnology, he and his team approach questions that have puzzled the medical community with a new perspective. Biophysical and analytical studies are tied together through the employment of novel lab-on-a-chip platforms which enable high throughput and low sample volume analysis to be performed with unprecedented signal-to-noise. Highly regarded for his innovation, Dr. Cremer is the recipient of awards including the Alfred P. Sloan Research Fellowship, Beckman Young Investigator Award, and the NSF CAREER Award. Therefore, his advanced research and sophisticated methods are likely to one day advance therapeutics and cures for conditions in which biomembrane interfaces are involved, including neurodegenerative disorders.

Current research includes:

  • Underlying Pathology: Dr. Cremer and his lab have found that copper ion from solution can be transferred to the membrane interface and stored in a reservoir because of the metal ions’ binding properties. Maintaining homeostasis of ions inside and outside of the cell is important for long term health. Dr. Cremer hypothesizes that when metal ions get out of balance, they may affect lipid membrane properties and thereby contribute to diseases like Alzheimer’s, and furthermore, may be responsible for a number of pathologies related to oxidative stress.

  • Drug Targets: 80% of drug targets are dependent upon membrane proteins. Although it is relatively easy to crystallize soluble proteins, it is far more difficult to isolate and crystallize transmembrane species. Therefore, Dr. Cremer and his team are exploring ways to take membranes containing proteins and specialized lipids and use electrophoresis to separate various components that will be useful. His fundamental research will help identify novel drug targets for future therapeutics.

  • Water and Biological Interfaces: Dr. Cremer is interested in biological interfaces on the molecular level. For instance, next to the lipid membrane of each cell, there is a water layer which is implicated in several processes like when a protein binds or a cell penetrating peptide delivers a drug. Dr. Cremer and his team use sophisticated techniques including nonlinear optics and vibrational techniques to explore the architecture, ions, and peptides that interact at interfaces in order to make sense of the rules that govern their interactions.

Dr. Paul Cremer started his undergraduate career in the social sciences. However, during his junior year, he became fascinated by basic science questions, like how light interacts with matter? And how do molecules make up people? Therefore, he moved towards research in the chemical sciences with the hope of helping answer these fundamental questions. This process of questioning and discovery eventually lead Dr. Cremer to materials science where he has continued to be motivated up to the present day by basic questions.

Interested in problems that pull from his curiosities and the unknown, Dr. Cremer is open to science by serendipity. Often, he and his lab stumble into a problem in his lab and he believes that it is his role to “encourage graduate students to explore the unexpected.” These moments of novel results are sometimes the turning point for his studies and become a pathway to unchartered discovery.

In his free time, aside from research, Dr. Cremer enjoys training with his family to compete in half marathons. He also enjoys spending time with his children and can be found frequently mountain biking alongside them. With a fondness for the outdoors, whether he is running, biking, or hiking, Dr. Cremer takes time to enjoy the world around him while spending time with his family.

Website: http://sites.psu.edu/cremer/

J. Lloyd Huck Chair in Natural Sciences, Penn State University (2013-Present)

Fellow, American Association for the Advancement of Science (2010)

Edith and Peter O’Donnell Award in Science, The Academy of Medicine, Engineering, and Science of Texas (2010)

Fellow, American Chemical Society (2009)

Pittsburgh Conference Achievement Award (2006)