The overarching research theme of the Wolfe Lab is combining chemistry and biology toward understanding the molecular basis of dementias, especially Alzheimer's disease, and developing prototype therapeutic agents. Small organic molecules are designed and used as probes to address biological questions (chemical biology), and such agents may also be optimized for their therapeutic potential (medicinal chemistry). In parallel, macromolecular structure and function is explored as well (biological chemistry). In this way, chemical biology, medicinal chemistry and biological chemistry are interwoven and brought to bear on the problem of dementias.

Another way of thinking about this interdisciplinary approach is to consider Pasteur’s Quadrant. Science that is very basic without focusing much on the practical aspects is Bohr’s Quadrant. Science that is very applied, without focusing much on discovering new underlying principles is Edison’s Quadrant. Those areas that focus on both highly basic and highly applied problems are in Pasteur’s Quadrant (D. E. Stokes, 1997). Likewise, chemical biology is highly basic, and medicinal chemistry is highly applied. With the right focus, however, small molecules that are tools for biology can also be pursued for their therapeutic potential, an area that can be dubbed “chemical biomedicine.” Chemical biomedicine is chemistry in Pasteur’s Quadrant, chemistry applied to both biology and medicine.

Chemical Biomedicine for Alzheimer's Disease