Mevalonate Pathway Research

The research I perform on the mevalonate pathway of isopentenyl pyrophosphate falls into the category of Scholarship of Discovery.

What is the mevalonate pathway?

In eukaryotes (multi-celled organisms) and gram-positive bacteria, such as Staphylococcus aureus and Enterococcus faecalis, the mevalonate pathway makes isopentenyl pyrophosphate, the precursor to all isoprenoid including cholesterol in humans and molecules important for the cell membrane and wall in bacteria. If organisms cannot make isopentenyl pyrophosphate, they cannot survive.

Why study the mevalonate pathway?

In humans, the mevalonate pathway is a potential target for cholesterol lowering drugs, such as Lipitor®.  In bacteria, the mevalonate pathway is a potential target for antimicrobial agents.

But if humans have the mevalonate pathway, won’t a drug against the bacterial mevalonate pathway affect the person taking it?

We have found based on sequence, the order of specific amino acids that make up the enzymes, that there appear to be several differences in the human and bacterial forms of the enzymes in the mevalonate pathway.  Much of our research looks at differences between the human and bacterial forms of the enzyme that might be exploited in the design of anti-microbial agents.

What do we study in the mevalonate pathway?

Over the past several years my research group has focused on three major projects:

  1. Differences between human and bacterial HMG-CoA Synthase, the second enzyme in the pathway.
  2. Interactions among the enzymes in the pathway
  3. Isolation of the first enzyme of the pathway

What kind of results have we obtained?

Overall, the last several years of biochemical research has been frustrating with glimmers of hope, but that is the nature of research. Where we are today is summarized below:

  1. We have created several mutants of HMG-CoA Synthase that allow us to try to determine differences between the human and bacteria form. As of yet, while there seem to be some differences, none have been discovered that could be exploited by an antibiotic. The best results we had for this area of research were published while I was an assistant professor.
  2. Preliminary data indicates that there may be interactions between these enzymes. We are working to repeat the results so that we may publish the data.
  3. We believe we have isolated this enzyme, but not in a functioning form.

Student Mentoring:

Most of the students I have mentored have been on these projects. My student researchers are listed on the Research Assistants page.

Publications:

I do not have recent publications in my biochemistry research, my recent publications are in the category of Scholarship of Teaching and Learning.

Presentations:

I have had several students present this research at the Undergraduate Research Festival which is detailed on the Conference Presentation page.

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