Stierle, Andrea

Research professor
Biomedical and Pharmaceutical Sciences
The University of Montana - Missoula
Professional Summary: 

I have been a Research Professor in the Department of Biomedical and Pharmaceutical Sciences since October 2009, when my collaborator Donald Stierle and I moved our research lab from Montana Tech of the University of Montana to the University of Montana-Missoula. There were several reasons for this move, but first and foremost was the need to relocate to a more research supportive environment with a biomedical/medicinal chemistry focus. Our move coincided with the establishment of the Medicinal Chemistry program at UM-Missoula so we hoped our expertise in drug discovery would make this a mutually beneficial arrangement. We celebrated our second anniversary as members of BMED research faculty on October 1, 2011. Our relocation to the University of Montana-Missoula has had a strong positive impact on the productivity, depth and impact of our research and has opened the doors to some strong collaborations.
The Stierle lab is essentially a drug discovery lab and our focus is the isolation and characterization of secondary metabolites from source organisms using bioassay guided fractionation. This is a flexible arrangement that can accommodate a variety of source organisms and a variety of bioassay schema. We are currently studying the secondary metabolites of two discrete organism collections, one microscopic, the other macroscopic:

1. The acid mine waste microorganisms growing in the waters and sediments of Berkeley Pit Lake in Butte, Montana.
2. The Ayurvedic medicinal plants Bacopa monnieri and Ashwaganda
3. We are also embarking on a new area of research, if our attempts at new funding are successful – drug discovery in human gut microflora.
One of the strengths of Natural Products Chemistry is its adaptability. Different biological assays can direct isolation efforts in a number of different directions. When coupled with Medicinal Chemistry, these same biological assays can direct semisynthetic modifications of lead compounds to yield more selective and/or more potent therapeutic agents. A new bioassay can broaden the potential application of the research or redirect it completely without changing the actual methodology inherent in drug discovery. These new directions however can open up the possibilities for new collaborations that can enhance the translational potential of the work. This has indeed been the case since our relocation to UM-Missoula.
We use specific signal transduction enzymes – matrix metalloproteinase-3, caspase-1 and caspase-3 – as our primary assays to guide the search for new compounds. Research in various labs has shown that inhibitors of each of these enzymes have been shown to have promising therapeutic potential. In our own research, novel enzyme inhibitors have been sent to the National Institutes of Health Developmental Therapeutics Program to be tested in their 60 human cancer cell-line screen. All of the compounds we have isolated have shown low-micromolar to nanomolar activity against specific human cancer cell lines. This approach continues at UM-Missoula, but new collaborations and facilities have broadened the scope and heightened the impact of our findings. Of particular interest to us are compounds that:
• block the onset and metastasis of cancer (MMP-3)
• target autoimmune, neurodegenerative, inflammatory disorders and leukemia (caspase-1)
• mitigate the damaging effects of stroke (caspase-3)
• enhance apoptosis of tumors (X-linked inhibitors of apoptosis proteins – XIAP)
We were excited to find that several faculty members of the Department of Biomedical and Pharmaceutical Sciences are involved in research that complements our own studies. These collaborations will be described.

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