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Grant Award Allows Research on a New Approach to Treat Rare Cancer

Jetze Tepe, a Michigan State University chemist, is the recipient of a highly competitive 2019 Brian D. Novis Senior Research Grant from the International Myeloma Foundation, or IMF. The $80,000 grant award will support his ongoing work on the development of a new approach to treating multiple myeloma, or MM, using proteasome enhancement.

Tepe, an associate professor in the Department of Chemistry in the MSU College of Natural Science, won this same award in 2013 at an earlier stage in his MM research and has only positive words about the foundation supporting his work and his lab.

“The International Myeloma Foundation is a wonderful organization that helps people,” Tepe said. “When someone receives a diagnosis of multiple myeloma, blood-borne cancer that manifests itself in the bone marrow, the IMF is there to guide them through all the physical and emotional burdens that arise for MM patients.”

Part of IMF’s patient support includes grassroots fundraisers, with members often creating their own events, such as 5K relays, to support research or other aspects of treatment for this uncommon cancer.

“The Brian D. Novis Senior Research Grant is supported in part by such fundraising,” Tepe said.  “The money comes from many, many individuals contributing to the work, making it very personal as our lab pursues this research to try to help with this illness. IMF invites grant recipients to San Diego, where we not only receive our award but also meet patients and their families, their physicians and the grant’s fundraisers and organizers. The investment all these people have made in supporting our research, personally and financially adds a whole new dimension to what our lab is doing. IMF’s goal is to cure multiple myeloma, and it’s an honor to be part of that goal.”

Current chemotherapy utilizes proteasome inhibitors, which prevent the recycling of proteins critical for cell survival, preventing cancer from expanding. This therapy has extended the average patient survival rate about five years. The problem arises when the patient becomes resistant to the treatment, which occurs in 98 percent of all patients; when that occurs, no other medical therapy is available to stop MM’s progression.

Tepe’s research is testing a different mechanism for treating MM, so that those patients who become resistant to the original treatment may live longer.

In 2013, Tepe’s team identified a molecule that was very effective against MM cells, but they needed to understand how it worked in order to continue their research. Using the first Brian D. Novis Senior Research Grant, they determined that the molecule operated through a unique mechanism that, instead of functioning as a protease inhibitor, works to increases activity of the proteasome in cells against unfolded proteins, that is, proteins that lack a defined three-dimensional structure. Unfolded cellular proteins that are not degraded (i.e., broken down) fast enough due to mutations or other cellular dysfunctions, accumulate in cells and some of those proteins are known to induce cancer. By increasing the activity of the proteasome on the proteins in these cells, these molecules help prevent the accumulation of those cancer-causing proteins.

“In summary, using this molecule results in an increased rate of degradation of proteins that contribute to MM cancer growth in the bone marrow, preventing the cancerous cells from multiplying,” Tepe said. “It’s a completely new approach to chemotherapy and that is what we’re very excited about.”

The current grant will be used to explore the potential side effects this molecule might have on bone marrow and other cells, specifically the negative effects so often associated with chemotherapies—Is it toxic? To what degree? Can it be safely combined with current MM treatments? Tepe and his lab must answer these questions—and many more—before any consideration of using these molecules as a therapy can be considered.

“This grant program is highly selective, globally competitive, and open to scientists and clinicians from all areas of cancer research,” said Robert Maleczka, chair of the MSU Department of Chemistry. “For professor Tepe to be selected as one of only two senior awardees this year is a terrific honor, made only more impressive by Jetzebeing only the third two-time awardee of this grant since 2013. Perhaps most importantly, the award is recognition that professor Tepe’s creative fusion of chemistry and biology is paving the way for what will hopefully become a cure for myeloma.”

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