U-M Center for the Discovery of New Medicines Announces New Grants

ANN ARBOR — The University of Michigan Center for the Discovery of New Medicines has awarded funding for five new drug discovery projects by U-M faculty that target cancer, obesity, blood clots and the dangerous side effects of opioid painkillers.

 “The CDNM Executive Committee was optimistic that the seeds of future therapeutics would grown from funding this round of strong and diverse projects,” says Vincent Groppi, Ph.D., the center’s director.

The center launched in 2012 as a partnership between the U-M Medical School, Comprehensive Cancer Center, College of Pharmacy, Life Sciences Institute and Provost’s Office to provide mentorship and early-stage support for drug discovery projects.

Grants of up to $50,000 each primarily support work in four university core laboratories — the Center for Chemical Genomics and Center for Structural Biology at the U-M Life Sciences Institute, and Pharmacokinetics Core and Vahlteich Medicinal Chemistry Core at the College of Pharmacy.

The latest grants were awarded to:

  • Zaneta Nikolovska-Coleska, Ph.D., an associate professor of pathology in the U-M Medical School, to perform screening and X-ray crystallography to study a binding domain present in a fusion protein associated with mixed lineage leukemia. Disruption of the domain’s interactions represent a novel potential therapy for aggressive leukemia.

  • Luis Diaz Gimenez, M.D., Ph.D., a research investigator in the lab of Roger Cone, Ph.D., at the U-M Life Sciences Institute, to conduct screening for antagonists of the melanocortin 3 receptor, which is involved in the brain’s regulation of energy storage. Hits among natural product extracts or small molecules may hold promise as a novel treatment for obesity. Ashootosh Tripathi, Ph.D., a research investigator in the lab of David H. Sherman, Ph.D., at the LSI, is a co-investigator on the grant.

  • Daniel Lawrence, Ph.D., the Frederick G L Huetwell Professor of Basic Research in Cardiovascular Medicine in the Department of Internal Medicine at the U-M Medical School, to conduct screening to develop small molecule inhibitors of alpha-2-antiplasmin, a potential target for treating blood clots. In animal models of stroke, removing or inhibiting a2AP significantly improved outcomes.

  • Alan Smrcka, Ph.D., professor of pharmacology at the U-M Medical School, for medicinal chemistry to continue to develop a small molecule inhibitor that can increase the effectiveness of opioid painkillers without the negative side effects. The novel approach could be used to administer narcotics at lower doses to achieve the same effect, or at higher doses, but more safely.

  • Daniel Wahl, M.D., Ph.D., a resident (and soon to be assistant professor) in the Department of Radiation Oncology at the U-M Medical School, for high-throughput screening to find inhibitors of the wild type form of isocitrate dehydrogenase 1, an enzyme that helps gliobastomas to proliferate. Inhibition of mutant IDH1 is advancing through clinical trials, but 90 percent of patients express the wild type. Theodore S. Lawrence, M.D., Ph.D., chair of the Department of Radiation Oncology, is a co-investigator on the grant.

Together, the Center for the Discovery of New Medicines and its affiliated cores help guide researchers through the many stages of the drug discovery process — from validation of a drug target to optimizing drug safety and effectiveness for human clinical trials.

The center’s executive committee includes top researchers from the U-M College of Pharmacy, Comprehensive Cancer Center, Medical School and Life Sciences Institute.

Since its establishment, the center has awarded 50 grants totaling more than $1.4 million. Several projects have already gone on to receive additional external funding, commercial licensing and patent protection.

The deadline for the next round of grant proposals is Friday, November 3. 

—Jul 6, 2017