Multidrug Resistance Study Awarded $1.3 Million Federal Grant
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Structural biologist Min Lu, PhD, was recently awarded a four-year, $1.3 million grant from the National Institutes of General Medical Sciences to investigate new therapeutic strategies to combat multidrug resistance (MDR).
MDR poses a major challenge to the development of new drug therapies for cancer and infectious diseases. It can reduce the effectiveness of drugs and result in adverse effects and increased chance of death. MDR has also been identified in other classes of drugs, including those for neurological disorders.
Dr. Lu’s study, “Molecular Basis of Substrate Translocation in the Drug/H+ Antiporter 1 (DHA1) Family,” will serve as a stepping stone to the development of new ways to inhibit multidrug transporters — a type of protein inside the cell membrane that moves specific molecules from the inside to the outside of a cell. Dr. Lu hopes to understand how the bacterial DHA1 multidrug transporters and their human counterparts (the SLC18 antiporters) can be modulated for potential therapeutic benefits.
“This project seeks a deep understanding of a major mechanism underlying multidrug resistance,” Dr. Lu said. “Our proposed work will also elucidate the molecular underpinnings of vesicular neurotransmitter and neurotoxin sequestration by the SLC18 antiporters, which may facilitate the treatment of a number of neurological disorders, such as alcoholism, autism, bipolar disorder, Huntington’s disease, major depressive disorder, Parkinson’s disease, schizophrenia and Tourette syndrome.”
Dr. Lu is an investigator in the Center for Proteomics and Molecular Therapeutics, one of 10 RFU centers and institutes working to improve health and well-being and advance innovation in health care. Ronald Kaplan, PhD, RFU executive vice president for research, commended both Dr. Lu and the NIH.
“The problem of multidrug resistance in brain diseases limits the use of new drugs very early into their life cycle,” he said. “If we can overcome this resistance, we extend the therapeutic repertoire of these drugs for effective use in patients.”