Wayne State researcher receives $1.95 million NIH grant to study impact of inositol homeostasis on essential cellular functions

DETROIT – A researcher from Wayne State University’s Department of Biological Sciences has received a five-year, $1.95 million grant from the National Institute of General Medical Sciences of the National Institutes of Health to identify mechanisms that regulate inositol synthesis in mammalian cells and determine the cellular consequences of inositol depletion.

Inositol is a type of sugar that is essential for the viability of eukaryotic cells. Myo-inositol is the precursor of all inositol compounds, which play pivotal roles in cell signaling and metabolism. Consistent with its importance, a disturbance of inositol homeostasis or balance within the body is associated with health issues as diverse as neurological and psychiatric illnesses, myopathies, cancer, and diabetes. Inositol depletion is a hypothesized therapeutic mechanism of action of drugs used to treat bipolar disorder, a devastating psychiatric illness that affects approximately 2% of the population. The identification of specific pathways that are perturbed as a result of inositol deprivation will provide insights into the tumor-suppressive effects of upregulating inositol synthesis and may suggest candidates for new mood-stabilizing, inositol-depleting drugs for the treatment of bipolar disorder.

The study, “Regulation of inositol biosynthesis and consequences of inositol depletion,” will be led by Miriam Greenberg, Ph.D., professor of biological sciences in the College of Liberal Arts and Sciences.  According to Greenberg, very little is known about inositol homeostasis in human cells.

“This research project seeks to determine how inositol synthesis is regulated and how its deprivation affects essential cellular functions in human cells,” said Greenberg. “My lab has identified the first negative transcriptional regulator of inositol synthesis in mammalian cells known as inositol hexakisphosphate kinase 1, or IP6K1.  IP6K1 represses expression of ISYNA1, the gene coding for the rate-limiting enzyme of inositol synthesis, myo-inositol-3-P synthase (MIPS).”

Successful completion of Greenberg’s proposed studies may lead to the first molecular model of regulation of inositol synthesis in mammalian cells and demonstrate how inositol deprivation affects the cellular stress response and mitochondrial function.

In January, Greenberg was named an American Association for the Advancement of Science Fellow for her distinguished contributions to the field of lipid function, particularly for elucidating the role of cardiolipin in Barth syndrome and identifying molecular mechanisms of control of inositol homeostasis. Greenberg has received numerous grants from the National Institutes of Health and other organizations since 1995 and has been featured in multiple publications. Along with her research, Greenberg has an impressive academic history. She attended Harvard University for her post-doctorate, Albert Einstein College of Medicine for her Ph.D., Loyola University for her M.S. and Reed College for her B.A. in biology.

The project number for this National Institute of General Medical Sciences award is R35GM149271.

About Wayne State University

Wayne State University is one of the nation’s pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit research.wayne.edu.