Cungui Mao, PhD ()

Cungui
Mao
PhD
Bioactive sphingolipids in cell growth, differentiation, apoptosis, and autophagy

For the past 10 years, scientist Cungui Mao, PhD, and his team have engaged in groundbreaking lipid research. They were the first, for example, to identify and clone three human alkaline ceramidases (ACER1, ACER2 and ACER3). These enzymes, which are made in different tissues, can induce tumor cell death and inhibit cell division or do the opposite — making them ideal subjects for potential new cancer therapies.

Recently, Dr. Mao and his team of five full-time researchers moved their research program to the Division of Cancer Prevention at Stony Brook University Cancer Center from the Hollings Cancer Center in South Carolina. With them comes a five-year grant from the NCI (preceded by a five-year NIH grant) to fund the research. “Our hope with this novel research is to find new approaches and compounds to treat cancers and perhaps enhance or perfect chemotherapy drugs,” says Dr. Mao. “Because the expression of these enzymes is altered in skin cancer and colon cancer, these might be the first areas for which the research might be applicable. However, at present, we are still working with cell cultures and animal models. A major goal is to see if normalizing the expression of these enzymes in cancer cells can inhibit tumor growth.”

Before the research can go from bench to bedside, the group needs a deeper understanding of the mechanism of how ACER1-3 regulate sphingolipids (the substrates and the products of the enzymes) and how this, in turn, influences biological response. Their current project is looking at three key areas:

(1) the role of the alkaline ceramidases in tumorigenesis; (2) the role of the alkaline ceramidases in angiogenesis; and (3) the role of the alkaline ceramidases in modulating anti-cancer activity of chemotherapeutic agents.

Paving the way for this research, says Dr. Mao, is the identification of two members of the alkaline ceramidase family, first in yeast cells. “We saw a similarity in protein sequence between yeast enzymes and some proteins with unknown function in humans, which then led us to the identification of the human enzymes. While we work with human enzymes, we also use yeast cells because, as a single-celled organism, they are relatively easier to study both biochemically and genetically.”

Dept of Medicine

15-023 Health Sciences Center, Stony Brook, NY 11794-8155

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