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St. Jude's Researcher Gives Falk Lecture

By Eddy Ball (with Robin Mackar)
December 2006

Van Houten and Doug Green
Host Ben Van Houten (left) welcomed Falk Lecturer Doug Green to NIEHS (Photo courtesy of Steve McCaw)

Doug Green
Green delivered on his promise to entertain his audience and make the intricacies of apoptosis fascinating even for the uninitiated. (Photo courtesy of Steve McCaw)

Mrs. Falk and Steven Falk
Mrs. Falk and son Steven were honored guests at the lecture. (Photo courtesy of Steve McCaw)

On November 14, immunologist Doug Green, Ph.D., became the twenty-second distinguished researcher to present a lecture in the Hans L. Falk Memorial Lecture Series. Green's lecture was sponsored by Ben Van Houten, Ph.D., DERT Program Analysis Branch chief and Laboratory of Molecular Genetics investigator. Green holds the Peter C. Dougherty Endowed Chair of Immunology at St. Jude's Children's Research Hospital and chairs the hospital's Department of Immunology. Green spoke on "Apoptosis: The Paths of Perdition" to an audience of scientists that included Falk's widow and son.

As Green said in the lecture, apoptosis is "a matter of life and death," affecting every cell type and organ system of the body. Apoptosis is the process that protects an organism from the spontaneous cell transformation that occurs in cancer. Although many aspects of the process are still not completely understood, productive research in the past decade has provided insights into strategies for blocking pathological cell loss or for killing unwanted cells.

Green's major research effort is to unravel the "dance of death" that is a normal stage of cell growth and to understand how apoptosis may be triggered to kill tumor cells without damaging healthy ones. Green has worked to elucidate the processes by which specialized "cutter" enzymes known as caspases orchestrate the process. Under normal conditions, specialized changes in the permeability of the mitochondrial outer membrane trigger the diffusion of death promoting proteins such as cytochrome c. Stimulated by these proteins, "initiator" carpases activate the "executioner" enzymes necessary for engaging the apoptotic cascade.

Green and his colleagues have explored signaling pathways in an effort to find ways to induce cytochrome c release and activate what he calls the "gates of death." In this way, he hopes to circumvent the defenses that allow tumor cells to defy the cell's numerous stressor-generated signals, including DNA damage and growth factor withdrawal, that should stimulate apoptosis, whether carpase-dependent or independent.

In many human cancers, tumors also develop resistance to chemotherapy. To discover where the normal progression of cell death for tumors is blocked, Green has examined a group of proteins, specifically the BCL-2 family, that serve as anti-apoptotic proteins, inhibiting the activation of the proteins essential for initiating the apoptotic cascade. Looking at promising developments emerging from research into the apoptotic signaling pathways, Green pointed to BCL-2 antagonists that may be able to strip away the rogue cell's last defenses and target tumor cells for death.

Green is a prolific author and tireless researcher who serves on the editorial boards of nine scientific journals. With over 350 peer-reviewed articles to his credit, Green publishes an average of 15 studies per year and reviews approximately three studies for every one he publishes. He is among the 20 most highly cited scientific researchers in the world and a recipient of a National Institute of General Medical Sciences Merit Award.

The Hans L. Falk Memorial Lecture Series honors the contributions of the chemical carcinogenesis researcher who served NIEHS as Associate Director for Laboratory Research and Associate Director for Health Hazard Assessment. Falk was an NIEHS pioneer, arriving at the institute in 1967, shortly after its founding. He is credited with helping to establish the spirit of freedom of scientific inquiry and the pursuit of excellence in science that the lecture series celebrates.

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