Fall 2004

Page 1



> Anthrax treatment research


> Infectious and Inflammatory Disease Center established

> Taking on tumors


The Burnham Report FALL 2004

Vol. 2, No. 2

Protecting against

biological threats.

New treatment avenues for anthrax were furthered in recent work led by Burnham Professor Robert C. Liddington. In a collaborative study published in the July 4 issue of the journal Nature, Liddington’s laboratory determined—at atomic resolution—how anthrax toxin attaches to one type of receptor in the body. The work may also aid the design of anthrax toxin as an anti-tumor agent.

It is a pleasure to bring you the current issue of The Burnham Report. In it, you’ll read about the establishment of our newest research center, the Infectious and Inflammatory Disease Center (IIDC). Our nation and our world face increasing threats from not only diseases such as arthritis and natural emerging pathogens including SARS and West Nile virus, but also from the threat of engineered agents of terror such as weaponized strains of anthrax or smallpox. Our cover story features a recent breakthrough in understanding of the anthrax toxin. We expect future investigations in the new IIDC will help lay the groundwork toward eliminating this and other threats to our health and security. Progress continues on the cancer front as well. Inside you’ll learn about recent work from Distinguished Professor Erkki Ruoslahti and his team that brings us a step closer to targeting therapies to breast cancer cells. I hope you enjoy reading about our latest research advances. On behalf of everyone at The Burnham Institute, thank you for your support. JOHN C. REED, M.D., PH.D.

President and CEO

Inhalation anthrax, unless diagnosed at

demonstrated by flooding cells with

a very early stage, is fatal—no current

“decoy” receptors that lure PA away

antidotes are effective once the bacte-

from those receptors on the cell surface

ria release toxin into the blood. Three

and prevent the toxin from penetrating.

proteins comprise the toxin: protec-

A second anthrax toxin receptor,

tive antigen (PA), lethal factor (LF),

called TEM8, is mainly found on the

and edema factor (EF). To gain entry

blood vessels that supply tumors with

into host cells, PA must recognize a

the oxygen and nutrients they need to

receptor molecule found on the cell’s

survive. Although the PA-TEM8 com-

surface. “Once attached to the cell

plex is yet to be solved, Liddington

surface,” says Liddington, “PA acts as a

expects the interaction to be similar to

molecular machine to deliver EF and

that of the PA-CMG2 complex. “We

LF into the cell.”

can exploit the differences to design PA

In the Nature study, investigators


molecules that bind better to TEM8

determined the structure at the inter-

than to CMG2,” says Liddington,

face of PA and the receptor known

“which would minimize the side

as CMG2. This receptor is found in

effects of toxin binding to normal tis-

most organs of the body, so drugs that

sues.” Because so many tumors rely on

block PA from attaching to it should

blood vessels, such an agent could be

stop the spread of anthrax poisoning.

used to treat a wide variety of cancers,

The viability of this approach has been

including breast, prostate, and colon.


Anthrax toxin enters cells by binding to a specific receptor.