Messenger - Vol. 2, No. 3, Page 11
Summer 1993
On Research
Garden pest hornswoggled into producing human protein

     David Usher has harnessed a garden pest, the green tobacco hornworm,
to help him conduct his research on human proteins that transport fats,
     Using genetic engineering, the associate professor of life and health
sciences inserts a gene for a specific human protein into a virus, a
"garden variety" virus sold over the counter to help consumers kill garden
insect pests. He then introduces the virus into the hornworm.
     "Lipoproteins produced by the hornworm are very different from those
of humans, but by introducing the human gene, we hope to convince the
animal to make 'human-like' lipoproteins," says Usher, who works with
postdoctoral researcher William J. Cain. The worm does so about six days
     "We can get a large amount of purified protein through this method,
which we use to study the mechanisms by which HDL is produced," Usher says.
High density lipoproteins, or HDLs, are often called "good cholesterol"
because they remove excess cholesterol from the body.
     Much of Usher's research has centered on a specific lipoprotein known
as Lp(a), a type of cholesterol-carrying particle that interferes with the
body's ability to dissolve clots in arteries. Discovered 25 years ago,
Lp(a) has only recently been linked to arteriosclerosis or clogging of
     "Understanding Lp(a) in relation to heart disease and stroke may lead
to better treatments of those at risk," says Usher, who has developed a
clinical test for Lp(a). His test is used in Europe and Japan and is
awaiting approval by the Federal Drug Administration.
     According to Usher, cholesterol is a necessary element in the diet,
used to form new cell membranes and to synthesize adrenaline and sex
hormones. When too much cholesterol is present, however, it can build up,
causing damage to blood vessels. If clots form in the damaged blood
vessels, a blood protein known as plasminogen dissolves them, but Lp(a)
seems to prevent plasminogen from dissolving clots.
     Consequently, the blockage of arteries is accelerated, causing
cardiovascular disease. This process may go on for years before problems
emerge, Usher says.
     The amount of Lp(a) in the bloodstream is thought to be genetically
controlled, says the Delaware researcher, adding that some scientists
believe those individuals who have a significant amount in their
bloodstream have six times the risk of heart attack. Lp(a) molecules vary
in size in different individuals, with some carrying heavy particles and
some light. Oddly enough, it is persons with the light particles that seem
most at risk, while those with heavy particles are less so, Usher says.
     In another collaborative project involving gene therapy, Usher and
Cain and colleagues at the National Institutes of Health are studying
several individuals who cannot get rid of LDL, low density lipoprotein, the
so-called "bad cholesterol." Individuals with high levels of LDL are at a
high risk to develop heart disease, and Lp(a) and LDL are very similar
     "We first asked if these individuals can get rid of Lp(a) or not,"
says Usher. The Delaware researchers determined from the first subject that
the Lp(a) is removed at a normal rate while LDL is removed at a very slow
     "It was exciting to find because it indicates that Lp(a)
concentrations are regulated totally independent of LDL," he says.
                                   -Sue Swyers Moncure and Cornelia Weil