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Assistant Professor, Department of Medicine; Associate Scientist, James Graham Brown Cancer Center
Research ProgramTumor Immunobiology
Research InterestsThe Jenson/Ghim laboratory (4D, BCC) is a translational, immunology laboratory that is working on humoral responses to prevent infection by papillomavirus. The laboratory is best known for production of papillomavirus vaccines, some of which have been patented and licensed to MedImmune/Smith Kline Beecham.
Dr. Ghim, who graduated from Claude Bernard-Lyon in France, is a molecular virologist and immunologist who has produced recombinant, prophylactic vaccines against more than 10 animal and human papillomaviruses. She has used the vaccine as substrate for several seroepidemiology studies using ELISA. She was largely responsible for developing the COPV animal model for vaccinating against cervical cancer. At present Dr. Ghim is identifying PV from and preparing vaccines for endangered species such as the manatee and snow leopard. She has been working almost a decade on expression of recombinant PV vaccines in tobacco plants. Although prophylactic PV vaccines have not as yet been produced in genetically engineered tobacco, her work at the Brown Cancer Center has provided for a collaboration to be undertaken with Large Scale Biology Corporation to develop recombinant antibodies that neutralize human papillomavirus virions by using the LSBC tobacco mosaic virus platform system designed for high output agripharmaceuticals.
Education
B.A., Korea University, Food Science, 1980
M.A., Ajou University, Chemical Engineering, 1983
D.E.A., Lyon I University, Microbiology, 1985
Ph.D.,Lyon I University, Microbiology, 1989
Research and Professional Experience
1987
Electron Microscopy, Pasteur Institute, Paris, France
1987
Cellular Genetics and Biology, Pasteur Institute, Paris, France
1988
Isolation of Infectious Virologic Agents, Pasteur Institute, Lyon, France
1988
Medical Virology, Pasteur Institute, Paris, France (Diploma)
1989
Genetic Engineering, Pasteur Institute, Paris, France
1989
Bacteriology, Pasteur Institute, Paris, France (Diploma)
1989-1992
Postdoctoral fellow, Department of Pathology, Georgetown University School of Medicine
1992-1993
Research Associate, Department of Pathology, Georgetown University School of Medicine
1993-2000
Assistant Professor, Department of Pathology, Georgetown University School of Medicine
2000-2002
Associate Director, Cervical Cancer Research Center, West Penn Hospital
2002-present
Assistant Professor and Associate Scientist, Brown Cancer Center, University of Louisville
Selected Awards and Professional Honors
1993-2000
Member, Lombardi Cancer Center
2000
Member Intragency/Ocenaria Manatee Working Group
2006-present
Member, Scientific Advisory Committee, Institute Pasteur - Korea
2007
Presentation Academy Tower Award for Women Leaders in Science and Health Care
2008
Champion 4 Her Award, University of Louisville, KY
2008
1st Mary Breckenridge Pioneer in Women's Health Award, Kentucky Commission on Women
PublicationsGhim, S, Newsome J, Bell J, Sundberg JP, Schlegel R, Jenson AB. Spontaneously regressing oral papillomas induce systemic antibodies that neutralize canine oral papillomavirus. Exp Mol Pathol 68:147-51, 2000
Jenson AB, Geyer S, Sundberg JP, Ghim S. Human papillomavirus and skin cancer. J Invest Dermatol 6:203-6, 2001
Ghim S, Sundberg JP, Delgado G, Jenson DP. The pathogenesis of advanced cervical cancer provides the basis for an empirical therapeutic vaccine. J. Exp Molec Pathol 71(3):181-85, 2001
Gregory D, Bossart GD, Ewing RY, Lowe M, Sweat M, Decker SJ, Walsh CJ, Ghim S, Jenson, AB. Viral Papillomatosis in Florida manatees (Trichechus manatus latirostris). Exp Mol Pathol 72:37-48, 2002
Ghim S, Basu PS, Jenson A. Cervical cancer: Etiology, pathogenesis, treatment, and future caccines. Asian Pac J Cancer Prev 3:207-14, 2002
Ghim,S, Delius H, Rector A, Sundburg JP, Jenson AB, van Ranst M. Equine papillomavirus type 1: complete nucleotide sequence and characterization of recombinant virus-like particles composed of the EcPV-1 L1 major capsid protein. Biochem Biophys Res Commun 324:1108-15. 2004
Recor A, Bossart GD, Ghim S, Sundberg JP, Jenson AP, van Ranst M. Characterization of a novel close-to-root papillomavirus from a Florida manatee by using multiply primed rolling-circle amplification: Trichechus manatus latirostris papillomavirus type 1. J Virol 78:12698-702. 2004
Rehtanz M, Ghim SJ, Rector A, Van Ranst M, Fair PA, Bossart GD, Jenson AB. Isolation and characterization of the first American bottlenose dolphin papillomavirus: Tursiops truncatus papillomavirus type 2. J Gen Virol 87(Pt 12):3559-65, 2006
Rector A, Lemey P, Tachezy R, Mostmans S, Ghim SJ, Van Doorslaer K, Roelke M, Bush M, Montali RJ, Joslin J, Burk RD, Jenson AB, Sundberg JP, Shapiro B, Van Ranst M. Ancient papillomavirus-host co-speciation in Felidae. Genome Biol 8(4):R57, 2007
Van Doorslaer K, Rector A, Jenson AB, Sundberg JP, Van Ranst M, Ghim SJ. Complete genomic characterization of a murine papillomavirus isolated from papillomatous lesions of a European harvest mouse (Micromys minutus). J Gen Virol 88(Pt 5):1484-8, 2007
Rehtanz M, Bossart GD, Doescher B, Rector A, Van Ranst M, Fair PA, Jenson AB, Ghim SJ. Bottlenose dolphin (Tursiops truncatus) papillomaviruses: Vaccine antigen candidates and screening test development. Vet Microbiol 2008 Jul 4. [Epub ahead of print]
Rector A, Stevens H, Lacave G, Lemey P, Mostmans S, Salbany A, Vos M, VanDoorslaer K, Ghim SJ, Rehtanz M, Bossart GD, Jenson AB, Van Ranst M. Genomic characterization of novel dolphin papillomaviruses provides indications for recombination within the Papillomaviridae. Virology 378(1):151-61, 2008
Related Stories This article was written by Laura Ungar, The Courier-Journal, and appeared on the front page on May 31, 2006 Wednesday, May 31, 2006 MEDICAL BREAKTHROUGH: CERVICAL CANCER
Two at U of L help invent vaccine
Researchers aiming to save future generations
By Laura Ungar
lungar@courier-journal.com
The Courier-Journal
A father's love for his daughters and a woman's love for her country led two Louisville researchers to a much-heralded medical breakthrough -- the world's first cervical cancer vaccine.
Dr. A. Bennett Jenson wanted to protect his three girls from the deadly disease. Shin-je Ghim wanted to help women in her native South Korea, where "so many" were dying.
The two researchers at the University of Louisville's James Graham Brown Cancer Center now are waiting for the vaccine they helped invent to hit the market, around July. They also are working to create a cheaper version, using tobacco plants, and another vaccine to treat the disease -- with the ultimate goal of wiping out cervical cancer.
"It's sort of a passion," said Jenson, who developed the vaccine with Ghim and another researcher at
Georgetown University. "It's a disease that shouldn't be present and yet, it kills. It's the second-biggest cancer killer of women worldwide."
Anna Bastin of Louisville, who survived cervical cancer 1½ years ago, is pleased that future generations of women may not face the same threat.
"First thing on my mind was my granddaughters and great-granddaughters. This would be great if it were there for them," said Bastin, 64. "Whenever you have to hear the word 'cancer,' you have no idea what it does to you. It totally devastates you. With this vaccine, think of the people who would not have to hear the word I had to hear."
Despite its potential benefits, the vaccine has been the subject of controversy because it targets the sexually transmitted HPV, or human papillomavirus, which causes most cervical cancers. It is most effective when given before a girl becomes sexually active, or around 9 to 13 years old. Federal officials could vote next month on recommending universal use, although states would allow people to opt out.
Some people suggest the vaccine might give girls implicit permission to have sex. They say parents should decide whether their children are vaccinated, and keep in mind the risks associated with having sex too early.
"We're delighted with the medical breakthrough of the vaccine. But it's clear that just because a parent
has purchased a new fire extinguisher for their home, that doesn't mean he should encourage his children
to play with matches," said Kent Ostrander, executive director of the Family Foundation, a politically conservative nonprofit group based in Lexington.
Dr. Paige Hertweck, director of pediatric adolescent gynecology at U of L, said, "This is really not a moral issue.
"This is a cancer-preventing vaccine. That's what people need to think about," she said. "This is actually medical history in the making."
Little initial interest
Jenson and Ghim -- along with Dr. Richard Schlegel, who is still at Georgetown -- began working on the
vaccine in 1989, cutting a gene from the papillomavirus' DNA, infecting a cell and showing that the protein that developed mimicked the protein that exists in the virus.
This protein clumps together to create "papillomavirus-like particles," which are the basis of the vaccine and were developed by other scientists.
Jenson noted that he never doubted the value of his work, even though initially, "none of the drug companies were interested in what we were doing."
He said he thought of his daughters, in their late teens and early 20s at the time.
"This is one thing I wanted them to be protected from," he said.
Ghim said she thought about how cervical cancer has continued to exact a heavy toll in many other countries, even though deaths in the United States dropped significantly after 1955 because of Pap tests.
Merck & Co. and GlaxoSmithKline Inc. are working on separate versions of the vaccine. An advisory committee to the U.S. Food and Drug Administration last week unanimously endorsed Merck's version
as safe and effective. Called Gardasil, it is expected to gain full federal approval in early June and hit the market two to four weeks later. GlaxoSmithKline's version is expected out next year.
Although Merck has not set a price, the vaccine is expected to cost $300 to $500 for three injections
over six months -- which critics contend is too expensive. "It'll take time to see if the cost will go down and whether it will be used," said Bettie Steinberg, an HPV expert in Manhasset, N.Y., who has followed the vaccine development.
Still, she called the vaccine a "major breakthrough."
"Scientists work all their lives for something that can make a difference," she said. "When it really pays off like this, it's wonderful."
Georgetown spokeswoman Laura Cavender said any royalties that come from vaccine patents are shared
with the inventors, although she wouldn't comment on this specific case.
And while U of L won't get money from Gardasil sales, spokeswoman Ellen de Graffenreid said the school is getting national attention. "When I expect it to get nuts is when the vaccine is finally
approved," she said.
Treatment vaccine in works
The Louisville researchers' work is not completed, and they've received more than $1 million for
ongoing research from Kentucky, the federal government and the Brown Cancer Center.
Jenson, 66, and Ghim, 47, said they are about three years away from completing the second-generation
preventive vaccine they are trying to grow by reproducing protein fragments in tobacco plants. They are working with a California researcher who will soon be moving to Kentucky Bioprocessing in
Owensboro. It is expected to cost only $6 to $8 for three shots.
"There is a commitment to deliver this vaccine to the undeveloped countries because they need it most,"
Jenson said. "And it's an alternate use of tobacco plants. Instead of using them to make nicotine
cigarettes that cause cancer, paradoxically, you use it for making a vaccine that protects women against cervical cancer."
Doctors warn that these vaccines won't negate the need for Pap tests, which can catch pre-cancer and
early cancer. Bastin said a Pap test detected her cancer early. She had a radical hysterectomy but didn't need chemotherapy.
Jenson and Ghim said they hope that the treatment vaccine they are also developing -- with scientists in
India -- someday helps cancer victims like Bastin.
"You think of retiring," said Jenson. "Then you think of everything that's still left to do."
Reporter Laura Ungar can be reached at (502) 582-7190.
From Los Angeles Times and AP Dispatches
Courier-Journal reporter Laura Ungar contributed to this story.
Friday, May 19, 2006
Cervical-cancer vaccine a 'wonderful step'
Advisory panel urges FDA to approve it
From Los Angeles Times and AP Dispatches
WASHINGTON — A vaccine with the potential to greatly reduce worldwide deaths from cervical
cancer, the No. 2 cancer killer in women, should be approved for sales in the United States, a federal panel said yesterday.
A Food and Drug Administration advisory committee voted 13-0 to endorse Merck and Co.'s Gardasil as
safe and effective. It blocks viruses that cause cervical cancer.
The company said the vaccine could cut worldwide deaths from the disease by two-thirds.
"This is certainly a wonderful, good step in addition to our screening processes" in helping eradicate
cervical cancer, said Dr. Monica M. Farley of the Emory University School of Medicine, acting chairwoman of the advisory panel.
Tests in more than 17,000 girls and women have shown that the vaccine is nearly 100 percent effective
in blocking cervical cancers caused by the sexually transmitted human papilloma virus. Two strains of
the virus are thought to be responsible for 70 percent of the 15,000 cervical cancers diagnosed and the
3,500 deaths caused by it in the United States each year.
Worldwide, 400,000 women are diagnosed with cervical cancer each year and more than 200,000 die of it.
The virus, commonly called HPV, is the most common sexually transmitted disease in this country, with about 20 million people infected.
The FDA panel stressed that Gardasil does not eliminate the need for cervical-cancer screening, such as the Pap smear test, because the vaccine does not protect against all HPV strains.
The vaccine is most effective when given to girls before they become sexually active, which would
require administration between the ages of 9 and 13.
The FDA is not required to follow the recommendations of its outside panels of experts, but usually does. The FDA is expected to decide by June 8.
`Impressive data'
Farley said Merck had submitted "very impressive data" to the panel about the vaccine's efficacy.
Public-health groups, nine of whom testified before the panel yesterday morning, were unanimous in recommending approval of the vaccine.
"It is common sense, good medicine and a groundbreaking step forward in the fight against cancer," said Cecile Richards, president of the Planned Parenthood Federation of America.
Making their case for approval, Merck officials suggested that Gardasil could be the biggest advance in preventing cervical cancer since the Pap test.
"Gardasil has the potential to meet an unmet medical need as the first vaccine to prevent cervical
cancer," Merck's Dr. Patrick Brill-Edwards told the Vaccine and Related Biological Products advisory committee.
A vaccine utilization committee of the Centers for Disease Control and Prevention is scheduled to meet
on June 29, at which time it could vote on whether to recommend universal use of Gardasil in females.
A draft proposal recommends vaccinating all girls ages 11 and 12.
Merck said the vaccine could be used in females age 9 to 26, but would work best when given to girls before they begin having sex.
Requirements for its use, however, can only be mandated by individual states.
Even if it should become a requirement, added Wendy Wright, president of Concerned Women of
America, all states allow children to opt out of mandatory vaccinations for medical or other reasons.
Moral concerns
Some conservative religious groups have expressed concerns about the vaccine, arguing that it may send an implicit message to young girls that sex is OK for them.
The opposition of such groups was responsible for the only recent instance in which FDA has not
followed the recommendation of an advisory committee: a similar panel recommended approval of Plan B, the so-called morning-after pill, in December 2003.
"We welcome the vaccine," said Pete Sprigg of the Family Research Council. But, he added, "Decisions
about sexual health are tied up in personal values, and parents should have the right to transmit personal values to their children."
The panel did not consider whether the vaccine should be used in males because there is not yet enough data to support its efficacy.
Dr. Eliav Barr of Merck told the panel that data about the efficacy studies in males should be available
in 2008, at which time the company would seek approval for that group.
Some experts had reservations about the practicality of the vaccine that were unrelated to its efficacy or
morality. Gardasil is expected to cost as much as $500 and must be administered in three injections over the course of six months.
The cost may put it out of the reach of many of the families in which girls are at the highest risk of
contracting the virus, and the need for three separate physician visits could severely limit its use.
"Cost is really going to present public-health agencies with a significant challenge," said Jeffrey Duchin,
head of immunizations for the Seattle & King County Public Health Department. The CDC committee
could recommend federal subsidies to make Gardasil available to poor families.
Dr. Albert Bennett Jenson and Shin-je Ghim, researchers who currently work at the University of
Louisville's James Graham Brown Cancer Center, were part of the research team that invented the vaccine.
They could not be reached for comment yesterday.
Dr. Jeffrey Goldberg, a gynecologic oncologist for Norton Healthcare, said he was happy to hear about
the committee's vote and thrilled about the development of the vaccine.
"It's a very exciting development " he said. "It's much better to prevent the precancerous changes that we end up treating."
Goldberg said routine Pap smears have already done a lot to reduce the threat of the disease in America,
but the vaccine will help both here and in countries where cervical cancer takes a large toll.
But he added that large-scale studies are needed to determine its effectiveness on a widespread basis.
Dr. Lynn Parker, director of the gynecologic oncology division at UofL, also said she was glad to hear about yesterday's development.
"I'm very excited it got to this point," Parker said. "I think it's going to have a major impact on women's
health care — not just in the U.S., but around the world."
Courier-Journal reporter Laura Ungar contributed to this story.
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