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Hebrew University of Jerusalem

Israel21c

Unraveling many of the mysteries of the body’s response to disease
and devising new methods of diagnosis and treatment, the top-level scientists at
the Hebrew University of Jerusalem are on the crest of the wave of exciting
medical advances.

“We aim for research that does not get lost in translation,” said Professor
Daniel Shouval, Dean of the university’s Hadassah Medical School. He was
speaking to a gathering of health reporters who were invited to meet half a dozen
leading researchers and hear about their latest findings. The medical school
includes the two Hadassah University Medical Centers, the HU-Hadassah School of
Public Health and Community Medicine, the Hadassah-HU School of Nursing, the HU
School of Pharmacy and the Hadassah-HU School of Occupational Therapy.

The faculty has 3,000 students, including 600 in the medical school; in the
past year alone, they have conducted 1,200 lab and clinical studies, said
Shouval. Researchers in the faculty publish more than 1200 papers a year in
prestigious journals.

“But just quantity is not enough; we seek quality. Our researchers get their
studies published in the best journals, and compete well for grants from the
best funding institutes,” he said before launching into an overview of the some
of the most interesting research going on at the school.

PET NUCLEAR MEDICINE TECHNOLOGY

Using nuclear medicine technology, Positron Emission Tomography – PET – (a
positron is an electron with a positive charge), Hadassah scientists are making
giant leaps in the science of pinpointing diagnosis and treatment of disease.

“PET offers major advantages over other imaging systems,” said Dr. Eyal
Mishani, a Senior Lecturer in the Department of Biophysics & Nuclear Medicine at
HU/Hadassah. The basis of PET are labeled bioprobes which are like a guided
missile directed at a target.

“Its ability to measure biochemistry and pharmacokinetics at the cellular
level makes it a superior tool for guided diagnosis and monitoring in many
disease states. Based on the growth rate of a malignant tumor, it can also determine
efficient treatment.”

The entrepreneurial Hadassah scientist demonstrated how PET imaging is used
to detect differences in the biochemistry of tumor cells, and with the help of
short-lived radioactive isotopes determine whether it is malignant or normal.
A malignant tumor literally “lights up.” In another case, what initially
appeared to be tumor in the lungs was quickly found to be nothing serious.

“Time and money and especially unnecessary patient concern are spared with
this new technology,” said Mishani.

The system is based on the use of medicinal radioactive biological markers.
These highly sensitive markers can be tracked as they travel through the body,
even at the molecular level. “They can detect a recurrent tumor and
differentiate between a tumor and post-radiation scarring,” said Mishani.

Hadassah researchers discovered that PET imaging of prostate and brain tumors
is much clearer when they used a novel radioactive bio-marker choline labeled
with the carbon-11 radioisotope (C-11). Sometimes a tumor is hidden in the
brain or a prostate gland, but it cannot escape the powerful, searching “eye” of
the bio-marker.

The Medical Biophysics & Nuclear Medicine group at Hadassah/HU is pushing the
envelope on the use of specific, labeled irreversible biological inhibitors
(radio-pharmaceutics) for the diagnosis and treatment of different kinds of
cancer. These labeled ininhibitors target the first link of a chain leading to
tumor cell growth.

Going beyond diagnosis and follow-up of disease, the Hadassah group has
discovered specific radio-pharmaceuticals that can be used for treatment of
disease.

“We are following the FDA guidelines which call for tailor-made
radiotherapy,” said Mishani. One of the aims of the Medical Biophysics and Nuclear Medine
department is to find new biological and biochemical markers for diagnosis and
follow-up.

“In PET diagnosis, the patient is exposed to minimal levels of
radioactivity,” assures Mishani. Only minute amounts are used and they are short-lived.
Minute amounts of radioactive material have been used for diagnostic thyroid tests
for more than 20 years without any harmful effects. Given its “clean bill of
health,” nuclear medicine seems like one of the safest bets for diagnosis and
treatment of disease states in the 21st century.

NATURAL KILLER

HU researchers are hot on the trail of NK Natural Killer (NK) cells, part of
the human body’s own built-in survival kit. NK cells lie in wait for the
appearance of tumors or viral infection to switch to an attack mode. Why they work,
and why they don’t work, understanding the mechanisms that trigger or
“restrain” these cells, opens up the road for the development of new medicines for
cancer patients and people with virus infections.

“Natural Killer (NK) cells usually ‘hang out’ in the blood stream,” says
Dr.Ofer Mandelboim, Senior Lecturer at the Lautenberg Center for General and Tumor
Immunology. “They lie low until activated by signals (chemical changes, a
call for help) in a cell that has been infected by cancer or a virus cells.”

The award-winning scientist joined the medical research center at Hebrew
University after completing a post-doc at Harvard. He had earned a B.A., Cum
Laude, from Bar Ilan University, and a Ph.D. Suma Cum Laude from the Weizmann
Institute of Science (both in Israel).

“In the last two years, our lab found an important clue to discovering why
certain types of melanoma are resistant to NK attack. It found inhibitory
receptors on the surface of the NK cells which interacted with proteins on the
target cells, inhibiting NK cells action,” says Mandelboim.

What are Natural Killer cells doing in the decidua, the membrane lining the
uterus of a pregnant woman? The HU researchers were amazed to discover a high
concentration of killer cells (70-80% of the leucocyte population) in the
uterus lining. The cells do not harm the fetus. “They may help the fetus develop,
and or protect it against infection which is particularly important when the
mother?s immune system is suppressed,” says Mandelboim.

A key interaction between the fetus and the mother was observed by the
researchers who discovered that the fetus secretes a material that attracts the NK
cells to the uterus lining.

“NK cells may prevent a virus attack on the mother. One of the most harmful,
is the cytomegalo virus. An attack during pregnancy can cause blindness and
retardation in the baby,” says the reseacher.

These finding have important implications, not only for a basic understanding
of the interactions between the fetus and the mother, but also for the
development of novel treatments for women with recurrent viral infection.

Equally important is the study of the lack of Natural Killer cell activity
which can lead to recurrent viral infections, and even death at a young age.
Scientists at HU are trying to discover the mechanisms that result in NK
deficiency. Mandelboim and his colleagues hope that this research can spark the
development of drugs to treat viral infection.

EMBRYONIC STEM CELL RESEARCH

Embryonic stem cell research promises to become a key tool for the treatment
of disease in the 21st century. Among the vanguard, scientists at Hebrew
University/Hadassah are charting new paths for treatment and cures for people
afflicted with neurological diseases, such as Parkinson’s, diabetes, and heart
failure, and a wide scope of diseases where there is degeneration and malfunction
of cells.

Over 1 million people in the U.S. suffer from Parkinson’s; in the world, 16
million people suffer from neurological diseases; 120 million have diabetes.

Hadassah, working together with Monash University in Australia and the
National University of Singapore was the second group in the world to derive stem
cells from human embryos. The researchers have succeeded in producing six of the
human embryonic stem cell lines that are available for federally-funded
research in the U.S. Five of these lines are among the 12 lines that are currently
distributed to U.S. researchers and are provided to more than 50 other
laboratories around the world involved in stem cell research.

“After one to two weeks in culture, embryonic cells begin to differentiate
into different kinds of stem cells, such as nerve and muscle cells,” explains
Professor Benjamin Reubinoff, Director of the Hadassah Human Embryonic Stem Cell
Research Center.

The Hadassah group was the first group, in parallel with a group from
Wisconsin, to identify and produce primitive nerve cells from human embryonic stem
cells. The results serve as a platform for producing more specialized nerve
cells for the treatment of conditions such as Parkinson’s disease and multiple
sclerosis.

“We are focusing our research on developing nerve and insulin-producing stem
cells of the pancreas,” says Reubinoff. A graduate of Hadassah Medical School,
and trained in obstetrics and gynocology, Reubinoff earned a M. Science
degree (summa cum laude) in neurobiology and completed a PhD in biology in
Australia.

Already, exciting strides have been achieved with nerve stem cells that were
derived from human ES cells. Results suggest that it is possible to transplant
these primitive embryonic nerve cells into the brain of newborn mice and that
they will participate in brain development.

“The transplanted cells integrated into the host brain responded to host
brain signals and were able to ‘communicate’ with the host brain cells,” said
Reubinoff.

The doctor/researcher hopes that the research achievement will also lead to
therapeutic treatment to ameliorate problems from genetic diseases. The success
gives a glimmer of the hidden treasure that embryonic stem cell research can
offer medical science.

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