Using the nuclear medicine technologycalled Positron Emission Tomography (PET), Hadassah scientists are making giant leaps in the science of pinpointing diagnosis and treatment of disease.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.
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.