The Malaria Parasite – A Clever Chameleon

It’s difficult to envision conducting research on a minuscule mosquito, let alone on the one-cell parasite it transmits to humans – a deadly parasite that causes the most lethal form of malaria.

A groundbreaking discovery by Hebrew University researchers has cast new light on the parasite and how it evades the human immune system. Transmitted by a simple mosquito bite, the parasite takes up residence in the human liver and proceeds to multiply rapidly in the human bloodstream. To avoid the response of the human immune system, it modifies the surface of the red blood cells. When the immune system reacts, the parasite alters its identity by changing the surface protein it displays from among the 60 in its repertoire.

Prof. Ron Dzikowski and Dr. Inbar Amit-Avraham of the Faculty of Medicine’s Department of Microbiology and Molecular Genetics and the Sanford F. Kuvin Center for the Study of Infectious and Tropical Diseases pinpointed the RNA molecules that signal the parasite to “switch masks” each time it is threatened. Understanding this mechanism could reveal all of the parasite’s masks or leave it with only one mask. Either discovery would present the possibility of finding an effective way to block this response and enhance the development of new drugs and vaccines.

Prof. Dzikowski and his colleagues are working on attaining a basic understanding of how the parasite tricks the body, so “we can then trick it back,” he says with a grin. They are also collaborating with chemists and colleagues at the University and abroad to develop a drug that kills the parasite but is not toxic to humans. Funded by a substantial grant, that research is now moving into animal studies.

Efforts to eradicate malaria have so far proved ineffective – and the incidence of the disease continues to rise. “Developing a drug therapy,” Prof. Dzikowski says, “would be a major step forward.”

The next step:

Translational Research: Infectious and Tropical Diseases

From the earliest days of the 20th century, conditions endemic to the Middle East and the continuous influx of immigrants from different parts of the world afforded local scientists, researchers and clinicians both the challenge and the opportunity to diagnose, study and treat a staggering array of infectious and tropical diseases. Of necessity, they were involved in developing vaccines and vaccination protocols and monitoring outbreaks of a multiplicity of diseases.

Translational research into infectious and tropical diseases will build upon the Hebrew University’s earliest experiences and extensive knowledge to advance interdisciplinary research on the diagnosis, monitoring and control of infectious diseases, develop new vaccines, drugs and effective delivery systems and prevent the spread of these potentially lethal diseases.

More than 3.4 billion of the world's most vulnerable citizens are at risk of contracting malaria. In sub-Saharan Africa alone, malaria claims more than 450,000 lives each year, predominantly among children.

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by Elliott Stein and Amiad Kushner

Imagine graduating from high school and dedicating the next 12 years of your life to serving your country. That’s precisely what students do when they enroll in Tsameret, the elite military medicine track at the Hebrew University-Hadassah School of Medicine.

Hebrew University launched Tsameret in 2009, in cooperation with the Israel Defense Forces (IDF), with the goal of alleviating the acute shortage of military physicians in Israel, and to close crucial gaps in medical knowledge in the military context.

To date, Tsameret has admitted 170 of Israel’s best students in three intakes, with a goal of 60 new students per year. Students take on a 12-year commitment, including service as military physicians for five years.

We sat down to chat with Netta Bar-Ilan, a third-year student in Tsameret, to learn more about the program.

Bar-Ilan described an extremely rigorous program that requires students to make a twelve year commitment upon their high school graduation. While their high school classmates embark on their mandatory IDF service of 2 years (women) or 3 years (men) upon graduating from high school, Tsameret students spend the next six years studying conventional medicine and receiving extensive training in military-related medicine, such as trauma and battlefield triage. At the same time, Tsameret students go through military basic training, the IDF Paramedics Course, and IDF Officer’s School.

In their seventh year, Tsameret students will focus on practical work and intern in one of Israel’s hospitals. Following that internship, the students will deploy in various IDF combat units, where they will serve as medical officers of battalions for their three year compulsory service and another two years as part of their career service in another position.

Despite the rigors of the program, Bar-Ilan and his Tsameret classmates still find time for other activities, including community engagement. Bar-Ilan and his classmates teach English as part of a tutoring project for underprivileged childrenl, and they volunteer at the Hadassah Medical Center. Recently, Bar-Ilan and several of his classmates trained for and ran in the Jerusalem marathon. As Bar-Ilan says, “if something’s important, you find time for it.”

The program attracts the country’s top students. Bar-Ilan is no exception. He comes from a family of distinguished academics and soldiers. His father, Avner Bar-Ilan, is a professor of economics at Haifa University and Dartmouth College in Hanover, New Hampshire, where Netta lived from 2003 to 2005 Netta has a twin brother and two older brothers, all of whom serve or have served in elite units of the IDF.

As a relatively young program with limited funding, Tsameret is seeking to raise funds for new facilities and programs. Bar-Ilan highlighted a few of the program’s funding needs. For example, Tsameret hopes to build a simulation center on Hebrew University’s campus, similar to the one that the IDF Medical Corp uses in Rishon Lezion. The simulation center will allow Tsameret students to train under conditions that are intended to replicate actual combat zones. Tsameret also hopes to raise funds to build new (and improve existing) military medicine labs that focus on medical research, with a particular focus on injuries specific to military pilots, combat divers, and submariners. Additional funds will also help Tsameret recruit Israel’s best and brightest students, many of whom may live in under-represented communities, need financial aid, and won’t have the time to earn extra income during their studies.

Tsameret’s goal – to develop the theory and practice of military medicine, with the goal of saving lives – is a worthy one, indicative of the great work Hebrew University is doing to serve the State of Israel and the world.

If you would like to support, or simply learn more about, Tsameret or the Hebrew University of Jerusalem, please contact Orlee Gutman by email or call 212-607-8517.

The views expressed in this article are those of the author and do not necessarily represent the views of, and should not be attributed to, Lowenstein Sandler PC.




Confronting Tumor Cells Head On

Cells within tumors are as individual and unpredictable as the people they attack – and the tumor is as complex as the body it is assaulting. Diverse in character and content, the cells constantly change as they multiply. “Our goal is to understand how this happens, which pathways can influence the identity they will acquire and how to use this knowledge as a potential means of effective therapy, ” says Dr. Ittai Ben-Porath, PhD, who heads a research team in the Faculty of Medicine’s Department of Developmental Biology and Cancer.

Dr. Ben-Porath and his team are studying the molecular mechanisms that determine tumor growth and metastasis – the functions cancer cells acquire – and the genes controlling them. “Our work is aimed at uncovering the genetic regulators whose activity dictates poor differentiation of breast cancers, focusing on regulatory genes known to play a role in controlling normal stem cell function.” Analysis of the gene expression data they derived led them to identify previously unknown functions of several stem cell-associated regulatory genes.

Cellular senescence – a program of cellular aging – is another central mechanism controlling cancer growth. Senescence represents an important “brake” on cancer development.

When the tumor cells start to multiply, this program leaps into action and prevents them from further dividing. Tumors must therefore get rid of this brake in order to develop. Since this is one of the most universal features of tumors, understanding how senescence works is very important. “The flip side of blocking tumors is aging. As we age, senescent cells accumulate in our body, contribute to disease – and in fact, shorten our life span.”

The aim of both research avenues is to turn the tables on the tumors using their unique characteristics to develop a treatment as individual as the person they are trying to destroy.

“When we know as much as we can, molecularly, about the tumor,” Dr. Ben-Porath says, “we can then determine which drugs apply to which tumor.”

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Liquid Biopsy

The biopsy – often an invasive and painful procedure – is currently the only way to determine the presence of cancerous cells. In some cases, the location of a suspected tumor makes conducting the procedure too complicated or too dangerous. “What keeps me awake at night is our effort to develop a new type of diagnostic blood test, one that detects the pathology of different tissues and indicates the presence or absence of disease,” says Prof. Yuval Dor, who heads a research team in the Faculty of Medicine’s Department of Developmental Biology and Cancer.

Their approach to diagnosis is based on two biological principles: first, that when cells die – as they do regularly – they release their DNA into the bloodstream; and second, that each cell type has special chemical markers on its DNA. By detecting these chemical markers in DNA circulating in blood, scientists can identify the source tissue of each DNA molecule and determine which cells in the body have recently died, which is tremendously important for clinical diagnosis of different diseases. Prof. Dor and his team have already used their new method to detect tissue-specific cell death in many medical situations including type 1 diabetes, cancer, neurodegeneration and trauma. In the future, they plan to develop their innovative technology into a new type of standard blood test that will detect diseases at earlier, more treatable stages.

Several years ago, Prof. Dor’s research team identified the key signal that prompts the production of insulin-producing beta cells in the pancreas. Their breakthrough has become the basis for further research on ways to restore or increase beta cell function and the development of a drug to direct beta cells to regenerate and replicate.

The next step:

Translational Research: Metabolic Diseases

Scientists and clinicians in the Faculty of Medicine have already published groundbreaking results from an extensive list of research projects that have important implications for the diagnosis and treatment of people suffering from the broad spectrum of metabolic diseases, particularly diabetes.

Translational research provides the environment and opportunity to intensify scientific efforts by combining the study of the diseases’ molecular and genetic structure with an understanding of their unique biochemistry and physiology.

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Rescuing Pregnancies with Placental Genes

With every new experiment and every new discovery, the power and potential of stem cells are reaffirmed. 

A research team led by Dr. Yosef Buganim of the Faculty of Medicine’s Department of Developmental Biology and Cancer Research has harnessed the technique of introducing master genes into adult cells and converting these cells into placental stem cells (induced trophoblast stem cells), which are responsible for the formation of most cells in the placenta. Their research has revealed that injection of these converted cells into early-stage embryos can contribute to the formation of a normal placenta. This work holds great promise for the treatment of recurrent miscarriages and placental dysfunction diseases.

Dr. Buganim and his team are using the same technique to address male fertility problems by creating sperm cell-supporting cells and sperm-producing cells from induced embryonic stem cells and also directly from adult stem cells. This would open the door for sterile men to reproduce offspring with their own genes.

The next step:

Translational Research: Stem Cell and Regenerative Medicine

Regenerative medicine focuses on unraveling the mysteries of human genetics so that people can receive adapted and transplanted cells to replace defective or damaged tissues and organs. For scientists and clinicians, stem cells hold the secrets and the solutions. Embryonic stem cells, which can give rise to every cell, tissue and organ in the fetus, have the potential to evolve into any cell in the human body. Adult stem cells, such as the blood stem cells found in human bone marrow and blood, already play an important role in medical treatments such as bone marrow transplantation.

Multidisciplinary translational research will help scientists enhance their understanding of stem cells and apply that knowledge to help regenerate particular tissues to combat specific diseases and injuries.

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