Personalized Medicine “It doesn't get more personal than this.”

44 Pages·2012·2.98 MB·English

2012 Issue
TAU International
Peres’ Young Scientists
Educating for Peace
TEL AVIV UNIVERSITY REVIEW
Personalized
Medicine
“It doesn’t get more
personal than this.”
Cultural
Immersion 14
The Marc Rich Program in the
Humanities and the Arts is leading
the way in revitalizing interest in the
liberal arts.
Cover story:
Up Close and
Rethinking
Personal 2
Adiction 16
Prof. Miguel Weil and his son, Nir,
are courageous poster boys for Tel Aviv University
the promise – and frustrations – scientists are
of genomic research at Tel Aviv researching new
University. therapies for
the treatment of
addiction and pain.
3D Frontiers 22
Advanced 3D Technology being
pioneered at TAU has implications for
TEL AVIV UNIVERSITY REVIEW everything from security to surgery.
sections
Issued by the Strategic Communications Dept. innovations 22
Development and Public Affairs Division
Tel Aviv University
Ramat Aviv 69978
leadership 25
Tel Aviv, Israel
From England
Tel: [phone]
Fax: + 972 3 6407080 with Love 28
E-mail:
Ofcers of Tel Aviv University a
Harvey M. Krueger
Chairman of the Board of Governors
Dr. Giora Yaron
Chairman of the Executive Council
Prof. Joseph Klafter
President
Prof. Aron Shai
Rector
Mordehai Kohn
Director-General
Prof. Raanan Rein
Vice President
Prof. Eran Rabani
Vice President for Research and Development Dear Friends,
Dr. Raymond R. Sackler,
Michael H. Steinhardt Te year 2012 began with the wonderful news
Honorary Chairmen of the Board of Governors that the Dean of Tel Aviv University’s Buchmann
Dr. h.c. Karl Heinz-Kipp, Marshall H. Polk Faculty of Law, Prof. Daphne Barak-Erez, was
Deputy Chairman of the Board of Governors appointed a Supreme Court Justice. Her selection underscores the continuing
Dr. h.c. Josef Buchmann,
– and highly infuential – role of TAU faculty members and graduates in
Stewart M. Colton, Prof. François Heilbronn,
Dr. h.c. Raya Jaglom, John Landerer AM CBE, shaping Israeli society through public service.
Adolfo Smolarz, Melvin S. Taub Te University’s drive to provide the very best conditions for
Vice Chairpersons of the Board of Governors interdisciplinary brain studies and research gained momentum with the
establishment of the School of Neuroscience and School of Psychological
Prof. Dina Prialnik
Sciences. We are dedicating the School of Neuroscience in the name of
Vice Rector
Prof. Dany Leviatan Israeli industrialist and philanthropist Sami Sagol, a TAU honorary doctor
Pro-Rector and governor, and a long-time supporter of brain research in Israel.
Prof. Hannah Naveh TAU International launched fve new English-language master’s
Dean of the Yolanda and David Katz programs this year and two undergraduate programs for next year, including
Faculty of the Arts Israel’s frst International BSc in Electrical Engineering. Our increasingly
Prof. Ehud Heyman
globalized campus welcomed 1,000 foreign students this year.
Dean of the Iby and Aladar Fleischman
Faculty of Engineering Tel Aviv University was the only university in Israel to be awarded a
Prof. Yaron Oz senior partnership in the three inaugural Centers for Research Excellence,
Dean of the Raymond and Beverly Sackler known as I-CORE, being set up with government and private funding.
Faculty of Exact Sciences One is in genomic science, the subject of this issue’s cover story; one
Prof. Eyal Zisser in cognitive science, and one in computer science, to be led by TAU’s
Dean of the Lester and Sally Entin
Blavatnik School of Computer Science. I-CORE funding will enable Tel
Faculty of Humanities
Prof. Daphne Barak-Erez Aviv University to recruit young faculty from top schools abroad, fulflling
Dean of the Buchmann Faculty of Law a top university and national priority and further strengthening TAU’s
Prof. Moshe Mevarech global standing as a leading center for academic research.
Dean of the George S. Wise
Faculty of Life Sciences
Prof. Asher Tishler
Dean of the Faculty of Management—Leon Yours sincerely,
Recanati Graduate School of Business
Administration
Prof. Yoseph Mekori
Dean of the Sackler Faculty of Medicine Professor Joseph Klafter
Prof. Tammie Ronen
TAU President
Dean of the Gershon H. Gordon
Faculty of Social Sciences
Prof. Yoav Ariel
Dean of Students
Personalizing Medicine
2
2012 Issue TEL VIA V U NI VERSITY REVIEW
Personalizing Medicine
Neurobiologist Miguel Weil has
little time left. Prof. Weil’s
son, Nir, an afable 21 year-old
who has just fnished his national
are changing the way we’re practicing
service, sufers from a Jewish
medicine,” says Israeli-American geneti-
cist Karen Avraham, Vice Dean of the
genetic disorder called Sackler Faculty of Medicine. She serves
on the board of the recently established
familial dysautonomia (FD). Israel Center of Research Excellence
(I-CORE) in Genomic Medicine, in
It’s a progressive disease that eats which TAU is a partner.
“We’re talking about using informa-
tion we have on the genetic origin of
away at the peripheral nervous
diseases among individuals and groups
to better target care,” Prof. Avraham
system, which regulates essential says.
Tel Aviv University’s strength in
bodily functions like blood the feld, stresses University President
Joseph Klafter, “draws on the robust
pressure. Victims die, on average, interdisciplinary research and teaching
environment we’ve created for tack-
at 25 years of age. ling complex problems, and especially
on our collaborative links with major
hospitals.”
Most Jewish genetic diseases are And using that knowledge to save lives.” Race for a curative compound
rare, explains Weil, with each claiming Weil belongs to a diverse group of Prof. Weil, a member of the
a few hundred suferers in the entire scientists at Tel Aviv University who Department of Cell Research and
world. Known as “orphan” diseases, are working in the area of personalized Immunology and Head of the Smolarz
they are far too uncommon for phar- medicine, also known as genomic medi- Family Graduate School of Life
maceutical companies to invest the cine. Researchers in the feld capitalize Sciences, George S. Wise Faculty of
tens of millions of dollars needed to on the growing amounts of data on the Life Sciences, is searching for new drug
develop a drug for treatment. complete genetic make-up of individu- candidates for Nir’s disease and other
“Tat’s where Tel Aviv University als to tailor preventive, diagnostic and heritable disorders.
comes in,” says Weil. “We have the treatment strategies for both rare and Funds given by a Mexican donor who
experimental set-up to tackle medical common diseases. recently lost two sons to another rare
problems that others do not, because “Whole genome sequencing and and devastating disease, called MNGIE,
our goal is not proft but knowledge. other advanced screening technologies enabled Weil to build the most sophisti-
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By Rava Eleasari
cated robotic facility in Israel today for service, and he is now preparing himself Today, as Director of Pediatric
fully automated drug screening. for university admission examinations. Genetic Services at the TAU-afliated
Te research team uses live stem cell While the research team aims to Schneider Children’s Hospital, Rabin
samples from patients as a lab-based develop personalized treatment for Medical Center, Dr. Basel receives
model for personalized medicine. First very small groups of suferers of FD young patients from all over Israel with
they compare the diseased cells with and MNGIE, they are also applying genetic disorders that have no descrip-
healthy ones, trying to fnd the biologi- their techniques and fndings to more tion in medical literature.
cal diferences between them. Ten they widespread genetic diseases such as ALS After taking a blood sample, she
attempt to identify the compound that and Huntington’s. uses sequencing technology to study
will counteract these diferences and the genetic material, searching for the
transform a sick cell into a healthy one. A disease of one gene mutation that causes the disease.
“It’s like looking for a needle in a What happens when a disease is so
haystack,” says Weil, “but the screening rare that only one person sufers from
equipment can analyze millions of dis- it, or one family, and doctors don’t even
eased cells a week that have had diferent know what to call it?
chemicals and drugs added to them.” “I’m interested in families that have
What Weil and his team are looking lost hope for a diagnosis for their sick
for is a “hit” – when the machine reads children,” says Lina Basel, a physician
that a compound has made a positive and specialist in orphan diseases who
diference. At that point, the researchers transfers, or in scientifc parlance,
have to investigate what’s happening “translates,” laboratory knowledge into
in the diseased cell on the molecular clinical answers.
level, and to use this understanding Born and raised in Lithuania, and
for developing a drug candidate. Te with a charming unidentifable lilt when
Cell Screening Facility in Personalized speaking, Basel received her MD from
Medicine established by the Mexican the University of Vilna, immigrated
Friends of TAU is the frst such unit in to Israel in 1991, and earned a doc-
the world that deals with rare Jewish torate in molecular genetics at TAU’s
diseases. Sackler Faculty of Medicine. Prof. Yosef
20,000 Number of genes in
the human genome
Once Basel has identifed the faulty
Rate of genetic variation among people gene, she can advise on how to better
.1% Estimated number of mutations in that .1%: 10-12 million manage the disease, and she can also
provide genetic counseling and pre-natal
diagnosis to family members to make
6,000-7,000 80% 60,000 250 million sure their future children will not be
Number of Percentage of Estimated Estimated similarly aficted.
rare, “orphan” rare diseases number of rare number of rare In one instance, she recounts, a fam-
diseases in the of genetic disease sufferers disease sufferers
world origin in Israel in the world ily came in with a teenage boy of 15
who sufered from scoliosis and weak,
fracture-prone bones. His hair was thin-
“What’s incredible here are the real Shiloh of the Department of Human ning and he looked prematurely old.
families involved – it’s not just about Molecular Genetics and Biochemistry Two uncles had the same syndrome,
technology,” says Weil. “Tis is person- was her PhD supervisor and “one-man but other than the three, there were
alized medicine that is as personal as absorption program,” she recalls, “in- no known cases in the world.
you can get.” Until just recently Weil’s viting me home to join his family for Basel succeeded in tracking down
son Nir worked as a lab assistant at Tel dinner and helping me forge my career the diseased gene. It was expressed, or
Aviv University as part of his national path.” active, in various tissues of the body
4
Dr. Lina Basel
counsels a family
at the TAU-affliated
Schneider Children’s
Hospital.
Dr. Basel’s key frustration: “That even if I
know what the culprit gene is, I can’t offer
a cure. People want it. They expect it. But
we’re not there yet.”
Dr. Basel’s key hope: “Because we can
now sequence the genome of individuals,
and especially in the bones, causing
we will soon have an answer for all those
severe osteoporosis. While there was
people who ask, ‘What’s wrong with me?’”
no cure for the boy, Basel could start
treating his osteoporosis with drugs and
prevent further damage. But what really
brought hope to the family was that the Basel has set up a national, Hebrew- disorder ataxia telangiectasia (A-T) –
disease was fnally diagnosed. It received language database, called Orphanet- can lead to breakthrough insights on
a name: Macrocephaly-Aalopecia-Cutis Israel, with information on rare genetic general cellular processes.
laxa-Scoliosis (MACS). diseases for doctors and patients. Te Prof. Shiloh recently became
“Te psychological dimension is idea originated in France, and Basel’s the frst Israeli scientist to win the
huge,” stresses Basel, who has so far goal is to create a network of all the G.H.A. Clowes Award of the American
identifed causative mutated genes for clinicians and scientists working on Association for Cancer Research for
10 previously undefned diseases that no orphan diseases in Israel. She has no discovering a key gene that protects
one else could. “You can’t imagine the funding for the database. She is doing the genome from radiation damage –
relief these families feel when someone it alone, at home, on the weekends. important for understanding genetic
fnally tells them what their child has.” Meanwhile, Basel’s mentor, Yossi predisposition to cancer. Shiloh, who
A former recipient of a TAU Shiloh, has shown that research on or- holds the David and Inez Myers Chair
Marguerite Stolz Research Fellowship, phan diseases – in his case, the genetic for Cancer Genetics and directs the
5
Specifc Pathogen Free (SPF) Facility responsible gene and also determined
housed in the David and Inez Meyers that it was recessive, that is, both par-
Building for Transgenic Modeling of ents had to have it. Armed with this
Human Disease, won the Israel Prize information, medical geneticists could
for 2011 and EMET Prize in 2005 for provide genetic counseling.
his work. “Here’s the most satisfying part,”
says Avraham. “By working with doc-
Diagnosing or preventing tors and fne-tuning genetic testing for
common diseases family members, we could break the
Mining people’s genetic material can chain of inheritance.”
unearth the cause of prevalent disorders, Among Avraham’s latest discoveries
not just rare ones. is the mechanism by which auditory
Prof. Karen Avraham began work- cells die in the ear. Tis fnding is im-
ing on hereditary deafness when she portant for possibly rescuing these cells,
joined the Sackler Faculty of Medicine’s or regenerating them, in the future.
Department of Human Molecular But what excites her most is a method
Genetics and Biochemistry in 1996. she’s developed in collaboration with
About 50% of hearing impairment Prof. Moien Kanaan from Bethlehem
can be traced to genetic causes, and University for improved diagnosis of
Avraham was intrigued to learn that, genetic hearing loss in patients. “Until
in the Middle East, many extended fairly recently, researchers could test for
families and clans were known to have one or a few deafness genes at a time,
a much higher incidence of deafness a costly, hit-or-miss process that could
than the rest of the population. take years,” explains Avraham. “With This machine reads faster than
you do. Dr. Noam Shomron by
Prof. Avraham quickly established our new method, we can scan all the 250
the genome high-throughput
connections with clinical genetic labs all known genes for deafness – simultane- sequencing machine on campus.
over Israel, as ously – for less than $500 per person,
well as in the and provide results in a few weeks.”
Palestinian Te joint Israeli-Palestinian research, cancer, diabetes and heart disease is
Aut hor it y, funded by the United States’ National “tricky” says new faculty member Eran
and has since Institutes of Health (NIH), capitalizes Halperin. He combines his knowledge
performed a on a shortcut gene sequencing technol- in human genetics, computer science
number of ogy called “exome sequencing.” It scans and mathematics to sleuth out disease-
studies on just those regions of DNA that encode causing mutations.
families and proteins – regions that comprise only “We might fnd a common gene vari-
villages that 1% of the human genome but that are ant that seems to be associated with a
generated scientifc gold: the discovery implicated in about 85% of disease- certain type of cancer,” Dr. Halperin
of 10 new genes implicated in hearing causing mutations. elaborates, “but there’s no one-to-one
Prof. Karen
Avraham loss. Major funding for this work has “Te important thing about this correspondence. We can’t say with certi-
come from the United States’ Ofce of technology – and about genomic tude that people who have the mutated
American Schools and Hospitals Abroad medicine in general – is that the fast- gene will get the disease, or that people
(ASHA), which supports a Laboratory er, cheaper methods can bring about who don’t have the mutated gene will
for Middle Eastern Genetic Diseases much earlier diagnoses for diseases,” not get the disease.
at TAU. says Avraham. “And the earlier and “Other, more hard-to-fnd muta-
One Jewish clan that Avraham stud- more accurate the diagnosis, the better tions may also be involved in trigger-
ied came originally from Mosul, Iraq. doctors can predict the course of the ing the cancer, in combination with
Intermarriage among extended family disease and prescribe treatment. each other or with environmental and
members had led to 40% of all ofspring lifestyle factors.”
going deaf by the age of 20 – compared Determining risk Halperin, who has a joint ap-
to less than 1% in the general popula- Pinpointing who is at greater ge- pointment at the Blavatnik School of
tion. Avraham and her team found the netic risk for complex diseases such as Computer Science and the Department
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2012 Issue TEL AVIV UNIVERSITY REVIEW
people succumb to more lethal versions
Sequencing Leap of diseases, while others do not?
The frst thing you see when you walk into Noam Shomron’s Genome Today, about a ffth of breast cancer
High-Throughput Sequencing Laboratory are names on the whiteboard. patients will develop metastasis and they
Dozens of them. These are the physicians at 7 major TAU-affliated will die. Scientists have long known
hospitals, together with some 25 basic scientists across the TAU which gene triggers metastasis. Called
campus, who collaborate with Dr. Shomron on producing comprehensive MET, it not only induces prolifera-
analyses of people’s genetic blueprints. tion of cancer cells, but also activates
It took $3 billion and 15 years to sketch out the frst complete picture their spontaneous spread. A battery of
of human genetic material under the Human Genome Project. The MET-inhibiting drugs are in late stage
subsequent development of high-throughput or “deep“ sequencing clinical trials and promise to save tens
technology reduced this process to $10,000 and one week. That was up of thousands of lives.
until a year or so ago. Now it can be done with $1,000 in one day. But how will doctors know who to
“This is a huge scientifc leap – comparable to going from a give them to?
magnifying glass to an electron microscope,” says Dr. Shomron, who Personalizing the risk assessment
completed his PhD at Tel Aviv University and his post-doctoral studies at is the goal of MET researcher Ilan
MIT. He was recruited three years ago to TAU’s Department of Cell and Tsarfaty, Chair of the Department of
Developmental Biology, Sackler Faculty of Medicine, to preside over one Human Microbiology and Immunology,
of two high-throughput sequencing machines purchased with the support Sackler Faculty of Medicine.
of the Wolfson Family Charitable Trust, UK. The other machine is at the “If oncologists give aggressive anti-
TAU-affliated Sheba Medical Center. Additional Wolfson funding this year MET therapy to all breast cancer pa-
will enable TAU to signifcantly expand its facility. tients, 80% of them won’t need it. Te
Calling himself a “genomicist,” Shomron’s own research combines MET in their tumor is switched of to
technological and computational methods to explore the role of begin with,” explains Prof. Tsarfaty.
microRNAs, tiny snippets that regulate gene activity, in the development “Meanwhile, the 20% of patients who
of diseases and in the way patients react to medications. He foresees are genetically predisposed to metastasis
therapeutic results from this work in fve to ten years. – whose MET will be activated – may
not necessarily receive the careful treat-
of Molecular Biology and Biotechnology, increase risk for coronary artery disease. ment and attention they need.”
worked with a group at UC Berkeley on “Te relevance of all this to per- Tsarfaty decided to fnd out which
non-Hodgkin’s lymphoma – a relatively sonalized medicine,” says Halperin, women were at risk. In a team that in-
common form of cancer. Te researchers “is that people at risk can be watched cluded TAU computer scientists Roded
measured 370,000 tiny genetic muta- more closely. Tey can be counseled to Sharan and Eytan Ruppin, MD-PhD
tions, or SNPs (pronounced “snips”), reduce other risk factors like smoking student/graduate Gidi Stein and then
that are known to be common among and poor diet, and they can be tested PhD student Nir Yosef, the researchers
Hodgkin’s suferers. Using computa- for the disease earlier.” identifed a genetic “signature” – 130
tional and statistical methods, they genes that respond, or are altered, upon
separated damage-causing SNPs from Paying closer attention activation of MET. Tey visualized the
irrelevant ones, or in lab parlance, “real When it comes to risk, genomic sci- network of molecular interactions,
signals from just noise.” Ultimately, they ence is beginning to provide answers called “pathways,” connecting MET
found the one SNP that points to higher for another mystery: Why do certain to the afected genes. And fnally they
risk for non-Hodgkins lymphoma.
Currently Halperin is work-
ing in a consortium of 20 research Left: Metastasis in
groups throughout Europe called action – Confocal
microscopy image of
“Cardiogram.” Tey have pooled their cancer cells, in red,
spreading into healthy
data on 20,000 heart patients and
tissue. Blood vessels
60,000 control subjects who donated in green.

samples for whole genome SNP analysis. Right: METwork – A
visualization of the
Findings so far have revealed 13 more
network of MET
previously unknown mutations that molecular pathways.
7
peopLe of the Book checked this network against tissue
samples from breast cancer patients to
Take the number of letters in 1,000 bibles, says
isolate 9 genes that, under laboratory
computer scientist Ron Shamir. That’s about the conditions, reliably predicted MET risk.
Soon, hopes Tsarfaty, doctors will be
number of “letters” – the 3 billion chemical bases –
able to screen for the 9 telltale genes in
making up each person’s total DNA.
a biopsy, and to ofer more timely and
However, only 2 percent of these letters spell out, or encode, the accurate therapy based on each patient’s
20,000 or so genes in our bodies. How can scientists know which genetic makeup.
sequence of letters translates into a working gene and which does not? Tsarfaty has also developed an imag-
Moreover, how can they determine which gene variant or mutation is ing technique at the Sackler Institute
responsible for diseases? for Molecular Medicine for showing
“This is where bioinformatics comes in – the point where biology in a patient’s body, in real time, when
and computer science intersect,” says Prof. Shamir, who heads TAU’s MET is active and, after targeted drug
Edmond J. Safra Bioinformatics Program. therapy, inactive. “Tis will personal-
The feld of bioinformatics emerged in the late 1980s and early 1990s ize the care to the highest degree. We
in response to the huge computational demands of the Human Genome will be able to actually see, as a live
Project. Embracing the feld early, Tel Aviv University has since produced image, if a certain drug is inhibiting
the largest group of bioinformatics specialists in Israel under the Edmond the MET or if we need to change the
J. Safra Program and ranks among the world’s leaders in the feld. medication,” he says.
“We’re coming up with new mathematical tools and software to analyze
the data,” elaborates Shamir, who is a faculty member of the Blavatnik Genetic component of drug
School of Computer Science at the Raymond and Beverly Sackler Faculty response
of Exact Sciences. “And the data sets are just getting bigger as genome “Te era of one medicine for eve-
sequencing becomes more widespread.” ryone is ending,” asserts SNP sleuth
One of the challenges is fguring out the genome’s rules. Researchers Dr. Halperin. “Te new paradigm will
must determine the sequence characteristics of the gene-coding regions involve doctors prescribing drugs ac-
versus the non-coding regions, and develop algorithms to statistically cording to an individual’s genetics.”
infer where the genes are. Complicating matters is the surprising fact that Advancing this goal is extremely im-
human genes are not contiguous in the DNA sequence. They can be made portant, given that in the United States
up of 5 to 30 unjoined segments. alone an estimated 2.2 million people
“That’s a low-end problem,” notes Shamir. Suppose, he continues, that either fail to respond to medications or
the 20,000 human genes and their corresponding proteins are identifed. experience serious reactions each year.
Yet in a living cell, all these proteins are co-existing and interacting, and An additional 100,000 people die from
this is what makes the cell and the living organism function. “Knowing harmful efects.
what each gene does still doesn’t tell you the whole story,” Shamir says. At the TAU-afliated Sheba Cancer
He offers another analogy to help understand the dimensions of the Research Center at Tel Hashomer
problem. “If the genome is like an orchestra with 20,000 instruments, Hospital, TAU professor Gideon
knowing what the fute plays does not help you hear the score or know the Rechavi leads one of the best-known
composition.” groups in the world for identifying
The need to understand biology not just on the molecular level but as a genes involved in cancer drug response
complex system has led to a new feld – systems biology – which TAU has and transferring this knowledge to the
been building up in recent years. clinic.
“Funding from the Edmond J. Safra Bioinformatics Program has In one project, Prof. Rechavi’s group
enabled us to recruit the best young researchers and nurture a strong is studying mutations that cause certain
body of interdisciplinary students,” stresses Shamir. “Theoreticians patients with chronic myeloid leuke-
collaborate with experimentalists, campus groups with hospital clinicians. mia, a cancer of the white blood cells,
The pace is break-neck. We have to be agile and quick.” to develop resistance to a life-saving
drug. Te scientists are developing a
genetic testing technique for fnding out
quickly and accurately who has these
8