LSI_10th_book_01

3
2 The Last 10Years
forward by Alan Salitel
4 Embracing Risk
Mary Sue Coleman
4 Built for Change
Built for Change
4 Exploring the Complexity
of Life
4 Publications
4 Students
4 Symposium
4 Centers of Collaborative
Drug Discovery
4 Global Citizens of Science
4 Art & Science
4 Photo Feature
A Machine for Research
4 Collaboration
A Machine for Research

4
thelast10years
4
cientifically, the last decade has been a whirlwind.
In 2003, the many scientists who worked on the
Human Genome Project — the largest collaborative
biological project to date — published their final results. Since the
from nearly $100 million to less than $10,000. Scientists didn’t
agree on a definition of the term epigenetics until 2008.
In the same time frame, the budget of the National Institutes
of Health has fallen 22 percent. The cost of developing drugs
is 10 times higher than it was in the 1970s, and it takes longer
than 10 years to bring a drug to market. The failure rate can
be disheartening.
The Life Sciences Institute has grappled with all of these interlocking
opportunities and challenges, seeing each trend and development
as a chance to innovate. As we celebrate our 10th anniversary,
we’ve been thinking about how rapid change, increased scientific
complexity, accelerating technology and financial challenges have
shaped our work, and thinking of the future.
Our Faculty
It should go without saying that the scientists are the institute
and our raison d’etre. Because our faculty is our single most
valuable investment and because the freedom from traditional
academic bounds means great potential for the LSI to be more
than a sum of its parts, we think very carefully about the
composition and number of scientists in the building.
We share the belief that today’s biomedical problems are
too vast and complex to be solved by any single scientist or
addressed by a single academic field. From the beginning, the
institute’s faculty was to be interdisciplinary and complementary.
We have also thought about a mix of junior and senior faculty,
and building a community that is intercultural as well as
interdisciplinary. In short, we mix it up in any way we can.
The faculty all has one thing in common, though: They are
dedicated basic scientists who are deeply engaged with a
passion for understanding how life works.
They are exceptional by the science world’s usual measures
of publications and awards. But the most important outcome
of our assembly the LSI’s faculty as been the creation of a distinct
culture. It’s qualitative and intangible, the evidence is anecdotal,
and we all know not to confuse correlation with causation. But if
you’ve experienced the LSI, you know what I’m talking about.
Organizational structure
The task force that initially proposed the creation of the institute
recommended a research center located outside of traditional
academic departments and the university hospital system, yet
connected to both. Being outside “the system” allowed us to
recruit top faculty from a range of fields around the world, rather
than from a single discipline. The LSI’s structure also allows
scientist focus on research above all. The institute is agile, able
to respond quickly to new opportunities and challenges, and
able to create a powerful independent identity on the bedrock
of a great public university.
Our independent status is not without its challenges. [As a small
player in large community? dispersed (rather than a bloc like a big
department), lots of education needed to explain the institute,
constantly need to make the case for its existence]
Results: Need some good examples of why this is a good thing?
Architecture and the working environment
In biology, we often say that form follows function. When the
architects from Venturi, Scott Brown and Associates designed
the LSI, they considered the desired function of the form. With
large open lab spaces — now de rigeur, but radical at the time
— copious natural light, materials with integrity and a thoughtful
S

5
execution, the design of the institute represented the ideals
of collaboration, creativity and inspiration. At the same time the
building incorporates visual references to midcentury factory
design in a way that celebrates work, efficiency and functionality.
The building has served its purpose. Spontaneous conversations
spring up through the space. If anything, we think about how
to create these between floors as well as throughout the long
corridors of research space. Shared equipment saves money
and space. Shared ideas lead to new approaches.
If the building runs like a finely tuned machine, it’s because
highly skilled mechanics keep it in top shape. Our facility team
manages everything from the glass-washing services on each
floor to the nitrogen tank on the roof and the mouse cages in
the basement.
And throughout the building, a collection of art inspired by and
exploring the ideas of science reminds everyone working within
of the ‘big picture’ of scientific inquiry — the search for truth
and the improvement of human life.
Students
The LSI unequivocally exists to support, catalyze and promote
scientific discovery.The same structure and resources also
allows students to thrive in the institute. In the last ten years
we’ve supported students through the Perrigo Undergraduate
Fellowship and the LSI Fellows program, a graduate class called
the Business of Biology and most recently the addition of the
Program in Chemical Biology.
Training the next generation of scientists in collaborative and
innovative way of working gives them a fresh set of tools to
share through their professional lives. But students also play an
important role in the institute: Free to move easily throughout the
building, they cross-pollinate the labs. In my lab, students will
come to me with a problem — and they’re already started
collaborating on the problem with a student from another lab.
It’s a cliché to say the teacher learns from the students, but
it’s real.
Culture
We follow the science.The importance of science so thoroughly
permeates everything that happens at the LSI that calling “a focus
on basic science” an innovation seems ridiculous. And after all, don’t
scientists everywhere do science? What’s so special about the LSI?
So many external factors can detract from the essential work
of science. Writing grant applications, managing a staff, maintaining
equipment, promoting your own work and the other basics
of running a lab eat up more and more of scientists’ time. At the
LSI we provide a professional staff that takes care of as much
of that as they can, allowing scientists to do experiments, write
and publish papers, speak at conferences and otherwise be
scientists, not managers, for as much of the day as possible.
We don’t emphasize funding or award.Those things matter in our
world, but they’re secondary to what really matters: Discovery.
By clearing the clutter from the scientific endeavor, upholding
excellence as the most important criteria, providing a structure
within which we can embrace risk — all of these things allow
the institute as a group to follow the science. And that is what
ultimately has the potential for impact on human health.
Alan Saltiel //
Mary Sue Coleman Director of the Life Sciences Institute

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EmbracingRisk
The LSI directorship
was named for President
Mary Sue Coleman in 2008.
6

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very day, we only need to read the news to see that major advances in science are taking place. While the importance
of scientific research to human health and to the economy cannot be underestimated, few outside of the scientific world
understand the time, money, appetite for risk, and comfort with failure that a career in science requires.
Since I arrived at the University of Michigan, we have invested more than $1 billion and nearly a million square feet of new space in
life sciences research and education. The Life Sciences Institute represents our most tangible commitment to the risk that is essential
to modern scientific discovery. The decision to invest in the life sciences was made by my predecessor, President Lee C. Bollinger; as
both president and a scientist, I fully embraced the vision and work of shepherding the initiative forward.
We live in a world defined by rapidly changing technology, and must be agile ourselves to continuously adapt. With a solid platform
for discovery at the LSI, we have been able to strategically embrace each new challenge and opportunity and make the most of each
new tool. This includes high-throughput screening for drug discovery. And the ability to see, in remarkable detail, proteins within the
body using advanced technologies such as cryo-electron microscopy and X-ray crystallography. And customizing medicine to treat
an individual’s disease.
The discoveries have been exhilarating.
The same is true for the scientific relationships. For a scientist, it is inspiring to engage with leading researchers from such a wide
range of areas—biochemists, biologists, geneticists, chemists and others—and have real conversations around common questions
about how life works. The constant dialogue is also a reminder of the complexity and immensity of the problems of disease and the
urgent need for collaboration, because none of us could possibly solve these problems alone.
The Life Sciences Institute has been instrumental in recruiting faculty to a number of departments across the University. Its collaborative
centers have become hubs of scientific activity for people across campus. Its international nature has helped solidify U-M’s global
impact, and its ties to the regional biotech community have contributed to Michigan’s economy.
LSI has brought to the fore synergies that are unique to Michigan. Myriad patents and commercialization opportunities have emerged
from the labs. And now the first potential drug is heading to clinical trials.
The Life Sciences Institute is the nucleus at U-M for emerging opportunities in the life sciences. We are on the threshold of understanding
life and living organisms at the most basic level and reaping the benefits of that understanding. It’s only been 10 years for the LSI, but
that decade coincides with the beginning of a golden age of discovery. The best science is about surprise. I cannot wait to see what
the next 10 years bring.
Mary sue coleman // President, University of Michigan
E

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Envisioning
Collaboration
The culture and the facilities
of the LSI promote informal and
formal collaborations between
scientists and lab members
throughout the institute. This
graph shows, for each LSI primary
investigator, his or her field,
diseases studied, model systems
used and academic department
at University of Michigan.The
center of the graph shows the
myriad connections and working
relationships between the
scientists as measured by shared
authorship of academic papers,
shared grants and self-reported
collaborative measurements.
Parts of the graph are enlarged
on the following pages.
A key to the graph is on page XXXX.

9
Understanding Disease
from All Directions
The quest for knowledge of how
life works on a cellular and
molecular level shape informs
our understanding of health
and disease.The basic science
conducted at the LSI translates
into potential drugs and treat-
ments for cancer, metabolic
disorders, neurological diseases
and other common problems
in human health.The LSI faculty
represents multiple scientific
disciplines; some move comfort-
ably across more than one
scientific field. Most conduct the
sort of fundamental research that
is ultimately relevant to multiple
human health problems, not
just a single disease.This graph
illustrates the multifaceted and
overlapping backgrounds and
interests of the faculty as a group.
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1010
Diseases and Tools
or Model Systems
The LSI scientists not only
represent a range of scientific
disciplines, they also vary wildly in
the way they conduct research.
Because scientists in the LSI work
in different animal model systems
and research technologies, the
institute’s faculty as a group is
able to address highly complex
life-science questions in creative
and innovate ways.This graph
shows the range of tools and
model systems employed by labs
in the institute and the diseases
studied by individual labs.
NOTE:
(Please make the key say “Tools
and model systems” for the
yellows)

11
More than the sum
of its parts
The working relationships
between the labs at the LSI
define its culture, make success
possible, and create possibilities
that no individual scientist would
have alone. This graph represents
a combination of shared publica-
tions and grants and self-report-
ed collaborative relationships
between faculty in the LSI in
June 2013.
11
Each faculty member is represented by a color in this graph.The color of the line connecting
the individuals represents the originator or lead in the collaboration.The thickness and saturation
of the connecting lines reflect the frequency and intensity of the collaborations.

BUILTFORCHANGE
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n the LSI, form and function seamlessly blend. Large open labs, connected by shared equipment corridors
and social interaction spaces, catalyze and complement the collaborative mission of LSI.
World-renowned architects Denise Scott Brown and Robert Venturi worked with laboratory design firmThe Smith
Group to create an Albert Kahn-inspired open laboratory facility on a previously underused parcel at the juncture
of Central Campus and the Medical Center.This site, now called the Palmer Campus, also includes the Undergraduate
Science Building and the Palmer Commons, a conference and meeting center that also houses the university’s Bioinfor-
matics Program. All three buildings face a public plaza that serves as a pedestrian thoroughfare connecting Michigan’s
central and medical campuses—a physical and intellectual bridge between these two parts of the university.
The 230,000 sq. ft. building is packed with collaborative centers and sophisticated research tools.The Centers
for Chemical Genomics and Structural Biology are located on the plaza-level 3rd floor along with core facilities in
NMR, flow cytometry, and DNA sequencing. Researchers throughout the university and from other institutions
collaborate with LSI scientists on projects in the core facilities and centers.
I

COLLABORATE
“The life sciences are in a period of remarkable intellectual growth and discovery.”
Exploringthe
ComplexityofLife
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“The life sciences are undergoing an
intellectual revolution that will potentially
transform our understanding of biological
life—its structures and functions, its care
and well-being.This potential revolution
promises to enhance our ability to promote
human health and to care for our environ-
ment, and has tremendous economic
development implications.”
– Lee C. Bollinger, University of Michigan president (1996-2002)

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The Life Sciences Commission, a 20-member
interdisciplinary group charged by then-President
Lee Bollinger with developing a plan to “participate
fully and preeminently in the exploration of this
extraordinary advance of knowledge” in
interdisciplinary life science.
February
“The life sciences are now poised
to move from understanding
biological phenomena at specific
levels, to understanding biological
interactions at multiple levels
of complexity.”
— Report from the Life Sciences
Commission, which was part of
the Life Sciences Initiative at the
University of Michigan
1999998

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2003
September
Ground broken on Palmer
Drive site for construction of a
six-story, 285,882 square foot
research building with labs
for 25 to 30 scientists
March
Alan Saltiel, former
distinguished research fellow and
senior director of the Department
of Cell Biology at the Parke-Davis
Pharmaceutical Research Division
of Warner-Lambert Company,
joins the institute as the first
faculty member
October
U-M Biological Chemistry
chair Jack Dixon and University
of California at San Diego
professor Scott Emr named
co-directors of the institute
October
Lee Bollinger announces
departure to become of president
of Columbia University
2000 2001
MILESTONES

17
January
Scott Emr elects to remain and
UCSD; Jack Dixon assumes
directorship of LSI
April
Liz Barry named managing director
May
First annual LSI Symposium:
“Structural Biology of
Cell Signaling”
2002 2003
JUNE
Rowena Matthews
elected to the National
Academy of Sciences
July
Jack Dixon announces
departure for University of
California, San Diego. He
went on to serve as Vice
President and Chief Scientific
Officer at the Howard
Hughes Medical Institute
from 2007 to 2013.
September
Mary Sue Coleman
named president of
University of Michigan
Alan Saltiel named
LSI director
September
LSI building complete
Five scientists move their labs into the building:
• Cell Biologist Alan R. Saltiel, Ph.D., (Director) John
Jacob Abel Collegiate Professor in the Life Sciences,
Professor of Internal Medicine and Physiology
• Geneticist David Ginsburg, M.D. (Charter faculty)
Warner-Lambert/Parke-Davis Professor of Genetics
and Internal Medicine, Howard Hughes Investigator
• Cell biologist Daniel J. Klionsky, Ph.D. (Charter faculty)
Professor of Molecular, Cellular and Developmental
Biology and Biological Chemistry
• Pathologist John B. Lowe, M.D. (Charter faculty)
Warner-Lambert/Parke-Davis Professor of Pathology
and Howard Hughes Investigator.
• Biochemist Rowena G. Matthews, Ph.D. (Charter faculty)
G. Robert Greenberg Professor of Biological Chemistry,
Senior Research Scientist in the Biophysics Research Division
New faculty members: Anuj Kumar, Kun-Liang Guan,
Zhaohui Xu
April
Global scientific milestone: The researchers
involved in the Human Genome Project, the
largest-ever collaborative biological project,
publishes the full sequence of human genes
May
Two LSI boards appointed: Advisory Board
— External board of industry leaders who
advise and advocate for the institute
Executive Committee— U-M executive
officers, deans and faculty members who
serve as part of institute governance
Second LSI Symposium: “Genetic Insights
into Biology and Disease”
2002 2003

18
MILESTONES
2004 2005
April
Perrigo Undergraduate Fellowship
Program established with a gift from the
Perrigo Company to bring undergraduate
students from across the state to work
in LSI labs during the summer.
May
Fourth annual LSI Symposium:
“Cancer Insights: Molecules
to Medicine”
September
U-M Center for Stem Cell
Biology established with $10.5
million in funding to support
adult and human embryonic
stem cell research
October
Five-year collaboration agreement
with ThermoFisher to develop
technologies in high-throughput
screening and detection, protein
expression, chemical diversity
and bioinformatics, with
funding for $1.5 million
September
LSI’s Business of Biology course, an
interdisciplinary graduate course on genomic
medicine, is launched by B. Joseph White,
former dean of Ross School of Business and
interim president of U-M, and Liz Barry,
LSI managing director
Sean Morrison receives a Presidential Early
Career Award for Scientists and Engineers
October
Rowena Matthews elected to the Institute of
Medicine of the National Academies
New faculty members:
Gabrielle Rudenko, David Sherman New faculty members:
Janet Smith, Shawn Xu,
John Tesmer, Jason Gestwicki,
Noah Rosenberg, Jiandie Lin,
Lois Weisman, Patrick Hu,
Sean Morrison
Caption
MAY
LSI announces new collaborative
centers: the Center for Chemical
Genomics, a high-throughput
screening center with technology to
test thousands of chemicals at a time
for possible effects as drugs, and the
Center for Structural Biology, a
collaboratory with a protein production
facility and an x-ray crystallography
suite where researchers can discover
the forms and structure of molecules
and understand how they interact.
Third LSI Symposium: “Exploring the
Complexity of Life
E.O. Wilson delivers keynote address:
“Unified Biology and the Future of Life” E.O. Wilson

19
February
Noah Rosenberg and Shawn Xu
selected as Alfred P. Sloan
Research Fellows
May
Fifth annual LSI Symposium:
“Molecular Insights into
Metabolic Disease”
January
100th paper published (after official grand
opening): “Increased inflammatory properties of
adipose tissue macrophages recruited during
diet-induced obesity,” Diabetes, Saltiel
May
David Ginsburg elected to National
Academy of Sciences
Sixth annual LSI Symposium:
“Frontiers in Stem Cell Biology”
LSI stages first art/science exhibit with
“The Seduction of Scale” featuring works
by faculty from UM’s School of Art and
Design and others”
month?
The Center for Structural Biology
obtains access to three beamlines
at Argonne National Laboratory’s
Advanced Photon Source
October
Alan R. Saltiel elected to the
Institute of Medicine of the
National Academy of Science
Alexy Kondrashov, Kate Carroll,
Sylvie Garneau-Tsodikova,
John Kim, Stephen Weiss,
Cheung-Yu Lee
June
Shawn Xu named a Pew Scholar in the
Biomedical Sciences
August
Center for Chemical Genomics licenses
first compound (CCG-1423, licensed to
Cayman Chemicals)
October
Steelcase Corporation conducts space-use
study and re-designs a 3rd floor laboratory to
facilitate interaction and use of technology
December
Center for Chemical Genomics completes
15 screens
Ivan Maillard, Yukiko Yamashita
2006 2007

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MILESTONES
2008 2009
May
Seventh annual LSI Symposium:
“Focus on Chemical Biology”
June
Innovation Partnership, a novel
program to shepherd promising
biomedical discoveries from
the lab bench to the marketplace,
is established
Yukiko Yamashita named
Searle Scholar
July
UM/Israeli Universities Research
Partnership launched to support
innovative, disease-based projects
involving both U-M and Israeli
research team members
May
Eighth annual LSI Symposium:
“Evolutionary Biology: 150 Years
After The Origin”
January
John Tesmer receives the John
J. Abel Award in Pharmacology
from The American Society for
Pharmacology and Experimental
Therapeutics (ASPET)
March
Cryo-EM laboratory completed,
allowing structural biologists to
visualize in detail macromolecular
architectures that are preserved in
a vitreous ice layer. Designed by
Georgios Skiniotis the lab was
one of about a dozen electron
cryomicroscopy labs in the U.S.
when it was built.
September
LSI Directorship named for
President Mary Sue Coleman
Johnson Johnson and
LSI begin 3-year collaboration
in metabolic disease
Center for Structural Biology
solves 100th structure
November
Michigan voters approve Proposal
2, lifting ban on human embryonic
stem cell research. The Center
for Stem Cell Biology was a
vocal and prominent advocate
for the proposal.
Ken Inoki, Mi Hee Lim, Georgios
Skiniotis, Bing Ye. Institute full.
June
John Kim named
as a Pew Scholar in the
Biomedical Sciences
September
First siRNA screen
completed in the Center
for Chemical Genomics

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2010 2011
February
Alan Saltiel receives the
Louis S. Goodman and
Alfred Gilman Award in Drug
Receptor Pharmacology from
The American Society for
Pharmacology and Experimental
Therapeutics (ASPET)
June
Bing Ye named as
a Pew Scholar in the
Biomedical Sciences
Ninth annual LSI Symposium:
“Macromolecular Complexes
in Cell Biology”
September
Innovation Partnership identifies
first four projects: a potential
treatment for neurodegenerative
disease, new diabetes treatment,
antibiotics that circumvent
resistance and a drug that
blocks cancer from spreading
throughout the body
October
David Ginsburg receives the
Association of American Medical
Colleges (AAMC) Distinguished
Research in the Biomedical
Sciences Award
September
Yukiko Yamashita receives
MacArthur Award (the so-called
“genius award)
December
More than 50 new technologies
stemming from LSI research have
been registered with UM’s Office
of Technology Transfer
Daniel Southworth
may
Tenth annual LSI Symposium:
“Autophagy in Health
and Disease”
June
Georgios Skiniotis
named aa Pew Scholar in
the Biomedical Sciences

22
MILESTONES
2012 2013
February
University of Michigan’s first
human embryonic stem cell line
placed on the U.S. National
Institutes of Health’s registry,
making the cells available for
federally funded research
Mi Hee Lim selected as Alfred P.
Sloan Research Fellow
May
Eleventh annual LSI Symposium:
“Development and Diseases
of the Nervous System”
for 25 to 30 scientists
February
Yukiko Yamashita receives
Keck Award
May
Yukiko Yamashita named
Howard Hughes Medical
Institute Investigator
The graduate Program in
Chemical Biology and its Masters
of Science in Cancer Chemical
Biology move to the LSI
July
Georgios Skiniotis receives the
Presidential Early Career Award
for Scientists and Engineers
(PECASE)
August
U-M launches the Center for the
Discovery of New Medicines
(CDNM) to coordinate and support
work in a range of departments
and schools to streamline drug
discovery and development,
support the translation of early
research toward patient use
Center for Chemical Genomic’s
Mscreen database reaches 10M
experimental data-points
June
Twelfth annual LSI Symposium:
“Exploring Epigenetics and RNA”
Anna Mapp, Vivian Cheung,
Jun Wu
JULY
Clinical trials begin for the
first drug discovered in the LSI
(amlexanox), which the Saltiel lab
found reversed obesity and
metabolic disorders in mice
September
LSI’s public lecture series,
Follow the Science, is launched
Anna Schork joins LSI as
managing director
2

FOLLOW THE
SCIENCE
HOW RESEARCH IS REVOLUTIONIZING
OUR APPROACH TO HEALTH, DISEASE
AND TREATMENT
PUBLIC LECTURE SERIES
Sept. 26, 2013 • 4:00 PM
Alan Saltiel, PhD
Director of the Life Sciences Institute
UNDERSTANDING OBESITY AS A DISEASE
Alan Saltiel researches insulin and how it relates to obesity, diabetes and other
metabolic disorders.
Nov. 7, 2013 • 4:00 PM
Stephen J. Weiss, MD
WHEN CANCER CELLS INVADE
Stephen Weiss studies the molecular machinery of cells—both healthy and
diseased—to understand how cancer cells metastasize, and to develop drugs
to stop them.
Jan. 23, 2014 • 4:00 PM
David Ginsburg, MD
TO BLEED OR NOT TO BLEED, THAT IS THE QUESTION
David Ginsburg studies blood clots and how abnormalities in clotting can result in
diseases like the hemophilias, deep vein thrombosis, heart attacks and stroke.
Feb. 20, 2014 • 4:00 PM
Janet Smith, PhD
CRYSTALS AS WINDOWS ON BIOLOGY
Janet Smith creates 3D images of molecules that manufacture antibiotics and that
come from infectious pathogens, particularly viruses like the ones that cause
West Nile disease and dengue hemorrhagic fever.
March 20, 2014 • 4:00 PM
Daniel Klionsky, PhD
HOW CELLS MAINTAIN HEALTH THROUGH SELF-EATING
Daniel Klionsky investigates how cells respond physiologically to damage, starvation
and other stress conditions.
lsi.umich.edu
QA and light refreshments in the Life Sciences Institute library after each lecture.
Forum Hall in Palmer Commons
100 Washtenaw Ave., Ann Arbor
Free Admission
23
2013

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PUBLICATIONS
As of 2013, the facultyof the LSI published
XX papers, including XX in top journals.
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
24

2626
A cutting-edge community
Before there was a brick-and-mortar Life Sciences Institute, there
was the Life Sciences Symposium. In 2002, while construction
was still underway, the LSI held its first symposium, on the
structural biology of cell signaling. Leading experts from institutions
around the world working in what was then an emerging area
of cross-disciplinary research spanning cell biology, physics and
chemistry converged in Ann Arbor to engage in conversation
and exchange perspectives.
The event continues to represent the LSI’s most important
values: excellence in science, investment in high-risk and
high-impact research, and especially the synergy that happens
when top scientists from a range of fields meet and share
their work around a common theme.
SYMPOSIUM
2003

28
CentersofCollaborative
DrugDiscovery
28
he LSI is home to collaborative centers where researchers from across University of Michigan
and outside of U-M can work with highly skilled scientists and access specialized instrumentation
and equipment for basic science and drug discovery.
CenterforChemicalGenomics
The Center for Chemical Genomics (CCG) conducts high-throughput screening experiments to answer basic biology
questions or discover potential new drugs. Dedicated staff members with years of pharmaceutical-industry experience
help researchers develop experiments, access U-M’s large database of past screens, and evaluate results.The CCG’s
compound libraries have yielded new chemical probes and drug leads, many with in vivo activity.
as of November 2012
157target screens
274students and post-docs trained
180,000
chemicals in library
T
Asof2013
180,000 chemicals in library
More than 5,000 natural product extracts
5 RNAi screens in development
52 CCG-related publications
12 million data points in MScreen database
274 students and post-docs trained
Therapeutic focus areas of CCG screens:
IN
PROGRESS

29
103High-throughput protein
lab projects
CenterforStructuralBiology
The Center for Structural Biology (CSB) is a “collaboratory” for X-ray crystallography, crystallization and protein engineer-
ing.The CSB provides comprehensive structural biology resources for researchers at U-M and surrounding areas.The
center includes a high-throughput protein lab for protein engineering, protein purification facilities for protein production,
macromolecular crystallization and cystallography labs for solving crystal structures of biological molecules, and on-site
X-ray facility and access to high-energy synchrotron radiation at Argonne National Laboratory through the Life Science
Collaborative AccessTeam.
CenterfortheDiscoveryofNewMedicines
As a virtual hub for drug discovery at U-M, the Center for the Discovery of New Medicines (CDNM), established in 2012,
coordinates and supports the development of therapeutics from discovery to the market.
U-M scientists are tackling challenging drug targets like protein-protein interactions, gene transcription mechanisms and
protein folding/chaperones — targets that require a high level of investment and involve substantial risk. Orphan diseases,
tuberculosis, drug-resistant bacteria, lethal viral infections, cancer, neurodegenerative diseases and depression represent
important areas of unmet medical need, yet pharmaceutical companies have reduced budgets for research and development.
A joint project of the LSI, Medical School, and College of Pharmacy, the CDNM works with departments of chemistry,
biology, dentistry and nursing and converges with U-M’s offices ofTechTransfer and Business Development to leverage
the potential of U-M’s extensive drug-discovery community.
The CDNM funded 14 projects in its first year.
3,444
hours of beam time at
Argonne National Laboratory
175Protein production
and crystallization projects
31 Cryo-EM projects
450 structures solved
SINCE2004
IN
PROGRESS

30
ANINTERNATIONALINSTITUTE
GLOBALCITIZENSOFSCIENCE
30
as of November 2012
50%Percentage of faculty members
who moved to the U.S. from
another country
134Number who hold visas
335Number of primary investigators,
post-docs, lab managers, students
and staff in the LSI

31
t U-M, the LSI has a global platform
for science. The university ranked 12th
in the Times of London World Reputation Rankings in
March 2012. And according to another survey, the QS
World University rankings, U-M is 17th in terms of most
international faculty of all institutions in the United States
and by the same measures is the most international
American public university.
But let’s dig a little deeper.The first in those rankings is
MIT, where the faculty is about 40 percent international.
Stanford University is about the same. At the LSI, more
than 50 percent of the faculty is from outside the U.S.The
LSI is more international than even the most international
universities in the country. This doesn’t surprise me.
It’s part of the LSI’s culture to seek different viewpoints,
and in that quest we naturally gravitate toward and
attract a diverse group.
In our building, leading scientists from Japan, China,
Korea, Greece and Switzerland work with an international
group of postdocs, who come from China, Japan,Taiwan,
Pakistan, Australia, Netherlands, Switzerland, Canada,
India, Ukraine, Sweden, Lebanon, Belize and many other
countries. If you include the hundred-plus international
students working in LSI labs during any given semester,
the picture becomes more kaleidoscopic.
31
A

32
macrocosmic
The desire to explore the complexities of life unites art and science at U-M.The art collection
on permanent display in the Life Sciences Institute explores the growing and ever-changing
interplay of art, science and technology.The collection underscores the commitment between
the LSI, the School of Art and Design, and the University of Michigan Museum of Art to
support collaborative, interdisciplinary projects.
Vibrantly colored quarks, gargantuan taste buds, and an insider’s view into the workings
of the brain are a few of the subjects in the words. All are products of collaborations that
highlight how art informs science and how science informs art.
David Mann
“After Before”
2007
65 ¼” x 72 ¼”
Oil and acrylic on canvas
stretched over board
Hanging above the LSI reception desk
is David Mann’s “After Before.” Mann’s
early inspiration for his paintings comes
from science, particularly images on a
scanning electron microscope. Mann
described his paintings as luminous
abstractions that “suggest primordial
phenomena and moments of organic
transformation rife with potential. In [the]
paintings, concise cellular forms perco-
late through, and often explode from,
mysterious plasmatic surroundings.”
32
ARTSCIENCE

33
microcosmic
David Mann
“Sonar”
2003
65 ¼” x 72 ¼”
Oil, alkyd, and acrylic on canvas
stretched over board
“Sonar” is a complement to “After
Before,” which hangs in the LSI reception
area. Like “After Before,” it incorporates
cellular forms, and there is a structural
similarity between the two paintings.
While “After Before” is meant to evoke a
macrocosmic world, “Sonar” is microcos-
mic, echoing the same sense of organic
transformation on a different scale.

34
PHOTOFEATURE
portraitsIN
collaboration
34
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estia quam, aut quatque aut res re illor santo Ra voluptat reptasp edigeniscid qui tendi dolupta volorum sequundis aritaturi
cuscipsandae exerum rero optaece rfercient ut es a sant.

38
“How do you get scientists to work together? I have pondered this question often
during my ten years in industry and sixteen years in academia as a leader and member
of different kinds of scientific organizations. Deep discussions I’ve had with leaders in
industry and academia, and not just in the life sciences, always come back to the same
dilemma, the tension between the “I” and the “We”, and the likelihood of tipping too
far to one side or the other. I’ve concluded that creating a culture of innovative discovery
depends critically on achieving the right balance, and developing a value system where
this tension is minimized, so that the “I” exists in harmony with the “We.”
I cannot overemphasize that it is not enough to simply assemble talent. Bringing
talented scientists together across disciplinary lines requires trust. Trust is difficult
for almost everyone, but is an especially challenging proposition for scientists who,
by nature, rely on seeing the primary data with their own eyes. After all, we’re putting
our projects — our lifeblood! — into each other’s hands. We have to rely on our
colleagues’ knowledge of their fields and their ability to teach the rest of us what we
need to know in order to collaborate successfully across our different perspectives.
To get at the heart of LSI’s mission, we have to deeply engage in the big questions in
each other’s disciplines. It’s not enough to simply attend presentations or read papers
in other fields. We have to develop ways to truly take part in each other’s science,
especially with the kind of experiments that none of could do on our own.
Great science is always done by great scientists.To a person, each of this new crowd has
a track record of independent successful inquiry on significant problems, an outstanding
training pedigree, boundless curiosity, and a disciplined work ethic. But what’s most
amazing about this group is the wide range of fields they represent. In fact, there is only
one feature common to all of these scientists- their excitement about each other.
Alan Saltiel // Mary Sue Coleman Director of the Life Sciences Institute
COLLABORATE

40
COLLABORATE
“I make nature-inspired molecules—inhibitors of protein/protein
interactions— with the intent to find out how those molecules influence
a biological process.”
“When I meet patients, I understand that what we’re doing scientifically
can be important to them personally. It makes me realize that our work has
direct relevance.”
“Understanding gene expression has a direct impact on disease, since disease
is almost always associated with an aberration of gene expression.”
David Ginsburg investigates the components of the blood-clotting system and how
disturbances in their function lead to human bleeding and blood-clotting disorders.
A world-renowned geneticist, he studies families with bleeding disorders like hemophilia
to understand the genes and biomolecules that control the blood-clotting response,
stroke and heart disease.
David Ginsburg
Geneticist
Joined the LSI in 2003
Sylvie Garneau-Tsodikova
Chemical biologist
Associate Professor of Pharmaceutical
Sciences, University of Kentucky
Time at LSI: 2006-2013
Sylvie Garneau-Tsodikova seeks to understand and exploit the enzymes involved in natural
product biosynthesis with the ultimate objective of developing novel biologically active compounds
to treat disease. She combines tools and strategies from molecular biology, biochemistry,
microbiology and synthetic organic chemistry to understand how these novel compounds may
inhibit microbial agents and cancer cells, and be used as treatment for Alzheimer’s.
Kate Carroll develops and applies new technologies that cut across the traditional boundaries
of chemical and biological sciences. Her research focuses on the changes in protein oxidation
associated with cancer, aging, and neurodegeneration, information that can be used to develop
new diagnostic and therapeutic approaches.
Kate Carroll
Chemical biologist
Associate Professor of Chemistry,
The Scripps Research Institute

41
“Science is like art—you never know what’s going to happen.When you
paint, you start with a blank canvas and create something, and when you
start mixing chemicals you never know what you are going to discover.”
“At the end of the day in chemistry, you have a solid in a flask or some
kind of oil.You’ve made something! It may not be the product you were hoping
for, but there are so many methods to characterize the isolated material it can
be a very rewarding puzzle to piece together.”
“Questions about how the blood clotting system works, especially
how it works in humans, thrive at the boundary between human medicine
and pure basic science.”
Kun-Liang Guan
Biochemist
Professor of Pharmacology,
University of California San Diego
Jason Gestwicki
Associate Professor, Department
of Pharmaceutical Chemistry,
Institute for Neurodegenerative Diseases,
University of California San Francisco
Vivian Cheung
Pediatrician
Joined LSI in 2013
Kun-Liang Guan investigates the mechanisms of cell growth regulation and organ
size control. His laboratory studies the TSC-mTOR pathway in cell growth in response
to growth factor and nutrient signals. He also explores the Hippo tumor suppressor
pathway in organ size control, tissue homeostasis, and tumorigenesis.
Jason Gestwicki uses chemistry and chemical biology to study and manipulate how
multi-protein complexes are formed. By understanding the regulation of multi-protein
ensembles, he hopes to identify new drugs and drug targets for infectious diseases
and neurodegenerative disorders, such as Alzheimer’s and Huntington’s diseases.
Vivian Cheung studies the effects of genotype (the sequence of DNA letters on a person’s
chromosomes) on phenotype (a person’s observable traits). She studies how human cells adapt
to metabolic needs and environmental or therapeutic perturbations. Her work relates these
responses to susceptibility to diseases. Cheung wants to advance basic understanding of cell
biology and genetic mechanisms to improve diagnosis and treatment of diseases.

42
COLLABORATE
“We have so much new data now, that we can ask questions that we
never could before.We’re on the cusp of some very interesting and important
advancements, and it’s an exciting time to be a biologist.”
Alexey Kondrashov
Genetic bioinformatics
Alexey Kondrashov investigates evolutionary differences over stretches of history using
high-powered computing. Using a comparative genomics approach, Dr. Kondrashov hopes
to increase our understanding of how natural selection works in protein and amino acid
evolution, and why many species rely on sexual reproduction.
“The collaborative atmosphere at the LSI has encouraged me to find
out more about the research carried out by my colleagues.This in turn
has led me into new areas that I had not previously considered.”
“The main reason I quit as a clinician was that I couldn’t give my
patients any better options. I decided to concentrate on research to help
find a cure or establish a new therapeutic method for diabetes.”
John Kim studies epigenetics, primarily focusing on microRNAs and other emerging classes
of small RNAs to understand how they control gene expression and to identify novel protein
factors that execute these processes during normal development and disease states. He works
in C. elegans and in mammalian cells and uses a wide range of approaches including genetics,
biochemistry, and genomics.
John K. Kim
Geneticist
Patrick Hu uses the roundworm C. elegans to study a conserved insulin-like growth factor
(IGF) signaling pathway that controls development, metabolism and aging with the goal
of developing strategies to prevent and treat diseases associated with aging such as cancer,
diabetes, cardiovascular diseases and osteoporosis. He is also an oncologist.
Patrick J. Hu
Cell biologist

43
Anuj Kumar
Cell biologist; Associate Professor
of Molecular, Cellular Developmental
Biology, Associate Chair of the Department
of Molecular, Cellular Developmental
Biology, The University of Michigan
The Kumar laboratory uses functional genomics and proteomics to dissect signaling pathways
important for eukaryotic stress responses and cell growth. This research has focused principally
upon a stress response observed in yeast and the human pathogen Candida albicans, with relevance
for signaling pathways involved in cancer biology and fungal virulence. In addition, the Kumar
laboratory strives to develop new and innovative technologies to advance these studies towards
an integrative understanding of complex mechanisms enabling eukaryotic signal transduction.
“Before, people were studying molecular biology and the genetic
code, and now we study which protein kicks the butt of another protein
and regulatory cascades … this is incredibly interesting.”
Daniel J. Klionsky
Cell biologist
Daniel Klionsky investigates fundamental aspects of cellular physiology — including protein
targeting, organelle biogenesis and autophagy — to determine how cells respond to stress
conditions, including starvation and organelle damage, and to understand the mechanisms involved
in membrane dynamics and protein-protein interactions that allow the cell to maintain viability.
“We’re working in a field of biology that until 1993 didn’t really exist. It’s opened
a curtain to a completely rich area of biology that we now realize is integrated
in every way with how we develop and live, from how we create memories
and suppress cancer to how our limbs are patterned and grow.”
Ken Inoki uses biochemical and genetic approaches to examine how cells monitor and
regulate insulin, energy levels, nutrient and growth hormones through the mTOR signaling
pathway. Disregulation of this pathway is involved in development of diseases including cancer
and diabetes; by investigating the function and regulation of mTOR, he hopes to develop new
therapies for these diseases.
Ken Inoki
Cell biologist
“It became clear to me after a very short period of time in the clinic that
patients with advanced cancer frequently do not have effective treatment
options. I wanted to help change that.”

44
COLLABORATE
“Harnessing scientific inquiry for the development of new drugs
is an exciting and important endeavor.”
Ivan Maillard
Stem cell biologist
“When I retired, I became a generalist again. Rather than focusing
on a particular area of research, I have the opportunity to think very broadly
about where science is going and how it should work.”
Ivan Maillard, a member of the U-M Center for Stem Cell Biology, investigates bone marrow
transplantations and the interaction of blood-forming stem cells with their environment.
A practicing oncologist, his research focuses on characterizing the mechanisms that regulate
the maintenance of stem cells at different stages of development, increasing understanding
of leukemia and other cancers and improving stem cell transplantation safety.
Jiandie Lin
Cell biologist
Jiandie Lin studies the network of genes that manages the storage and consumption of energy
in cells and organisms. Dr. Lin uses genetic, genomic, and proteomic tools to better understand
the regulatory mechanisms and why they may sometimes become unbalanced. He is working
towards new therapies for major health problems including type 2 diabetes, fatty liver disease
and cardiovascular disease.
“To study neurodegenerative disease you have to have a lot of people from
different approaches working together, because the brain is very complex.”
Cheng-Yu Lee uses neural stem cells from Drosophila to study the regulation of stem
cell function in normal brain development and brain tumor initiation. He uses a combined
genetic, biochemical, and genomic approach and his research has implications for the
evolution of intelligence in human brains, the initiation of brain tumor malignancy
and human neurodegenerative diseases.
Cheng-Yu Lee
Stem cell biologist

45
“Seeing actual patients with real problems is a significant reality check.
It reminds me of why we’re doing this.”
Focusing primarily on vitamin B12 and folic acid, Rowena Matthews investigated the role
vitamins play in complex chemical reactions that can lead to heart disease and development
of neural tube defects in the fetus. Now retired, she serves in an advisory capacity at the LSI
and as a member of the medical advisory board at the Howard Hughes Medical Institute.
Rowena Matthews
Structural biologist
Emeritus, at LSI 2003-2009
John B. Lowe
Pathologist
Senior Director of Pathology,
Genentech in San Francisco
While at the LSI, John Lowe explored the complex sugars that coat the outside of animal cells to
better understand cellular signaling and inflammatory diseases including arthritis, psoriasis and
hardening of the arteries. His department at Genentech currently researches molecular heteroge-
neity in breast cancer, how problems in the mucosal immune system relates to inflammatory
bowel diseases, and the therapeutic possibilities in basic mechanisms of angiogenesis.
“At the LSI, you can find colleagues studying biological questions using
completely different tools.The interdisciplinary aspect was extremely attractive
to me. It’s generating the kind of interactions difficult to find in other places.”
Mi Hee Lim
Chemical biologist
Mi Hee Lim’s research interests lie in the broad field of inorganic chemistry as it interfaces
with biological and medicinal chemistry. Studying the role of oxidative stress and its implications
for neurodegenerative diseases, Dr. Lim is developing a special generation of nontoxic, small
molecules that may offer a new way to treat Alzheimer’s disease.
“Finding cures for brain tumors requires biomedical researchers from
distinct disciplines who employ different approaches to work together,
because all possible options must be considered and tested.”

46
COLLABORATE
“Any molecule has a potential to be developed into a drug if you can
find the right target—that’s what we’re trying to do.”
Alan R. Saltiel
Cell biologist
“It’s an incredibly exciting time to be working.Things are really changing right
now — the field is incredibly fast-paced.”
Alan Saltiel, Mary Sue Coleman Director of the LSI, investigates the hormone insulin and its role
in regulating cellular sugar levels, including how cells send and receive signals. Understanding
these processes may shed light on dysfunctioning glucose and lipid metabolism, particularly as
it related to type 2 diabetes. He hopes to elucidate the precise function of these pathways, and
their roles in the pathogenesis of diabetes, with the goal of developing new therapeutic
approaches to the treatment of diabetes and related disorders.
Noah Rosenberg
Bioinformatics
Associate Professor of Biology,
Stanford University
Noah Rosenberg, now at Stanford University, exploits the power of mathematics and computing
to explore the genetic basis of human evolution. He sifts through key landmarks in the human
genome to see how genetic variants relate between individuals, across continents, and through
time, providing important information that can be used to develop tools for unraveling the
genetic basis of human disease.
“We simply do not yet know what kinds of stem cells will yield the
scientific breakthroughs of the future or what kinds of stem cells will
yield new treatments for disease.Therefore, we must pursue all forms
of stem cell research in order to have the greatest chance of
developing new therapies sooner rather than later.”
Anna Mapp uses organic molecules and organic reactions as cellular probes to uncover the
details of gene transcription. By defining specific interactions between proteins that regulate
this process, the Mapp lab can identify therapeutic targets for human diseases in which the
transcriptional process is malfunctioning.
Anna Mapp
Chemical biologist
Joined LSI in 2013

47
“We often become overly focused on uncovering the small truths that seem
to confound us, while forgetting the impact our work can have on real people
facing much more difficult challenges. It is important for us to persist in the
face of uncertainty, frustration and failure.”
David Sherman explores the biochemical pathways of marine microorganisms with the
goal of finding new drug candidates for infectious diseases and cancers. Diving off the coast
of Costa Rica and Papua New Guinea, he collects samples in hopes of harnessing the
capabilities of unique natural chemical products using a diverse set of tools, including
molecular genetics, metabolic engineering and combinatorial biosynthesis.
David H. Sherman
Chemical biologist
Joined the LSI in 2003-
Gabrielle Rudenko
Gabby Rudenko uses a variety of tools to determine the precise three-dimensional shape and
function of biological molecules, a key to understanding the disease process and designing of
new drugs. She focuses on proteins that directly mediate synapse formation, maturation and
maintenance. Understanding how the trillions of synapses work in our brain and mediate
communication between neurons is likely of vital importance to understanding the molecular
bases of many neuro-psychiatric disorders such as autism, schizophrenia and drug addiction.
“There are applications of math in all kinds of different areas of biology.”
Sean Morrison
Stem cell biologist; Professor of Pediatrics,
Director of Children’s Research Institute,
Mary McDermott Cook Chair in Pediatric
Genetics, University of Texas Southwestern;
Howard Hughes Medical Institute Investigator
Sean Morrison, who served as Director of the Center for Stem Cell Biology while at the LSI,
investigates the mechanisms that regulate stem cell self-renewal, aging, and organogenesis.
His research focuses on the stem cells that give rise to the peripheral nervous system and all
blood and immune system cells. Morrison also studies the role of self-renewal mechanisms in
cancer, as cancer cells can commandeer these mechanisms.
“In transcription, the traditional techniques don’t work that well for telling you
that Protein A is directly interacting with Protein B, and that’s what you need to
know if you really want to discover drugs that target those interactions.”

48
COLLABORATE
“I always tell people this is no different from being an artist, a novelist, or a
musician, in that every year you’re trying to enhance your intellectual portfolio
so you can imaginatively tackle bigger, more difficult projects and bring
them to fruition. It’s all about being curious.”
Lois Weisman studies intracellular motility and signaling. These processes are key features
of ordinary cell division and embryonic development. Defects in these processes cause many
diseases, including neurodegeneration, cancer and diabetes. The overall goals of the laboratory
are to determine the mechanisms of myosin V based transport, and phosphoinositide signaling,
with the ultimate aim of developing novel therapies.
Lois Weisman
Cell biologist
“Being at the LSI is like being at the center of the Life Sciences universe here
at U-M. I wouldn’t be doing work with C. elegans if Shawn Xu’s lab was not in
close proximity, nor on drug development on IKKe if not for the Saltiel lab. “
Daniel Southworth studies how molecular chaperones and co-regulatory proteins function at the
interface of protein folding, activation and degradation pathways. Using cryo-electron microscopy
and in vitro biochemical methods, Southworth focuses on the structure and function of Hsp90
and Hsp70 chaperone assemblies involved in the triage of key signaling substrate proteins such
as the p53 tumor suppressor. This work aims to advance fundamental understanding of protein
folding and regulation mechanisms central to cellular homeostasis and the progression of
diseases including Alzheimer’s disease and cancer.
Daniel Southworth
Cell biologist
“How does nature use proteins? Nature knows, but we don’t know, how the
sequence of how amino acids codes for the beautiful protein structures we
discover. And it’s the 3-D structures that are nature’s tools.”
Georgios Skiniotis employs molecular electron microscopy techniques, including cryo-electron
microscopy, to directly visualize and recreate models of protein complexes involved in crucial
biological processes. Complemented by a variety of biochemical and biophysical methods, he aims
to address structural and mechanistic issues in important biological processes, which could lead
to better understanding of human health problems and improved pharmacological target designs.
Georgios Skiniotis

49
“Electron microscopy is a powerful tool for visualizing complex protein
assemblies at the single molecule level that are otherwise impossible to
dissect by other structural methods.”
“If you determine pathways that are fundamental to cell function, the answers
obtained will contribute to understanding human health and disease.”
Stephen J. Weiss
Cell biologist
Dr. Weiss’ research efforts focus on the mechanisms used by cancer cells, immune cells, stromal
cells and the vascular network to remodel tissue structure during events ranging from cancer
and inflammation to angiogenesis and metastasis. By applying new insights into the molecular
machinery that controls tissue remodeling programs, novel targets and therapeutics are being
designed as potential interventions in disease states ranging from cancer and obesity to
rheumatoid arthritis and cancer.
John Tesmer investigates a class of protein molecules that carry signals transduced across
the membranes of cells, called G proteins. This mechanism of cell-to-cell communication is
required for the sensations of sight and smell, for regulation of blood pressure and heart rate,
and for many other physiological events.
John Tesmer
Janet L. Smith
Janet Smith, Director of the Center for Structural Biology, uses X-ray crystallography
to examine the structures and functions of proteins from infectious pathogens, including the
viruses that cause West Nile disease, yellow fever and dengue hemorrhagic fever, and to
understand how microbes make antibiotics and anti-cancer compounds.
“The inventions of all sorts of microscopes, turned to the skies or to the
cells that make up life on earth, has radically changed our understanding of the
world and of ourselves.The electron microscopes we use at the LSI allow us to
directly visualize how cellular machines form and work—knowledge that can
be used in all kinds of ways to improve human health.”

50
COLLABORATE
Jun Wu
Joined LSI in 2013
Bing Ye addresses how neuronal dendrites and axons develop, with the goal of defining
how polarized neurons are assembled into functional neural circuits and how defects in this
process lead to human diseases like Down syndrome and autism. He primarily uses Drosophila
neurons as a system to investigate the differential development of dendrites and axons and
the establishment of synapse specificity. Ye also uses mammals to test whether the
mechanisms that he discovers in Drosophila are evolutionary conserved.
Bing Ye
Cell biologist
“If we can figure out how cells are dividing this way, the scientific
understanding of how the body develops—and how it breaks down with aging and
disease—could change. It is very basic science, but it could have wide-ranging
implications that could be exploited in therapeutics and drug discovery.”
Zhaohui Xu
Zhaohui Xu uses the tools of structural biology, in particular high resolution X-ray
crystallography, to study the underlying molecular mechanisms that control the intracellular
protein trafficking. His research has therapeutic implications for many human diseases
ranging from cancer, HIV infection to neurodegenerative diseases such as Alzheimer’s
and Parkinson’s.
“We are interested in understanding some of the fundamental questions in
neuroscience: How are sensory inputs perceived by the nervous system, how
do neural circuits process information to generate behavior, and how do genes
and drugs of abuse regulate these processes?”
Jun Wu focuses on a recently identified form of fat cells called “beige cells.” In mice,
genetic manipulations creating more of these fat cells bring about strong anti-obesity
and anti-diabetic effects. Further understanding of beige fat biology, including molecular
regulation of beige fat function, therapeutic potential of human beige fat, and the
developmental origin of beige precursors, will present novel therapeutic avenues
and identify potential targets for intervention.

51
“If you want to regenerate an axon to repair an injury, you have to take care
of the other end of the neuron—the dendrite—too.”
Yukiko Yamashita
Stem cell biologist
Yukiko Yamahshita, a member of the U-M Center for Stem Cell Biology, uses the fruit fly
Drosophila to better understand stem cell division, specifically how adult stem cells decide
upon their fate to maintain tissue homeostasis. Her work aims to illuminate the mechanisms
underlying the loss of control over stem cell division, which is regarded as the primary cause
of many human diseases.
“Although what we do seems rather basic, such as figuring out how proteins
fold, how they are moved around in the cell and how they are degraded, the
insights we gain could have wide-ranging implications that could be exploited
in therapeutics and drug discovery.”
X.Z. Shawn Xu
Cell biologist
Joined in LSI in 2005-
Shawn Xu uses C. elegans and takes a multidisciplinary approach combining functional
imaging, molecular genetics, behavioral analysis and electrophysiology to understand
fundamental questions in neuroscience and physiology: How do animals detect sensory
cues such as touch, light, chemicals and temperature? How do neural circuits and synapses
process sensory information to produce behavior, and how do genes and drugs regulate
these processes? How do sensory cues regulate longevity?
“The profound health consequences associated with obesity emphasize
the importance of developing effective therapeutic interventions, and the
therapeutic potential of beige fat cells is clear.”

52
TheNextGeneration
ofScientists
52
Undergraduates, graduate students and post-doctoral fellows train in the labs at the LSI. Upon
joining our laboratories these students and fellows are at once immersed in both high-level
questions and the day-to-day experiments that must be precisely executed to answer them. At the LSI,
research tools may be high-tech, but the education at the bench is old-fashioned: one-on-one.
T

53
92 Ph.D. students who did research in LSI labs have successfully
Ninth year of Business of Biology, co-taught by Liz Barry and David Canter, Executive Director, NCRC
Perrigo Undergraduate Fellowship Program supported a total of 63 undergraduates from across the state of Michigan who
spent the summer working in a lab in the LSI
Home of the Chemical Biology interdepartmental Ph.D. Degree and the Masters in Cancer Biology program
“Being in the LSI has accelerated my research and allowed us to pursue questions and strategies that might not be possible
elsewhere.We are surrounded by groups with the expertise, insight, and equipment necessary to take my project in which-
ever direction it needs to go.”—Kathleen Dumas, formerly a post-doc in the lab of Patrick Hu; now a researcher at the Buck
Institute for Research on Aging
“The natural world always fascinated me, and living on a small island in the Caribbean, the opportunities for experimenta-
tion were endless. As I got older, I became interested in viral pathogens like Dengue fever virus, yellow fever virus and HIV
that were infecting our small population in large numbers. It was this interested in virology that compelled me to join Janet
Smith’s lab at the LSI to study how RNA viruses package and cap their genomes.The support I received from LSI faculty and
staff were essential to the success of our projects.”— Donald Damian Raymond, Ph.D. 2012, now a research fellow in biologi-
cal chemistry and molecular pharmacology at Children’s Hospital Boston, a teaching hospital affiliated with Harvard Medical
School.

54
Partnersin
Problem-Solving
54
11
Cathy Andrews //
Director of Operations
I manage operational activities for LSI,
including information technology,
facilities management, procurement
and lab services. I’ve held several
positions at the University of Michigan
since I joined in 1986, started at the
LSI as administrative associate for the
director of operations and became
director in 2008.
I’ve had days where I have discussed
topics ranging from space planning
and the mating of mice to employee
concerns and equipment issues. And
there are always facilities emergencies
—just to keep things interesting.
Working at the LSI has given me an
appreciation for the passion and drive
of the people doing this type of work.
It’s inspiring and contagious. There
is an environment of mutual respect
and gratitude between each of the
working parts of the LSI.
he staff at the Life Sciences Institute upholds the same values as the
researchers — collaboration, creativity and excellence. Lots of specialized
technology and instrumentation. A building with different chemical needs, safety
concerns, animal models and unpredictable facility needs. A work force that is more
than half international. Students from different schools throughout the university,
from other schools in Michigan, visiting scholars from around the world. Highly
technical scientific publications that need to be explained to the public. A complex
mix of government funding and private support. LSI’s administrative team thrives on
meeting the challenges of supporting high-level science and on knowing the research
they help make happen every day has an impact on human health and wellbeing.
years at LSI
T

55
5
Brad Battey //
IT Manager
I’m constantly amazed at the ways that
science that can leverage technology,
sometimes in very unexpected ways.
Shortly after I joined the LSI, I met
Janet Smith and members of her
lab for one of their marathon data
collection sessions at Argonne
National Lab’s Advanced Photon
Source at University of Chicago.
I was still understanding the IT needs
of crystallographers in the building:
how data is collected and processed,
and how the ever-growing number
of gigabytes was managed. In the
experiment hall of the APS I was in
awe of what I saw. Our researchers
used robotic automation, custom
software, video feeds, and coherent,
focused, high energy x-rays to generate
dataset after dataset. Getting those
datasets home was a challenge. The
folks from the lab made this look easy
— only later did I understand how
many months, if not years, of work
went into those datasets and that good
data wasn’t guaranteed. Now, in 2013,
a new detector allows researchers to
collect four times more data in 24
hours than they could then.
2
Alyson Carter //
Senior Development Assistant
I do prospect research, database
management, gift recording and
processing, accounting, special-
events planning and oversight
and donor relations for the LSI’s
development team.
I don’t have a science background,
so everything is really interesting
—even the cost of lab mice. The
most rewarding part of my job so
far has been being part of the team
that secured the second largest
gift in the LSI’s history.
9
maggie herron //
research process coordinator
I handle the pre- and post-award
accounting for LSI faculty—
assisting with grant applications and
monitoring and managing sponsored
and discretionary research accounts.
I have worked for the University
of Michigan for 16 years; before that
I worked for the St. Clair County
Community Foundation Kellogg
Foundation on a healthy community
project for three years. Before that
I worked in banking for 12 years.
When I hear one of our scientists
speak about their work—for
example, about the importance
of protein functions and genes, or
autophagy and the recycling or self
eating of cells— in lay terms, I’m
fascinated each and every time.
12
Erin Stephens //
Director of Human Resources
I began working for the University
of Michigan in 1998 and the LSI’s
Human Resource Director in 2008.
It’s challenging when a faculty
member joins the LSI. You are dealing
with people who are in the middle
of a major transition in their life, and
our job is to make that transition as
smooth and seamless as possible.
It truly is a team effort by the entire
administrative staff.
Our faculty members are not only
experts in their field, but they are
experts in describing their research
to a person with little to no scientific
background. Those conversations
have really opened my eyes and my
heart—I’m able to understand and
appreciate the significant impact
that their research has had and will
continue to have on human health.
years at LSI years at LSI years at LSI years at LSI

5656
PartnersinInnovation:
LeadershipCouncil
hen we were launching the LSI, we decided to adopt a feature common at pharmaceutical and biotech
start-up companies but unusual in academic: the external advisory board.
The Leadership Council, a group of biomedical industry leaders, venture capitalists and government officials that meets
yearly and weighs in regularly on major decisions about the direction of the institute, has been critical as we’ve grown and
responded to changes in technology, the financial climate and the realities of drug discovery and development. Without their
opinions, expertise, willingness to contradict us and ach other and dedication to supporting us with enthusiasm and integrity,
establishing the LSI would have been a whole lot harder. And they certainly help ensure we don’t become complacent.
It was this group that established the Innovation Partnership, a program for advising and supporting promising drug-related
research that would fall into the “valley of death” without them.The Innovation Partnership combines scientific excellence
and entrepreneurial acumen and has enabled projects related to cancer, obesity, Alzheimer’s and other diseases progress
beyond the lab. – Alan Saltiel
W
The Leadership Council has supported commercialization steps for four research projects since established the Innovation Partnership in 2009.
Left: Council co-chair Paul Meister talks with Alan Saltiel, director of the LSI, and Jerry May, Vice-President for Development at U-M.
Right: Saltiel talks with a lab member. Facing: David Ginsburg, LSI faculty member, with researchers in his lab.

57
2005 2006 2007 2008 2009 2010 2011 2012 2013
Rajesh Alva
William K. Brehm
Mary Campbell
David Canter
Jillian Castrucci
Michael Cole
Richard Douglas
Michael A. Finney
James Flynn
James Hackett
William K. Hall
Toni Hoover
David Kroin
Shiraz Ladiwala
Louis G. Lange
Julius Li
Ernest G. Ludy
Greg Margolies
Joel Martin
Paul M. Meister
William Newell
Garry Neil
Roger Newton
James Niedel
John Osborn
Craig Parker
Liam Ratcliffe
Hollings C. Renton
Terry Rosen
Joe Schwarz
Lily Shen
Barry Sherman
Greg Simon
Michael Staebler
David Walt
James Wesco
Deborah Widener
Wendell Wierenga
RAYMONd WITHY
Michael Witt
Robert Zerbe
Leadershipcouncilmembership2005-2013

58
Developing a new drug to treat Type 2 diabetes
Investigator: Alan Saltiel, PhD, Mary Sue Coleman Director
of the Life Sciences Institute and Professor of Internal Medicine
and Molecular and Integrative Physiology. Former Senior Director
at Parke-Davis, Inc.
Disease Problem: Tens of millions of Americans have been
diagnosed with Type 2 diabetes and millions more remain
undiagnosed. Most patients with type 2 diabetes are obese,
and Saltiel and his lab explore how the conditions are linked.
They honed in on an interesting new hypothesis:The link is
inflammation caused by obesity, and that inflammation causes
Type 2 diabetes. Saltiel’s lab identified a gene, IKKE, which
appears to act in the inflammation pathway to moderate energy
expenditure and its downstream effects like weight and
sensitivity to insulin.
Partnership: Through screening of tens of thousands of
chemical compounds in LSI’s Center for Chemical Genomics,
the scientists discovered that an off-patent drug, amlexanox,
blocked the activity of IKKE. Follow-up studies revealed that
amlexanox caused diet-induced and genetically obese mice to
lose weight and prevented problems like diabetes and fatty liver
disease. This breakthrough was published in Nature Medicine.
The Innovation Partnership is funding follow-up studies on
modifying the compound for testing in human trials.
Outcome: A small clinical trial in humans is underway. U-M
has filed a patent on the use of amlexanox for treating metabolic
disease and on related chemical compounds. Follow-on funding
is being sought from government and private investors.
Creating novel anti-metastatic drugs
for treating cancer
Investigator: Stephen J. Weiss, MD, Professor
of Internal Medicine
Disease Problem: The vast majority of cancer deaths are due
to metastasis, yet the mechanisms underlying this process remain
poorly understood.TheWeiss lab has been interested in understand-
ing how and why cancer cells move through tissues to distant sites.
Partnership: Building on a novel 3-D research platform and
a data-driven experimental approach conceived by Weiss, the
partnership funded studies to find monoclonal antibodies to
metastasis of breast, pancreatic and glioblastoma cancer
cells. The approach has yielded more than 50 potential leads
for promising antibodies. With with the advice and guidance
of the LSI’s Leadership Council, a handful of these have been
further investigated showing efficacy in halting metastasis
in animal models.
Outcome: University of Michigan has filed for patents on three
of the most promising lead antibodies. The research platform
continues to produce exciting possibilities across several types
of cancer as well as yield insights into the underlying biology
of metastasis. Follow-on funding is being sought from investors
and business alliances are being explored.
INNOVATIONPARTNERSHIP:
fromdiscoveriestotreaTMENTS
PROJECTS
The rate of discovery of promising potential new drugs and therapeutic approaches has recently increased in university labs, fueled by
advances in both research technology and genomic medicine. However, the gap between the lab and the market—the “valley of death”—
continues to widen as both government and investor funding of biomedicine decline.
The Innovation Partnership takes on the challenge of crossing the valley of death by infusing the projects of LSI scientists with funding and
expertise from leaders in the top ranks of business, venture capital and the biomedical industry. With $1.2 million raised from donors, the
Innovation Partnership has funded four faculty projects, all of which have achieved critical commercialization milestones with mentorship
from the ranks of the Leadership Council.
“This is a perfect example of an approach that would not be suitable
for traditional funding—it’s a great idea but just needed the experimental
traction that could only be obtained through innovative funding.”
David Dudley // LSI associate research scientist in the Weiss lab

59
Focusing on a key pathway that controls
the virulence of strep and other infections
Investigator: David Ginsburg, MD, Howard Hughes Medical
Institute Investigator and Professor of Internal Medicine and
Human Genetics.
Disease Problem: There are several million cases of strep
throat and more than 10,000 cases of invasive group A Strep (GAS)
diseases in the U.S. each year. Some are fatal. Interested in the
relationship between the blood-clotting system and how we
protect ourselves from bacterial infections, LSI faculty member
David Ginsburg and his lab discovered that the human body uses
blood clots to surround the Strep A bacterial infection as a
natural defense. However, the Strep A bugs make a protein
called streptokinase that activates human plasminogen and
dissolves the blood clots, allowing the infection to spread rapidly
throughout the body. This observation led the Ginsburg team to
wonder whether they could render the bacteria innocuous by
blocking production of streptokinase and in the process also
reduce the threat of antibiotic resistance.
Partnership: The lab, along with collaborators at the U-M Vahlteich
Medicinal Chemistry Core and at the University of Missouri,
searched for small molecules that turned off the production of the
protein in live bacteria, with the hope that they could interfere with
the mechanism used by the bacteria to spread the infection.
After screening tens of thousands of chemicals in the LSI’s
Center for Chemical Genomics and other facilities, the team
identified many promising lead compounds and refined two of
them for further exploration.
Outcome: University of Michigan filed patents on the two leading
compounds. The chemical screening also helped the team refine
its hypothesis about the biological target being exploited by the
bacteria; this discovery was published in the Proceedings on the
National Academy of Sciences [link]. Armed with this knowledge,
the team is applying for new government research funds to further
explore the target and accelerate the drug discovery efforts.
Targeting the protein quality control pathway yields
results in treating Alzheimer’s and other diseases
Investigator: Jason Gestwicki, PhD, now Associate
Professor of Pharmaceutical Chemistry at University of California,
San Francisco
Disease Problem: About 5.3 million people have Alzheimer’s
disease, which is caused by abnormal protein misfolding and
accumulation that leads to the formation of a neurotoxic tangled
structure in the brain that kills neurons for good. Former LSI faculty
member Jason Gestwicki was interested in this question: What
prevents this from happening in everyone?
Partnership: The team searched for small molecules that
stimulate the activity of a protein called Hsp70, which prevents
the protein misfolding in brain cells that causes progressive
neurological diseases like Alzheimer’s. After screening tens
of thousands of potential compounds in the LSI’s Center for
Chemical Genomics, the Gestwicki team identified two
particularly interesting chemicals and figured out how they
bind to and regulate Hsp70.
Outcome: The university filed composition of matter patents
on the two chemical leads. In addition, Gestwicki entered into
agreements with two companies, Proteostatis Therapeutics, Inc.
and Abbott Laboratories, to screen an additional 65,000 compounds.
An additional $750,000 in external funding from multiple sources
was secured to continue the drug discovery process.
“We wouldn’t have pursued the project to the stage that we’re at now
without the funding and advice provided by the Innovation Partnership.”
David Ginsburg

60
DONORS
60
“We have enjoyed our involvement with the LSI — and have been
particularly thrilled with the progress made in the last ten years.
Dr. Saltiel has assembled a world-class group of scientists, developed
the LSI as a model of collaborative research, and positioned the
LSI within the University of Michigan so that exceptional science can
be translated into applications that will impact human health.The
LSI enters its next phase ready to bring excellence in collaborative
research, a spirit of innovation and creativity, and strong connections
to the health system to bear on improving health. It will also serve
as a template to guide many others with similar aspirations.
To us, this is the Michigan Difference!”
Dr. Susan and Paul Meister // Paul Meister serves as co-chair
on the LSI Leadership Council and is also on the LSI Scientific Advisory Board
“Many of the young scientists who have joined the LSI over
the last eight years have had offers from other top universities but
have chosen the LSI specifically to be in a culture of interdisciplinary
collaboration.Their enthusiasm for science and desire to work
across traditional boundaries inspires my passion for the LSI.”
Craig Parker // U.S. Venture Partners // LSI Leadership Council (Co-chair) //
LSI Scientific Advisory Board
“Probably the most important thing LSI has to offer is the experience
of working in a genuinely collaborative environment. In the real
world, science and innovation get done through collaboration by
teams of scientists, engineers, mathematicians, computer scientists
and business experts. Immersion in that kind of environment, as
is done at LSI, is the best possible training ground for students.”
David Walt // Tufts University // LSI Leadership Council //
LSI Scientific Advisory Board

61
“To undertake this initiative potentially impacts the world in a positive way through the noble pursuit of research and the
advancement of science.These objectives inspired us to act and support a collaboration between the University of Michigan
and Israel with our time, energy, effort and philanthropy. We are very excited to help this vision come to fruition.”
David B. Kaplan // Ares Management, LLC
“My support for the LSI combines my professional passion for life sciences with my personal commitment to helping Michigan.
All too often the universities get very little return on their investment in basic research.The Innovation Partnership not only
supports innovative research into curing disease, it also allows the LSI and the university to pursue this work in a self-sufficient
and self-sustaining way.”
Rajesh Alva // Credit Suisse // LSI Leadership Council
“It’s almost certain that someone in any family has been afflicted with one of the diseases for which LSI is trying to find
a cure.The need hits them on a personal level.
Greg Margolies // Ares Management // LSI Leadership Council
“The attitude that permeates the LSI is one of collaboration, and in that environment, people work better and could really
do something seminal.There’s a lot of potential for discovery through vibrant teamwork.”
Roger Newton // Esperion Therapeutics // LSI Leadership Council
“I believe that that collaboration really can make a
difference, particularly in the big areas of science like
cancer research and diabetes, these broad areas.”
Donna Weiss // Terrapin Palisades Ventures, LLC
“It’s a leveling of the playing field, to see growth capital
being placed in this effort of collaboration with Israeli
academics and scientists.”
Jason Weiss // Terrapin Palisades Ventures, LLC
“I have had the pleasure of spending some time with the scientists at the LSI.They are so great at explaining the impact
of their work. An afternoon there is an opportunity to hear about the most cutting-edge of medical research in the world.”
Ari Spar // Barclays
“Life science is an extraordinary area of opportunity for our times—not only in the value of pursuing knowledge
that improves the lives of people, but also in terms of the economic opportunity and job creation.”
James P. Hackett // Steelcase Inc. // LSI Leadership Council

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