Spring 2015, volume 11 , no. 2
Accelerating Discoveries, Saving Lives
TSRI Scientists Find More DNA and Extra Copies of Disease Gene in Alzheimer’s Brain Cells
Drug Candidates Block Pathway Associated with Cell Death in Parkinson’s Disease
Nicotine Vaccine Provokes Robust Immune Response
Kerri Mowen: The Accidental Advocate
and more...
A Newsletter for Philanthropists Published Quarterly by The Scripps Research Institute
IN THIS ISSUE
3-5
RESEARCH UPDATES
TSRI Scientists Find More DNA and Extra Copies of Disease Gene in Alzheimer’s Brain Cells
Drug Candidates Block Pathway Associated with Cell Death in Parkinson’s Disease
Scripps Florida Scientists Develop Novel Platform for Treatment of Breast, Pancreatic Cancer
Scientists Create Mimic of ‘Good’ Cholesterol to Fight Heart Disease and Stroke
Nicotine Vaccine Provokes Robust Immune Response
Team Discovers Possible New Target for Treating Brain Inflammation
Researchers Find How Mutant Gene Can Cause Deafness
Scientists Unveil New Targets and Test to Develop Treatments for Memory Disorders
5
GIVING
Make a Simple, Meaningful Gift to TSRI that Costs You Nothing
6-9
PROFILES
Donor Profile - Leonard and Norma Klorfine: ‘Finding Cures Impacts Everyone’
Three Minutes with TSRI Assistant Professor Kerri Mowen
10-11
APPOINTMENTS, AWARDS, HONORS
TSRI Names New Directors of Philanthropy in California and Florida
Six TSRI Graduate Students Named ARCS Scholars
Jessica Sheu-Gruttadauria Wins Heart Association Fellowship
11-12
EVENTS
Female Faculty Host Gathering for Donors and Friends
Luncheon Acknowledges and Thanks TSRI Supporters
Scripps Florida Recognizes Dedicated Donors at ‘Breakfast at Tiffany’s’
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publisher: david blinder, senior vice president for external affairs
editors and contributing writers: elliot wolf and mika ono
photographers: john dole, james mcentee, Leonard Bryant Photography
RESEARCH UPDATES
TSRI Scientists Find More DNA and Extra Copies of Disease
Gene in Alzheimer’s Brain Cells
Scientists at The Scripps Research Institute (TSRI) have found diverse
genomic changes in single neurons from the brains of Alzheimer’s patients,
pointing to an unexpected factor that may underpin the most common
form of the disease.
A new study, published February 4, 2015, in the online journal eLife,
shows that Alzheimer’s brains commonly have many neurons with
significantly more DNA and genomic copies of the Alzheimer’s-linked
gene APP than normal brains.
“Our findings open a new window into the normal and diseased brain by
providing the first evidence that DNA variation in individual neurons
could be related to brain function and Alzheimer’s disease,” said Jerold
Chun, professor at TSRI and its Dorris Neuroscience Center and senior
author of the new study.
Future studies in the Chun lab will investigate potential new drug targets
present in the millions of extra base-pairs found in single Alzheimer’s
disease neurons.
Drug Candidates Block Pathway Associated with Cell Death
in Parkinson’s Disease
In a pair of related studies, scientists from Scripps Florida have shown their
drug candidates can target biological pathways involved in the destruction
of brain cells in Parkinson’s disease.
The studies suggest that it is possible to design highly effective and highly
selective (targeted) drug candidates that can protect the function of
mitochondria, which provide the cell with energy, ultimately preventing
brain cell death.
These drug candidates act on what are known as the JNK (pronounced
“junk”) kinases—JNK1, JNK2, and JNK3—each an enzyme with a unique
biological function. JNK is linked to many of the hallmark components of
Parkinson’s disease, such as oxidative stress and programmed cell death.
“These are the first isoform selective JNK 2/3 inhibitors that can penetrate
the brain and the first shown to be active in functional cell-based tests that
measure mitochondrial dysfunction,” said Philip LoGrasso, a TSRI professor
who led both studies.
The new studies raise the hope that such a therapy could prevent the
gradual degeneration of brain cells in Parkinson’s disease and halt these
patients’ decline.
3
Scripps Florida Scientists Develop Novel Platform
for Treatment of Breast, Pancreatic Cancer
Researchers Find How Mutant Gene Can Cause
Deafness
Scientists from TSRI’s Florida campus have identified a
novel synthetic compound that sharply inhibits the activity
of a protein that plays an important role in the progression of
breast and pancreatic cancers.
Scientists at TSRI have discovered how one gene is essential
to hearing, uncovering a cause of deafness and suggesting
new avenues for therapies.
In the new study, published in the February 2015 print edition
of the journal Molecular Pharmacology, the scientists showed
that the compound, known as SR1848, reduces the activity
and expression of the cancer-related protein called “liver
receptor homolog-1” or LRH-1.
“Our study shows that SR1848 removes LRH1 from DNA,
shutting down expression of LRH-1 target genes, and halts cell
proliferation,” said Patrick Griffin, chair of the TSRI Department
of Molecular Therapeutics and director of the Translational
Research Institute at Scripps Florida. “It’s a compound that
appears to be a promising chemical scaffold for fighting
tumors that are non-responsive to standard therapies.”
Scientists Unveil New Targets and Test to Develop
Treatments for Memory Disorders
In a pair of related studies, scientists from TSRI’s Florida
campus have identified a number of new therapeutic targets
for memory disorders and have developed a new screening
test to uncover compounds that may one day work against
those disorders.
The two studies, one published in the journal Proceedings
of the National Academy of Sciences (PNAS), the other in
the journal ASSAY and Drug Development Technologies,
could lead to new approaches to some of the most problematic
diseases facing a rapidly aging world population, including
Alzheimer’s and Huntington’s diseases and dementia.
“We are actively looking at molecules critical to memory
formation, so these two studies work in parallel,” said
Sathyanarayanan V. Puthanveettil, a TSRI biologist who
led both studies. “In one study, we’re reaching for a basic
understanding of the process, and in the other, we’re finding
new ways to identify drug candidates so that we can cure
these diseases.”
The new study, published in the journal Neuron, shows how
mutations in a gene called Tmie can cause deafness from birth.
Underlining the
critical nature
of their findings,
researchers
were able to
reintroduce the
gene in mice
and restore the
process underpinning hearing.
“This raises
hopes that we
could, in
principle, use
gene-therapy
approaches to
restore function
in hair cells and “This [new study] raises hopes that we
thus develop
could, in principle, use gene-therapy
new treatment approaches to restore function in hair
cells and thus develop new treatment
options for
options for hearing loss,” says Professor
hearing loss,”
Ulrich Müller. Shown here are some of
said Professor
the hair cells essential to hearing.
Ulrich Müller,
senior author
of the new study, chair of the Department of Molecular and
Cellular Neuroscience and director of the Dorris Neuroscience
Center at TSRI.
Scientists Create Mimic of ‘Good’ Cholesterol to
Fight Heart Disease and Stroke
TSRI scientists have created a synthetic molecule that mimics
“good” cholesterol and have shown it can reduce plaque
buildup in the arteries of animal models. The molecule,
taken orally, improved cholesterol in just two weeks.
This research, published in Journal of Lipid Research, points
scientists toward a new method for treating atherosclerosis,
a condition where plaque buildup in the arteries can cause
heart attacks and strokes.
“Atherosclerosis is the number one killer in the developed
world,” said TSRI Professor M. Reza Ghadiri, senior author
of the new study with TSRI Assistant Professor of Chemistry
Luke Leman. “This research clears a big step toward clinical
implementation of new therapies.”
Team Discovers Possible New Target for Treating
Brain Inflammation
A team led by scientists at TSRI has identified an enzyme
that produces a class of inflammatory lipid molecules in the
brain. Abnormally high levels of these molecules appear to
cause a rare inherited neurodegenerative disorder, and that
disorder now may be treatable if researchers can develop
suitable drug candidates that inhibit this enzyme.
This treatment approach may also turn out to be useful against
more common conditions that involve brain inflammation—
a category that includes multiple sclerosis, Alzheimer’s,
Parkinson’s, ALS, and secondary damage after stroke and
head injuries. Such inflammation often fails to respond to
standard anti-inflammatory drugs.
“This finding is a good example of what can be gained from
studying enzymes linked to rare human genetic disorders,” said
Benjamin F. Cravatt, chair of TSRI’s Department of Chemical
Physiology and member of TSRI’s Skaggs Institute for
Chemical Biology and Dorris Neuroscience Center.
Nicotine Vaccine Provokes Robust
Immune Response
When a promising nicotine vaccine failed in clinical trials a
few years ago, scientists from TSRI were determined to keep
trying to help smokers overcome their addiction.
Now the team has designed a more effective nicotine vaccine
and proven that the structures of molecules used in vaccines
is critical. The study was published recently in the Journal of
Medicinal Chemistry.
“This study provides new hope that one could make a nicotine
vaccine that succeeds in clinical trials,” said Kim Janda, the
Ely R. Callaway Jr. Professor of Chemistry and member of
the Skaggs Institute for Chemical Biology at TSRI.
According to the National Cancer Institute, smoking is the
leading cause of eight types of cancer, including lung cancer
and fast-moving pancreatic cancer.
“This is just one area where we are looking outside the box
to try to treat addiction,” Janda said. 
GIVING
Make a Simple, Meaningful Gift to TSRI that Costs You Nothing
Did you know you can make a gift to The Scripps Research
Institute that costs you nothing during your lifetime?
Naming The Scripps Research Institute as a beneficiary in
your will or trust builds our long-term financial strength and
allows you to create a meaningful legacy.
• It’s Simple:
One paragraph in your will can set up your gift. A bequest
doesn’t take effect until your death. It’s a gift that doesn’t
affect your current asset balance or cash flow.
•It’s Flexible:
You can give us a specific asset, or a share of what’s left
after your gifts to your family and friends. Your bequest
can support a particular program or allow us to use it for
our greatest needs when your gift is received.
•It’s Revocable:
If your plans or circumstances change, you can easily
change your will.
Want to learn more? Simply visit our planned giving
website…Discover the Benefits of Giving Wisely at
www.plannedgiving.scripps.edu. There you will find a
useful resource of ideas and information to help support
our cutting-edge life-saving research.
Of course, if you would like to contact us directly, we would
be happy to help assist you maximize your charitable and
financial goals. For more information about your giving options,
please contact Geoff Graham, director of planned giving
and estates, at (858) 784-9365 or gcgraham@scripps.edu.
In Florida, contact Irv Geffen, director of philanthropy, at
(561) 228-2017 or igeffen@scripps.edu.
When considering charitable gifts, you are urged to seek
the advice of your own financial and legal advisor(s)
about your specific situation. 
5
DONOR PROFILE
Leonard and Norma Klorfine: ‘Finding
Cures Impacts Everyone’
Philanthropists Leonard and Norma Klorfine have a strong interest in
supporting medical research and finding cures, both for the benefit of
friends and loved ones as well as for future generations.
“Finding cures to the illnesses and diseases that face humanity impacts
everyone,” said Leonard. “Health-related issues touch us all in some way.
Even if you’re able to avoid serious illness, your friends or loved ones
may not be so fortunate. We believe in supporting organizations dedicated
to finding cures. By investing in medical research, we feel we’re not only
advancing present healthcare, but also working to help future generations
live better, healthier lives.”
At Scripps Florida, the Klorfines have supported a couple of two-year
postdoctoral training fellowships under the direction of Professor Patrick
Griffin, with the research emphasizing the development of novel treatments
for diabetes, rheumatoid arthritis, and osteoporosis. They have also
supported the preclinical development of a novel therapy for chronic
lymphocytic leukemia, under Associate Professor Christoph Rader.
Philanthropists Leonard and
Norma Klorfine
“Before we made our gifts, we visited both of the Scripps campuses in
La Jolla and Jupiter, and we continue to stay abreast of Scripps Florida’s
research at events we attend,” said Leonard. “We’re impressed with the
groundbreaking research at Scripps Florida and wanted to support the
promising work. We see the therapeutic potential of this research and
hope that our financial support will result in forward progress for these
first-rate projects.
“We also know that research involves a lot of ‘pick and shovel’ work and
it’s time-consuming and laborious, but TSRI has lots of good scientists
and we’re confident that its research will be impactful.”
Leonard and Norma established The Klorfine Foundation in 1993. The
foundation empowers nonprofits to achieve tangible results that benefit
their communities within the areas of medical research, education, the
environment, and arts and culture. Their children, Stuart Klorfine and
Melissa K. Ewing, are also involved in the foundation. Last year, the
foundation disbursed more than $1 million to nonprofits improving their
communities in a variety of ways.
“We enjoy being in the fortunate position to help various organizations,”
said Leonard. “We want to create a better tomorrow and an impact through
our support of nonprofits that are working hard, but need a hand. We’re
passionate about our causes.
6
“We also believe in the value of using data to measure tangible outcomes
and promote accountability.”
“We enjoy being in the fortunate
position to help various
organizations.”
Leonard Klorfine
In the area of medical research, aside from TSRI, the foundation also supports
Benaroya Research Institute, Fred Hutchinson Cancer Research Center,
and Bascom Palmer Eye Institute.
The Klorfines divide their time between homes in Singer Island, Florida
and Seattle, Washington. Leonard is a retired real-estate investor and was
once a schoolteacher. Aside from his philanthropy, he enjoys spending
time reading, researching, and sometimes practicing the art of financial
investments in the stock market. Norma is a trustee of the Bellevue Arts
Museum in Washington and the Pratt Fine Arts Center in Seattle, and is
an active member and past president of the Woman’s Committee of the
Philadelphia Museum of Art.
TSRI and the many other organizations the Klorfines support are very
grateful for their quiet and impactful philanthropy. 
7
Tell us about your research, the diseases it impacts, and
any breakthroughs.
SCIENTIST PROFILE
The goal of our lab is to try to understand how rheumatoid arthritis and
other autoimmune diseases, such as multiple sclerosis, get started in the first
place. If we understand the process better both at the molecular level as
well as in the organism as a whole, we can intervene with useful treatments.
Three Minutes with: We’ve had some success. I was recently involved in the launch of a company
TSRI Assistant Professor Kerri Mowen called Padlock Therapeutics that discovers novel therapeutics targeting
the protein arginine deiminases (PADs), an emerging class of enzymes with
roles in rheumatoid arthritis and autoimmunity. Padlock’s technology was
developed in my lab as well as the lab of my colleague, Paul Thompson,
at Scripps Florida. Paul has since moved on to UMass, Worcester.
Padlock recently raised $23 million in financing based on reaching its
early milestones. This will fuel our efforts to zero in on the PAD enzymes,
or the “rocket fuel” for the immune system, and exploit them to make new
drugs for rheumatoid arthritis, multiple sclerosis, and other autoimmune
diseases without leaving the body vulnerable to nasty infections and
complications. Hopefully, we’ll be able to begin human trials in the next
two to three years. It has been amazing to be a part of this quest for the
discovery and design of a potential therapeutic.
You are a vigorous advocate for more research funding for the
National Institutes of Health. Tell us about your advocacy.
The federal government’s investment in science and discovery research
has been declining—this is potentially catastrophic. After my lab was cut
to less than a third of the size it was a few years ago and many of our
research projects were halted, I decided to try to do something about it.
And we’re one of many labs across the country facing the same issue—
we’re all losing research projects that we know have a strong potential
to better human health.
So I started a petition on the website, Change.org, that called for an
increase in the National Institutes of Health (NIH) budget, and received
thousands of signatures. The NIH supports over 80% of the nonprofit
research endeavors in the USA, myself included, and helps all of us.
The NIH budget has been flat for some time, and, when you factor in
inflation, flat funding is an equivalent of a funding cut.
I feel that as scientists, we haven’t done a very good job at communicating
what we do. The bottom line is when you go to the pharmacy to pick up
a prescription you have the NIH—and the funding it gave to research
that went into creating that drug 15 to 20 years ago—to thank for it.
Supporting the NIH is an investment for all of our futures.
After the petition, I was contacted by many media outlets and began doing
interviews. It has been a really good experience. I even spent some time
talking to Hillary Clinton about why the funding of science is so important.
8
Has private philanthropy helped your lab? How can it help?
The graduate students who work in our lab are supported through
philanthropy so it’s a big help for our work. Several years ago, I was also
the beneficiary of a Young Career Scientist Award from the Donald and Delia
Baxter Foundation, an organization that helps prepare and support new
investigators as they begin their careers. It helped me to build my research
program to the point where I could compete effectively for other funding.
“Additional philanthropy could
bolster our resources and provide
new insights into how inflammation is
regulated, not only in the
autoimmune diseases we study,
but also in other diseases where it
plays a role, such as Alzheimer’s
and cancer.”
Kerri Mowen, PhD
Aside from our main focus, we also have some good projects in other related
areas where we’ve had some unexpected findings, but unfortunately, they’ve
been on the shelf for a few years. Additional philanthropy could bolster
our resources and provide new insights into how inflammation is regulated,
not only in the autoimmune diseases we study, but also in other diseases
where it plays a role, such as Alzheimer’s and cancer.
Why did you come to TSRI?
After completing my PhD at UCSD and postdoctoral studies at Harvard, I
could have started my career at another university, but I found that TSRI
is a unique place.
Thanks to the collaborative spirit and lack of boundaries between disciplines
at TSRI, it’s very easy to interact with my colleagues, and I have been
fortunate to take advantage of many unique tools that they have developed—
such as new techniques capable of screening thousands of compounds that
help us find good drug candidates. Many labs here are developing cuttingedge technologies that empower other labs’ work, and we’re certainly
able to benefit from that. It’s a very supportive, synergistic environment.
How did you get interested in science?
I used to like reading our family medical reference book as a kid. I grew
up in Petersburg, Illinois, a town of about 3,000 people. We had the only
stoplight in the county, and kids came from towns from miles around to
practice for their driving test at the signal. You would think there wouldn’t
be much opportunity to learn about science there, but I was inspired by
my amazing high school biology teacher, Charlene Koelling, who won
numerous awards and was able to provide a highly technological and
acclaimed biology program at our school. 
9
inspire
APPOINTMENTS, AWARDS
and HONORS
,
TSRI Names New Directors of Philanthropy in California
and Florida
We are pleased to announce two new appointments in the Office of
Philanthropy in La Jolla and Jupiter.
Christopher Lee has joined TSRI as Director of Philanthropy in
California. Chris was most recently vice president of PCI (Project
Concern International), where he managed all private fundraising
operations, marketing, and communications for the global health and
development organization headquartered in San Diego. Prior to his
position at PCI, Chris served for seven years at the Sanford-Burnham
Medical Research Institute as vice president for external relations and
as director of external relations.
Christopher Lee
Before that, Chris served in various other fundraising leadership capacities
in the Northeast, including with a major international development agency
and a prominent university. Finally, Chris worked as a key member of the
Capitol Hill staff of a United States House of Representative member.
Chris earned an MBA from Villanova University and a BA in political
science from West Virginia University.
On the Florida campus, Irv Geffen has been promoted to Director of
Philanthropy. Irv came to Scripps Florida in November 2013 after a
distinguished career as a fundraiser and executive officer with the
Jewish Federations in Palm Beach County, Greater Philadelphia, and
Richmond, Virginia.
Six TSRI Graduate Students Named ARCS Scholars
Irv Geffen
Six TSRI graduate students have received Scholar Awards from the
San Diego chapter of the Achievement Rewards for College Scientists
(ARCS) Foundation, a national organization advancing science in the
United States through grants to academically outstanding U.S. citizens
pursuing degrees in science, engineering, or medical research.
The TSRI fellowship recipients are:
•
Josh Silverman
•
John Tat
•
Sarah LeBeouf
•
Nicole Schirle
•
George Campbell
•
Jessica Bruhn-Johannsen.
The program is funded through corporate, foundation, and individual
donors. Since 1997, the ARCS Foundation has awarded $847,500 to
TSRI students.
10
Jessica Sheu-Gruttadauria Wins Heart Association Fellowship
Jessica Sheu-Gruttadauria, graduate student in the MacRae lab, has been
awarded an American Heart Association (AHA) research fellowship, designed
to help students initiate careers in cardiovascular and stroke research.
The AHA fellowships support research broadly related to cardiovascular
function/disease and stroke or to related clinical, bioengineering or
biotechnology, basic science, and public health problems, including
multidisciplinary efforts.
Sheu-Gruttadauria’s research, “The Structure and Mechanism of
Higher-Order microRNA-Induced Silencing Complexes,” focuses on
elucidating the structural and mechanistic elements underlying the
assembly of higher-order silencing complexes that mediate miRNA
repression, providing tools to probe the role of miRNA regulation in
cellular and cardiovascular disease processes and thereby facilitating
targeted design of miRNA-based therapeutics.
EVENTS
Female Faculty Host Gathering for Donors and Friends
TSRI’s female faculty recently hosted an event for more than 50 donors
and friends at the TSRI Faculty Club. At the gathering, brief research
updates in the areas of cancer, Ebola, and regenerative medicine were
provided by Drs. Brunhilde Felding, Erica Ollmann Saphire, and
Kristin Baldwin.
“We are very proud of our accomplishments at TSRI and very enthusiastic
about telling the public about our science,” said TSRI Professor and
Trustee Linda Sherman. 
TSRI friend Susan Buckley (left), Legacy Member and donor Caroline DeMar
(center), and TSRI Professor and Trustee Linda Sherman chat at the reception.
11
EVENTS THANK TSRI SUPPORTERS
A recent luncheon at the Torrey Pines Lodge in La Jolla
feted TSRI’s loyal supporters who have made major
annual contributions or named the institute as a
beneficiary of their will or trust. Here, TSRI Acting
President and CEO Jim Paulson (center) visits with
Legacy Members Judy and Norbert Dean.
Scripps Florida recently recognized some dedicated
donors at a gathering at Tiffany & Co. in the Gardens
Mall. “Breakfast at Tiffany’s” honored individuals and
organizations at the Founders, President’s Circle, and
Patrons of Science levels. After breakfast, honorees
were treated to guided tours of Scripps Florida booths
at the CELLebrate Science community event. Shown
here are Ron Davis (left), Chair of the Department of
Neuroscience, Patron of Science donor Nancy Hogan
(center), and Jeff Krebs, philanthropy officer.
To learn more about supporting TSRI’s cutting-edge research, please contact:
Christopher Lee
(858) 784-2037 or (800) 788.4931
clee@scripps.edu
CA: 10550 North Torrey Pines Road, TPC-2
Irv Geffen
(561) 228-2017
igeffen@scripps.edu
FL: 130 Scripps Way, 4B2
La Jolla, CA 92037
Jupiter, FL 33458
www.supportscrippsresearch.org
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Registration does not imply endorsement, approval, or recommendation by the State.