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VOLUME 6 NUMBER 2 | SUMMER 2009 From Research,The Power to Cure INSIDE >BURNHAM NEWS >FLORIDA UPDATES >PHILANTHROPY Meeting The Stem Cell Challenge

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Volume 6 | Number 2

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VOLUME 6 NUMBER 2 | SUMMER 2009

From Research, The Power to Cure

InsIde >BURNhaM NEwS >FLORIDa UPDaTES >PhIL aNThROPy

Meeting The Stem Cell Challenge

B U r n h a m R E P O R T

I N T h I S I S S U E

B U R N h a M R E S E a R c h

Meeting the Stem Cell Challenge 1

What is a Stem Cell? 3

The Stem Cell Community 5

B U R N h a M N E w S

Science News 6

Florida News 8

P h I L a N T h R O P y

Updates 10

Bring It! 11

A Tribute to Malin Burnham 12

a R O U N D B U R N h a M

Fulfilling the Promise of Stem Cells: President’s Message 13

Partners in Science 14

BL aIR BLUM Senior Vice President External Relations

ELIzaBETh GIaNINI Vice President External Relations

EDGaR GILLENwaTERS Vice President External Relations

chRIS LEE Vice President External Relations

aNDREa MOSER Vice President Communications

O N T h E c O V E R

Vincent Chen, M.D.,

Ph.D., and Mark Mercola,

Ph.D., investigate stem

cells for new ways to treat

heart disease—but come at

the problem from different

angles. Dr. Chen works

with embryonic stem

cells to create pacemaker

cells and hopes to make

a biological pacemaker. Dr. Mercola wants his stem cells to

become cardiomyocytes or beating heart cells. Their collabora-

tion is bearing fruit, as both cell types come from the same

progenitors and failure in one lab can lead to success in the

other.

JOSh BaxT Editor, Burnham Report

GaVIN & GaVIN aDVERTISING Design

hOwaRD cOhEN MaRk DaSTRUPMELISSa JacOBS NaDIa BOROwSkI ScOTT Photography

Please address inquiries to: [email protected]

www.burnham.org

Burnham Institute for Medical Research10901 North Torrey Pines Road, La Jolla, CA 92037 • 858.646.3100

Burnham Institute for Medical Research at Lake Nona 6400 Sanger Road, Orlando, FL 32827 • 407.745.2000/407.745.2001

Founders

wILLIaM h. F IShMaN, Ph.D. L ILLIaN FIShMaN

honorary Trustees

JOE LEwIS cONRaD T. PREByS T. DENNy SaNFORD

Trustees and Officers

MaLIN BURNhaM Chairman

JOhN c. REED, M.D. , Ph.D. President & Chief Executive Officer Professor and Donald Bren Presidential Chair

GaRy F. RaISL, ED.D. Chief Administrative Officer Treasurer

MaRGaRET M. DUNBaR Secretary

Trustees

Linden S. BlueMary F. BradleyBrigitte M. BrenArthur BrodyHoward I. CohenShehan DissanayakeM. Wainwright Fishburn, Jr.

Trustees, continued

Jeannie M. Fontana, M.D., Ph.D.Alan A. GleicherW.D. GrantDavid F. HaleJeanne Herberger, Ph.D.Brent JacobsJames E. Jardon IIDaniel P. Kelly, M.D.Robert J. LauerSheila B. LipinskyGregory T. LucierPapa Doug ManchesterRobert A. MandellNicolas C. NierenbergDouglas H. ObenshainPeter PreussStuart TanzJan Tuttleman, Ph.D., MBAAndrew J. Viterbi, Ph.D.Kristiina Vuori, M.D., Ph.D.Bobbi WarrenAllen R. WeissJudy WhiteGayle E. WilsonDiane WinokurKenneth J. Woolcott

Ex-Officio

Raymond L. White, Ph.D.

B U r n h a m S T E M c E L L R E S E a R c h

www.burnham.org | The BUrnham reporT 1

A few months ago my uncle was diagnosed with ALS (amyotrophic lateral sclerosis). It started with some speech problems but since then his condition is constantly worsening. It is very painful for me to know that he is in such a difficult position and that there is no cure for it. However, with the latest stem cell research, there might be some hope. He is very willing to participate in any kind of experiments. So my question is - is there any way that you can take him into your research program and see if there is any potential to cure ALS or at least to improve his condi-tion? If not - can you recommend any programs? Any help or suggestion would be very much appreciated.

— Bellevue, Washington

Meeting theStem Cell Challenge

Smooth muscles cells derived from embryonic stem cells

Burnham scientists

frequently receive letters like

this. They remind everyone at

the Institute how important

the research is, as well as how

much work needs to be done.

In recent years, there has been

intense focus on embryonic

stem cells because they can

form more than 200 different

tissue types. This flexibility,

or plasticity, could make them

ideal to treat diabetes, neuro-

degenerative diseases, heart

problems, cancer and many

other conditions. But where

does the promise of stem cell

therapies meet the reality? And

what will those therapies ulti-

mately look like?

Back TO BaSIcS

While stem cells (See box

on page 3) offer great potential

as future therapies, they are not

always obedient. Sometimes

they differentiate into other cell

types when researchers want

them to remain stem cells—or

vice versa. They can become

glial cells (non-neuronal brain

cells) when the goal is to create

neurons. They can form tumors,

called teratomas. To solve these

problems, researchers must deci-

pher the signaling mechanisms

that direct stem cells towards a

specific fate. By understanding

the developmental biology, scien-

tists can potentially replicate it

and assert control over stem cells.

Mark Mercola, Ph.D.,

associate director of the Del

E. Webb Neuroscience, Aging

and Stem Cell Research

Center, has discovered signals

that make embryonic stem

cells differentiate into cardio-

myocytes (beating heart cells),

which could be used to repair

damaged heart muscle.

Early on, Dr. Mercola and

other stem cell researchers were

frustrated by their inability to

direct stem cells to become

cardiomyocytes, or other cell

types, any more efficiently than

they would without human

intervention.

“We just didn’t know enough

about embryology,” says Dr.

Mercola. “We needed to under-

stand where the heart actually

comes from and what natural

signals in the early embryo

stimulate undifferentiated cells

to form a heart.” Studying how

embryos make hearts was a

good strategy. Dr. Mercola and

others succeeded in unraveling

many of the signals that tell

cells to form heart tissue.

Dr. Mercola then returned to

embryonic stem cells to find

the right chemical compounds,

proteins or microRNAs (ribonu-

cleic acids) to take pluripotent

stem cells through the multiple

stages they must travel to

become cardiomyocytes.

“Now we know quite a

bit about the early steps of

stem cell differentiation from

embryology,” says Dr. Mercola.

“But the major prize is to find

small molecules that influence

the latter steps. With those,

we could potentially create

drugs that help damaged hearts

rebuild themselves.”

To discover these molecules,

his laboratory uses high-

throughput screening in the

Conrad Prebys Center for

Chemical Genomics.

“We already have several

promising new compounds,

as well as a couple of existing

drugs, that are candidates to

stimulate a patient’s own heart

to regenerate cardiomyocytes,”

says Dr. Mercola.

BUILDING a BIOLOGIcaL PacEMakER

“Everything Mark Mercola

wants to do, I want to do in

mirror image,” says Vincent

Chen, M.D., Ph.D., who works

closely with Dr. Mercola.

Dr. Chen’s goal is to create

cardiac pacemaker cells to

treat arrhythmias and other

dangerous heart rhythm disor-

ders. The research being done

by each laboratory informs the

other’s work, as both cardiomyo-

cytes and pacemaker cells come

from the same precursor cells

but require different signals to

become the two types of heart

tissue. A practicing electro-

physiologist, Dr. Chen routinely

implants electronic pacemakers

and recognizes how that tech-

nology has evolved over the past

35 years.

“Current pacemakers have

very sophisticated algorithms

to make them pace the heart

appropriately and make them

failsafe,” says Dr. Chen. “They

need to respond to exercise,

and they need to recognize

when you are trying to sleep. If

we want to create a biological

pacemaker, we need to match

or exceed the standard of elec-

tronic pacemakers.”

The cellular pacemakers

Dr. Chen envisions would

fully integrate into the heart.

In other words, they would

respond to the nervous system

like the original cells they

must replace. Using human

embryonic stem cells, he has

developed a system to monitor

the formation of pacemaker

cells — a critical step towards

discovering molecules to build a

biological pacemaker.

B U r n h a m S T E M c E L L R E S E a R c h

2 The BUrnham reporT | www.burnham.org

Theresearchbeingdonebyeachlaboratory

informs the other’s work,asboth

cardiomyocytesandpacemakercellscomefromthe

sameprecursor cells

Brandon Nelson, manager of Burnham’s Stem Cell Core, removes cells from cryogenic storage.

The core provides expertise to grow, differentiate and analyze embryonic stem cells.

MOTIVaTING ENDOGENOUS cELLS

A major goal of Burnham

researchers is to develop drugs

that can coax endogenous

somatic stem cells (progenitor

cells within our bodies) to

rebuild damaged tissue. In

collaboration with other labs,

Pilar Ruiz-Lozano, Ph.D.,

is working to pinpoint the

heart cells that cause normal

regeneration.

“It appears that endogenous

stem or progenitor cells can

heal very small traumas,” says

Dr. Ruiz-Lozano. “In nature, if

it happens at all, then it should

be possible to stimulate those

natural abilities to do more.

We need to understand how

various cells contribute to repair

processes to develop therapies.”

The Ruiz-Lozano lab has

discovered important cells in the

epicardium, the protective layer

surrounding the heart. These

epicardial cells provide signals

that minimize the impact of

heart disease on muscle cells.

With Dr. Mercola, Dr. Ruiz-

Lozano is working to discover

B U r n h a m S T E M c E L L R E S E a R c h

www.burnham.org | The BUrnham reporT 3 www.burnham.org | The BUrnham reporT 3

Stem cells are cells that

can both replicate themselves

and differentiate into other

types of cells. In a developing

embryo, pluripotent stem

cells, which can differentiate

into all cell types, are told

through complex signaling to

differentiate into other cells.

Embryonic stem cells go

through several stages before

becoming functional neurons,

cardiomyocytes (beating heart

cells), pancreatic beta cells or

other types of tissue.

Once an embryonic stem

cell starts to differentiate,

it becomes multipotent and

can become many cell types.

These cells are moving

towards a cellular identity

but still have the flexibility

to become different types of

tissue. In other words, the cell

knows its address and will

migrate to the heart, liver,

brain or other part of the body

and differentiate into more

specific cells types. Certain

tissues in adults have their

own multipotent stem cells,

often called somatic stem cells

or “adult stem cells.” However,

the latter term is somewhat

misleading as these cells are

also found in embryos and

children.

Perhaps the most

intriguing types of stem

cells are induced pluripo-

tent stem (iPS) cells. These

cells are created from fully

differentiated cells, often

skin cells, which have been

reprogrammed to become

pluripotent stem cells. Like

their embryonic cousins,

iPS cells can form all cell

types. This approach offers a

number of benefits. For one,

iPS cells may be ideal for

transplantation, as they could

be taken from a patient and

would not face rejection from

the patient’s immune system.

Also, iPS cells could be used

to study diseases on a cellular

level.

“These iPS cells will give

us the ability to study the

molecular underpinnings of

disease,” says Stuart Lipton,

M.D., Ph.D., director, Del E.

Webb Neuroscience, Aging

and Stem Cell Research

Center. “We can set up

models for Parkinson’s and

figure out what is going wrong

with those cells.”

Currently, iPS cells have

their drawbacks. Some of the

methods used to create them

make them unsuitable for

clinical use. They replicate

slowly, making them difficult

to study. Also, scientists don’t

know if iPS cells are identical

to embryonic stem cells. More

study is needed, but break-

throughs are being announced

with great frequency.

“The technology for iPS

cells is changing every day,”

says Dr. Lipton. “They have

great potential, but we need to

learn whether they are iden-

tical to embryonic stem cells,

and we just don’t know yet.”

What is a Stem Cell?

Pilar Ruiz-Lozano, Ph.D.

synthetic compounds that can

enhance or mimic the epicardi-

um’s regenerative effects.

Epicardial cells can also

be isolated from patients

and expanded in culture or

chemically modified and used

for transplantation. “These

cells would be ideal, as they

would come from the patient

and would not cause an

immune response,” says Dr.

Ruiz-Lozano.

Lorenzo Puri, M.D., Ph.D.,

is doing similar work with

skeletal muscle progenitor cells.

“Muscle cells continually turn

over,” says Dr. Puri. “When you

go to the gym for strenuous

exercise, the body perceives this

as damage and the muscle stem

cells work to repair that damage.”

Controlling muscle stem

cells could have important

clinical implications. For

example, muscular dystrophy

(MD) causes debilitating

muscle weakness and eventu-

ally death. Compounds that

encourage muscle progenitors

to form new muscle could be

the next generation of treat-

ments for muscular dystrophy

and other muscle disorders.

But it’s important to know

when intervention can be most

effective.

“We need to understand

whether there is a clock,” says

Dr. Puri. “For a boy with MD,

18 might be too late. But at 3,

we might be able to reset the

cells.” His research has led to

encouraging pre-clinical drugs

that enhance regeneration by

modulating native stem cells in

muscle.

ThE MySTERy OF caNcER STEM cELLS

Stem cells, by definition,

are cells that can either self-

renew to ensure a source of

continued growth or differen-

tiate to become different cell

types. Studying stem cells has

led to an interesting hypothesis

about cancer: Perhaps some

cancers have their roots in

“cancer stem cells” that can

continuously feed malignant

cells to a tumor. This scenario

could be likened to an ant

colony: you can kill workers,

but to wipe it out you must

get the queen. This could

explain why certain tumors

initially respond to treatment

but return with a vengeance.

If this hypothesis is accurate,

clinicians must do more than

shrink the tumor; they must

also treat the source.

Robert Oshima, Ph.D.,

co-director of the Tumor

Development Program in

Burnham’s Cancer Center,

is investigating the role of

the MELK gene in normal

mammary epithelial stem

cells. MELK is often over-

expressed in breast tumors.

The Oshima lab has found

that MELK is also highly

expressed in mammary

epithelial progenitor cells.

“We’re trying to understand

the role of MELK in these

tumors,” says Dr. Oshima. “If

you have a cancer stem cell,

you can screen for chemicals

that will push it to differen-

tiate to a benign state and

those could be less toxic.”

Dr. Oshima is cautiously

optimistic. “The cancer stem

cell idea could be valuable

early on in a cancer’s progres-

sion,” says Dr. Oshima.

“However, tumors evolve and

find ways to grow.”

STEM cELLS FOR cLINIcaL USE

The ultimate goal for stem

cell research is clinical appli-

cation. To get there, scientists

B U r n h a m S T E M c E L L R E S E a R c h

4 The BUrnham reporT | www.burnham.org

Robert Oshima, Ph.D.

Ph.D. student Karen Wei at work in the stem cell core.

B U r n h a m S T E M c E L L R E S E a R c h

www.burnham.org | The BUrnham reporT 5

Like many in the research community, Stuart A. Lipton, M.D., Ph.D., was very pleased when President Barack Obama announced new federal rules governing embryonic stem cell research.

He is particularly excited that the renewed federal support for basic stem cell research will mean more funding from the California Institute for Regenerative Medicine (CIRM) for disease-focused investigations.

“The landscape is changing,” says Dr. Lipton. “The California money is going to become more about translational research

and finding treatments for disease.”

CIRM was estab-lished by Proposition 71, the California Stem Cell Research and Cures Initiative, which provided $3 billion to fund stem cell research. This stable source of funding has made California a leader in stem cell research, helping inves-tigators find the preliminary data that is so important to getting NIH grants. CIRM plays a unique role by funding the stages between basic research and clinical trials, a critical gap that must be bridged to get treatments to patients.

a UNIqUE cOLL aBORaTION

In 2006, Burnham, The Scripps Research Institute, The Salk Institute and the University of California, San Diego united to create the San Diego Consortium for Regenerative Medicine. This collaboration is now known as the Sanford Consortium after receiving a $30 million gift from T. Denny Sanford in 2008. The consortium was created to unite the expertise of these four world-renowned research institutions to move stem cell research forward more quickly.

“The Sanford Consortium fills gaps,” says Evan Snyder, M.D., Ph.D., Program Director, Stem Cell and Regenerative Biology. “None of us researchers individually are as smart as all of us together. So we fill each other’s gaps. You don’t need to duplicate efforts, or replicate expertise that another member of the consortium has.”

To maximize this efficiency, the Sanford Consortium is building a research facility within walking distance of all four institutions. By putting the collective expertise under one roof, the Consortium hopes to reduce the distance to new treatments.

The Stem Cell Community

must discover methods, or

protocols, to consistently

create the desired cells every

single time.

Alexey Terskikh, Ph.D., and

colleagues have developed a

protocol to rapidly differentiate

human embryonic stem cells

into neural progenitor cells that

may be ideal for transplanta-

tion. Their research could be

adapted to produce committed

neural precursor cells, one

of the key requirements for

clinical applications. When the

neural precursors created using

this protocol were transplanted

into mice, they became active

neurons and integrated into the

cortex and olfactory bulb. No

signs of cellular overgrowth or

tumors were found.

“The uniform conver-

sion of embryonic stem cells

into neural progenitors is the

first step in the development

of cell-based therapies for

neurodegenerative disorders

or traumatic injuries,” said

Dr. Terskikh. “Many of the

methods used to generate

neural precursor cells for

research in the lab would never

work in therapeutic applica-

tions. This protocol is very well

suited for clinical application

because it is controllable,

robust and reproducible.”

Evan Snyder, M.D., Ph.D.

Infantile hypophosphatasia (HPP) is a horrible disease and often fatal. A rare form of rickets, HPP makes bones dangerously fragile.

When Baby Amy was flown from her home in Ireland to Winnipeg, Canada, to be treated for HPP, she was transported in an insulated box to prevent her bones from breaking. However, after receiving an enzyme replace-ment therapy developed by José Luis Millán, Ph.D., and

collaborators, Baby Amy was healthy enough to be held by her mother and make the trip home to Ireland.

“While physicians may be familiar with the feeling of helping other human beings and alleviating their suffering on a day-to-day basis, it is very rare for a basic scientist to experience that,” says Dr. Millán. “Baby Amy has allowed me to experience that satisfaction. It has been very rewarding to see this therapy improve the quality

of life of the first patient ever to receive it.”

The drug, called ENB-0040, progressed from design to orphan drug status in just three years and was the result of a strong collaboration between Dr. Millán’s lab, ENOBIA Pharma (a small Canadian biotech) and Michael P. Whyte, M.D., of Shriner’s Hospital for Children in St. Louis.

Dr. Millán is now working to prove that the treatment can also help patients with

more advanced disease. His lab is developing models of adult hypophosphatasia and assessing if this treatment can improve quality of life for patients with milder, but still debilitating, disease.

B U r n h a m S c I E N c E N E w S

6 The BUrnham reporT | www.burnham.org

Treating Baby Amy

The Lipton lab has demonstrated that attacks on the mito-chondrial protein Drp1 by the free radical nitric oxide, a process called

S-nitrosylation, controls the synaptic degradation associated with Alzheimer’s disease. Mitochondria are the energy store-houses of the cell, and their compromise causes synaptic injury and eventually nerve cell death.

Prior to this study, the molecular mechanism by which beta-amyloid proteins damaged neurons was unknown. These findings

suggest that preventing S-nitrosylation of Drp1 may reduce or even prevent neurodegeneration in Alzheimer’s patients. The paper was published in the April 3 issue of the journal Science.

The team, led by neuroscientist and clinical neurologist Stuart A. Lipton, M.D., Ph.D., director of the Del E. Webb Center for Neuroscience, Aging and Stem Cell Research, showed that S-nitrosylated Drp1 facilitates mitochondrial fragmentation, thus damaging synapses, which are critical for learning and memory. Synaptic impairment leads to the dementia seen in Alzheimer’s.

“We now have a better understanding of the mechanism by which beta-amyloid protein causes neurodegeneration in Alzheimer’s disease,” says Dr. Lipton. “By identifying Drp1 as the protein responsible for synaptic injury, we now have a new target for developing drugs that may slow or stop the progression of Alzheimer’s.”

Stuart A. Lipton, M.D., Ph.D.

José Luis Millán, Ph.D.

Alzheimer’s Disease Linked to

Mitochondrial Damage

Pam Itkin-Ansari, Ph.D., Seung-Hee Lee, Ph.D., and colleagues have demonstrated in mice that transplanted pancreatic beta cells are protected from the immune system when encapsulated in a polytetrafluorethylene (PTFE) device.

The study, which suggests a new approach to treating type 1 diabetes, was published online on April 8 in the journal Transplantation.

The team showed that, after transplantation, the precursor cells mature into functional beta cells that are glucose-responsive and control blood sugar levels. Also, the study demonstrated that using precursor cells, instead of more committed beta cells, enhanced the cell transplant’s chances of success.

“The results exceeded our expectations,” said Dr. Itkin-Ansari, assistant adjunct professor at Burnham and the UC San Diego School of Medicine. “We thought that T-cells, although unable to penetrate the device, would cluster around it. But we found no evidence of an active immune

response, suggesting that the cells in the device were invisible to the immune system.”

The investigators used two different mouse models in the study. The team trans-planted mouse islet cells into other mice to show that the cells were protected from the immune system when encap-sulated in PTFE. Human cells encased in PTFE were then transplanted into immunodefi-

cient mice to study the viability and function of both mature beta cells and precursor cells inside the device. Itkin-Ansari’s team found that by using precursor cells that had not completely differentiated, the transplanted cells could regenerate into fully functional beta cells. This has important implications for how stem cell-derived tissue should be transplanted in the future.

B U r n h a m S c I E N c E N E w S

www.burnham.org | The BUrnham reporT 7

Pam Itkin-Ansari, Ph.D.

Pancreatic Beta Cells

and the Immune System

Investigators in the Wolf lab have deciphered a large percentage of the total protein complement

(proteome) in Schizosaccharomyces pombe (S. pombe) fission yeast.

Laurence Brill, Khatereh Motamedchaboki, Ph.D., and lead investigator Dieter Wolf, Ph.D., developed a novel method to iden-tify 4,600 proteins in the organism using an array of sophisticated techniques. The research was published online on March 9 in the journal Methods.

“Analysis of the proteome of an organism tells us so much more than simple DNA sequence analysis,” says Dr. Wolf. “Proteome analysis gives us a snapshot of what proteins are being expressed in the cell at any given point in time. This can tell us how protein expression changes in response to certain stimuli and in disease states, which may help identify new biomarkers for diseases. We are now applying the methodology to protein profiling of human stem cells in collaboration with Burnham’s stem cell program director, Dr. Evan Snyder.”

DNA analysis of the yeast’s genome predicts 5,027 proteins. The team identified 4,600 proteins, which is not quite the entire proteome. The remaining 400 are only expressed during S.pombe’smating state.

Wolf Lab Deciphers

Yeast Proteome

Dieter Wolf, Ph.D.

Anatomy of a MoveIn late April, Burnham began the three-week process of packing and transporting files, beakers and high-tech equip-ment to its new campus at Lake Nona in Orlando, Florida. More than a dozen moving companies and equipment specialists participated in the multi-phase move.

This was not a simple feat. Moving sensitive microscopes, robots

and finely calibrated equipment requires specially-designed crates

to protect the cargo, liquid nitrogen to freeze delicate cells to

minus 346 degrees Fahrenheit (10 times colder than ice), lab-

trained movers and 3,000 feet of bubble wrap.

Björn Tyrberg, Ph.D., a diabetes researcher, moved a sophis-

ticated microscope while taking special precautions to protect

tiny insulin-producing cells during transport. Layton Smith,

Ph.D., who studies obesity-related heart disease, froze 10 million

cells in advance, so he could quickly restart his research.

“This is a complicated process,” said Cyril Doucet, vice

president of operations for Burnham Lake Nona. “But we started

planning for the move more than eight months ago. We had to

plan thoroughly to minimize the impact on our research and to

keep our science moving forward.”

In all, scientists moved more than 350 pieces of equipment,

from a vortexer (the size of a tea kettle), to a four by eight-foot

bio-safety cabinet. Each piece of equipment was disassembled,

reassembled and recalibrated. Because the equipment is so sensi-

tive, if a piece breaks, it can take months to repair or replace.

Burnham is the first facility to be completed at the new

medical city at Lake Nona, which will include the University

of Central Florida College of Medicine, Nemours Children’s

Hospital, VA Medical Center, M.D. Anderson Cancer Center

Orlando and a proposed University of Florida research facility.

8 The BUrnham reporT | www.burnham.org

B U r n h a m F l o r I d a N E w S

LaytonSmith,Ph.D.,whostudiesobesity-relatedheartdisease,froze 10

million cellsinadvance,sohecouldquickly restart his research.

Layton Smith, Ph.D.

B U r n h a m F l o r I d a N E w S

www.burnham.org | The BUrnham reporT 9

Burnham’s new facility in Lake Nona, Florida was designed with open labs and extensive telecom-munications technology, so scientists can easily collaborate with colleagues in the next lab or around the world.

The new facility will house a variety of specialists, from biochemists to cell biologists, pharmacologists and medic-inal chemists, and is intended to encourage collaboration among these specialties to advance science.

“When you put different disciplines together in a building like this, exciting things happen,” says architect Gary C. Shaw.

In addition, the 175,000 square foot facility is poised to become the largest private research institute in Florida with a Gold Level Leadership in Energy and Environmental Design (LEED) certification, which will be awarded after two to three months.

“Burnham is on its way to a Gold Level certificate, which indicates that it is one of the greenest of the green, and has been built to the highest environmental standards,” says Shaw.

The building’s design and construction must meet a variety of criteria to gain LEED certification. For example, a project must use at least 10 percent of its materials from regional sources to reduce emissions from long distance transpor-tation. More than 20 percent of Burnham’s materials were made within 500 miles of the site.

Building an energy-efficient scientific building offered unique challenges because of the labs’ exten-sive exhaust and air filtration needs. “We incorporated a tremendous amount of reflective, glazed window glass into the construction to allow low levels of solar heat while welcoming ample natural light,” says Shaw.

MEaSURING ThE SaVINGS

While building a green facility is very demanding, the rewards are substantial, both environmentally and monetarily. For example, 95 percent of construction waste was diverted from landfills. Metal was recycled, concrete waste was crushed and used for road base and wood was chopped into mulch. Even leftover drywall scraps were ground into fertilizer for local sod farmers.

Energy costs at Burnham Lake Nona are expected to be 25 percent below those of a comparable building. The roof is made of a special membrane that reflects heat, and labs and offices have motion sensors to control lighting. The building is oriented east/west with over-

hangs and shading devices on exterior walls to minimize heat and sun reflection. More than 90 percent of the interior spaces have an outside view, decreasing the energy needed to light them. Burnham’s annual energy savings will be equivalent to the average yearly consump-tion of 6,600 homes.

“Burnham is proud to have participated in the design and construction of a state-of-the-art research facility that was built using environmen-tally-friendly methods and will require less energy and water than a similar scientific struc-ture,” says Daniel Kelly, M.D., Burnham’s Scientific Director at Lake Nona.

Intellectually Sound,

Energy Efficient

Burnham Lake Nona

p h I l a n T h r o p y U P D a T E

10 The BUrnham reporT | www.burnham.org

Caroline Nierenberg and Kathryn Stephens will chair this

year’s gala. No strangers to high-profile charitable events, both

have independently chaired the Las Patronas Jewel Ball.

Why focus on the power to cure? Burnham discoveries benefit

people of all ages, and Burnham researchers have discovered valu-

able new treatments. The Institute has generated more than 250

patents, and applications are pending on 300 more.

“The benefit that Burnham research brings to the world is

beyond calculation,” says Nierenberg. “We want to celebrate that

contribution and highlight the beauty of the work they do.”

This year’s presenting sponsor is Life Technologies. Greg

Lucier, CEO of Life Technologies, is vice chair of Burnham’s Board

For 32 years, Melvin Clause worked for Convair as a test pilot, flight engineer and field service engineer. He was onboard a 42-hour, non-stop, non-refueling flight, tested the XC99 transport (one of the largest planes ever flown) and flew everything from 2-cylinder prop planes to 168-cylinder jets. But the biggest chal-lenge he ever faced was watching his wife Phyllis McArdle die of Alzheimer’s disease.

“Phyllis lived in fear that she

would inherit the disease, which

did indeed happen,” says Clause.

“She was diagnosed in 2001 and

passed away in 2008.”

Phyllis had a long career as a

school counselor and teacher in

Salt Lake City. She played violin

in the symphony and liked to

camp, fish and four-wheel drive

through the back country.

“She tolerated my accordion,

and even put up with a month

in a tepee,” says Clause.

Melvin Clause pays tribute

to Phyllis through the Melvin

and Phyllis McArdle Clause

Scholarship Fund at Burnham.

Created through a bequest, the

scholarships are both a gift and

a challenge to the next genera-

tion of scientists: find a cure for

Alzheimer’s disease.

“She was an angel, or as

close to one as you could find,”

says Clause. “The hardest part

is that the woman I loved grad-

ually faded away. I want to keep

her memory alive through this

scholarship fund and support

scientists in search of a cure.”

Ifyouwouldliketoestablish

anamedscholarshipfundto

supportgraduateandpost-

graduateeducationatBurnham

throughanestategift,please

contactPattyFullerat858-795-

[email protected].

Save the Date: The 2009 Burnham Gala

The Power to Cure willbeheldattheHyattRegency

LaJollaAventineonNovember14.

of Trustees. Additional lead sponsors include Jeanne and Gary

Herberger, Peggy and Peter Preuss and Roberta and Malin Burnham.

Formoreinformation,pleasecontactChelseaJonesat

[email protected].

Honoring an AngelBy PaTT y FULLER

Caption: Gala co-chairs Caroline Nierenberg and Kathryn Stephens stand next to Burnham’s

Shimadzu Xcise robot, which Las Patronas helped purchase.

Phyllis McArdle and Melvin Clause

p h I l a n T h r o p y U P D a T E

www.burnham.org | The BUrnham reporT 11

Forget the fine food and wine, the cheering crowd, the red carpet, the noise-makers. Forget all that.

At 7:30, the games began

and people got down to

some serious fun. On April

30, more than 300 guests

packed a transformed Mission

Tower Ballroom at the Del

Mar Fairgrounds to BringIt!

Presented by Burnham and

the HeadNorth Foundation,

the event was a crazy combi-

nation of trivia questions,

game show enthusiasm

and spirited competition to

support stem cell research

at Burnham to treat chronic

spinal cord injuries.

Imagine 30 teams of 10

facing off in a series of trivia

contests with wacky chal-

lenges thrown in, leading to

the final face-off for the cham-

pionship. Between games,

Eric Northbrook introduced

the fund-a-need; StandUp

forEric. And people did stand

up. BringIt! raised nearly

$170,000 to support the

HeadNorth Chronic Spinal

Cord Injury Project.

Congratulations to

2009 BringIt! champions,

Team HeadNorth. Also,

many thanks to emcee Bill

Menish, lead sponsors Life

Technologies and Biomed

Realty and co-chairs Stath and

Terry Karras.

Did you miss it? Sorry

to hear that, but it’s okay.

Burnham and HeadNorth

are doing it again next

year—bigger, better, faster,

funner—on April 24, 2010, at

the Del Mar Fairgrounds. Is

someone going to take the title

away from Team HeadNorth?

They dare you.

Formoreinformation,

contactChelseaJones

at858-795-5239or

[email protected].

Bring It!

5Above, Ryan Baker belts out

the song he’s listening to during

the iPod challenge.

4Right , Team HeadNorth:

Matt Carlson, Eric Northbrook,

Chris High—Bring It! 2009 Champions

6Below, the frost-a-cake

challenge nearly escalated into an

on-stage food fight. Andrew Morse,

James Pires, John Garrigan, David

Thomas, Ron Lack, Dawn Saunders,

Chris High and Mary Macie.

As Malin Burnham steps down as Board of Trustees chair,

many people are noting what a profound impact he and his

family have had on the Institute. For nearly three decades, the

Burnham family has donated their time, talent and treasure to

grow the organization and advance basic biomedical science.

Here are some reflections on Malin Burnham’s 14 years as chair

and his ongoing passion for Burnham Institute for Medical

Research.

“AtthefirstNationalCancerInstitute(NCI)sitevisit,inresponsetoourapplicationforacancercentergrant,weneededtodemonstratewidecommunitysupport.Malinappearedinpersontotestifyonourbehalf.Tothisday,wearestillsupportedbyanNCIcancercentergrant.

“ButMalin’seffortsdidnotendthere.Hecontributedsignificantlybyjoiningtheboardoftrustees.Hisleadershipaschairmansetthestageforourfuturegrowth,andhealsohelpedbuildtheboardbyrecruitingstrongleaderswhowereenthusiasticaboutourmission.”

—LillianFishman,co-founder

“Malinisoneofthoselargerthanlifepeoplewhohasanimpactoneverythinghegetsinvolvedwith.HeisbroadlyfocusedonSanDiegoandistheguardianofourregion’swellbeing.AddinghisnametotheInstituteandservingaschairmanoftheboardputtheInstituteonthelocalmap.ThescientificteamfollowedthroughbyputtingBurnhamontheworldmapofbestresearchinstitutes.”

—DuaneRoth,CEO,CONNECT

“TherearenoshortageofpositiveadjectivestodescribeMalinBurnham.Heisdedicatedtothemission,decisive,experienced,persuasive,engagedandproactive.HeiscompletelyvestedinthesuccessofBurnhamInstituteforMedicalResearch.”

—GayleWilson,BurnhamTrustee

Editor’snote:TheInstituterecentlycommissionedaformalportrait

ofRobertaandMalinBurnhamthatwillhangintheexecutivesuite.

ItwillserveasaremindertoBurnhamleadership,staffandallwho

visitourcampusoftheimpacttheBurnhamfamilyhashadonthe

Institute.

When I first visited the La Jolla Cancer Research Foundation (LJCRF) in 1982, I was extremely impressed.

I especially liked what

I heard and saw about co-

founders Dr. William and

Lillian Fishman. I recognized

their scientific talent and the

quality of the culture they had

established, which was very

open and

transparent.

Everyone

was in it

together, and

there were no

silos, artificial

walls or rules

to inhibit

collaboration. I came to the

conclusion that LJCRF was a

hidden gem, and that I should

do what I could to help.

One of the more personal

aspects of my relationship

with the Institute was my

own experience, about seven

years ago, with cancer. I had a

PSA test come back high, and

the biopsy showed that I did

indeed have prostate cancer.

I was lucky we found it early.

But it’s important to note that

the PSA was perfected as a

result of work done by Dr. Eva

Engval, a Burnham researcher.

Roberta and I, along with

the Burnham family, have had

the wonderful opportunity of

supporting

the

Burnham

Institute

for Medical

Research.

I particu-

larly enjoy

providing a

combination of our financial

resources with shoe leather

and brain power. Of all the

things I have done, business

and community-wise, helping

the Burnham Institute has

given me the most satisfaction.

B U r n h a m L E a D E R S h I P

12 The BUrnham reporT | www.burnham.org

In His Own Words

A Tribute to Malin Burnham

Malin and Roberta Burnham

p r e s I d e n T ’ s M E S S a G E

www.burnham.org | The BUrnham reporT 13

15. JohnReedessay

Fulfilling the Promise of Stem CellsIn 1974, Burnham co-founder Dr. William Fishman discovered placental alkaline phosphatase,

a pregnancy protein, in an adult human lung tumor. Soon thereafter, Dr. Fishman found several

examples of tumors producing fetal proteins, prompting him to hypothesize that cancer might be

caused by adult cells reverting back to the primitive fetal state during which cells divide rapidly and

migrate through the developing body. This breakthrough helped create the field of oncodevelop-

mental biology and informed much of the early research at Burnham. We now recognize that the

primitive cells Dr. Fishman observed were actually adult stem cells that had become cancerous.

Our bodies have small numbers of stem cells that constantly renew tissues and organs with fresh

cells. Today, scientists believe that these adult stem cells are the source of many cancers. By

delving into the relationships between fetal development and cancer, Dr. Fishman’s work set the

stage for Burnham’s current work in stem cell biology.

Stem cell research provides a powerful approach to unlocking the mysteries of human disease.

Burnham scientists, for example, make disease models by synthetically creating the equivalent of

embryonic stem cells from patients with genetic predispositions to diseases, then converting those

synthetically-derived stem cells into specific types of cells in which the disease manifests (brain

cells, heart cells, insulin-producing cells). With these disease-specific cell lines, we can expand

our understanding of the complex biological mechanisms that lead to cancer, Parkinson’s disease,

diabetes and other conditions. We can test new medicines, rapidly gaining insights into the best

candidates to take, eventually, to clinical trials.

In addition, regenerative therapies have the potential to treat many conditions by replacing cells

lost to disease, trauma or aging. Once clinical protocols are perfected, stem cells will be grown and

differentiated into heart cells, nerve cells, insulin-producing cells and other therapeutically useful

cell types and transplanted into patients. But transplantation is only one way stem cells can benefit

human health. As forecasted by Dr. Fishman’s seminal work, our bodies also contain endogenous

adult stem cells that heal tissue damage, though inefficiently. Burnham researchers are working to

harness these cells and boost their efficiency. This research may lead to medicines that mobilize

endogenous adult stem cells to regenerate the heart, brain, spinal cord, liver or other tissues.

While we are excited about the enormous potential of stem cell research, we must recognize

that this line of investigation is at an early stage. Because stem cell-based therapies are largely

unproven, pharmaceutical companies are reluctant to invest resources to study how they work, and

thus that responsibility falls to non-profit organizations like Burnham. We encourage you to join

in supporting our mission to make stem cell-based therapeutics not just the passion of dedicated

scientists and the dream of those suffering from debilitating disease, but a reality that saves lives.

John C. Reed, M.D., Ph.D.

PresidentandCEO

ProfessorandDonaldBren

PresidentialChair

Withthesedisease-specificcelllines,wecanexpandourunderstandingofthecomplexbiologicalmechanismsthatleadtocancer,Parkinson’sandotherdiseasesandtestnew generationsofmedicinestotreatthem.

p h I l a n T h r o p y

Printedonrecycledpaper

Afteramotorcycleaccident

severedhisspinalcord,Eric

NorthbrookfoundedtheHeadNorth

Foundationtosupportthosewith

similarinjuriesandchampionspinal

cordresearch.Hiseffortsledhimto

EvanSnyder,M.D.,Ph.D.,director

ofBurnham’sPrograminStemCell

andRegenerativeBiology,whose

groundbreakingstemcellresearch

couldleadtonewtreatmentsfor

paralysis.Dr.SnyderandDr.Mark

TuszynskiatUCSanDiegohave

receivedagrantfromHeadNorth

todevelopstemcelltherapiesfor

chronicspinalcorddamage.

Partners in Science: EricNorthbrook

andDr.EvanSnyder

Nonprofit OrganizationU.S. Postage

PaIDThe Burnham Institute

“Livingwithachronic spinal cord injuryisaserious challenge,”saysNorthbrook.“TheHeadNorthChronic SpinalCordResearchProjectcouldbethesolution for thousandswholivewiththiscondition.”

Nonprofit OrganizationU.S. Postage

PaIDThe Burnham Institute

10901 North Torrey Pines Road

La Jolla, CA 92037

P h i l a n t h r o P y

Printed on recycled paper

After a motorcycle accident

severed his spinal cord, Eric

Northbrook founded the HeadNorth

Foundation to support those with

similar injuries and champion spinal

cord research. His efforts led him to

Evan Snyder, M.D., Ph.D., director

of Burnham’s Program in Stem Cell

and Regenerative Biology, whose

groundbreaking stem cell research

could lead to new treatments for

paralysis. Dr. Snyder and Dr. Mark

Tuszynski at UC San Diego have

received a grant from HeadNorth

to develop stem cell therapies for

chronic spinal cord damage.

Partners in Science: Eric Northbrook

and Dr. Evan Snyder

Nonprofit OrganizationU.S. Postage

PAIDThe Burnham Institute

“Living with a chronic spinal cord injury is a serious challenge,” says Northbrook. “The HeadNorth Chronic Spinal Cord Research Project could be the solution for thousands who live with this condition.”

6400 Sanger Road

Orlando, FL 32827