Presentation Prepared for

Richard Longeras, Ph.D.

03/29/11

richard.longeras@jax.org
About Jackson

richard.longeras@jax.org
How it all began…

Clarence Cook Little

•  Experiments initiated to create the first inbred

mouse strain ~1907

•  Innovative and bold new insights into complex

traits and cancer biology

• Founded The Jackson Laboratory in 1929

“The mission of the Roscoe B. Jackson Memorial Laboratory is to eliminate

the chief scourge of mankind -cancer.”
-Clarence Cook Little

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The Jackson Laboratory then…

The Jackson Laboratory, 1929

Research Staff, 1930

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Human Health Advances
1940s
George Snell, PhD & Nobel Prize Recipient
Discoveries of immune system function formed the
foundation for tissue and organ transplantation

1950s
Leroy Stevens, PhD
Laid the foundation for modern stem cell research

1960s

Elizabeth Russell, PhD

Pioneered the use of bone marrow transplants

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The Jackson Laboratory now…
Basic Research, Genetic Resources, Preclinical Research Services, Education

World renown non-profit genetics

research institute and international
training center

Bar Harbor, ME

Leading provider of genetically defined

mice and services including pre-clinical
research
Sacramento, CA

richard.longeras@jax.org
The Jackson Laboratory:
•  Research: Genetics and
biology of human disease with
currently 39 Primary
Investigators
•  Resources: JAX® Mice,
JAX® Services, bioinformatics
databases
•  Education: World-class
courses, conferences, and
training programs

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The Opportunity

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The Changing Drug Discovery Landscape
Academia
•  Focused on early discovery/model development
•  Generation of peer reviewed preclinical data
•  Use of patents to maximize utility of new developments

Increased Pharma/Academia Collaborations

•  Pharma looking for low risk, to lower cost of failure
•  Requires extensive proof-of -concept to consider licensing
•  Robust patent protection needed for major therapeutic
development

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The Changing Drug Discovery Landscape
Increased NIH funding in translational research
•  Transform basic discovery to clinical relevancy
•  Accelerate data translation from bench to the bedside

NIH embracing stem cell research

•  Change in administration will lead to
increased funding opportunities
•  Process for translating stem cell therapy to
the clinic needs to be established

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richard.longeras@jax.org
JAX® In Vivo Services

richard.longeras@jax.org
Why the Mouse: Proof of Concept
The power of mouse genetics
•  Almost every human gene has a mouse counterpart
•  Spontaneous mutations in mice mimic many human diseases
•  The mouse genome can be readily manipulated
(transgenics, knock-outs, knock-ins, tissue specific & inducible
expression, reporter genes)

Mouse models of human disease

•  100’s of models for common diseases
(obesity, diabetes, atherosclerosis, cancer, hypertension, arthritis,
Alzheimer’s, neuromuscular, autoimmunity…)
•  Humanized models emerging for many diseases
•  Complete physiological disease characterization and in vivo
efficacy testing

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How JAX® In Vivo Services can help:
•  Provide seamless access to the worlds largest collection
of mouse models of human disease

•  Allows inventors to rapidly and confidentially;

–  Confirm their findings in a independent laboratory
–  Increase the scale of experiments to improve statistical
power of conclusions
–  Make direct comparisons to other reference models
–  Expand the utility of their discoveries (many of today’s
targets impact multiple therapeutic areas)
–  Generate new discoveries

•  Provide timely data for patent filings

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JAX Mice & Services: Resources for Discovery
Mouse Models
• Over 5,000 strains of JAX® Mice
• Novel strain creation
• Pretreatment e.g. diet, chemical,
surgical modification
Colony Management
• IVF-based expansion
• Sperm Cryopreservation
• 79 years experience in maintaining
genetically defined mice
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Model Characterization
• High throughput, non-invasive
phenotyping platforms.
• Gene Expression analysis
• Histopathology
Drug Efficacy Testing
• Standard and emerging disease models
• Skilled in all commonly used dosing routes
and procedures
• Backed by the scientific expertise of The
Jackson Laboratory
JAX® In Vivo Services
•  Experienced and long tenured technical staff

•  Flexible, highly customizable study design

•  Documented success in rapid implementation of new

methods and protocols

•  Supported by the expertise of Jackson research scientists

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 Therapeutic Areas Investigated to Date
Metabolic disorders Oncology
•  Obesity •  Xenograft (NCI-60 plus WSU-DLCL2 NHL cell line)
•  Type 2 Diabetes •  Orthotopic transplant
•  Cardiovascular disease •  Spontaneous/genetic models
•  Phenylketonuria •  Teratoma pluripotency
•  Glycogen Storage Disease •  Engraftment of human primary tumor samples*
Inflammation and autoimmune Skin disorders
•  Asthma •  Psoriasis
•  Arthritis •  Contact Dermatitis
•  EAE-Multiple Sclerosis •  Alopecia
•  Inflammatory Bowel Disease
•  Graft vs Host Disease* Regenerative medicine
•  Type 1 Diabetes •  Wound healing
•  Bone loss
Neurodegenerative/Neuromuscular diseases
•  Amyotrophic Lateral Sclerosis Blood disorders
•  Ataxia telangiectasia •  Sickle Cell Anemia
•  Parkinsons’ disease* •  Thrombocytopenia
•  Duchenne Muscular Dystrophy •  Bleeding disorders
*in validation

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 General Methods and Procedures
•  Dosing by all commonly used routes:
–  IP, IV, SC, PO, IM, ID, HTV
–  IV catheter
–  Intrarectal
–  Osmotic pump
–  In food or water

•  Experienced with a wide range of agents

–  Small molecules
–  Peptides
–  Antibodies
–  siRNAs
–  Embryonic stem cells

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In Vivo Services: Supporting Services
Histopathology:
The Jackson Laboratory
UC Davis Comparative Pathology Lab

Blood chemistry:
The Jackson Laboratory
UC Davis Comparative Pathology Lab

Cytokines, adipokines, etc:

Millipore

Immunocytochemistry:
Premier Laboratory

Analytical Analysis:
PharmOptima

RNA Analysis:
The Jackson Laboratory

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JAX® In Vivo Services

New Models and Services

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Leading Model for Humanization: NSG
Strain name: NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ
Common name: NOD scid gamma (NSG)
Stock number: 005557

Deficient in multiple
cytokine signaling pathways

No B cells No T cells

No NK cells No complement 5

Reduced dendritic cell function

Webpage: http://jaxmice.jax.org/strain/005557.html
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Online user discussion forum: http://community.jax.org/forums/5.aspx
Leading Model for Humanization: NSG
Features:
•  Severe defects in both innate and adaptive immunity
•  Develops functional human immune system following
engraftment

Applications:
•  Investigation of leukemic stem cells (Ishikawa F, et al. 2007. Nat Biotechnol)
•  Preservation of primary human tumor structure (Simpson-Abelson MR, et al.
2008. J Immunol)
•  Evaluation of potential anti-HIV therapies (Kumar P, et al. 2008. Cell)
•  Identification of multipotent hematopoietic progenitors (Majeti R, et al. 2007.
Cell Stem Cell)
•  Examination of tumorigenic cells in human melanoma (Quintana, et al. 2008.
Nature)
•  Investigation of human mammary stem cells (Eirew, et al. 2008. Nat Medicine)

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In Vivo Services for Therapeutic Stem
Cells
Model Application Status
Pluripotency Assay Establish pluripotent Available
potential of new stem cell
lines

STZ Induction Type 1 Pancreatic Islet Available

diabetes Replacement

MPTP Model of Cell replacement In Development

Parkinson’s

Stroke Cell replacement In Development

Spinal Cord Injury Cell replacement Planned

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Working with us:

•  Projects developed and managed by Ph.D. Study Directors

•  Study initiation usually begins within 2 to 4 weeks

•  Data updates provided weekly or as requested

•  Final report is provided within 30 days of study completion,

unless otherwise specified.

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richard.longeras@jax.org
We discover the genetic basis for preventing, treating and curing human disease,
and we enable research and education for the global biomedical community.