The Jackson Laboratory
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Transcript of The Jackson Laboratory
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How it all began…
“The mission of the Roscoe B. Jackson Memorial Laboratory is to eliminate the chief scourge of mankind -cancer.” -Clarence Cook Little
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
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Human Health Advances
Elizabeth Russell, PhD Pioneered the use of bone marrow transplants
George Snell, PhD & Nobel Prize Recipient Discoveries of immune system function formed the
foundation for tissue and organ transplantation
Leroy Stevens, PhD Laid the foundation for modern stem cell research
1940s
1950s
1960s
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The Jackson Laboratory now… Basic Research, Genetic Resources, Preclinical Research Services, Education
Leading provider of genetically defined mice and services including pre-clinical research
World renown non-profit genetics research institute and international training center
Bar Harbor, ME
Sacramento, CA
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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 Changing Drug Discovery Landscape
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
Academia • Focused on early discovery/model development
• Generation of peer reviewed preclinical data
• Use of patents to maximize utility of new developments
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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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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
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
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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 • Obesity • Type 2 Diabetes • Cardiovascular disease • Phenylketonuria • Glycogen Storage Disease
Neurodegenerative/Neuromuscular diseases • Amyotrophic Lateral Sclerosis • Ataxia telangiectasia • Parkinsons’ disease* • Duchenne Muscular Dystrophy
Oncology • Xenograft (NCI-60 plus WSU-DLCL2 NHL cell line) • Orthotopic transplant • Spontaneous/genetic models • Teratoma pluripotency • Engraftment of human primary tumor samples*
Inflammation and autoimmune • Asthma • Arthritis • EAE-Multiple Sclerosis • Inflammatory Bowel Disease • Graft vs Host Disease* • Type 1 Diabetes
Skin disorders • Psoriasis • Contact Dermatitis • Alopecia
Blood disorders • Sickle Cell Anemia • Thrombocytopenia • Bleeding disorders
Regenerative medicine • Wound healing • Bone loss
7
*in validation
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• 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
General Methods and Procedures
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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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Leading Model for Humanization: NSG Strain name: NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ Common name: NOD scid gamma (NSG) Stock number: 005557
1
No B cells No T cells
Deficient in multiple cytokine signaling pathways
No complement 5 No NK cells
Reduced dendritic cell function
Webpage: http://jaxmice.jax.org/strain/005557.html
Online user discussion forum: http://community.jax.org/forums/5.aspx
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Leading Model for Humanization: NSG
2
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 potential of new stem cell lines
Available
STZ Induction Type 1 diabetes
Pancreatic Islet Replacement
Available
MPTP Model of Parkinson’s
Cell replacement In Development
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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We discover the genetic basis for preventing, treating and curing human disease, and we enable research and education for the global biomedical community.