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Presentation by Dr. Richard Longeras to members of the New Orleans bioscience community. Hosted by BioDistrict New Orleans on Tuesday March 29, 2011.
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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
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
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
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
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
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
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
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
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
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
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
• 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
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
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
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)
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
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.
We discover the genetic basis for preventing, treating and curing human disease, and we enable research and education for the global biomedical community.
