Innovation Enabled by Flow Cytometry Center
Keck Graduate Institute of Applied Life Sciences
PI: James D. Sterling
Co PIs: Jim Osborne, Angelika Niemz, Ziyad Duron, Elizabeth Orwin
NSF Award #IIP- 0917906
3 Year Award
Start Date: 1 August 2009
Brief Project Overview:
Key Attributes of our
Innovation Ecosystem:
This translational and collaborative PFI project involves industry (Beckman Coulter, Inc. (BCI)), a nonprofit organization (National Organization of Rare Disorders (NORD)) and academia (Harvey Mudd
College (HMC) and Keck Graduate Institute (KGI)) to educate translational scientists and to discover
and commercialize new disease-specific biomarkers. As part of the proposed work, we have
established the Center for Biomarker Research (CBR) on the KGI campus and have equipped the
facility with analytical instruments, including a flow cytometer. Research in CBR will focus on
development and validation of biomarker assays for rare diseases. A database of biomarkers is being
created and will provide a means for classifying and stratifying disease populations. The entire
database of biomarkers and disease characteristics will be accessible to the academic and corporate
communities for data mining. CBR will select diseases for further study from the database that have
effective therapies, but are difficult to diagnose due to a lack of specific biomarkers, and work with
NORD, patient advocacy groups and the medical community for access to biospecimens. The Center
will educate Master of Bioscience students at KGI and undergraduate engineering students at HMC in
the development of diagnostic tools for biomarker discovery. The students will learn to operate in a
Good Laboratory Practice (GLP) facility that handles human samples, an experience that provides
excellent preparation for the industrial laboratory work environment. The protocols for the GLP facility
will be adopted from existing BCI standard operating procedures and BCI will assist in their full
implementation. Through exposure to this facility, the students will gain valuable hands-on experience
in quality assurance, assay validation and regulatory compliance, areas that are not commonly
addressed in an academic setting. HMC and KGI will arrange for 3-4 students per year to participate
in a 10 week summer undergraduate research program at KGI, engaging in team based research
related to the PFI award. Dr. Niemz, Dr. Orwin and Dr. Osborne will collaborate on integrating PFI
related topics to existing courses at HMC and KGI. Relevant courses include: Engr164/Biol164Introduction to Biomedical Engineering; ALS320-Medical Diagnostics; ALS301-Molecular Basis of
Disease; ALS408-In Vitro Diagnostics; ALS409-High Throughput Technologies.
Questioning & Curiosity:
• Rare Diseases are defined as those with fewer than
200,000 cases per year in the US
• The Orphan Drug Act creates seven year market
exclusivity for new therapeutic products for rare
diseases
• However, diagnosis of many of the known 6000-7000
rare diseases is very difficult
Risk Taking:
Program Activities:
• Patient risk: we may not find a useful biomarker for
particular diseases, resulting in continued poor diagnosis
• Commercialization of biomarkers: no guarantee that
certain biomarkers will be commercialized due to low
prevalence of rare diseases
Openness:
•
A public domain containing a searchable biomarker
database for rare diseases will be available for the
academic and industry sectors
•
KGI will apply for patents on identified biomarkers to
facilitate commercialization
•
KGI is open to collaboration with companies interested
in commercial development of identified biomarkers
Collaboration Across Fields:
Disease description: Hereditary Inclusion Body Myopathies (HIBM) are a diverse group of muscle
wasting disorders that share similar histopathology with sporadic Inclusion Body Myositis and
senile plaques seen in Alzheimer's brain disease. Although histologically similar, various forms of
HIBM are genetically and clinically diverse. The autosomal recessive form (IBM2) is the most
common. It usually affects young adults, between the age of 20-35 years, and often leads to
severe disability and confinement to a wheelchair in 10-15 years. Although worldwide it is an
“orphan” disease, IBM2 is most prevalent amongst people of Iranian-Jewish heritage due to a
common founder mutation (GNE:p.M712T), accounting for a carrier frequency of 1-2 in 20, and an
prevalence of 1-2 in 1000 persons. IBM2 is a recessive genetic disorder, which means it can
happen to anyone, even without family history of the disease. Most of the patients have healthy
parents who were carriers of the disease without knowing -- the patients and their families had
never heard of IBM2 prior to their devastating diagnosis.
HRG: HIBM Research Group (HRG) is a California non-profit public benefit corporation, founded
by Dr. Daniel Darvish, engaging in medical research on HIBM. Over the past few years, HRG has
established a depository center for maintaining and distributing reagents and resources necessary
for research on IBM2. They have formed fruitful collaborations with biomedical investigators at
universities and at the National Institutes of Health. The major goals of HRG are: 1) further
clarifying the molecular mechanism that leads to IBM2 muscle damage, 2) prevention of muscle
damage cause by IBM2, and 3) muscle regeneration.
HRG and KGI collaboration: As in many rare disorders, for IBM2 there is a significant need to
develop biomarkers that can be useful in clinical and molecular evaluation of the disease. Such
biomarkers will allow us to monitor progression of the disease and determine the effectiveness
therapy early in clinical trials, which may translate to significant cost and time savings. KGI and
HRG have begun a team oriented effort to develop and validate IBM2 specific biomarkers.
Partners:
To address roadblocks in innovation and commercialization,
a unique partnership is formed between:
• Keck Graduate Institute and Harvey Mudd College
(Academic) providing the expertise and space for
facilities
Top Contributions:
• National Organization of Rare Disorders (Non-profit) with
access to patient advocacy groups
1. Adding flow cytometry and DNA sequencing
capabilities in a Good Laboratory Practice
facility on the KGI campus
• Beckman Coulter, Inc. (Corporate) providing
standardized operating procedures and analytical
instruments for biomarker analysis
2. Education of the medical community on the
molecular basis of disease, which is
fundamental to adoption of personalized
medicine
• FDA-Center for Rare Disease Therapy Workshop on
Orphan Drug Applications
3. Development of intellectual property for
entrepreneurial activity and licensing
opportunities for rare disease diagnostics and
therapies
Top Challenges:
1. Identifying diseases that have effective
therapies, but poor diagnostic biomarkers
Placing Partners in “New
Environments” & “Playgrounds”:
Goal: to bridge the gap between discovery and
commercialization, enabling a crucial discovery to translate
into a useful product that will improve the lives of the many
people with rare diseases
2. Securing the necessary biospecimens for
testing
3. Creating a biomarker database that contains
information useful for educational purposes as
well as for return on investment in commercial
applications
.
National Science Foundation Partnerships For Innovation
.
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Grantee’s
Meeting
April
25-27,
2010
Arlington, VA
PFI