Translational Research:

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Translational Research Working as a Team We
Can Reach the Summit Leslie M. Shaw,
Ph.D. University of Massachusetts Medical School
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Translational Research

• Seminar Goals
• Define Translational Research
• Discuss why Translational Research is important
• Discuss how preparing a Translational grant
  differs from preparing a basic science proposal
• Discuss pre- and post-funding considerations for
  Translational Research grants

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Translational Research
NIH Roadmap for Medical Research To improve
human health, scientific discoveries must be
translated into practical applications. Such
discoveries typically begin at the bench with
basic research in which scientists study
disease at a molecular or cellular level then
progress to the clinical level, or the patient's
bedside. This bench-to-bedside approach to
translational research is really a two-way
street. Basic scientists provide clinicians with
new tools for use in patients and for assessment
of their impact, and clinical researchers make
novel observations about the nature and
progression of disease that often stimulate basic
investigations.
Basic Science
Patients
Source NIH Roadmap for Medical Research
http//nihroadmap.nih.gov/clinicalresearch/overvie
w-translational.asp
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Translational Research

• The NCI Translational Research Working Group
  (TRWG) defines Translational Research in the
  following way
• Translational research transforms scientific
  discoveries arising from laboratory, clinical, or
  population studies into clinical applications to
  reduce cancer incidence, morbidity, and
  mortality."

Source National Cancer Institute Translational
Working Group http//www.cancer.gov/trwg/TRWG-defi
nition-and-TR-continuum
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Translational Research

• Translational Research Project
• A project that characterizes the molecular
  mechanism underlying a pathology in the
  laboratory, determines a way to measure this in
  the human disease state in situ and develops a
  beneficial intervention in the clinic.
• Translational Researcher
• Aims to improve diagnosis or prognosis in
  patients
• Aims to improve prevention in patients
• Aims to conceive and execute a new treatment in
  patients
• Translational Team vs. Individual Investigator
• - Laboratory-based Investigators
• - Clinical Investigators
• - Statisticians
• - Research Nurses
• - Data Managers

Source http//www.nature.com/nm/journal/v8/n7/fu
ll/nm0702-647.html
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Translational Research

• Two Main NIH Funded Translational Roadmap
  Research Programs
• Clinical and Translational Science Awards (CTSA)
  Consortium
• - 12 awarded in October 2006 to academic health
  centers located throughout the nation
• - Increased to 24 in September 2007
• - When fully implemented in 2012, 60
  institutions will have been awarded CTSA grants
•  
• The purpose of the CTSA Program, which NCRR is
  leading on behalf of the NIH Roadmap for Medical
  Research, is to assist institutions to forge a
  uniquely transformative, novel, and integrative
  academic home for Clinical and Translational
  Science that has the consolidated resources to
  1) captivate, advance, and nurture a cadre of
  well-trained multi- and inter-disciplinary
  investigators and research teams 2) create an
  incubator for innovative research tools and
  information technologies and 3) synergize
  multi-disciplinary and inter-disciplinary
  clinical and translational research and
  researchers to catalyze the application of new
  knowledge and techniques to clinical practice at
  the front lines of patient care.

Source http//nihroadmap.nih.gov/clinicalresearch
/overview-translational.asp
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Translational Research

• Two Main NIH Funded Translational Roadmap
  Research Programs
• (2) Rapid Access to Interventional Development
  (RAID) 
• High-risk ideas or therapies for uncommon
  disorders frequently do not attract private
  sector investment. Where private sector capacity
  is limited or not available, public resources can
  bridge the gap between discovery and clinical
  testing so that more efficient translation of
  promising discoveries may take place. To help
  address this need, the NIH established a pilot
  program to make available, at no charge, certain
  critical resources needed for the development of
  new therapeutic agents. The NIH Rapid Access to
  Interventional Development (RAID) Pilot Program
  reduces some of the common barriers between
  laboratory discoveries and clinical trials for
  new therapies. The NIH-RAID Pilot will accept
  requests through 2011.

Source http//nihroadmap.nih.gov/clinicalresearch
/overview-translational.asp
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Translational Research
Other Translational Grant Opportunities By
communicating and collaborating with clinicians,
basic researchers can make a stronger case that
their contributions may lead to treatments for
mental or behavioral disorders, and, as such, are
translational, says Steven Breckler, PhD,
American Psychological Association's executive
director for science. The National Institute of
Mental Health (NIMH), for example, recently
created three divisions devoted entirely to
funding basic research that contributes to the
treatment of mental disorders--known as
"translational research. DOD Prostate Cancer
Translational Research Award (TRA) supports
translational research focused on a
health-related central problem or question in one
of the 21 FY08 PRMRP topic areas. Translational
research may be defined as an integration of
basic science and clinical observations.
Observations that drive a research idea may be
derived from a laboratory discovery,
population-based studies, or a clinicians first
hand knowledge of patients and anecdotal
data. The Epilepsy Research Foundation (ERF) and
the Milken Family Foundation today announced
three recipients of translational research funds
totaling over 250,000. The research awards are
designed to support exciting, innovative
therapies through laboratory research or early
clinical development and are being presented to
physicians and scientists actively advancing the
research with important, near-term patient
benefits.

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Translational Research
Other Translational Grant Opportunities The
Cooleys Anemia Foundation invites national and
international applications for 2009-2010 grants
in translational research in adult thalassemia.
The National Osteoporosis Foundation (NOF)
seeks to expand the understanding of osteoporosis
through its Research Program that awards annual
grants in support of projects in translational
and clinical research investigating the
epidemiology, pathogenesis, prevention, diagnosis
and treatment of osteoporosis. One of the
Polycystic Kidney Disease (PKD) Foundations
principal goals is the development of new
clinical interventions for the treatment of PKD.
Traditionally, the Foundation pursued this goal
through the support of basic laboratory research
aimed at increasing understanding of the genetic
and pathological processes involved in PKD. While
this remains an important strategy, recent
advances and extraordinary scientific momentum
have led the Foundation to conclude that it is
time to expand its funding programs to include
accelerating the translation of the most
promising basic science findings towards clinical
applications. Accordingly, the PKD Foundation has
established the Translational Research
Program. The V Foundation for Cancer Research
has announced the recipients of the 2007 V
Foundation Translational Research Grants.
Translational research serves as a bridge between
the lab bench discoveries and the patient
bedside. Information collected at the patient
bedside can circle back to the laboratory to fuel
additional discoveries.

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Translational Research
Other Translational Grant Opportunities The
Leukemia Lymphoma Society's (LLS) Translational
Research Program (TRP) was established to
encourage and provide support for new and novel
clinical research. The goal of the program is to
accelerate transfer of findings from the
laboratory to clinical application. The program's
purpose is to fund research that shows high
promise for translating basic biomedical
knowledge to prevention or new treatments and,
ultimately, to prolong and enhance
life. Foundation for Digestive Health and
Nutrition One award will be made to support
translational research in gastroenterology and/or
hepatology. Translational research will be
defined as the process of applying ideas,
insights and discovery generated through basic
science research to the diagnosis, treatment or
prevention of human disease. This award must be
applied for jointly by a team of researchers
including at least one researcher with
significant training and experience in a basic
science discipline and at least one researcher
who is qualified to provide direct clinical care
to patients.

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Translational Research
The IRS Proteins and Herceptin
Resistance Synergistic IDEA Award Department
of Defense Breast Cancer Program Co-PIs Leslie
Shaw, Ph.D and Ashraf Khan, MD Collaborator
Kathy Edmiston, MD Brought together a research
team that includes a basic scientist and two
clinicians. Goal is to determine if the
expression of the IRS proteins can predict
clinical outcomes
Pathologist
Basic Scientist
Medical Oncologist
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Translational Research
Major Goals of the Grant Evaluate the impact of
the IRS proteins on HER2 function using human
cell lines and mouse models of mammary
tumorigenesis (Basic Science component). Examine
the expression of the IRS proteins in human HER2
positive breast tumors and assess correlations
with patient outcomes (Basic Science/Translational
component). Enroll patients in a prospective
trial to evaluate the impact of the IRS proteins
on response to Neo-adjuvant Herceptin therapy
(Clinical/Translational component).
Basic Scientist
Pathologist
Medical Oncologist
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Translational Research
What are the funding considerations for
translational grants? Evaluate the impact on the
IRS proteins on HER2 function using human cell
lines and mouse models of mammary tumorigenesis
(Basic Science component). Personnel
Laboratory supplies Animal purchase/housing
costs Travel Core facilities charges Approvals I
ACUC (Title of protocol may need to match the
title of grant or obtain letter of
concurrence) Biosafety
Basic Scientist
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Translational Research
What are the funding considerations for
translational grants? Examine the expression of
the IRS proteins in human HER2 positive breast
tumors and assess correlations with patient
outcomes (Basic Science/Clinical
component). Personnel Clinical vs.
academic salaries? Laboratory supplies Travel Core
facilities charges Approvals IRB (Exempt or
Non-exempt?) If using discarded tissue with no
identifiers, exempt. If associated with
patient outcomes, might require full IRB
protocol. Biosafety
Pathologist
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Translational Research
What are the funding considerations for
translational grants? Enroll patients in a
prospective trial to evaluate the impact of the
IRS proteins on response to Neo-adjuvant
Herceptin therapy (Clinical/Translational
component). Personnel Clinical vs.
academic salaries? Procedure costs If
independent procedure is performed for the
purposes of the grant it cannot be charged to
insurance. Must account for this in the budget
of the grant. Patient costs not included in
indirects. Approvals IRB Full IRB protocol
is usually required. Patient consent and
enrollment required. Must anticipate the
number of patients that will be required and
demonstrate the feasibility of enrolling enough
patients. Logistics Scheduling patient visits.
Separate visit for purposes of the grant or
combined with normal patient appointment?
Medical Oncologist
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Translational Research
Translational Research Grant vs.
Clinical Research Grant Includes a basic
science component No basic science
component Research team includes Laboratory-base
d Investigators Clinical Investigators Clinical
Investigators Statisticians Statisticians
Research Nurses Data Managers Scale of
clinical trial Generally small scale, proof of
concept Can be small or large
scale
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Translational Research

• How do you develop a Translational Research
  collaboration?
• Communication between basic scientists and
  clinicians is essential
• 1) Establish working groups with common
  interests
• 2) Develop a seminar series that focuses on a
  specific disease topic
• At UMass Medical School we organized disease
  based translational research conferences that
  brought together basic scientists and clinicians
  with common interests. From this group we
  developed the DOD Synergistic Award.
• Identify grant mechanisms that will support
  Translation Research
• 1) Basic scientists and clinicians can seek out
  collaborators if there is a specific grant that
  requires a research team

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Translational Research

• Where do you go to find Translational Research
  Grant opportunities?
• Community of Science (http//www.cos.com)
• Find funding with COS Funding Opportunities
• Search the world's most comprehensive funding
  resource, with more than 25,000 records
  representing nearly 400,000 opportunities, worth
  over 33 billion.
• 14,000 opportunities listed under Translational
  Research
• GoogleTranslational Research Grants