1. science
2. medicine
3. medical research

The Children’s Hospital of Philadelphia®
A pediatric healthcare network
Bench
May 2003
to Bedside
RESEARCH AT THE CHILDREN’S HOSPITAL OF PHILADELPHIA
New NIH Grant Aimed at Training
Pediatric Subspecialists
Opportunities for basic and clinical
research relevant to pediatric populations
have never been greater. However, pediatric subspecialists willing and able to
conduct pediatric-based research are in
short supply, due, in part, to the insufficient training available to pediatric fellows
for establishing independent research
careers and becoming physician-scientists.
A training grant recently awarded to
Children’s Hospital aims to improve the
situation by providing fellows more
research experience than is the norm for
most pediatric subspecialty training programs and giving them the tools needed
to build research programs.
The 5-year, $1.2 million National
Research Services Award (“Training
Grant”) from the National Institute of
Child Health and Human Development
(NICHD) provides Children’s Hospital
with the funds to support 3 to 4 fellows
for 2 to 3 years of research training. The
program uniquely supports both basic
and clinical research in all areas of
research relevant to child health. In this
way, it complements other more discipline-focused training grants the Hospital
holds, as it is not tied to a specific
research area. Alan Cohen, M.D., physician-in-chief, serves as the principal investigator for this broad-based training program. David Pleasure, M.D., director of
the Joseph Stokes Jr. Research Institute,
serves as program director.
The major component of the training
program is the opportunity for fellows to
acquire research skills from mentors over
a sustained period of time. Expected to
devote 90 percent of their effort toward
research during this time, these trainees
will also have an opportunity to learn
more about biostatistics, ethics, hypothesis formation and study design through
formal coursework and in-house training
programs. Participants in the program
will be eligible to participate in the NIH’s
new debt repayment program.
The training faculty consists of 46
mentors from a variety of pediatric subspecialties who are productive investigators. The program offers fellows research
training in a wide range of basic and clinical research areas. Twenty-six of the mentors have medical degrees and will also
serve as role models for program participants.
The program will build upon the
Hospital’s strengths as a pediatric academic institution with an outstanding pool of
subspecialty fellows, experienced mentors
with cutting-edge research programs, a
well-supported and resource-rich research
environment and a proven tradition of
research training.
Katherine High, M.D., Becomes
Hughes Investigator
In recognition of her pioneering research, Katherine
High, M.D., director of hematology research at
Children’s Hospital, has been named a Howard
Hughes Medical Institute investigator. Dr. High is
one of 12 physician-scientists recently selected by
the prestigious research organization for major
accomplishments in patient-oriented research. Her
appointment to this prestigious position became
effective in March 2003.
Dr. High is internationally prominent for her studies
of the molecular biology of hemophilia. Over the
past decade, she has investigated a gene transfer
approach to treating hemophilia B. This approach
holds the potential for treating human disease at a
fundamental level by delivering therapeutic genes
directly into a patient’s cells.
In 1999, Dr. High’s research team showed that gene
therapy could achieve long-term improvement in
dogs having naturally occurring hemophilia. Based
on these studies, she and her collaborators have
undertaken human gene therapy trials seeking to
improve blood clotting in patients with severe
hemophilia B.
Established in 1953, the Howard Hughes Medical
Institute is a nonprofit medical research organization
that currently supports approximately 320 investigators throughout the United States. Based in Chevy
Chase, Md., the Institute conducts medical research
and supports science education in the United States
and biomedical scientists in other countries.
The most recent group of 12 investigators was
chosen because their combination of scientific expertise and medical training holds great potential for
translating basic science discoveries into useful
medical treatments.
New Research Employees
(1/16/03-3/31/03)
Welcome to the following new
research employees:
Accounts Payable
Clerk
Susan Jacobs
Research Associate
Alexander
Schlachterman
Administrative
Assistants
Jacqueline
Gibbs-Jones
Catherine Keating
Lelisha Rios
JoAnn Weiss
Research
Coordinator
Stephanie Sargent
Business Manager
John Josefowski
Research
Technicians
Stephanie Ciosek
Megan Erne
Jennifer
McCallum
Heather Mitchell
Kian Tian
Angelika Vilchez
Yanjian Wang
Kristin Wills
Jzng Tao You
Yi Zhang
Clinical Research
Specialist
Jason Catanzaro
Clinical Trials
Manager
Maria
Skotleski-Irwin
Data Entry
Operators
Lorraine Hunter
Eric Poe
Nurse Practitioner
Barbara Hieb
Operations
Manager
Kathleen Murphey
Research
Assistants
Stefani Brown
Aileen Imperial
Jean Rodwell
Kimberly Schadt
Tamika Scott
Research Data
Analyst
Marian Droz
Resource
Coordinator
Marisa DeJesus
School Readiness
Specialist
Lauri Jindra
Staff Accountant
Eboni Ealey
Stem Cell Transplant Advances Hold Hope for
Clinical Applications
Significant advancements in the use of stem
cells have been made by Children’s Hospital
investigators, paving the way for the potential
future use of the stem cell transplant procedure
to treat genetic diseases.
Along with his colleagues, Alan Flake, M.D.,
director of the Children’s Institute for Surgical
Science at Children’s Hospital, produced high
levels of transplanted, healthy stem cells in
mice while reducing the effects of graft vs. host
disease (GVHD), a serious side effect of cell
and organ transplants. Immune tolerance in
mice was achieved by combining prenatal
transplants of blood-forming cells with manipulated blood cells after birth. The technique
allowed donor cells to multiply without toxic
side effects. The finding could greatly broaden
the use of cell and organ transplants for genetic
diseases detected before birth, including
leukemia, sickle cell disease, muscular dystrophy, and some kidney and liver disorders.
Dr. Flake’s team used a prenatal procedure
called in utero hematopoietic stem cell transplantation (IUHSCT). The IUHSCT procedure first makes a recipient’s immune system
tolerant of low levels of donor cells; a second,
nontoxic procedure after birth provides a competitive advantage for the transplanted donor
cells, allowing them to multiply.
The second, postnatal step of the treatment
compromises host blood cells and allows the
donor cells to engraft themselves in the recipient’s bone marrow and bloodstream. Because
the prenatal transplant has made the host animal tolerant of donor cells, the postnatal procedure can be less toxic than conventional treatments that use harsh chemotherapy drugs or
high-dose radiation to wipe out the host’s existing immune system.
In one study, Dr. Flake used donor lymphocyte
infusion (DLI) as the postnatal treatment.
Currently used against some leukemias, DLI
supplies lymphocytes. In the other study, the
postnatal treatment was low-dose full-body
irradiation followed by bone marrow transplantation. GVHD was minimal during the DLI
study and did not occur in the other study.
The procedures achieved complete or nearcomplete chimerism – all or nearly all of the
animal’s blood cells were derived from the
donor stem cells, even though the donors were
not matched with the recipients. This marked
the first time that complete chimerism was
achieved across mismatched donors and recipients without using toxic therapy. If the strategy can be made to work in humans, there are
broad implications for treating human disease.
The studies, which appeared in related articles
in the August and September 2002 issues of
the journal Blood, were funded by grants from
the National Institutes of Health, the Muscular
Dystrophy Association, and the Ruth and Tristram C. Colket, Jr. Endowed Chair in Pediatric
Surgery at Children’s Hospital. Co-authors
with Dr. Flake on both papers were Satoshi
Hayashi, M.D.; William H. Peranteau, M.D.;
New Flow Cytometer in BSL3 Facility
Thanks to the receipt of a Shared Instrumentation Grant (SIG) from the NIH, the
Hospital’s BSL 3 facility has acquired an Ultrahigh Speed Flow Cytometer. A critical addition
to The Children’s Hospital's and the University
of Pennsylvania's research community, this stateof-the-art shared resource facilitates the study of
biohazardous agents, as well as ensures the ability to continue to work with human blood as
new and more restrictive federal regulations are
implemented.
Since the cytometer, frequently referred to as the
“Mo-Flo,” is located within the BSL 3 facility
Bench to Bedside
on the 12th floor of the Abramson Center,
access is limited to BSL 3 staff; no self-service
is permitted.
Terri Finkel, M.D., Ph.D., of the Division of
Rheumatology, was instrumental in preparing
the SIG proposal, leading the planning process
for renovating the BSL 3 facility and establishing the core’s services. We also wish to acknowledge Steven D. Douglas, M.D., of the Division
of Immunology and Infectious Diseases, and
colleagues at Children’s Hospital and the
University of Pennsylvania for their help
and expertise.
RESEARCH at The Children’s Hospital of Philadelphia
Monoclonal Antibody May Help Control
Crohn’s Disease
Crohn’s disease, a painful inflammation of
the gastrointestinal tract, affects more than
100,000 children in the United States, causing emotional and social difficulties in addition to its physical symptoms. A drug used
to treat adults with Crohn’s disease has
shown promise in treating children with the
disease as well. The drug infliximab, a monoclonal antibody, was found to be safe and
effective when used to treat children afflicted
with Crohn’s disease.
In addition to providing a potential new
treatment, infliximab may reduce the need
for steroids, which are associated with significant side effects. Some of the side effects of
the current treatments for Crohn’s disease –
corticosteroids and drugs that affect the
immune system – include acne, weight gain,
impaired growth, osteoporosis, the risk of
hepatitis and bone marrow suppression.
The study, a retrospective chart and database
review, was conducted by Robert Baldassano,
M.D., director of the Hospital’s Center for
Inflammatory Bowel Disease, and colleagues.
The investigators looked at 82 patients who
received monoclonal antibody treatment at
Children's Hospital. This study population
was the largest cohort of pediatric patients
receiving this treatment for Crohn's disease.
Forty patients were being treated with corticosteroid at the start of treatment with infliximab; 33 were eligible to participate. Nineteen of those 33 patients were able to discontinue corticosteroid usage. Few complications or problems were reported in the study,
providing strong evidence that short-term
use of infliximab may benefit children with
Crohn’s disease and may reduce the need for
streroid treatment.
Crohn’s disease is a chronic bowel disorder
characterized by inflammation of the gastrointestinal tract. Tumor necrosis factor
alpha (TNF-a), a protein produced by the
immune system, is among the causes of
inflammation. It is becoming a common
chronic pediatric disease, with the average
age of onset occurring much younger than
before. The average age for diagnosis is 1011 years, though it can also occur during the
adolescent and adult years. Symptoms may
include pain, severe abdominal discomfort
and more than 30 bowel movements each
day. Most children with the disease experience ongoing disease activity over the course
of their lives, which may be complicated by
the need for prolonged medication and
numerous surgeries.
Infliximab is a genetically engineered monoclonal antibody that acts against TNF-a.
Infliximab is engineered from both human
and mouse material.
Together with Dr. Baldassano, who is the
lead author of the study, investigators on the
study include Michael C. Stephens, M.D.,
Melissa A. Shepanski, M.S., Petar Mamula,
M.D., Jonathan E. Markowitz, M.D. and
Kurt A. Brown, M.D. The study was published in the January 2003 issue of the
American Journal of Gastroenterology.
Research Education and Training Specialist Hired
After a six-month internship with
Research Administration, Wendy
Williams, Ph.D., has joined Stokes
as a Research Education and Training
Specialist. In this role, Wendy works
with Madeline Alexander, Ph.D., director of Research Education, to develop
and implement training programs for the
Hospital’s research community. These
programs include training for working
with lab animals, special programs for
postdoctoral fellows and training programs for research coordinators.
Wendy earned a bachelor’s degree in
zoology from Howard University and a
doctorate degree in biology from Johns
Hopkins University. After completing
her degree, she spent a year conducting
molecular biology research as a postdoctoral fellow at the U.S. Department of
Agriculture and then came to Children’s
Hospital in 2000 for a postdoctoral
fellowship in oncology. The Research
Administration internship allowed
Wendy to explore alternative careers
in science.
HIPAA FAQs
Below are some frequently asked
questions (FAQs) about the effect
of HIPAA regulations on research.
Additional FAQs will be featured in
subsequent issues of Bench to Bedside.
How is it that one “may perform
most, if not all of [one’s] current
pre-screening activities” and remain
HIPAA compliant in the eyes of
Hospital’s Institutional Review
Board (IRB)?
If you are pre-screening to ascertain
the feasibility of conducting a research
study (prior to IRB approval of that
study), you must first submit a
“Review Preparatory to Research” form
to the IRB. To contact patients to
recruit subjects for a study, a protocol
must be in place that has been
approved by the IRB. Any investigator enrolling subjects with a written
consent form already in place after
April 14, 2003, needs a HIPAA
addendum form attached to the consent. A HIPAA attestation form must
be completed and returned to the IRB.
All forms are available from the
Regulatory Affairs office.
Does the Hospital have procedures
in place for reviews preparatory to
research? Must an application be
submitted to review charts, unit
censuses, procedure logs, etc. in order
to identify prospective subjects?
Yes, Children’s Hospital has procedures
in place. The IRB Web site features a
link to access a “Review Preparatory to
Research” form, which must be completed and submitted to the IRB when
reviewing charts prior to IRB approval
of a study.
Non-Traditional Research Personnel Registration
Academic collaborators, graduate students
pursuing rotations or thesis research, unpaid
research interns, federal work-study students,
and part-time student employees all play an
important role in the Hospital’s research programs and augment the efforts of Hospital
staff and faculty.
The Non-traditional Personnel (NTP) program was created to facilitate the inclusion
of these individuals in Hospital research
while respecting the need to know who is
conducting research in Hospital space, to
comply with institutional and legal requirements and to provide a safe environment for
all research staff.
Whether working in a laboratory or office
setting, these individuals must be registered
as NTP before they start working. How long
NTP registration takes depends largely on
whether an individual is informed in advance
of the necessary forms, signatures and health
records. When investigators/sponsors identify
an individual who will work in the Hospital’s
facilities or on a Hospital project (and fits
one of the NTP categories), the candidate
should be provided with the NTP registration forms, which are located on the Stokes
intranet under “Services and Support.” Parttime/temporary student employees must also
submit a CV, personnel requisition and a job
description.
Forms may be e-mailed in advance to NTP
personnel. Students may obtain the required
immunization information and current PPD
test results from their university student
health services and should seek the records
before arriving to begin work. Doing so saves
students the expense of visiting their family
FYI
Tech Transfer FY02 Stats: The Technology Transfer Department negotiated and executed
249 agreements in FY02, compared to 171 in FY00. Of these, 71 were confidentiality
agreements, 88 were material transfer agreements, 60 were clinical trial agreements, 12
were sponsored research agreements and 18 were negotiated on behalf of the Children's
Clinical Research Institute. In addition, during FY02 there were 37 invention disclosures
(16 in FY00); 34 provisional patent applications filed (9 in FY00); and 8 patents issued (4
in FY00). Technology fields currently listed for license include genetic/chromosomal alterations and their detection, gene therapy, immunology/infection, metabolism and nutrition, neurosciences, hematopoeisis, injury/safety, respiratory, implantable devices, protein
conformation, stem cell biology, tissue engineering, tumor biology and research tools.
Phone number changes: In April, the phone numbers for many departments changed
and now feature a 267 area code and a 426 dialing prefix. For internal dialing, these
extensions will be preceded by 6 instead of 4 (6XXXX). Despite this change, both 215590-XXXX and 267-426-XXXX numbers will continue to be used within the research
programs at both the Abramson Center and 3535 Market Street. All existing research
programs and research support services, with the exception of Research Finance, Research
Purchasing and Research Human Resources, will retain their currently assigned phone
numbers. All requests for new telephone numbers in research will receive a 267-426XXXX number.
We congratulate Gerald Travis for successfully completing the American Association of
Laboratory Animal Science’s Assistant Laboratory Animal Technician certification examination. Gerald joined the Environmental Services Department in July 1998 and transferred to the animal facility in April 2001.
Have News?
physicians to obtain the necessary information. Individuals who have previously reacted
positively to the TB test must bring a chest
X-ray or latest evidence of screening. Problems obtaining these records or taking new
tests is the single most frequent reason that
NTP registration is delayed.
Contact Carol Sazama (ext. 40563) or Marie
Ward (ext. 43800) for assistance in determining the appropriate NTP category or accessing the necessary materials. Information on
the purpose and nature of the anticipated
work and whether the individual will be paid
must be included in the forms to help determine the correct NTP category. All forms
should be submitted to Marie Ward.
NIH Salary Cap Increase
For more than a decade, Congress has
implemented a cap on the individual salary
amount that could be charged on NIH
awards. In recent years, the NIH appropriation bills have tied the grantee cap to the
salary provided by the federal government
to individuals qualified for the Executive
Level I salary. This year's NIH appropriations were signed into law in March. Until
the federal budget was finalized it was
uncertain whether the salary cap would be
in place for FY03 and, if so, whether the
cap would be tied to Executive Level I or a
lower federal employee grade, which would
reduce the level of the cap.
Those questions were resolved recently
by a notice issued in the NIH Guide of
March 21, 2002, which stated that the
NIH salary cap has been increased to the
new $171,900 Executive Level I salary that
went into effect January 1, 2003. This figure should now be used to calculate appropriate salary charges for those whose compensation meets or exceeds the salary cap.
Contact Jennifer Long at ext. 42105
or via e-mail at [email protected].
A pediatric healthcare network
34th Street and Civic Center Boulevard, Philadelphia, PA 19104-4399
1-800-TRY CHOP
www.chop.edu
Produced by the Joseph Stokes Jr. Research Institute for The Children’s Hospital of Philadelphia.
Copyright © 2003 by The Children's Hospital of Philadelphia.
3368/2,500/05-03
The Children’s Hospital of Philadelphia®