CTN POSTER FORMAT

1
The Center for Translational Neuroscience after 4
years E Garcia-Rill, PhD Center for
Translational Neuroscience, Department of
Neurobiology and Developmental Sciences,
University of Arkansas for Medical Sciences,
Little Rock, AR
Major Discoveries, New Treatments, Patents
MENTORED SCIENTISTS
RESULTS
ABSTRACT

• Investigators-
• John Dornhoffer, MD, mentored by the Year 1
  Recruit M. Mennemeier, PhD,
• 2) Alice Fann, MD, mentored by E. Garcia-Rill,
  PhD, in Year 1, then by the Year 2 Recruit
• E. Al-Chaer, PhD,
• 3) R. Whit Hall, MD, mentored by K.J.S. Anand,
  MD, in Year 1, then by E. Garcia-Rill, PhD,
• 4, 5) Thomas Kiser, MD, and Nancy Reese, PT, PhD
  (UCA), mentored by Visiting Mentor,
• S. Mori, MD, PhD, and Robert Skinner, PhD,
• 6) Melanie MacNicol, PhD, mentored by Gwen
  Childs, PhD, Chair Neurobiology Dev. Sci.,
• 7) Jeffery R. Kaiser, MD, became Replacement
  Investigator mentored by Year 3 Recruit,
• Hayar, PhD,
• 8) Catherine Cole, RN, mentored by Year 1 Recruit
  M. Mennemeier, PhD,
• 9) Michael Mancino, MD, co-mentored by Drs.
  Allison Oliveto, PhD, and Edgar Garcia-Rill,
• PhD,
• 10) Charlotte Yates, PT, PhD (UCA), mentored by
  Edgar Garcia-Rill, PhD,
• William Fantegrossi, PhD, mentored by Michael
  Borrelli, PhD, will become a Replacement
• Investigator in Year 5.
• Pilot Study Awardees-
• Yi-Hong Zhou, PhD, received the Year 1 Pilot
  Study award,
• Mary Aitken, MD, Year 2 Pilot Study award,
  mentored by M. Mennemeier, PhD,

Objective Our aims were to establish 1) a Career
Development Program with mentoring/funding for 5
projects and 6 promising investigators without a
history of support, 2) a multi-disciplinary
Center, a Pilot Study Program, and recruitment
of two senior and three junior investigators to
build the critical mass of researchers, and 3)
two Core Facilities, Administrative and
Experimental, to support research. All aims
were met and exceeded. Methods We developed a
Career Development Program and Center so that
promising clinician and basic scientists could be
mentored to secure funding. Results We have
mentored and supported 10 promising
investigators without a history of support. In
addition to funding 5 projects and 6
investigators with designated Mentors, we
provided access to Core Facilities to 4 other
investigators, and assigned them Mentors to help
guide their efforts. We awarded 5 instead of 4
pilot study grants and assigned Mentors to each
recipient to improve output. We recruited 3
senior and 2 junior faculty and established 6
(instead of 2) new Core Facilities. We
discovered two new cures, two novel treatments
and one new mechanism, all with clinical
implications. We generated gt12 million in new
awards, published gt100 articles and gt100
abstracts. Discussion and Conclusions The
oversight of a dedicated external advisory
committee and considerable institutional support
were critical to our success, along with
selfless mentoring by dedicated senior
scientists.

• 1) We found (Project I- Dornhoffer, Mennemeier)
  that TMS could alleviate tinnitus for weeks at a
  time, but, more importantly, have now developed a
  treatment that produces virtually permanent
  symptom relief after 1-3 treatments. A case
  report is in press but several other patients
  have already been found to respond.
• 2) We found (Project III- Hall, Anand,
  Wallace-Huitt) that ex-preterm adolescents show a
  spectrum of arousal, attentional and frontal lobe
  flow disorders that segregate into three distinct
  groups who require treatment with different
  drugs. The ability to diagnose these
  sub-populations will improve therapeutic
  outcomes. An intervention designed to reduce
  these deficits will be incorporated into future
  studies in order to apply the finding to the
  clinic.
• We found (Project IV- Kaiser, Reese) that passive
  exercise could eliminate hyper-reflexia in spinal
  cord transected rats, and developed a device for
  testing in humans, the Motorized Bicycle Exercise
  Trainer (MBET). A patent was secured and
  licensed to Ozark Systems Manufacturing, Siloam
  Springs, AR, which is manufacturing and selling
  the MBET.
• We found (Project IV- Reese, Yates) that
  treatment with a stimulant that increases
  electrical coupling led to elimination of
  hyper-reflexia in spinal transected rats. A
  patent for the novel use of this agent was filed.
  A number of grant applications have resulted
  from this finding that are under review.
• 5) We found (Mennemeier, Garcia-Rill) that
  spatial neglect due to large strokes of the right
  hemisphere, which typically do not resolve as do
  left-sided damage, can be totally alleviated by
  modafinil, a wake-promoting agent, within days.
  Spatial neglect due to right hemisphere stroke
  has been assumed to be untreatable, but every
  patient to date has responded positively.
• 6) We found (Charlesworth, Heister, Hayar,
  Garcia-Rill, Ye) that cells in the reticular
  activating system controlling sleep and waking
  are electrically coupled, leading to novel
  treatments for several disorders. Since some
  anesthetics block gap junctions and a new
  stimulant increases electrical coupling, the role
  of coupling becomes a new mechanism for
  sleep-wake control. This discovery was featured
  in the Fall 2007 issue of NCRR Reporter. The
  implications of this discovery and the potential
  for novel therapies for sleep and psychiatric
  disorders will be explored.

PERFORMANCE MILESTONES

• Every Project PI must submit a grant application
  by the end of the second year of funding or
  before. Outcome Access to the Office of Grants
  and Scientific Publications at UAMS was supported
  by the CTN in order to optimize style and
  organization. This milestone was met by all
  investigators without exception.
• Such applications must be submitted to the
  Director two months before the deadline to allow
  internal and/or external reviews prior to
  submission. Outcome This milestone was not met,
  requiring flexibility on the part of the Director
  and the Mentor, mainly to reduce stress and
  promote a more nurturing environment. A one
  month deadline was set.
• If such an application is not submitted, the
  Director and the IAC, will work with the Project
  PI to determine the cause(s) and find solutions.
  a timetable will be set up to ensure timely
  progress, to be monitored by the Director. the
  Director and the IAC may decide that funding will
  be terminated, if the EAC and NCRR also concur
  will a replacement Project PI be sought.
  Outcome We did terminate funding of two
  investigators due to lack of progress, but did
  not need to do so in any other case due to our
  successes in funding.
• If the application submitted is not funded, a
  resubmission by the end of the third year of
  funding will be required. Outcome This
  milestone was met by all investigators.
• If the application is funded, the Project PI will
  be considered to have graduated from the
  program and will retain access to the Cores,
  unless the funded grant is in a different area.
  In that case, the obligations of the Project PI
  will continue, requiring an additional
  application by the end of one additional year of
  funding in order to maintain CTN funding.
  Outcomes Project I. We continue to fund
  Dornhoffer, who received one award and has
  promising additional results using TMS to cure
  tinnitus. Project II. We replaced Fann, who left
  UAMS, with two Pilot Study awardees for the rest
  of the grant year, Charlesworth, who received
  funding for a parallel line of research and
  became Director of the Molecular Biology Core,
  and Fantegrossi, who will be a Replacement
  Investigator next year. Project III. Hall
  received funding for his Neopain Project, but
  has become Director of the CoBRE Core Facility
  and will seek funding for a Center for community
  based research and education. Kaiser became
  Replacement Investigator for Project III, and
  immediately secured R01 support. Project IV. We
  ceased funding the human component of the spinal
  cord injury project due to recruitment problems
  and lack of progress (Kiser), but the animal
  component (Reese, Yates) keeps publishing and
  submitting scored applications. Project V.
  MacNicol has received considerable funding as
  Co-I, and has applications pending on this
  Project. Pilot Study Awards All of the
  awardees were assigned Mentors in order to
  expedite their research. Other Investigators
  Three other investigators were assigned Mentors
  and provided support by the CTN Cores.

INTRODUCTION
The original aims of the Center for Translational
Neuroscience (CTN) included the establishment of
? a Career Development Program with mentoring
and funding for 5 projects and 6 promising
investigators without a history of support to
make them competitive for independent funding,
? a multi-disciplinary center, a Pilot Study
Program, and recruitment of two senior and three
junior investigators to build the critical mass
of researchers at the CTN, and ? two Core
Facilities, Administrative and Experimental, to
support research by CTN investigators. All of
these aims were met and exceeded, as described
below.
CORE FACILITIES
NEW GRANTS

• Core Facilities- The need for flexible and
  diverse Core Facilities is perhaps greater when
  performing translational research on clinical
  populations and parallel studies in animals. The
  challenge has been to develop Cores that use
  complementary techniques and preparations. The
  originally proposed 2 Core Facilities,
  Administrative and Experimental, were increased
  gradually such that the Experimental Core was
  expanded into
• 1) a Human Electrophysiology Core (P50 evoked
  potential, reaction time and frontal lobe blood
  flow measures, including a mobile unit for
  on-site recordings, along with a satellite
  facility for spinal reflex testing), an ancillary
  Animal Electrophysiology Core (P13 evoked
  potential, reflex testing, and surgical
  capacity), and
• 2) an Image Analysis Core (confocal and
  fluorescence microscopy, freezer and contributed
  equipment in the form of a cryostat, baths,
  incubators and hoods for immunocytochemistry) in
  Year 1. In Year 2, we established
• 3) a Transcranial Magnetic Stimulation (TMS)
  Core (in Year 5, we will develop our capacity to
  use TMS on animals by purchasing equipment for
  our Animal Electrophysiology Core), and began
  purchasing equipment for the
• 4) Molecular Biology Core, which was completed
  and became operational in Year 3. Also in Year
  3, we expanded the Animal Electrophysiology Core
  to include patch-clamp recordings with image
  analysis of calcium and voltage-sensitive dyes,
  and established the
• 5) Community Based Research and Education Core,
  which was expanded in Year 4 (partly using a
  Supplement from NCRR) to include real-time
  teleconferencing and diagnostic quality imaging
  equipment for 15 rural hospitals and a central
  Mediasite facility at Arkansas Childrens
  Hospital. W have accomplished in a few short
  years the ability to perform research on
  molecular, cellular, system, individual and
  community based research, providing the basis for
  comprehensively addressing clinical problems form
  the lab to the bedside (T1) and the clinic to the
  community (T2). We have become a truly
  translational neuroscience research hub.
• 6) The Administrative Core is managed by an
  experienced administrator, Ms Linda Luster, MS,
  with gt20 years experience in UAMS administration.
  Accounting, purchasing, payroll, travel,
  functions, personnel and other matters are
  efficiently handled with grace and on a timely
  basis. The highly organized procedures we have
  developed are now finely honed and productive.

New Grants brought into the CTN
Recruits Mentored Investigators TOTAL
Year Name Amount () Name Amount
() 8/04-7/05 Mennemeier 1 256,960
Mennemeier 2 142,000 Mennemeier 3
15,000 413,960 413,960 8/05-7/06
Al-Chaer 1 335,362 Al-Chaer 2
400,425 Al-Chaer 3 132,438
Al-Chaer 4 232,648
1,100,873 1,100,873 8/06-7/07
Hayar 1 1,000,000 Dornhoffer 1 300,000
Hayar 2 150,000 Cole 1 142,900 Cole
2 283,838 Cole 3 15,000 Cole 4
31,481 1,150,000 773,219
1,923,219 8/07-4/08 Al-Chaer 5
221,550 Aitken 1 50,000 Al-Chaer 6
249,669 Aitken 2 741,000 Al-Chaer 7
1,250,000 Aitken 3 594,642 Mennemeier
100,000 Aitken 4 749,963 Aitken
5 168,000 Charlesworth 1 600,000 Hall
1 1,800,000 Kaiser 1
2,131,535 1,821,219
6,835,140 8,656,359
Cumulative total 4 years
12,094,411 Letter of award not yet received
METHODS
We designed a Career Development Program with an
a) Established Mentor Program identified local
established basic and clinician scientists in the
areas of expertise of our promising scientists
and facilitated their collaboration using Project
grants, Pilot Study grants and support at no
charge from our Core facilities, including
subsidizing technical help and supplies. We
assigned established Mentors to our Pilot Study
awardees and Core users and expanded our
mentorship of promising scientists from an
initial 6 to 14 promising investigators b)
Visiting Mentor Program We invited a retired
senior scientist to help mentor one Project for
two six-month periods over two years with great
success. The majority of these costs were
incurred from departmental sources c) External
Speaker Program A total of 4-5 lectures per
year were held. Interspersed with these
lectures, Investigators presented their findings
to the CTN, and included Bench-to-Bedside
seminars in which a clinician and a basic
scientist presented an integrated view of the
same problem/project d) Biostatistics and
Experimental Design We established a formal
process for experimental design and power
analysis in the drafting of grant applications
and experiments, as well as advice and
participation in reporting and publishing
results e) Grant writing We used UAMS yearly
grant writing workshops and the Department of
Neurobiology Grant Strategy Sessions for
critiques both in advance of applications and for
resubmissions. Oversight by an External Advisory
Committee (EAC)- included two COBRE PIs, E.
Anderson, MD, PhD (Univ. Oklahoma) and S.
Whittemore, PhD (Univ. Louisville), as well as
established nationally recognized scientists such
as D. Humphrey, PhD (Emory Univ.) and W. Willis,
MD, PhD (Univ. Texas Med. Branch), and retired
NIH SRA K. Murray, PhD and an Internal Advisory
Committee (IAC)- included the Chairs of the
departments involved, Neurobiology (G. Childs),
Pediatrics (D. Fiser/R. Jacobs), Physical
Medicine Rehabilitation (K. Means),
Otolaryngology (J. Suen), and recently
Pharmacology (N. Rusch). Our EAC and IAC were
extremely helpful in a number of sensitive areas
including funding decisions, granting of faculty
positions for Recruits, support for space needs,
and in the response to recruitment and retention
issues.
Conclusions
Our progress during the first funding period has
been exceptional, having exceeded our aims by
mentoring almost three times the number of
investigators as initially proposed,
establishing three times the number of Cores
originally envisioned, and securing three times
the amount of extramural support estimated.
The numbers of articles or chapters published
(gt120), abstracts or presentations done (gt150),
and grants submitted and funded by Investigators,
Recruits and other faculty supported by the CTN
are increasing in number and success rate. We
have learned as much as we have taught and are
having a dramatic impact in the careers of our
young scientists as well as our seasoned Mentors,
and are changing the way our research is
disseminated and applied to improve the health
of our citizens. We now know better how to
mentor and execute our charge more efficiently.
We believe we can become a model national
system for translational research, given
continuing support from our previous reviewers,
who can feel proud of our accomplishments to
date, and from our current reviewers, who can be
assured of the great potential the future holds
for the CTN and its promising investigators.
S
SUPPORT
NCRR Grant RR020146 to the Center for
Translational Neuroscience