A Proposal for a
Center for
Regulatory and Environmental
Analytical Metabolomics
By
Dr. Teresa Fan
Associate Professor
Department of Chemistry
University of Louisville
Louisville, KY 40292
502.852.6448
502.852.6448
[email protected]
TABLE OF CONTENTS:
Purpose of CREAM .......................................................................................................... 3
Center Organization .......................................................................................................... 4
Needs of Center................................................................................................................. 5
Space Requirements .......................................................................................................... 6
Equipment/Resources ....................................................................................................... 6
Funds Needed.................................................................................................................... 7
Source of Revenue ............................................................................................................ 7
Evaluation ......................................................................................................................... 7
Written Statement from A&S Dean, University Libraries........................................... 9-11
Form 1 ............................................................................................................................. 12
Form 2 ............................................................................................................................. 16
Appendices ................................................................................................................. 18-24
Faculty curriculum vitae ............................................................................................ 25-37
2
1. PURPOSE OF CREAM
The University of Louisville has been awarded a large NSF/EPSCoR infrastructure grant ($3,628,951)
headed by the Department of Chemistry, to establish the proposed Center for Regulatory, Environmental,
Analytical Metabolomics (CREAM). The grant’s “Metabolomics Initiative” outlines CREAM’s mission to
develop cutting-edge methodologies, approaches, and applications for the emerging discipline of
“Metabolomics” to support systems biochemical research. Metabolomics has the potential to revolutionize
biological research in the 21st century by their ability to tackle biological complexity. Thus, metabolomics
development will find applications in a broad array of pressing societal problems ranging from human
health (e.g. cancers, cardiovascular disorders, diabetes, emerging bioweapons, and infectious diseases),
biotechnology (e.g. biofuel production), to environmental pollution (e.g. air pollution & toxicity) and
ecosystem health.
Initially, the Center will work closely with the core faculty involved directly in the NSF/EPSCoR grant,
who are members of the Department of Chemistry (Teresa Fan, Richard Higashi, George Pack, Robert
Buchanan, Cecilia Yappert, Craig Grapperhaus) (College of Arts and Sciences), the J. Graham Brown
Cancer Center (Donald Miller, Andrew Lane), Department of Pharmacology and Toxicology (William
Pierce), and Department of Biochemistry and Molecular Biology (Kenneth Ramos) (School of Medicine).
In addition to the NSF core faculty, the Center will also collaborate and serve the need of those member
faculty listed in section 2. This diverse and talented group of investigators has a wide range of biological
and chemical expertise for investigating a broad array of metabolic questions across multiple biological
scales of organization. The inaugural portfolio of research ranges from plant stress functions, host-pathogen
interactions, to carcinogenesis, cancer prevention/therapeutics, and oxidative stress which is key to cancers,
aging and many other important biological disorders.
It has been challenging to resolve the complex mechanism(s) underlying the above research problems with
conventional single-purpose approaches. The metabolomics development and our express goal of
integration with other “’omics” technologies (i.e. genomics and proteomics) will help circumvent this
difficulty by enabling integrative, multi-purpose approaches. Such state-of-the-science developments
require the concerted effort of a Center staffed by scientists having enabling expertise and state-of-the-art
facilities. The NSF/EPSCoR grant provided the core of the instrumentation resources, and spurred further
human resources. These include the addition of two new faculty members (Dr. Richard Higashi and a
BiochemoInformatic faculty, under recruitment), one mass spectrometer (MS) manager (recruitment nearly
completed) and a set of state-of-the-science MS instruments: MS-filtered Fourier transform–MS (MS-FTMS); inductively coupled plasma mass spectrometry (ICPMS) with LC and laser ablation capabilities;
isotope-ratio MS (irMS) with liquid introduction capabilities; a GC-tandem MS (GC-MSn); and a “training”
liquid chromatography-MS (LC-MS). These resources are housed in the new Belknap Research Building
with space custom-renovated for accommodating the new instruments (see section 4 for an example).
The proposed CREAM blended with existing infrastructure strength (Dr. Andrew Lane and the 18.8 T NMR
spectrometer obtained from a previous EPSCoR grant) will place UofL in a unique position to lead
development in metabolomics. Such leadership, in turn, will enable those UofL and Kentuckian researchers
who utilize the Center resources to maintain a competitive edge in attracting extramural funds and
collaboration. The basic knowledge to be gained from such a holistic approach should also lend itself to
innovative and groundbreaking commercial development
3
2. CENTER ORGANIZATION
Director
Dr. Teresa Fan, Department of Chemistry, will devote 10-20% of effort (annually variable) to directing the
Center scientific and technical developments. Dr. Fan has over 20 years of research experience in
metabolomics. Together with Drs. Higashi and Lane, she pioneered the combined use of nuclear magnetic
resonance spectroscopy (NMR) and tandem mass spectrometry (MS) in metabolite profiling for
investigating stress metabolism in a variety of biological systems. In the last years, she developed an
integrative approach that links metabolomics with transcriptomics to greatly extend the utility of either
omics technology in systems biology.
Associate Director of Mass Spectrometry Development
Dr. Richard Higashi, Department of Chemistry, will devote 15-50% of effort (annually variable) to directing
the mass spectrometry application for metabolomics. Dr. Higashi has started at UofL Feb., 2006. He
pioneered the GC-MS development for metabolite profiling and over the last two decades, he has applied
various other MS platforms to environmental systems biology and chemistry. His directorship is crucial to
expanding the development of MS applications in metabolomics. He has been responsible for the evaluation
and installation of the new instrumentation.
Associate Director of NMR Development
Dr. Andrew Lane, J. Graham Brown Cancer Center, will devote 5% of effort (0.6 months) for directing the
NMR application for metabolomics. Dr. Lane has an international reputation in biological NMR. He has
been instrumental in NMR methodology development for metabolite profiling. His directorship is crucial to
further development of NMR applications in metabolomics.
Broader Impacts of the Director and two Associate Directors
In addition to the individual credentials, the Director and two Associate Directors have a collective impact
on international metabolomics efforts, as follows.
All three are:
 Founding members of Metabolomics Society
 Members of Editorial Boards on 3 Int'l Journals
 Organizers of 2nd & 3rd Metabolomics Society Meetings
 Organizer of the 1st and 2nd Louisville International Environmental Metabolomics Symposium
 Members of NIH Metabolomics Reporting Standards Committee
 Invited Presenters at five National Workshops on Metabolomics
 Editors of Metabolomics Handbook
(Methods of Pharmacology & Toxicology Series, Humana Press)
 Authors of a planned metabolomics textbook (Wiley)
Two are:
 Editorial Board of Metabolomics J. (Springer)
 NSF Grants Panel - Metabolic Biochemistry
 Organizers, Metabolomics Analytical Workshop (June '06, '07)
BiochemoInformatic Development
A tenure-track faculty who is under recruitment will devote approximately 50% of effort in developing
automated data analysis for NMR or MS.
4
Mass Spectrometry Facility Manager
Recruitment in progress, Department of Chemistry, will devote 100% of effort for implementing mass
spectrometry methods, instrument operation/maintenance, and training
Account & Workshop Manager
Teresa Cassel, M.S., Dept. of Chemistry, will devote 80% of effort for managing Center’s account and
organizing training & other workshops
Ms. Cassel has both administrative and technical experience pertaining to metabolomics.
Program Coordinator
Teresa Cassel, M.S. will be employed to assist in the Center’s administration and research coordination.
Ms. Cassel has extensive experience with multi-university research coordination, student training, and
national workshop organization.
External Science Advisory Board
Dr. Angela Gronenborn, Chairman of Structural Biology, University of Pittsburg
Dr. Daniel Liebler, Director of Mass Spectrometry Research Center, Vanderbilt University
Dr. Rima Kaddurah-Daouk, President of the Metabolomics Society, Duke University
Internal Steering Committee
The internal Steering Committee shall consist of three actively-participating Center Member Faculty (see
list below), rotating appointments every three years. The composition of this Committee is currently
Professors William M. Pierce, George R. Pack, Donald M. Miller, and Kenneth S. Ramos. The Director
and Co-Directors are to be Ex-Officio members of the Committee.
Affiliated Center Member Faculty – will collaborate and access CREAM facility on research of joint
interest
1. Dr. William M. Pierce, Department of Pharmacology & Toxicology
2. Dr. Harrell Hurst, Department of Pharmacology & Toxicology
3. Dr. Cecilia Yappert, Department of Chemistry
4. Dr. George R. Pack, Department of Chemistry
5. Dr. Robert M. Buchanan, Department of Chemistry
6. Dr. Craig Grapperhaus, Department of Chemistry
7. Dr. Donald M. Miller, J. Graham Brown Cancer Center
8. Dr. John Eaton, J. Graham Brown Cancer Center
9. Dr. John Trent, J. Graham Brown Cancer Center
10. Dr. Mariusz Ratajczak, J. Graham Brown Cancer Center
11. Dr. Janina Ratajczak, J. Graham Brown Cancer Center
12. Dr. Paula Bates, J. Graham Brown Cancer Center
13. Dr. Jason Chesney, J. Graham Brown Cancer Center
14. Dr. Kenneth S. Ramos, Department of Biochemistry & Molecular Biology
15. Dr. Claudio Maldonado, Department of Physiology and Biophysics
3. NEEDS OF CENTER
The complexity of instrumentation and approaches demanded by the metabolomics research obligate the
establishment of the Center. It will not be practical to maintain the suite of sophisticated instrumentation and
develop integrative approaches without such a Center. In addition, the immense problem of data handling,
processing, and interpretation will require continued development and interfacing with biochemoinformatics.
Again, without a Center’s umbrella, integration of hardware with software development will be much less
5
effective. Moreover, the Center will provide leverage for metabolomics-oriented researchers in competing for
extramural research funds, which is a rapidly growing area of resources.
The staff need for the CREAM is listed in the table below. See also the section above and Form 1 (p.12-13) for
more details.
Staff
% Commitmenta Years of Commitment
Teresa Fan
10-20
undetermined
Richard Higashi
30-50
undetermined
Andrew Lane
5
undetermined
Recruitment in progress 50
undetermined
Recruitment in progress 100
undetermined
Teresa Cassel
100
3
a
Please see Form 1 (p.12-13 for further detail)
Function
Director
Assoc. Director, MS
Assoc. Director, NMR
BiochemoInformatic Faculty
MS Facility Manager
Research Program Coordinator
4. CENTER SPACE
Instrumentation:
The space presently utilized by NSF-EPSCoR instrumentation is as follows:
Major Instrument facility
Location
MS-filtered FT-MS and LC-tandem MS
Rm 318, BRB (see Appendix 1 for floor plan)
Training LC-MS
Rm 318, BRB
LC-ICPMS with laser ablation
Rm 326, BRB
LC-irMS
Rm 326, BRB
GC-tandem MS
Rm 336, BRB
Sample preparation facility
Extraction, chemical derivatization, acid digestion
Rm 336, BRB
Faculty & Staff
Teresa Fan
Richard Higashi
BiochemoInformatic faculty (under recruitment)
MS Facility Manager (under recruitment)
Research Program Coordinator
Rm 335 (lab), 348 (office) BRB
Rm 333, 330 (lab), 347 (office) BRB
Rm (TBD), 349 (office) BRB
Rm 341
Rm 341
5. EQUIPMENT
Equipment has been purchased (see gray-shaded sections of Appendix 3 for the NSF-EPSCoR budget) and
installed, which are listed in Table 1 below.
6
Table 1. CREAM instruments purchased and installed.
P.O. #
3000059629
3000058894
3000059603
3000058532
3000058891
3000060352
3000060516
Instrument
Thermo Electron LTQ-FT, XSeriesII ICP-MS, Isolink DeltaV
Mass Tech AP-MALDI
Dionex Ultimate nanoLC system
Advion Triversa Nanomate
AlwaysOn UPS
New Wave UP213 Laser Ablation System
Elemental Scientific SC2 Autosampler
P.O. Amount
1,434,127.25
61,497.00
99,743.60
70,000.00
26,075.00
93,138.75
12,060.00
Total
1,796,641.60
The major anchors are the newly acquired mass spectrometer instruments, which are:
MS-filtered FT-MS – To provide distribution of a wide range of metabolites and their turnover pathways.
LC-ICPMS with laser ablation capability – To provide distribution of bioelements and metal-containing
metabolites and proteins
Isotope-ratio MS – To trace metabolic fate of isotopically labeled precursors.
6. OPERATING EXPENSES AND FINANCIAL PLAN
Detailed operating cost and financial plan for the 1 st three years is listed in Forms 1 and 2, which references
Appendices 2, 3, and 4.
7. WRITTEN STATEMENT FROM DEAN & UNIVERSITY LIBRARIES (attached p. 8-10)
8. REVENUE
Revenues are detailed in Form 2, which references Appendices 3 and 4.
Source
NSF/EPSCoR grant for the 1st year
Dean, Arts and Science
Amount
See Form 2 for details
In-kind match of FTEF salaries
Partial 1st Year of Coordinator salary + benefit
Permanent hire of Manager starting Year 2
See Appendix 2
To be determined
User recharge
Extramural grants
9. MEANS FOR EVALUATION
Objectives/Outcomes
The Center’s objectives are:
1. To provide state-of-the-art mass spec analytical capabilities for UofL and the Kentuckiana Region
2. To provide metabolomic tools and to continue development of these tools.
3. To support applications of investigator-initiated and program grant proposals
4. To provide education and training on metabolomics for undergraduate/graduate students and postgraduate
researchers
The fulfillment of the above goals will greatly enhance research competitiveness of UofL researchers, prepare
our graduates for a new growing job market in biotechnology, environmental technology, medicine, and
pharmaceutical industries. In addition, the success of the Center should help enhance national and international
visibility of UofL.
7
Assessment Tools
Center will be evaluated by the following criteria:
Collaborative projects, research training (incl workshops & symposia), publications, extramural grants.
Schedule for Reporting Data
Report on Center’s finance, activity, and achievement will be made annually.
Implementing Changes
The External Advisory Board of three members will be convened to advise on technical and scientific directions.
An Internal Steering Committee of five members will oversee the CREAM’s operation and research activities.
Signature of Submitter
Name
____________________________________ Date
8
______________________
UNIVERSITYofLOUISVILLE
______________________________________________________________________________
College of Arts and Sciences
Office of the Dean
University of Louisville
Louisville, KY 40292
Office: 502-852-6490
Fax:
502-852-6888
June 1, 2007
Dr. Daniel Mahony
Associate University Provost
University of Louisville
Dear Dr. Mahony:
This memorandum serves as my strong endorsement of the attached proposal for the
creation of the “Center for Regulatory and Environmental Analytical Metabolomics” (CREAM)
under the College of Arts and Sciences. As noted in the proposal, the Center “will develop
cutting-edge methodologies, approaches, and applications for the emerging discipline of
metabolomics to support systems biochemical research.”
The fundamentally interdisciplinary nature of metabolomics necessitates the creation of a
fundamentally new model. Consequently, while the Center will be administered by Dr. Teresa
Fan, Associate Professor in the Department of Chemistry , it will rely on close collaboration with
faculty based in the J. Graham Brown Cancer Center, the Department of Pharmacology and
Toxicology, and Department of Biochemistry and Molecular Biology—all of the School of
Medicine. In recognition of the tremendous potential of CREAM, the College has made the
following commitments over the first three years of the Center’s existence:
Professor Richard Higashi: $110,126 (salary) * 1.25 (fringe) =
Professor Teresa Fan: $25,653 (salary) * 1.25 (fringe) =
MS facility manager $155,277 (salary) * 1.25(fringe) =
Administrative Assistant (Teresa Cassel) $27,600 * 1.25 (fringe) =
Cheminformatics faculty member: $88,091 (salary) * 1.25(fringe) =
Total. =
$ 137,657
32,066
194,096
34,501
110,113
$ 508,433
I believe that the creation of the Center is an exciting and timely step for the College and
the University, and recommend without reservation its approval by all subsequent reviewing
bodies.
Please let me know if any additional information would be helpful.
Sincerely,
9
Dr. J. Blaine Hudson
Dean, College of Arts and Sciences
Professor, Department of Pan-African Studies
cc:
Dr. Robert Buchanan, Associate Dean for Graduate Education and Research
Dr. Teresa Fan, Associate Professor, Department of Chemistry and Director,
CREAM
10
11
FORM 1
DEPARTMENTAL EXPENDITURES FOR CENTERS AND INSTITUTES
Year 1 (2007-08)
Year 2 (2008-09)
Year 3 (2009-10)
0.9125
$68,101
$17,025
$77,678
$0
$0
none
none
$0
none
none
$0
$92,829
$34,501
$0
1.1
$72,426
$18,106
$99,586
$0
$0
none
$0
none
$0
none
none
$0
$95,614
$0
$0
1.1
$74,599
$18,650
$102,573
$0
$0
none
$0
none
$0
none
none
$0
$98,482
$0
$0
$205,007
$195,199
$201,055
$36,000
$2,000
$24,000
$0
$24,000
$2,000
$24,000
$0
$24,000
$2,000
$24,000
$0
none
$255
none
none
none
$255
none
none
none
$255
none
none
none
none
none
$0
$0
$0
$33,400
$0
$0
$0
$33,400
none
none
$83,655
$83,655
TOTAL
I. Personnel
1. Full-time ranked
faculty (FTEF)
a. Number of FTEF 1
b. Average salary 2
c. Fringes per avg. salary 3
d. Cost of FTEF: a x (b+c)
2. Part-time faculty (PTF)
a. Course credit hours
taught by PTF
b. Average PTF salary
per credit hour
c. Average PTF fringes
per credit hour
d. Cost of PTF: a x (b+c)
3. Other (specify)
MS Facility manager incl. Fringe 4
Program Coordinator incl. Fringe 5
Cost of Other
Total Personnel Costs 6:
$215,126
$53,781
$279,837
$286,924
$34,501
$0
$601,261
II: Operating Costs:
1. Supplies
2. Travel
3. Workshop, Symposium, SAB
4. Faculty startup
5. Library Budget (in addition to
current expenditures)
a. Books
b. Journals 7
c. Electronic Resources none
d. Other (please specify)
6. Student support (assistantships,
fellowships, tuition waiver)
7. Equipment 8
FT-ICR-MS w/service contract & UPS
ICP-MS w/service contract & UPS
ir-MS w/service contract & UPS
Ancillary equipment & service contracts 8
a. Instructional
b. Research
c. Computer equipment and software
d. Other
Total Operating Costs:
III. Capital Costs
$0
$0
$0
$17,700
Above equipment
Above equipment
Included in above equipment
none
$79,955
12
$247,265
1. Facilities
a. New Construction
b. Renovation
c. Furnishings
2. Other (please specify)
Total Capital Costs:
Total Expenditures:
None
None
None
None
None
None
None
None
None
$0
$0
$0
$284,962
$278,854
$284,710
$848,526
1
Aggregate % commitment to CREAM for three FTEFs (using yearly % positions for each FTEF from Appendix 4), computed as follows:
Prof. Fan has a 20% CREAM commitment of her 50% A&S position, which amounts to 10% FTEF for all three years.
Prof. Higashi has for Year 1, a 50% CREAM commitment on an average 62.5% A&S position, which amounts to 31.25% FTEF
For Years 2 & 3, Prof. Higashi is 50% CREAM committmet on 100% A&S position, which amounts to 50% FTEF.
The BiochemoInformatics faculty has a 50% CREAM committmet on 100% A&S position, which amounts to 50% FTEF for all three years.
Therefore for Year 1, Number of FTEF = 0.2 + 0.3125 + 0.5 = 0.9125. For Years 2 & 3, Number of FTEF = 10 + 50 + 50 = 1.1
2
The average salary is calculated from the aggregate % commitment of the % A&S support for each of the FTEF salaries.
The origin of the salaries is Appendix 4 (detailed In-Kind match commitments from A&S).
3
Fringe benefits are calculated at 25%
4
The Facility Manager's salary is budgeted in the NSF/EPSCoR grant for the first Year (2007-08). Subsequent salary will be entirely from A&S.
Fringe benefits are calculated at 25%. For the origin of these figures, please see Appendix 4 for detailed In-Kind match commitments from A&S.
5
Research Program Coordinator is $39,830 x 69.296% for the first year, which is the 2007-08 residual from a total dollar commitment
to this position from A&S. This amounts to approximately 8.28 months in FY 2007-08. There is no salary for this position beyond Year 1.
Fringe benefits are calculated at 25%. For the origin of these figures, please see Appendix 4 for detailed In-Kind match commitments from A&S.
6
Year 1 total corresponds to the In-Kind salary match for Year 3 of the NSF-EPSCoR Metabolomics Initiative, which is highlighted in Appendix 3.
7
For support of journals, see Section 7.
8
See Appendix 2 for listing of all major equipment, ancilliary equipment, and the cost of service contracts.
Due to the fact that the equipment had to be acquired prior to June 2006, during the first year of the NSF-EPSCoR grant (2005-06),
there are no equipment costs in any of the three years. The equipment was acquired using deficit spending.
Although the equipment funds are already effectively expended, for information only, the major equipment budget can be viewed in Appendix 3.
Color Coding Guide. Please refer to the Table below for assistance in reading Forms 1 & 2.
COLOR-CODING GUIDE TO FORMS 1 & 2
Color
Blue
Violet
Orange
Green
Yellow
In:
Form
Form
Form
Form
Form
Comes from:
Appendix 3, Year 3
Appendix 4, Grand Total
Appendix 3, Year 3
Appendix 3, Year 3
Appendix 4, Total A&S Commitment
1
1
2
2
2
Form 1-A: Rationale for All Costs
I. Personnel. The Center will have three FTEFs, two of them new (see Section 2) as specified in
the Metabolomics Initiative grant from NSF-EPSCoR (see Appendix 3). Please see footnote #1
for an explanation of the calculation for the Number of FTEF. The percent commitment of the
FTEFs with CREAM is variable from year-to-year, because it is subject to negotiation with the
Department Chair of Chemistry (Dr. G. Pack) through the Annual Work Plan; accordingly, the
estimate of the % commitment of the three FTEFs is obtained from Appendix 4 (commitments
by the College of A&S). In addition, existing in-kind matches NOT on this Form are: (a) 5%
time each for the co-PIs of the Metabolomics Initiative grant from NSF-EPSCoR, the list of
which is Andrew N. Lane (James Graham Brown Cancer Center), Donald M. Miller (J.G.
Brown Cancer Center), George Pack (Department of Chemistry), William M. Pierce
13
(Department of Pharmacology and Toxicology), and Kenneth Ramos (Department of
Biochemistry & Molecular Biology), all at Univ. of Louisville; (b) undetermined and likely
variable % time for the Senior Investigators of the grant, the list of which is currently Robert
Buchanan, Craig A. Grapperhaus, and M. Cecilia Yappert, all of the Department of Chemistry,
Univ. of Louisville; (c) undetermined and likely variable % time for Collaborators of the grant,
the initial list of which is found in a copy of the grant proposal (available upon request). The list
of Collaborators is not stated here, as the list will be variable from year to year, unknown for
future years, and from international institutions – in some cases, we will not be able to obtain
their % commitment nor their salary levels. In fact, because the very point of CREAM is to
provide services and collaborations, collaborators are not a part of the Center.
There are no PTFs associated with CREAM.
The MS Facility Manager (see Section 2) will be supported by the Metabolomics Initiative for
the first year of CREAM (2007-08), as specified in the grant from NSF-EPSCoR, (see Appendix
3) which is then supported by the College of A&S for subsequent years (see Appendix 4).
The Program Coordinator (see Section 2) will be supported by the A&S College for a portion of
the first year. Please see footnote #5 for the explanation, and Appendix 4 for salary figures.
This position could be supported by CREAM for subsequent years (not stated in Form 1), subject
to availability of funds.
Other Personnel. There are no other personnel planned.
II. Operating Costs
Supplies. Supplies are based on estimated costs of operation of the equipment, including
cryogens for maintaining the ICR-MS (approx. $10,000/yr), gases for operation of all
instruments (approx. $4,000/yr), chemicals for operation of all instruments as well as other
supplies such as chromatography columns and fittings (approx. $10,000/yr). The supply cost is
highest in Year 1 when we expect the most amount of method development.
Travel. Travel is requested for CREAM business, including presentation of CREAM
organization and/or technical results at regional, national, and international meetings. Travel for
the External Advisory Board (see Section 2) is not included here, which will be funded by the
NSF-EPSCoR grant (see Appendix 3) for Year 1, then as part of the Workshop and Symposium
(see next item).
Workshop and Symposium. Year 1 is the estimated from the cost of the past 2 nd International
Environmental Metabolomics Symposium, March 25-26, 2007, Louisville, KY. Subsequent
years are estimated at similar costs.
Faculty Startup. This amount is currently unknown, because it is subject to hiring negotiatons
for the new BiochemoInformatics FTEF.
Library Budget. This amount is based on the support letter from the Library (see attachment).
Equipment. There are no costs listed for major equipment, which was fully justified and outlined
the NSF-EPSCoR grant proposal and funded budget (see Appendix 3). This is because all of the
major and ancillary equipment were purchased prior to June 2006, the proposed start of
CREAM. Costs for subsequent years in this category are based on Service Contract costs for
each of the instrument vendors (see Appendix 2 for details).
14
III. Capital Costs
There are no Capital Costs associated with CREAM.
15
FORM 2 AMOUNT AND SOURCES OF REVENUE
Year 1 (2007-08)
Year 2 (2008-09)
Year 3 (2009-10)
1. Regular state appropriation and
tuition and fees
a. New money
b. Internal reallocation 1
TOTALS
$0
$0
$112,178
$0
$195,199
$0
$201,055
2. Institutional allocation from
restricted endowment
$0
$0
$0
3. Institutional allocation from
unrestricted endowment
$0
$0
$0
$4,000
$1,000
$1,000
$5,000
$1,000
$500
$4,000
$1,000
$1,000
$5,000
$1,000
$500
$4,000
$1,000
$1,000
$5,000
$1,000
$500
$0
$0
$0
$0
$0
$78,969
$105,939
$0
$0
$0
$0
$0
$0
$0
$0
$0
$0
$0
7. Capitation
$0
$0
$0
8. Capital
$0
$0
$0
$12,000
$5,000
$0
$20,000
$15,000
$5,000
$35,000
$30,000
$15,000
$67,000
$50,000
$20,000
$326,586
$247,699
$293,555
$867,841
4. Gifts 2
Brown & Williamson
Varian NMR
LECO
Thermo Electron
Advion Biosciences
Isotec
5. Extraordinary state appropriation
6. Grants or contracts
a. Private sector
b. Local government
c. State Match 3
d. Federal (direct) 3
e. Other
9. Other 4
Core Facility Users (estimated)
Other Academic Users (estimated)
Non-academic Users (estimated)
Total Revenues
16
$508,433
$12,000
$3,000
$3,000
$15,000
$3,000
$1,500
$78,969
$105,939
1
Internal reallocation is the salaries+benefit of the three FTEF, plus Program Coordinator for Year 1, plus Facility Manager for Years 2 & 3.
Fringe benefits are calculated at 25%. For the origin of these figures, please see Appendix 4 for detailed In-Kind match commitments from A&S.
Year 1 here correspond to In-Kind salary match for Year 3 of the NSF-EPSCoR Metabolomics Initiative (Appendix 3).
2
The gift funds amount reflect the income experience from organizing the 2nd international metabolomics symposium at UofL, March 25-26, 2007.
The nature of gifts makes it difficult to estimate future funds, so the past contributions are projected here.
3
These figures are drawn from Appendix 3 (NSF-EPSCoR budget), which are the total State Match and Federal funds, minus equipment.
Year 1 here corresponds to Year 3 (Appendix 3). Equipment is excluded because those funds were encumbered before June 2006.
4
There are low user charges revenue for the first year, due to the late timing of the establishment of CREAM.
Form 2-A: Explanation of Revenue
Internal Reallocation. For Year 1, this is the UofL In-Kind Match for EPSCoR Year 3
(Appendix 3). For Years 2 and 3, the figures are the continuing A&S commitments (Appendix
4).
Gifts. See Footnote 2. The gift revenues are based on experience in organizing the 2nd
International Environmental Metabolomics Symposium, March 25-26, 2007, Louisville, KY.
Funds in this category are projected to be similar income for future years.
Grants or Contracts. The NSF-EPSCoR Metabolomics Initiative (budget is Appendix 3)
proposed to establish a scientific center, which will be the “Center for Regulatory and
Environmental Analytical Metabolomics” (CREAM). The revenues in this category are based
on the NSF-EPSCoR Year 3 budget (see Appendix 3) of the State Match and direct Federal
funds, excluding equipment because all of the major and ancillary equipment were purchased
prior to June 2006,
Other. The revenues in this category are based on best-guess instrument use (# of hrs)
projections, utilizing the proposed recharge schedule shown in Appendix 2. There are low user
charges revenue for Year 1, due to the late timing of the establishment of CREAM.
17
APPENDIX 1
Rm 318 (FT-MS room) layout
18
APPENDIX 2
SERVICE CONTRACT COSTS
Service Contracts from CREAM Operating Budget
2007-08
Year 2
Thermo LTQ-FT
Thermo X-SeriesII
Thermo Isolink DeltaV
Advion Nanomate
New Wave Laser Ablation
MassTech AP-MALDI
ESI Autosampler
Dionex Ultimate System
Thermo Polaris System
Thermo LCQ-Duo System
TOTALS
2008-09
Year 3
2009-10
Year 4
2010-11
Year 5
2011-12
Year 6
Total 5 Years
0
0
0
0
0
0
0
0
0
0
0
0
0
7,000
9,500
0
1,200
0
0
0
0
0
0
7,000
9,500
6,200
1,200
9,500
0
0
0
0
0
7,000
9,500
6,200
1,200
9,500
9,000
8,000
38,500
13,500
14,700
7,000
9,500
6,200
1,200
9,500
9,000
8,000
38,500
13,500
14,700
28,000
38,000
18,600
4,800
28,500
18,000
16,000
0
17,700
33,400
50,400
117,100
218,600
PROPOSED RECHARGE RATES
Note that some of the charges below are for 4hr durations
PROPOSED RECHARGE RATES w/Certified Users 1
MS Development & Installation, Maintenance, and Repair Users2
Core Facility Users 3
Academic Users 4
Non-academic, not-for-profit 5
Industry 6
PROPOSED RECHARGE RATES w/Facility Operator
Core Facility Users
Academic Users
Non-academic, non-for-profit
Industry & all others
ICR-MS
NC
$36 /4hr
$48 /4hr
N/A
N/A
ICP-MS
NC
$3 /hr
$5 /hr
N/A
N/A
irMS
NC
$3 /hr
$5 /hr
N/A
N/A
Multi-nanospray
NC
$8 /4hr
$12 /4hr
N/A
N/A
nanoLC
NC
$8 /4hr
$12 /4hr
N/A
N/A
Laser Ablation
NC
$2 /hr
$5 /hr
N/A
N/A
LCQ-Duo
NC
$8 /4hr
$12 /4hr
N/A
N/A
Polaris GCMS
NC
$8 /4hr
$12 /4hr
N/A
N/A
$48 /4hr
$60 /4hr
$72 /4hr
$1200 /4hr
$5 /hr
$7 /hr
$9 /hr
$50 /hr
$5 /hr
$7 /hr
$9 /hr
$50 /hr
$12 /4hr
$16 /4hr
$20 /4hr
$250 /4hr
$12 /4hr
$16 /4hr
$20 /4hr
$250 /4hr
$3 /hr
$4 /hr
$5 /hr
$40 /hr
$12 /4hr
$16 /4hr
$20 /4hr
$250 /4hr
$12 /4hr
$16 /4hr
$20 /4hr
$250 /4hr
1) "Certified" users are those whom have undergone CREAM-approved instrument and safety training. CREAM will provide such training periodically.
2) There will be no charge for certified users performing core method development for all users, instrument/software installation, maintenance, or repair.
3) Core facility users consists of faculty, or employees of faculty, involved in the Metabolomics Initiative.
4) Academic users consist of all non-core faculty, or employees of faculty at an academic institution.
5) Non-academic, but otherwise not-for-profit users consist of research institutes, governmental agencies, and other such entities.
6) This category consist of all other users.
19
Note regarding Appendix 3: Year 3 of the EPSCoR corresponds to Year 1 of the Center
proposal. Thus, EPSCoR Years 1 & 2 and Cumulative budgets are included here for
completeness, but only Year 3 of this appendix is relevant to the Center proposal.
APPENDIX 3: NSF-EPSCoR Metabolomics Initiative
Year 1 (2005-06)
A. SENIOR PERSONNEL
NSF
STATE (Match)
UNIV. In-Kind
(Match)
NSF+STATE
TOTAL (Match)
TOTAL
Mos.
1. Te res a Fan (co-PI)
1.2
$
-
$
-
$
-
$
8,300
$
8,300
$
8,300
2. New Hire (Metabolomics)
1.5
$
-
$
-
$
-
$
10,137
$
10,137
$
10,137
3. New Hire (Cheminf ormatics)
6
$
-
$
-
$
-
$
28,500
$
28,500
$
28,500
4. New Hire (MS Facility Manager)
12
$
46,667
$
23,333
$
70,000
$
-
$
23,333
$
70,000
5.
0
$
-
$
-
$
-
$
-
$
-
$
-
6. (4) Other
0
$
-
$
-
$
-
$
-
$
-
$
46,667
$
23,333
$
70,000
$
46,937
$
70,270
$
116,937
(8) Total Senior Personnel
B. OTHER PERSONNEL
Mos.
1. (0) Post-Doc(s)
0
$
-
$
-
$
-
$
-
$
-
$
-
2. (0) Other Prof essional(s)
0
$
-
$
-
$
-
$
-
$
-
$
-
3. (0) Graduate Student(s)
$
-
$
-
$
-
$
-
$
-
$
-
4. (0) Undergraduate Student(s)
$
-
$
-
$
-
$
-
$
-
$
-
5. (0) Secretarial-Clerical
$
-
$
-
$
-
$
-
$
-
$
-
6. (0) Other
$
-
$
-
$
-
$
-
$
-
$
-
$
46,667
$
23,333
$
70,000
$
46,937
$
70,270
$
116,937
Total Salarie s & Wage s (A+B)
C. FRINGE BENEFITS
$
5,833
$
17,500
$
17,567
$
29,234
Total Salary, Wages & Fringe
$
58,334
11,667 $
$
29,166
$
87,500
$
58,671
11,734 $
$
87,837
$
146,171
1. MS Filtered FT-ICR-MS
$
444,301
$
197,150
$
641,451
$
-
$
197,150
$
641,451
2.
$
-
$
-
$
-
$
-
$
-
$
-
3.
$
-
$
-
$
-
$
-
$
-
$
-
$
197,150
$
641,451
$
-
$
197,150
$
641,451
2,000
D. EQUIPMENT
Total Equipment
$
444,301
E. TRAVEL
1. Domestic
$
-
$
2,000
$
2,000
$
-
$
2,000
$
2. Foreign
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
2,000
$
2,000
$
-
$
2,000
$
2,000
1. Stipends
$
-
$
-
$
-
$
-
$
-
$
-
2. Travel
$
-
$
-
$
-
$
-
$
-
$
-
3. Subsistence
$
-
$
-
$
-
$
-
$
-
$
-
4. Other
$
-
$
4,000
$
4,000
$
-
$
4,000
$
4,000
Total Participant Costs
$
-
$
4,000
$
4,000
$
-
$
4,000
$
4,000
G. OTHER DIRECT COSTS
1. Materials & Supplies
11,667 $
11,667 $
35,000
Total Travel
F. PARTICIPANT SUPPORT COSTS
$
23,333
$
35,000
$
-
$
2. Pub. Costs/Documentation/Dissemination
$
-
$
-
$
-
$
-
$
-
$
-
3. Consultant Services
$
-
$
-
$
-
$
-
$
-
$
-
4. Computer Services
$
-
$
-
$
-
$
-
$
-
$
-
5. Subaw ards
6. Other (Faculty Start-up Packages)
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
450,000
$
450,000
$
450,000
Total Other Direct Costs
Total Direct Costs LESS EQUIPMENT
$
$
23,333
81,667
$
$
11,667
46,833
$
$
35,000
128,500
$
$
450,000
508,671
$
$
461,667
555,504
$
$
485,000
637,171
Total Direct Costs
Total Indirect Costs*
Total Direct & Indirect
$
$
$
525,968
38,383
564,351
$
$
$
243,983
243,983
$
$
$
769,951
38,383
808,334
$
$
$
508,671
20,132
528,803
$
$
$
752,654
20,132
772,786
(UL) Indirect Rate
47.00%
Calculated Cell
*UL Indirect = Indirect Rate * MTDC. MTDC = TDC less equipment and participant support
costs. Indirect is not collect (i.e. w aived) on "STATE (Match)" f unds by all participants.
20
$ 1,278,622
$
58,515
$ 1,337,137
Calculated:
Waived Indirect on "STATE (Match)". That is, "STATE (Match) MTDC" *
Indirect Rate
APPENDIX 3: NSF-EPSCoR Metabolomics Initiative
Year 2 (2006-07)
A. SENIOR PERSONNEL
NSF
STATE (Match)
UNIV. In-Kind
(Match)
NSF+STATE
TOTAL (Match)
TOTAL
Mos.
1. Te res a Fan (co-PI)
1.2
$
-
$
-
$
-
$
8,300
$
8,300
$
8,300
2. New Hire (Metabolomics)
1.5
$
-
$
-
$
-
$
10,137
$
10,137
$
10,137
3. New Hire (Cheminf ormatics)
6
$
-
$
-
$
-
$
28,500
$
28,500
$
28,500
4. New Hire (MS Facility Manager)
12
$
48,067
$
24,033
$
72,100
$
-
$
24,033
$
72,100
5.
0
$
-
$
-
$
-
$
-
$
-
$
-
6. (4) Other
10
$
-
$
-
$
-
$
32,225
$
32,225
$
32,225
$
48,067
$
24,033
$
72,100
$
79,162
$
103,195
$
151,262
(8) Total Senior Personnel
B. OTHER PERSONNEL
Mos.
1. (0) Post-Doc(s)
0
$
-
$
-
$
-
$
-
$
-
$
-
2. (0) Other Prof essional(s)
0
$
-
$
-
$
-
$
-
$
-
$
-
3. (0) Graduate Student(s)
$
-
$
-
$
-
$
-
$
-
$
-
4. (0) Undergraduate Student(s)
$
-
$
-
$
-
$
-
$
-
$
-
5. (0) Secretarial-Clerical
$
-
$
-
$
-
$
-
$
-
$
-
6. (0) Other
$
-
$
-
$
-
$
-
$
-
$
-
$
48,067
$
24,033
$
72,100
$
79,162
$
103,195
$
151,262
Total Salarie s & Wage s (A+B)
C. FRINGE BENEFITS
$
12,017
$
6,008
$
18,025
$
19,791
$
25,799
$
37,816
Total Salary, Wages & Fringe
$
60,084
$
30,041
$
90,125
$
98,953
$
128,994
$
189,078
1. MS Filtered FT-ICR-MS
$
273,543
$
124,272
$
397,815
$
-
$
124,272
$
397,815
2. Collision Cell-Based ICP-MS
$
129,733
$
52,367
$
182,100
$
-
$
52,367
$
182,100
3.
$
-
$
-
$
-
$
-
$
-
$
-
$
176,639
$
579,915
$
-
$
176,639
$
579,915
2,000
D. EQUIPMENT
Total Equipment
$
403,276
E. TRAVEL
1. Domestic
$
-
$
2,000
$
2,000
$
-
$
2,000
$
2. Foreign
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
2,000
$
2,000
$
-
$
2,000
$
2,000
1. Stipends
$
-
$
-
$
-
$
-
$
-
$
-
2. Travel
$
-
$
12,000
$
12,000
$
-
$
12,000
$
12,000
3. Subsistence
$
-
$
10,000
$
10,000
$
-
$
10,000
$
10,000
4. Other
$
-
$
2,000
$
2,000
$
-
$
2,000
$
2,000
Total Participant Costs
$
-
$
24,000
$
24,000
$
-
$
24,000
$
24,000
G. OTHER DIRECT COSTS
1. Materials & Supplies
Total Travel
F. PARTICIPANT SUPPORT COSTS
$
42,667
$
21,333
$
64,000
$
-
$
21,333
$
64,000
2. Pub. Costs/Documentation/Dissemination
$
-
$
-
$
-
$
-
$
-
$
-
3. Consultant Services
$
-
$
-
$
-
$
-
$
-
$
-
4. Computer Services
$
-
$
-
$
-
$
-
$
-
$
-
5. Subaw ards
6. Other (Faculty Start-up Packages)
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
Total Other Direct Costs
Total Direct Costs LESS EQUIPMENT
$
$
42,667
102,751
$
$
21,333
77,374
$
$
64,000
180,125
$
$
98,953
$
$
21,333
176,327
$
$
64,000
279,078
Total Direct Costs
Total Indirect Costs*
Total Direct & Indirect
$
$
$
506,027
48,293
554,320
$
$
$
254,013
254,013
$
$
$
760,040
48,293
808,333
$
$
$
98,953
25,086
124,039
$
$
$
352,966
25,086
378,052
$
$
$
858,993
73,379
932,372
(UL) Indirect Rate
47.00%
Calculated Cell
*UL Indirect = Indirect Rate * MTDC. MTDC = TDC less equipment and participant support
costs. Indirect is not collect (i.e. w aived) on "STATE (Match)" f unds by all participants.
21
Calculated:
Waived Indirect on "STATE (Match)". That is, "STATE (Match) MTDC" *
Indirect Rate
APPENDIX 3: NSF-EPSCoR Metabolomics Initiative
Year 3 (2007-08)
A. SENIOR PERSONNEL
NSF
STATE (Match)
UNIV. In-Kind
(Match)
NSF+STATE
TOTAL (Match)
TOTAL
Mos.
1. Te res a Fan (co-PI)
1.2
$
-
$
-
$
-
$
8,300
$
8,300
$
8,300
2. New Hire (Metabolomics)
3.75
$
-
$
-
$
-
$
25,343
$
25,343
$
25,343
3. New Hire (Cheminf ormatics)
6
$
-
$
-
$
-
$
28,500
$
28,500
$
28,500
4. New Hire (MS Facility Manager)
12
$
49,509
$
24,754
$
74,263
$
-
$
24,754
$
74,263
5.
0
$
-
$
-
$
-
$
-
$
-
$
-
9.56
$
-
$
-
$
-
$
27,600
$
27,600
$
27,600
$
49,509
$
24,754
$
74,263
$
89,743
$
114,497 $
164,006
6. (4) Other
(8) Total Senior Personnel
B. OTHER PERSONNEL
Mos.
1. (0) Post-Doc(s)
0
$
-
$
-
$
-
$
-
$
-
$
-
2. (0) Other Prof essional(s)
0
$
-
$
-
$
-
$
-
$
-
$
-
3. (0) Graduate Student(s)
$
-
$
-
$
-
$
-
$
-
$
-
4. (0) Undergraduate Student(s)
$
-
$
-
$
-
$
-
$
-
$
-
5. (0) Secretarial-Clerical
$
-
$
-
$
-
$
-
$
-
$
-
6. (0) Other
$
-
$
-
$
-
$
-
$
-
$
-
$
49,509
$
24,754
$
74,263
$
89,743
$
114,497 $
164,006
Total Salarie s & Wage s (A+B)
C. FRINGE BENEFITS
$
12,377
$
6,189
$
18,566
$
22,436
$
28,625
$
41,002
Total Salary, Wages & Fringe
$
61,886
$
30,943
$
92,829
$
112,179
$
143,122
$
205,008
1. MS Filtered FT-ICR-MS
$
195,489
$
91,495
$
286,984
$
-
$
91,495
$
286,984
2. Collision Cell-Based ICP-MS
$
136,933
$
55,967
$
192,900
$
-
$
55,967
$
192,900
3. Laser Capture Microdissection System
$
66,667
$
27,083
$
93,750
$
-
$
27,083
$
93,750
$
174,545
$
573,634
$
-
$
174,545
$
573,634
2,000
D. EQUIPMENT
Total Equipment
$
399,089
E. TRAVEL
1. Domestic
$
-
$
2,000
$
2,000
$
-
$
2,000
$
2. Foreign
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
2,000
$
2,000
$
-
$
2,000
$
2,000
1. Stipends
$
-
$
-
$
-
$
-
$
-
$
-
2. Travel
$
-
$
12,000
$
12,000
$
-
$
12,000
$
12,000
3. Subsistence
$
-
$
10,000
$
10,000
$
-
$
10,000
$
10,000
4. Other
$
-
$
2,000
$
2,000
$
-
$
2,000
$
2,000
Total Participant Costs
$
-
$
24,000
$
24,000
$
-
$
24,000
$
24,000
G. OTHER DIRECT COSTS
1. Materials & Supplies
Total Travel
F. PARTICIPANT SUPPORT COSTS
$
44,053
$
22,026
$
66,079
$
-
$
22,026
$
66,079
2. Pub. Costs/Documentation/Dissemination
$
-
$
-
$
-
$
-
$
-
$
-
3. Consultant Services
$
-
$
-
$
-
$
-
$
-
$
-
4. Computer Services
$
-
$
-
$
-
$
-
$
-
$
-
5. Subaw ards
6. Other (Faculty Start-up Packages)
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
Total Other Direct Costs
Total Direct Costs LESS EQUIPMENT
$
$
44,053
105,939
$
$
22,026
78,969
$
$
66,079
184,908
$
$
112,179
$
$
22,026
191,148
$
$
66,079
297,087
Total Direct Costs
Total Indirect Costs*
Total Direct & Indirect
$
$
$
505,028
49,791
554,819
$
$
$
253,514
253,514
$
$
$
758,542
49,791
808,333
$
$
$
112,179
25,835
138,014
$
$
$
365,693
25,835
391,528
$
$
$
870,721
75,626
946,347
(UL) Indirect Rate
47.00%
Calculated Cell
*UL Indirect = Indirect Rate * MTDC. MTDC = TDC less equipment and participant support
costs. Indirect is not collect (i.e. w aived) on "STATE (Match)" f unds by all participants.
22
Calculated:
Waived Indirect on "STATE (Match)". That is, "STATE (Match) MTDC" *
Indirect Rate
APPENDIX 3: NSF-EPSCoR Metabolomics Initiative
Cumulative (2005-08)
A. SENIOR PERSONNEL
NSF
STATE (Match)
UNIV. In-Kind
(Match)
NSF+STATE
TOTAL (Match)
TOTAL
Mos.
1. Te res a Fan (co-PI)
3.6
$
-
$
-
$
-
$
24,900
$
24,900
$
24,900
2. New Hire (Metabolomics)
6.75
$
-
$
-
$
-
$
45,617
$
45,617
$
45,617
3. New Hire (Cheminf ormatics)
18
$
-
$
-
$
-
$
85,500
$
85,500
$
85,500
4. New Hire (MS Facility Manager)
36
$
144,243
$
72,120
$
216,363
$
-
$
72,120
$
216,363
0
5.
6. (4) Other
(8) Total Senior Personnel
B. OTHER PERSONNEL
$
-
$
-
$
-
$
-
$
-
$
-
19.56 $
-
$
-
$
-
$
59,825
$
59,825
$
59,825
$
144,243
$
72,120
$
216,363
$
215,842
$
287,962
$
432,205
Mos.
1. (0) Post-Doc(s)
0
$
-
$
-
$
-
$
-
$
-
$
-
2. (0) Other Prof essional(s)
0
$
-
$
-
$
-
$
-
$
-
$
-
3. (0) Graduate Student(s)
$
-
$
-
$
-
$
-
$
-
$
-
4. (0) Undergraduate Student(s)
$
-
$
-
$
-
$
-
$
-
$
-
5. (0) Secretarial-Clerical
$
-
$
-
$
-
$
-
$
-
$
-
6. (0) Other
$
-
$
-
$
-
$
-
$
-
$
-
$
144,243
$
72,120
$
216,363
$
215,842
$
287,962
$
432,205
Total Salarie s & Wage s (A+B)
C. FRINGE BENEFITS
$
36,061
$
18,030
$
54,091
$
53,961
$
71,991
$
108,052
Total Salary, Wages & Fringe
$
180,304
$
90,150
$
270,454
$
269,803
$
359,953
$
540,257
1. MS Filtered FT-ICR-MS
$
913,333
$
412,917
$
1,326,250
$
-
$
412,917
$
1,326,250
2. Collision Cell-Based ICP-MS
$
266,666
$
108,334
$
375,000
$
-
$
108,334
$
375,000
3. Laser Capture Microdissection System
$
66,667
$
27,083
$
93,750
$
-
$
27,083
$
93,750
$
548,334
$
1,795,000
$
-
$
548,334
$
1,795,000
6,000
D. EQUIPMENT
Total Equipment
$
1,246,666
E. TRAVEL
1. Domestic
$
-
$
6,000
$
6,000
$
-
$
6,000
$
2. Foreign
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
6,000
$
6,000
$
-
$
6,000
$
6,000
1. Stipends
$
-
$
-
$
-
$
-
$
-
$
-
2. Travel
$
-
$
24,000
$
24,000
$
-
$
24,000
$
24,000
3. Subsistence
$
-
$
20,000
$
20,000
$
-
$
20,000
$
20,000
4. Other
$
-
$
8,000
$
8,000
$
-
$
8,000
$
8,000
Total Participant Costs
$
-
$
52,000
$
52,000
$
-
$
52,000
$
52,000
G. OTHER DIRECT COSTS
1. Materials & Supplies
$
110,053 $
Total Travel
F. PARTICIPANT SUPPORT COSTS
55,026
$
165,079
$
-
$
55,026
$
165,079
2. Pub. Costs/Documentation/Dissemination
$
-
$
-
$
-
$
-
$
-
$
-
3. Consultant Services
$
-
$
-
$
-
$
-
$
-
$
-
4. Computer Services
$
-
$
-
$
-
$
-
$
-
$
-
5. Subaw ards
6. Other (Faculty Start-up Packages)
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
-
$
450,000
$
450,000
$
450,000
110,053 $
290,357 $
55,026
203,176
$
$
165,079
493,533
$
$
450,000
719,803
$
$
505,026
922,979
$
$
615,079
1,213,336
$ 2,288,533
$
136,467
$ 2,425,000
$
$
$
719,803
71,053
790,856
Total Other Direct Costs
Total Direct Costs LESS EQUIPMENT
$
$
Total Direct Costs
Total Indirect Costs*
Total Direct & Indirect
$ 1,537,023
$
136,467
$ 1,673,490
(UL) Indirect Rate
47.00%
$
$
$
751,510
751,510
Calculated Cell
*UL Indirect = Indirect Rate * MTDC. MTDC = TDC less equipment and participant support
costs. Indirect is not collect (i.e. w aived) on "STATE (Match)" f unds by all participants.
23
$ 1,471,313
$
71,053
$ 1,542,366
$ 3,008,336
$
207,520
$ 3,215,856
Calculated:
Waived Indirect on "STATE (Match)". That is, "STATE (Match) MTDC" *
Indirect Rate
Appendix 4: SALARY COMMITMENTS OF A&S AND EPSCoR
July 2007 - June 2010
Total
Total Salary w/Fringe
Total w/Fringe
from
from
from A&S
EPSCoR
EPSCoR
Fan salary
Year 1 (2007-08)
Year 2 (2008-09)
Year 3 (2009-10)
Base
82,995
85,485
88,049
Higashi salary
Year 1 (6 mo.)
Year 1 (6 mo.)
Base
40,549
40,549
Year 2 (2008-09)
Year 3 (2009-10)
83,530
86,036
Biochemoinf salary
Year 1 (2007-08)
Year 2 (2008-09)
Year 3 (2009-10)
MS Facility Manager
salary
Year 1 (2007-08)
Year 2 (2008-09)
Year 3 (2009-10)
Res.Prog. Coordinator
salary
Year 1 (2007-08)
Year 2 (2008-09)
Year 3 (2009-10)
Base
57,000
58,710
60,471
Base
74,263
76,491
78,786
Base
39,830
0
0
TOTALS
% A&S % AWP to CREAM
0.5
0.2
0.5
0.2
0.5
0.2
Total =
Total Cost to
A&S
8,300
8,548
8,805
25,653
32,066
32,066
% A&S % AWP to CREAM
0.25
0.5
1
0.5
TOTAL Yr1 =
1
0.5
1
0.5
Total =
Total Cost to
A&S
5,069
20,274
25,343
41,765
43,018
110,126
137,657
137,657
% A&S % AWP to CREAM
1
0.5
1
0.5
1
0.5
Total =
Total Cost to
A&S
28,500
29,355
30,236
88,091
110,113
110,113
% A&S % AWP to CREAM
0
1
1
1
1
1
Total =
Total Cost to
A&S
0
76,491
78,786
155,277
194,096
% A&S % AWP to CREAM
0.69295583
1
0
0
0
0
Total =
Total Cost to
A&S
27,600
0
0
27,600
34,501
74,263
508,433
24
74,263
92,829
286,924
34,501
92,829
601,261
NAME
POSITION TITLE
Fan, Teresa W-M.
Assoc. Professor, Dept. Chemistry
eRA COMMONS USER NAME
TWFAN001
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
BS
1973-1977
MS
PhD
1977-1978
1978-1983
National Taiwan University, Taipei
University of Hawaii, Manoa
University of California, Davis
FIELD OF STUDY
Public Health
(Environmental Science)
Food Science
Biochemistry
A. Positions and Honors.
1986-1988
Postdoctoral Affiliate, Stanford University
1986-1986
Visiting Postdoctoral, University of California, Davis
1986-1989
Postgraduate Research Biochemist, University of California, Davis
1989-1998
Assistant Research Biochemist, University of California, Davis
1998-present Associate Research Biochemist, University of California, Davis
2002-present Associate Professor, Department of Chemistry, University of Louisville
2003-present Associate Professor, Department of Pharmacology and Toxicology, University of
Louisville
Professional Activities:
2004-present
Editorial Board Metabolomics Journal
2004-present
Editorial Board Environmental Health Perspectives
2005-present
Organizing Committee, Annual meeting of the Metabolomics Society,
Boston, 2006
B. Selected peer-reviewed publications (in chronological order) (from 54).
1. Fan T.W-M., R.M. Higashi, A.N. Lane, and O. Jardetzky.(1986) "Combined Use of 1H NMR
and GC/MS for Metabolite Monitoring and In Vivo 1H NMR Assignments", Biochim.
Biophysica Acta 882:154-67
2. T.W.-M. Fan, T.D. Colmer, A.N. Lane, and R.M. Higashi. (1993). "Determination of
Metabolites by 1H NMR and GC: Analysis for Organic Osmolytes in Crude Tissue
Extracts", Anal. Biochemistry, 214, 260-271
3. T.W.-M. Fan, R.M. Higashi, and J.M. Macdonald, "Emergence and Recovery Response of
Phosphate Metabolites and Intracellular pH in Intact Mytilus edulis as Examined In Situ by
In Vivo 31P NMR", Biochimica et Biophysica Acta, 1092, 39-47 (1991).
4. T. W.-M. Fan, R.M. Higashi, and A.N. Lane, "Effects of Temperature on In Vivo
Unidirectional Rates of ATP Turnover in Tail Muscle of Intact Ridgeback Prawn (Sycionia
ingentis) as Measured by 31P NMR Saturation Transfer", Biochimica et Biophysica Acta
1135, 44-49 (1992).
5. T. W.-M. Fan and A.N. Lane, "Identification of Glycerophosphorylcholine in Mussel Ovarian
Extracts by Two-Dimensional Nuclear Magnetic Resonance", Analytical Biochemistry 206,
251-255 (1992).
6. T.W.-M. Fan, R.M. Higashi, G.N. Cherr, and M. Pillai (1992) "Use of Noninvasive NMR
Spectrocospy and Imaging for Assessing Produced Water Effects on Mussel
25
Reproduction", in: Produced Water Technological/Environmental Issues and Solutions, J.P.
Ray and F.R. Engelhardt, eds., Plenum Press, New York, pp.403-414.
7. G.N. Cherr, T.W.-M. Fan, M.C. Pillai, T. Shields, and R.M. Higashi, (1993) "Electrophoretic
Separation, Characterization, and Quantification of Biologically Active Lignin-Derived
Macromolecules", Analytical Biochemistry 214, 521-527
8. T.W.-M. Fan, A.J. Clifford, and R.M. Higashi (1994) "In Vivo 13C NMR Analysis of
composition and Organization of Perirenal Lipids in Rats Fed Vegetable and Fish Oils", J.
Lipid Res. 35(4), 678-689
9. T.W.-M. Fan (1996) "Metabolite Profiling by One and Two-Dimensional NMR Analysis of
Complex Mixtures", Progress in Nuclear Magnetic Resonance Spectroscopy, 28, 161-219
10. T.W.-M. Fan (1996) "Recent Advancement in Profiling Plant Metabolites by Multi-Nuclear
and Multi-dimensional NMR", In: Nuclear Magnetic Resonance in Plant Biology, Y.
Shachar-Hill and P.E. Pfeffer, eds., American Society of Plant Physiologists, Rockville, MD,
pp. 181-254
11. T.W.-M. Fan, R.M. Higashi, T.A. Frenkiel, and A.N. Lane. (1997). “Anaerobic Nitrate and
Ammonium Metabolism in Flood-Tolerant Rice Coleoptiles”, J. Exp. Bot. 48(314), 16551666
12. T.W.-M. Fan, A.N.Lane, and R.M. Higashi (1997) Selenium Biotransformations by a
Euryhaline Microalga Isolated from a Saline Evaporation Pond”, Environmental Science
and Technology, 31, 569-576
13. T.W.-M.Fan, R.M. Higashi, and A.N. Lane (1998) “Biotransformations of Selenium
Oxyanion by Filamentous Cyanophyte-Dominated Mat Cultured from Agricultural Drainage
Waters”, Environ. Sci. Technol. 32, 3185-3193
14. T.W.-M.Fan, A.N. Lane, D. Martens, R.M. Higashi, (1998) “Synthesis and structure
characterization of selenium metabolites”, Analyst 123(5), 875-884
15. Gradwell, M, T.W.-M. Fan, and A.N. Lane (1998) “Analysis of Phosphorylated Metabolites
in Crayfish Extracts by Two-Dimensional 1H–31P NMR Heteronuclear Total Correlation
Spectroscopy (heteroTOCSY)”, Anal. Biochem. 263 (2) 139-149
16. Larsen, E. H., Hansen, M., Fan, T., Vahl, M., J. (2001) “Speciation of selenoamino acids,
selenonium ions and inorganic selenium by ion exchange HPLC with mass spectrometric
detection and its application to yeast and algae”, Anal. At. Spectrom., 16(12), 1403-1408
17. Fan, T.W.-M, Lane, A.N., Shenker, M., Bartley, J.P., Crowley, D. and Higashi, R.M. (2001)
“Comprehensive chemical profiling of gramineous plant root exudates using high-resolution
NMR and MS”. Phytochem. 57, 209-221
18. Fan, T.W.-M., Teh, S., Hinton, D.E., and Higashi, R.M., (2002) “Selenium
biotransformations into proteinaceous forms by foodweb organisms of selenium-laden
drainage waters in California”, Aquatic Toxicology, a special Se issue with Fan as a guest
editor, 57, 65-84
19. Fan TWM, Pruszkowski E, & Shuttleworth S. (2002) 'Speciation of selenoproteins in Secontaminated wildlife by gel electrophoresis and laser ablation-ICP-MS' J Anal Atom
Spectrom. 17,1621-1623
20. Fan, T. W-M. Lane, A.N. & Higashi, R.M. (2003) In Vivo and In Vitro Metabolomic Analysis
of Anaerobic Rice Coleoptiles Revealed Unexpected Pathways. Russ. J. Plant Physiol. 50,
787-793
21. Teh SJ, Deng X, Deng DF, Teh FC, Hung SSO, Fan TWM, Liu J, Higashi RM (2004)
Chronic effects of dietary selenium on juvenile Sacramento splittail (Pogonichthys
macrolepidotus) Environ. Sci. Tech. 38, 6085-6093
26
22. Fan, T.W-M., Higashi, R.M. & Lane, A.N. (2004) "A Rapid Electrophoretic Profiling Method
for Thiol-Rich Peptides and Proteins". Phytochem. Anal. 15, 175-183
23. Ramos, A., Lane, A.N., Hollingworth, D. & Fan, T.W-M. (2004) NMR determination of the
secondary structure of the selenocysteine insertion element. Nucl. Acids Res. 32, 17461755.
24. Fan, T. W-M., Lane, A.N. & Higashi, R.M. (2004) The Promise of Metabolomics in Cancer
Molecular Therapeutics. Current Opin. Molec. Ther. 6:584-592 (invited review)
25. Fan, T. W-M., Bandura, L.L., Lane, A.N. & Higashi, R.M. (2005) Metabolomics-Edited
26. Transcriptomics Analysis of Se Anticancer Action in human lung cancer cells. Metabolomics J.
1, 325-339
27. Teresa W.-M. Fan, Richard M. Higashi, and Andrew N. Lane (in press) Integrating
Metabolomics and Transcriptomics for Probing Se Anticancer Mechanisms. Drug Metabolism
Review (invited review).
28. Lane, A.N., T.W.-M. Fan, and R.M. Higashi. Isotopomer-based metabolomic analysis by NMR
and mass spectrometry. in Biophysical Tools for Biologists, J.J. Correia and H.W. Detrich, Ed.
(in press) Academic Press: San Diego. Chapter 22.
C. Research Support.
Current:
5RO1 CA101199-02
T. W-M. Fan PI
03/01/0302/28/07
NIH/NCI
“Selenium Prevention of Tobacco Smoke-Induced Lung Cancers”
The long-term objectives are to understand the biochemical mechanism(s) of supranutritional
Se in chemoprevention and to utilize this information for mechanistic clinical studies.
BCTR0503648
04/30/07
co-PI (A. Lane PI)
05/01/05-
Susan G. Komen Foundation
“Metabolomics of breast cancer”
This grant uses metabolomics methods to analyze Se effects on breast cancer cells in culture
NSF-EPSCoR
T. W-M. Fan PI
06/05-05/08
“MS Infrastructure Grant Center for Regulatory Metabolomics: From Molecules to
Communities. A Research and Education Initiative “
The goal of this project is to establish a multidisciplinary metabolomics center to develop stateof-the-science metabolomic approaches to investigate regulatory processes occurring at
cellular to community levels
DEB0343577
02/28/08
T. W-M. Fan, co-PI
03/01/04-
NSF “Microbial Communities as Biochemical Inputs to Forest Soil Humification processes”
The goal of the project is understand how microbial biomass from different soil and climate
conditions may be humified, thereby contributing to carbon sequestration process in soil.
Recently Completed:
KSEF-296-RDE-3
06/30/06
T. W-M. Fan PI
07/01/03-
Kentucky Science and Engineering Foundation
“NMR and MS- a new tool for studying human Megakaryopoiesis”
27
The goal of this project is to profile metabolites and pathways associated with megakaryocyte
development induced by chemokines and cytokines using a combined NMR and MS
EPA319h
T. W-M. Fan PI
07/01/0102/28/05
State Water Resources Control Board
“Development of Ecotoxic indicators in Fish for Selenium TMDL Regulation in the San
Francisco Bay-Delta and San Joaquin River “
The goal of this project is to uncover reliable ecotoxic and toxic indicators for Se so that better
Se regulation can be implemented based on these indicators.
EPA R-882867601
T. W-M. Fan Investigator (S. Anderson PI)
3/1/002/28/05
EPA-NCERQA/Western Ctr for Ecosystem Indicator Res Biogeochemistry & Bioavailability
Component
DACA72-03-P-0013
T. W-M. Fan PI
4/1/0312/31/05
DoD/SERDP
“Facilitated immobilization of heavy metals in soil by manipulation with plant byproducts”
KLCRP
T. W-M. Fan PI
06/30/04
Commonwealth of Kentucky Lung Cancer Research Program
“Metabolomics of Human Cancer Cells and Anticancer Efficacy”
07/01/02-
This project provided a postdoctoral fellowship to Dr. Laura Bandura to participate in the integration
of metabolomics with cell biology for probing the anticancer action of Se compounds in lung cancer
cells.
28
NAME
POSITION TITLE
Richard M. Higashi
Associate Professor
eRA COMMONS USER NAME
RMHIGA01
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
FIELD OF STUDY
B.S.
Ph.D.
1977
1987
Post-doc
1987-1989
Chemistry
Environmental Chemistry
Environmental & Analytical
Biochemistry
University of Hawaii
University of California, Davis
Bodega Marine Laboratory, UC Davis
A.
Positions and Honors.
Appointments
1989-2000
Assistant Research Chemist, UC Bodega Marine Laboratory
1998-2001
Co-leader, Analytical and Biomarkers Core, UC EPA Center for Ecological Health
Research
1998-present Head, Environmental Chemistry Group, C Crocker Nuclear Laboratory
2001-present Section Lead, Biogeochemistry and Bioavailability Component, EPA-Pacific Estuarine
Ecosystem Indicators Research Program
2001-2006
Associate Research Chemist, John Muir Institute of the Environment’s Center for Health
and Environment, joint appointment at Crocker Nuclear Laboratory, UC Davis
2006-present Associate Professor, Dept. of Chemistry, University of Louisville
Other Experience and Professional Memberships
1984-1985
Technical Subcommittee, Environmental Hazards Assessment Comm., CA Dept. Food &
Agriculture
1986-1987
Reviewer, Draft Phase I Toxicity Identification Evaluation procedure, U.S. Environmental
Protection Agency (EPA)
1986-1990
Technical Advisory Group, U.S. EPA-California Water Quality Control Board, North Coast
NPDES Permit to Louisiana-Pacific Corp. and Simpson Paper Co.
1995
Technical Advisor, California Regional Water Quality Control Board and RMC Lonestar
Inc. on broad-screen analyses for water-column small-molecule organic and fulvic
compounds
1998
Review Panel, EPA-DOE-NSF-ONR Joint Bioremediation Program
1998-1999
Technical Committee, Evaporation Ponds section, 1990 Plan Update by San Joaquin
Valley Drainage Implementation Program/University of California
2000
Review Panel, DOE-Natural and Accelerated Bioremediation (NABIR) Program
2002
Review Panel, USEPA Superfund Minority Institutions
2003
Invited panelist, DOE Office of Science workshop on “Research Opportunities for
Studies of Contaminant Transport in Fluvial Systems at the Savannah River Site”
2003
Review Panel, USEPA Superfund Minority Institutions
2004
Peer Review of Propanil Environmental Regulations for California EPA
2004
Review Panel, NSF Division of Earth Sciences, Major Research Instrumentation Program
2005
Review Panel, NSF Metabolic Biochemistry Program
B.
Selected peer-reviewed publications (in chronological order)
Fan, T.W-M., R.M. Higashi, A.N. Lane, and O. Jardetzky. (1986) Combined use of 1H NMR and GC/MS
for metabolite monitoring and in vivo 1H NMR Assignments. Biochimica et Biophysica Acta 882:
154-167
Fan, T.W-M., R.M. Higashi, and A.N. Lane (1986). Monitoring of hypoxic metabolism in superfused plant
tissues by in vivo 1H NMR. Archives of Biochemistry and Biophysics 251(2): 674-687.
29
Fan, T.W.-M., R.M. Higashi, and A.N. Lane.(1988) An in vivo 1H and 31P NMR investigation of the effect
of nitrate on hypoxic metabolism in maize roots. Archives of Biochemistry and Biophysics 266(2):
592-606.
Fan, T. W-M. and R.M. Higashi. (1989) Reproducible NMR surface coil fabrication by combining
computer-aided-design and photoresist process. Analytical Chemistry 61: 636-638.
Fan, T.W-M., R.M. Higashi, J. Norlyn, and E. Epstein. (1989) In vivo 23Na and 31P NMR measurement of
a tonoplast Na+/H+ exchange process and its characteristics in two barley cultivars. Proceedings of
the National Academy of Sciences (USA) 86: 9856-9860.
Higashi, R.M., T. W-M. Fan, and J.M. Macdonald. (1989) Monitoring of metabolite responses of intact
Haliotis (abalones) under salinity stress by 31P surface probe localized NMR. Journal of
Experimental Zoology 249: 350-356.
Fan, T.W.-M., R.M. Higashi, and J.M. Macdonald. (1991) Emergence and recovery response of
phosphate metabolites and intracellular pH in intact Mytilus edulis as examined in situ by in vivo 31P
NMR. Biochimica et Biophysica Acta, 1092: 39-47.
Tjeerdema, R.S., T.W.-M. Fan, D.G. Crosby, and R.M. Higashi. (1991) Effects of pentachlorophenol on
intermediary metabolism and intracellular pH in abalone (Haliotis rufescens) as measured by in vivo
31P NMR spectroscopy.
Journal of Biochemical Toxicology 6(1): 45-56.
Fan, T. W.-M., R.M. Higashi, and A.N. Lane (1992). Temperature dependence of arginine kinase
reaction in the tail muscle of live Sycionia ingentis as measured in vivo by 31P NMR driven saturation
transfer. Biochimica et
Biophysica Acta 1135: 44-49
Higashi, R.M., G.N. Cherr, J.M. Shenker, J.M. Macdonald, and D.G. Crosby. (1992) A polar high
molecular mass constituent of bleached kraft mill effluent is toxic to marine organisms.
Environmental Science and Technology, 26: 2413-2420.
Fan, T.W.-M, A.N. Lane, and R.M. Higashi. (1992) Hypoxia does not affect rate of ATP synthesis and
energy metabolism n rice shoot tips as measured by 31P NMR in vivo. Archives of Biochemistry and
Biophysics 294(1): 314-318.
G.N. Cherr, T.W.-M. Fan, M.C. Pillai, T. Shields, and R.M. Higashi. (1993) Electrophoretic separation,
characterization, and quantification of biologically active lignin-derived macromolecules, Analytical
Biochemistry 214: 521-527.
Fan, T.W-M., T.D. Colmer, A.N. Lane, and R.M. Higashi. (1993) Determination of metabolites by 1H NMR
and GC: analysis for organic osmolytes in crude tissue extracts, Analytical Biochemistry 214: 260271.
Fan, T.W-M., A.J. Clifford, and R.M. Higashi. (1994) In vivo 13C NMR analysis of acyl carbon chain
composition and organization of perirenal triacylglycerides in rats fed vegetable and fish oils. J. Lipid
Research 35: 678-689.
Colmer, T.D., T.W-M. Fan, R.M. Higashi, and A. Läuchli. (1994) Interactions of Ca2+ and NaCl stress on
the ion relations and intracellular pH of Sorghum bicolor root tips: An in vivo 31P-NMR study. J. Exp.
Botany 45: 1037-1044.
Fan, T.W-M., A.N. Lane, J. Pedler, D. Crowley, and R.M. Higashi. (1994) Comprehensive analysis of
organic ligands in whole root exudate using nuclear magnetic resonance and gas chromatographymass spectrometry. Analytical Biochemistry, 251: 57-68.
Fan, T.W-M., A.N. Lane, and R.M. Higashi. (1997) Selenium biotransformations by a euryhaline
microalga isolated from a saline evaporation pond. Environmental Science and Technology, 31: 569576.
Fan, T.W.-M., A.N. Lane, T. A. Frenkiel, and R.M. Higashi. (1997) Anaerobic Nitrate and ammonium
metabolism in flood-tolerant rice coleoptiles. Journal of Experimental Botany, 48: 1655-1666.
Fan, T.W-M., Higashi, R.M. Biochemical fate of selenium in microphytes: natural bioremediation by
volatilization and sedimentation in aquatic environments. In: Environmental Chemistry of Selenium,
W.T. Frankenberger and R.A. Engberg, Eds, Marcel Dekker Inc., New York, pp. 545-563. [peer
reviewed]
Fan, T.W-M., R.M. Higashi, and A.N. Lane. (1998) Biotransformations of selenium oxyanion by
filamentous cyanophyte-dominated mat cultured from agricultural drainage waters. Environmental
Science and Technology, 32: 3185-3193.
Fan, T.W-M., A.N. Lane, D. Martens, and R.M. Higashi. (1998) Synthesis and structure characterization
30
of selenium metabolites. The Analyst, 123: 875-884
Fan, T.W-M., Lane, A.N., Shenker, M., Bartley, J.P., Crowley, D., Higashi, R.M. (2001) Comprehensive
chemical profiling of gramineous plant root exudates using high-resolution NMR and MS.
Phytochemistry 57: 209-221
Fan, T.W-M., Teh, S.J., Hinton, D.E., Higashi, R.M. (2002) Selenium biotransformations into
proteinaceous forms by foodweb organisms of selenium-laden drainage waters in California. Aquatic
Toxicology 57(1-2):65-84.
Fan, T.W-M., Lane, A.N., and Higashi, R.M. (2003) In vivo and in vitro metabolomic analysis of anaerobic
rice coleoptiles revealed unexpected pathways. Russian J. Plant Phys., 50: 787-793.
Fan, T.W-M., Lane, A.N., and Higashi, R.M. (2004) An electrophoretic profiling method for thiol-rich
phytochelatins and metallothioneins, Phytochemical Anal. 15: 175-183.
Fan, T.W-M., Lane, A.L., Chekmenev, E., Wittebort, R.J., Higashi, R.M. (2004) Synthesis and PhysicoChemical Properties of Peptides in Soil Humic Substances, Journal of Peptide Research 63: 1-12.
Teh, S.J., Deng, X., Deng, D-F., Teh, F-C., Hung, S.O., Fan, T. W-M., Liu, J., Higashi, R.M. (2004)
Chronic Effects of Dietary Selenium on Juvenile Sacramento Splittail (Pogonichthys Macrolepidotus),
Env. Sci. Technol., 38: 6085-6093.
Rejmánková, E.J., Higashi, R.M., Grieco, J., Achee, N., Roberts, D. (2005) Volatile substances from
larval habitats as species specific oviposition stimulants for Anopheles mosquitoes. J. Medical
Entomology, 42: 95-103.
Fan, T. W-M., Lane, A.N., Higashi, R.M. (2004) The Promise of Metabolomics in Cancer Molecular
Therapeutics. Current Opinion in Molecular Therapeutics, 6: 584-592.
Fan, T.W-M., Bandura, L.L., Higashi, R.M., Lane, A.N. (2005) Metabolomics-Edited Transcriptomics
Analysis of Se Anticancer Action in human lung cancer cell. Metabolomics J., 1: 325-339.
Fan, T. W-M., Higashi, R.M., Lane, A.N.. (2006) Integrating Metabolomics and Transcriptomis for Probing
Se Anticancer Mechanisms, Drug Metabolism Reviews, 38: 1-25.
Lane A.N. Fan, T. WM., & Higashi R.M. Isotopomer-based metabolomic analysis by NMR and mass
spectrometry. In: "Biophysical Techniques: A Volume of Methods in Cell Biology, Edited by John J.
Correia and H. William Detrich, III, Academic Press, IN PRESS.
C.
Research Support
Active support
NSF (Higashi, R.)
2004 - 2008
NSF to UCD (in process of transferring to Univ. of Louisville)
Collaborative Research: Microbial Communities as Biochemical Inputs to Forest Soil Humification
Processes
Role: PI
Objectives: the formation of soil organic matter (SOM), humification, encompasses a complex suite of
biochemical processes. An often-overlooked influence of soil microorganisms on humification is that their
biomass are primary building blocks of humic substances. Since microbial communities can differ
substantially in their biochemical composition and activity across ecosystems, we hypothesize that soil
microbial community composition influences rates of humification and the amount and stability of humic
substances formed. Defining the role of microbial community metabolite composition will enhance our
conceptual understanding of SOM formation, an important step in reliably predicting C dynamics in forest
ecosystems. The biochemical and biogeochemical fate of C in microbial bodies will be followed from 8
fungal and bacterial groups isolated from a temperate and a tropical forest soil.
R01 CA101199 (Fan, T.)
2003-2006
NIH/NCI to UCD
Selenium Prevention of Tobacco Smoke-Induced Lung Cancer
Role: Co-PI
Objectives: to understand the biochemical mechanism(s) of supranutritional Se in chemoprevention and
to utilize this information for mechanistic clinical studies. A section of this involves tracing of biochemical
pathways of Se.
31
Recently Completed support
00-230-250-0 (Fan, T.)
06/15/01-03/01/05
SWRCB to UCD
Development of Ecotoxic Indicators in Fish for Selenium TMDL Regulation in the San Francisco BayDelta and San Joaquin River
Role: Co-PI
Objectives: probe the ecotoxic biochemical mechanisms underlying Se impact on indigenous aquatic
wildlife in contaminated watersheds connecting to the Bay-Delta using state-of-the science
biogeochemical and cellular biomarker tools. Utilize the results to uncover selenoproteins with the
potential to be assayed conveniently, which can then be deployed as an early warning tool for impending
Se ecotoxicity. Test the selenoprotein indicators in field studies with the aim of assessing the
effectiveness of Se Total Maximum Daily Load (TMDL) regulation on a site-specific basis.
2002-34484-12184 (Flocchini, R.)
2001-2005
USDA to UCD
Agricultural Sources of PM-10 and Ozone Precursors
Role: Co-PI
Objectives: There is a lack of information on agricultural sources of PM-10 such as fugitive dust and the
volatile non-methane reactive organic gasses (ROGs) that are precursors for ozone formation. The
serious non-attainment of PM-10 and ozone in several regions of the U.S., including California’s San
Joaquin Valley (SJV), is in large part due to lack of, or mis-information, regarding agricultural sources. In
addition, there are major changes underway in the SJV “waterscape” which – based on our earlier studies
– has the potential to cause corresponding large changes in the “airscape” of ROGs. This grant mostly
addresses ROGs, with a smaller part devoted to modeling of our existing agricultural field PM-10 data
spanning over 10 years. Full speciation of ROGs will be attempted using cryotrapping of air followed by
GC-tandem MS analyses, as well as DNPH-trapping of airborne carbonyls followed by LC-tandem MS
analyses. The initial focus is on dairy facilities in the SJV.
R-82867601 (Anderson, S.)
03/01/01-02/28/05
EPA to UCD Bodega to UCD
Pacific Estuarine Ecosystem Indicators Research Program
Role: Co-PI and Component Lead
Objectives: the overall goals of the PEEIR are to develop indicators that environmental managers can
use for 1) wetland ecosystem integrity and to develop an approach for synthesizing indicators into
technically-defensible assessments of wetland health, 2) biotic integrity for fish and invertebrate
populations within wetland communities and 3) toxicant-induced stress and bioavailability for wetland
biota. Higashi leads the Biogeochemistry and Bioavailability Component.
5-R01AI049726-02 (Rejmankova)
2000-2005
NIH to UCD
Environmental Determinants of Malaria in Belize, C.A.
Role: Co-PI
Objectives: Abundance of mosquito larvae in aquatic habitats reflect the oviposition preference of
females as well as the survival capability of larvae, regulated by a variety of ecosystem processes. Since
the bacterial community serves as food for larvae, a change in any component of the ecosystem structure
may have a substantial impact on mosquito population or replacement of one species with another.
While there are many descriptive studies of malaria vectors and their environment, key ecological factors
such as habitat selection and response to habitat change have not been adequately addressed. This
research relies on both field and experimental studies on both habitat and landscape scales, employing
combinations of nutritional and metabolite profiling, biogeochemistry, field manipulations, and remote
sensing.
32
NAME
POSITION TITLE
Lane Andrew N.
Professor of Medicine
eRA COMMONS USER NAME
ANLANE01
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
University College London
University College London
Biozentrum Basel
Stanford University
DEGREE
(if applicable)
BSc
PhD
Post doc
Post doc
YEAR(s)
1972-1975
1975-1979
1979-1983
1983-1986
FIELD OF STUDY
Biochemistry
Biochemistry
Biophysics
Biophysics
B. Positions and Honors.
Positions and Employment
1986-1994
1994-2001
London
2001-present
2002-present
Staff Scientist, National Institute for Medical Research, London
Senior Staff Scientist, National Institute for Medical Research,
Professor of Medicine, University of Louisville
Director, JG Brown NMR Facility
Joint appointments as Professor of Chemistry and of
Biochemistry, University of Louisville
Associate Director, Center for Regulatory and
2005-present
Analytical
Metabolomics, U. Louisville.
Other Experience and Professional Memberships
Editorial Board Nucleic Acids Research 2000-present
Editorial Board J. Structural and Functional Genomics 1999-2007
Committee British Biophysical Society 1997-2001
Editor, Biophysics, Central European Journal of Biology since 2006
Honors
Honorary Research Fellow, Department of Biochemistry and Molecular Biology, University
College London
EMBO Fellow at Stanford University 1983-1985
James Graham Brown endowed chair of Structural Biology, University of Louisville.
B. Selected peer-reviewed publications (in chronological order). From 138 publications
1. Roberts, J.K.M., Lane, A.N., Clark, R.A. & Niemann, R.H. (1985) Relationships Between the
Rate of Synthesis of ATP and the Mass Action Ratio for ATP Hydrolysis in Maize Root Tips,
Determined by 31P NMR. Arch. Biochem. Biophys. 240 712-722
2. Fan T.W-M., R.M. Higashi, A.N. Lane, and O. Jardetzky.(1986) "Combined Use of 1H NMR
and GC/MS for Metabolite Monitoring and In Vivo 1H NMR Assignments", Biochim. Biophysica
Acta 882,154-67
3. Fan, T. W-M., Higashi, R.M. & Lane, A.N. (1988) An in vivo 1H and 31P NMR Investigation
of the Effect of Nitrate on Hypoxic Metabolism in Maize Roots. Arch. Biochem. Biophys. 266
592-606
4. Lane, A.N. (1990) Determination of solution structures of nucleic acids by NMR. Biochim.
Biophys. Acta. 1049 189-204
33
5. Fan, T. W-M., Higashi, R. M. & Lane, A.N. (1992) Temperature dependence of the arginine
kinase reaction in the tail muscle of live Sycionia ingentis as measured in vivo by 31P NMR
driven saturation transfer. Biochim. Biophys. Acta. 1135 44-49
6. Fan, T. W-M. & Lane, A.N. (1992) Identification of glycerophosphorylcholine in mussel
ovarian extracts by two-dimensional NMR. Anal. Biochem. 206 251-255
7. Lane, A.N. (1993) "NMR Studies of Dynamics in Nucleic Acids". Prog. NMR Spectroscopy 25
481-505
8. Lane, A.N. & Lefèvre, J-F. (1994) "NMR measurements of slow conformational dynamics in
macromolecules". Meths Enzymol. 239 596-619
9. Fan, W-M., Lane, A.N. and Higashi, R.M. (1997) Se biotransformations by a euryhaline
microalga isolated from a saline evaporation pond. Environ Sci.Tech. 31, 569-576
10. Gradwell, M.J., Fan, T. W-M., and Lane, A.N. (1998) Analysis of phosphorylated
metabolites by 31P{1H} NMR heteronuclear total correlation spectroscopy (HeteroTOCSY). Anal
Biochem. 263, 139-149
11. Gyi, J.I., Lane, A.N., Conn, G.L. & Brown, T. (1998) Solution structures of DNA.RNA hybrids
with purine-rich and pyrimidine-rich strands: comparison with the homologous DNA and RNA
duplexes. Biochemistry 37, 73-80
12. Asensio, J-L., Brown, T. & Lane, A.N. (1998) Comparison of the solution conformations of
two parallel DNA triple helices containing adjacent and non-adjacent CG.C+ triplets. Nucl. Acids
Res. 26, 3677-3686
13. McIntosh, P.B, Taylor, I.A, Frenkiel, T.A., Smerdon, S.J. & Lane, A.N. (1999) NMR
assignments of Mbp1 and its complex with DNA. J. Biomol. NMR. 13, 397-398
14. Asensio, J-L., Carr, R., Brown, T. & Lane, A.N. (1999) Conformational and thermodynamic
properties of parallel intramolecular triple helices containing a DNA, RNA or 2'-OMeDNA third
strand. J. Am. Chem. Soc. 121, 11063-11070
15. McIntosh, P.B., Taylor, I.A., Frenkiel, T.A., Smerdon, S.J. & Lane, A.N. (2000) The
influence of DNA-binding on the backbone dynamics of the yeast cell-cycle protein Mbp1. J.
Biomolec. NMR. 16, 183-196
16. Lane, A.N., Hays, L.M., Tsvetkova, N., Feeney, R.E., Crowe, L.M. and Crowe, J.H. (2000)
Comparison of the solution conformation and dynamics of antifreeze glycoproteins from
Antarctic fish. Biophys. J. 78, 3195-3207.
17. Fan, T. W-M. & Lane, A.N. (2000) "Nuclear Magnetic Resonance in Analysis of Plant-Soil
Environments". Encyclopedia of Analytical Chemistry, (R.A. Meyers, Ed.) pp 4092-4108. Wiley,
Chichester.
18. Lane, A.N. (2001) "Determination of the structures of drug-DNA complexes in solution by
NMR". Methods Enzymol. 340, 252-281
19. Alexandrovich, A., Czisch, M., Frenkiel, T.A., Moolenaar, G.F., Goosen, N., Sanderson,
M.R.& Lane, A.N. (2001) Quaternary structure, thermodynamics and dynamics of the C-terminal
domain of UvrB. J. Biol. Ster. Dyn. 19, 219-236
20. Lane, A.N., Kelly, G., Ramos, A. & Frenkiel, T.A. (2001) Determining binding sites in proteinnucleic acid complexes by cross-saturation. J. Biomolec. NMR 21, 127-139
21. Nair, M., McIntosh, P.B., Frenkiel, T.A., Kelly, G., Taylor,I.A., Smerdon, S.J., & Lane A.N.
(2003) NMR Structure of the DNA-binding Domain of the Cell Cycle protein, Mbp1 from
Saccharomyces cerevisiae. Biochemistry, 42 1266 –1273
22. Gyi, J.I., Gao, D., Conn, G.L., Trent, J.O., Brown, T. & Lane, A.N. (2003) The solution
structure of a DNA·RNA duplex containing 5-propynyl U and C; comparison with 5-Me
modifications. Nucl. Acids Res 31, 2683-2693.
23. Fan, T. W-M. Lane, A.N. & Higashi, R.M. (2003) In Vivo and In Vitro Metabolomic Analysis
of Anaerobic Rice Coleoptiles Revealed Unexpected Pathways. Russ. J. Plant Physiol. 50,
787-793
34
24. Fan, T.W-M., Higashi, R.M. & Lane, A.N. (2004) "A Rapid Electrophoretic Profiling Method
for Thiol-Rich Peptides and Proteins". Phytochem. Anal. 15, 175-183
25. Ramos, A., Lane, A.N., Hollingworth, D. & Fan, T.W-M. (2004) NMR determination of the
secondary structure of the selenocysteine insertion element. Nucl. Acids Res. 32, 1746-1755
26. Fan, T. W-M., Lane, A.N. & Higashi, R.M., (2004) The Promise of Metabolomics in Cancer
Molecular Therapeutics. Current Opin. Molec. Ther. 6:584-592 (invited review)
27. Lane, A.N. & Sengodagounder Arumugam (2005). Improving NMR sensitivity in room
temperature and cooled probes with dipolar ions. J. Magn. Reson. 173, 339-34
28. Booth, J., Brown, T., Vadhia, S.J., Lack, O., Cummins,W.J., John O. Trent, J.O., & Lane
A.N. .(2005) Determining the origin of the stabilization of DNA by 5-aminopropynylation of
pyrimidines. Biochemistry. 44,4710-4719
29. Arumugam, S., Gray, R.D. & Lane. A.N. (2005) 1H, 15N and 13C assignments of the alkaline
proteinase inhibitor APRin from Pseudomonas aeruginosa. J. Biomolec. NMR. 11, 265-266
30. Fan, T. W-M., Bandura, L.L., Lane, A.N. & Higashi, R.M. (2005) Metabolomics-Edited
Transcriptomics Analysis of Se Anticancer Action in human lung cancer cells. Metabolomics J.
1, 325-339
31. Telang S. Yalcin A., Clem A. L.,Bucala R., Lane A. N., Eaton, J. W., & Chesney J. A. (2006)
Ras Transformation Requires Metabolic Control by 6-Phosphofructo-2-Kinase. Oncogene 25:
7225-7234
32. Fan, T. W-M., Bandura, L.L. Lane, A.N. & Higashi, R.M., (2006) “ Integrating Genomics and
Metabolomics for Probing Se Anticancer Mechanisms”. Drug Metabolism Reviews 38, 1-25
33. Lane, A.N., Fan, T-WM. & Higashi, R.M. (2007) “Isotopomer-based metabolomic analysis
by NMR and mass spectrometry". Biophysical Tools for Biologists, Volume 1, edited by Drs.
John J. Correia and H. William Detrich. Ch 22. In press
34. Lane, A.N. & Fan, T. W-M. (2007) Determination of positional isotopomers in metabolites.
Metabolomics In Press
35. Fan, T.W-M. & Lane, A.N. (2007) Structure-based profiling of Metabolites and Isotopomers
by NMR, Prog. NMR Spectrosc. In Press
C. Research Support
Ongoing support:
PI 05/05-04-07 BCTR0503648 Susan G. Komen Foundation “Metabolomics of breast cancer”
Co-PI 05/05-04/10. NIH RO1 CA113735-01 “Development of Nucleolin targeted anticancer
components” (J. Trent PI) My role is to oversee protein expression and NMR analysis.
PI. 04/04 to 03/07 Commonwealth of Kentucky Lung Cancer Research Program.
“Expression and Characterization of the CXCR4 Receptor Protein”. This project is to
express and purify CXCR4 receptor and the ligands SDF-1 and vMIPII and characterize
them by biophysical methods.
PI. 06/03-06/06 1RO1 CA101199. NCI “Selenium Prevention of Tobacco Smoke-Induced
Lung Cancers”. (subcontract from UC Davis). This project involves biochemical and
biophysical analysis of lung tissue from a mouse lung cancer model, in response to dietary
Se supplementation. 1 year extension to 07/07.
PI. JG Brown Chair in Structural Biology, Kentucky’s Research Challenge Trust Fund.
35
and The James Graham Brown Foundation. Support for research and activities in any area
related to cancer biology.
Co-investigator 08/03-07/08 NIH FP RR-02-007 (P.I. Miller, D.M.) NIH "COBRE"
My role is to provide support for protein expression and NMR in projects supported by the
grant.
Co-I 06/05-05/10 NIH RO1 “Targeting of 6-phosphofructokinase2 in cancer” (J. Chesney,
PI).My role is to provide NMR-based metabolomics support.
Co-PI 06/05-05/08 NSF-EPSCoR EPS-0447479 “Center for Regulatory Metabolomics: From
Molecules to Communities. A Research and Education Initiative”. (T. Fan, PI)
This is an infrastructure grant that provides mass spectrometry instrumentation and support.
Completed Research:
PI 04/05-03/06 NIH, S10 GRNT041005, "Analytical Ultracentrifuge”.
This was an instrumentation grant to provide infrastructure for the Biophysics Core facility.
Co-investigator (J.O. Trent, P.I.) Department of Defense Breast Cancer Initiative New Idea
Award BC011113 “Mechanisms for blocking breast cancer metastasis:CXCR4, a novel
target”. 04/01/02 to 03/31/05.
The goal of this project is to apply structure-based drug design to inhibiting CXCR4. This
includes the development of membrane protein modeling in solvated lipid bilayers. I am
responsible for the NMR and biophysics experiments.
Co-investigator. (J.O. Trent, P.I.) Commonwealth of Kentucky Lung Cancer Research Program
"Design of Nucleolin inhibitors". 07/02-06/05
This project assesses G-rich oligonucleotides as anti-proliferative agents by targeting nucleolin.
My role is in the analysis of the oligonucleotides and their interaction with nucleolin.
Co-investigator 07/03-06/06 KSEF-296-RDE-3 (T. W-M Fan, PI) “NMR and MS a new tool
for studying
human megakaryopoiesis”. I provide the NMR expertise for metabolic analysis of cell
extracts.
36