OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME: Walter Thomas Klimecki
eRA COMMONS USER NAME (credential, e.g., agency login): WKLIMECKI
POSITION TITLE: Associate Professor of Pharmacology/Toxicology
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training
and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
Completion
Date
MM/YYYY
FIELD OF STUDY
Ohio State University
B.Sc
06/1980
Animal Science
Ohio State University
D.V.M.
06/1984
Veterinary Medicine
University of Arizona
Ph.D.
06/1994
Pharmacol./Toxicology
University of Arizona
Post. Doc
10/1997
Cancer Biology
A. Personal Statement
My research over the years has focused on the study of a carcinogenic environmental toxicant, arsenic. I have
contributed both to an understanding of its carcinogenic mechanism of action, as well as human populationlevel determinants of individual variability in susceptibility to arsenic toxicity. The publications from human
studies that I have led directly speak to the importance of my membership in the University of Arizona Cancer
Center (UACC). My work defined both genetic and non-genetic determinants of “safe” and “risky” metabolism
phenotypes in arsenic-exposed human populations. These metabolic phenotypes have been repeatedly
shown in epidemiology studies to impact cancer risk resulting from arsenic exposure. My laboratory also
studies the mechanistic underpinnings of arsenic carcinogenesis. My research group has recently published a
seminal observation describing the ability of non-cytotoxic concentrations of arsenic to impair mitochondrial
energy production, and alter fundamental cellular metabolism. We went on to relate this induction of the
Warburg effect to the ability of arsenic to effect malignant transformation of lung epithelial cells. Our work
depended on active collaborations with UACC members (Bernard Futscher), as well as UACC shared
resources. In the true spirit of Center programs, my work contributes to, and benefits from, the synergy
created under the umbrella of the UACC.
B. Positions and Honors
Positions and Employment
1997-2000
Section Manager, Genotyping Assays, Motorola Biosciences, Phoenix, Arizona
2000-Present:
Associate Research Scientist, Arizona Respiratory Center, University of Arizona
2004-Present:
Research Assistant Professor of Medicine, College of Medicine, Univ. of Arizona
2006-Present:
Professor of Pharmacology/Toxicology, University of Arizona
2008-Present:
Co-Director: Integrative Health Sciences Facility Core, Southwest Environmental Health
Sciences Center, University of Arizona
2012-Present:
Associate Professor of Pharmacology/Toxicology, University of Arizona
2013-Present:
Associate Department Head, Pharmacology and Toxicology, University of Arizona
2015-Present:
Department Head (Interim), Pharmacology and Toxicology, University of Arizona
Other Experience and Professional Memberships
1994-1996
NRSA Post-doctoral fellowship, National Cancer Institute, NIH
1999-2005
NIH Study Section Member, ZRG1-SSS-L, (SBIR,STTR, Drug Development)
2002, 2005
Study Section, Genome Canada
2005
NIH Study Section Member, ZRG1-CFS
2007, 2008
2008
2009
2010
NIH Study Section Member, ZAT1 SM
NIH Special Emphasis Panel for RFA-HL-08-008
NIH Study Section Member, ZAT1 SM
Scientific Organizing Committee, “Arsenic 2010” Biennial Meeting, Tainan City, Taiwan
2015
2015
Member
Member
Member
NIH Special Emphasis Panel (P50 in Health Disparities) ZRG1 HDM S 50
NCI Special Emphasis Panel (XCA1-SRB-L (J1)
Society of Toxicology, Vice President, Metals Specialty Section
Mountain West Regional Society of Toxicology
International Society of Environmental Epidemiology
C. Contribution to Science
My research, which has spanned the translational spectrum, focuses on the human health consequences of
exposure to environmental arsenic. One of the most important determinants of individual susceptibility to
several arsenic-associated diseases in exposed human populations is variable arsenic metabolism, reflected in
altered ratios of methylated arsenic metabolites. This methylation of arsenic is a function of the gene, AS3MT.
My laboratory published the first detailed catalog of commonly occurring genetic variation in the AS3MT gene
in human populations. In addition we published the first genetic association study of the impact of genetic
variation in the AS3MT gene on arsenic metabolism. That work established the importance of non-coding DNA
variants in AS3MT in their association with “lower risk” arsenic metabolism (relatively high urinary
dimethylarsinic acid). Many studies from other groups have followed this work using other genomic testing
platforms, confirming the importance of this genetic association.
a. Meza M, Gandolfi AJ, Klimecki WT. Developmental and genetic modulation of arsenic
biotransformation: a gene by environment interaction? Toxicology and applied pharmacology.
2007;222(3):381-7. PubMed PMID: 17306849; PubMed Central PMCID: PMC2040165.
b. Gomez-Rubio P, Roberge J, Arendell L, Harris RB, O'Rourke MK, Chen Z, Cantu-Soto E, MezaMontenegro MM, Billheimer D, Lu Z, Klimecki WT. Association between body mass index and arsenic
methylation efficiency in adult women from southwest U.S. and northwest Mexico. Toxicology and
applied pharmacology. 2011;252(2):176-82. PubMed PMID: 21320519; PMCID: PMC3075343.
c. Gomez-Rubio P, Meza-Montenegro MM, Cantu-Soto E, Klimecki WT. Genetic association between
intronic variants in AS3MT and arsenic methylation efficiency is focused on a large linkage
disequilibrium cluster in chromosome 10. J Appl Toxicol. 2010;30(3):260-70. PubMed PMID: 20014157;
PMCID: PMC2862143.
A complementary effort in my lab has been understanding the cellular processes that are disrupted by low
level, environmentally relevant arsenic exposure. That work has uncovered two cellular processes that are
perturbed by arsenic exposure. We established that arsenic exposure disrupts the homeostatic process of
autophagy, which describes a process of the delivery of cargo to the lysosome for degradation and recycling.
The impact of that work is reflected in the lab’s continued research, and in publications and grants from other
groups pursuing the interaction of arsenic with cellular autophagy. Because of the relationship of autophagy
with energy metabolism, we were interested the ability of arsenic to disrupt fundamental energy metabolism.
Recent work in my lab has shown that low-level arsenic exposure induces the Warburg effect, or glycolysis
under oxygen-replete conditions. The impact of energy metabolism disruption on chronic disease is an intense
current area of contemporary research focus, and we are excited to conduct funded work that allows us to
understand how arsenic exposure could, through disrupted energy metabolism, drive important cell biology
phenotypes such as malignant transformation.
a. Zhao F, Severson P, Pacheco S, Futscher BW, Klimecki WT. Arsenic exposure induces the Warburg
effect in cultured human cells. Toxicol Appl Pharmacol. 2013. doi: 10.1016/j.taap.2013.04.020. PubMed
PMID: 23648393; PMCID: PMC3714307
b. Zhao F, Malm SW, Hinchman AN, Li H, Beeks CG, Klimecki WT. Arsenite-induced pseudo-hypoxia
results in loss of anchorage-dependent growth in BEAS-2B pulmonary epithelial cells. PlosOne PLoS
One. 2014 Dec 16;9(12):e114549. doi:10.1371/journal.pone.0114549. eCollection 2014. PMID:
25513814
c. Zhao F, Klimecki WT. Culture conditions profoundly imkpact phenotype in BEAS-2B, a human
pulmonary epithelial model. J. Appl. Toxicol. 2014 Dec 19. doi: 10.1002/jat.3094. [Epub ahead of print]
PMID: 25524072
d. Bolt AM, Douglas RM, Klimecki WT. Arsenite exposure in human lymphoblastoid cell lines induces
autophagy and coordinated induction of lysosomal genes. Toxicol Lett. 2010;199(2):153-9. PubMed
PMID: 20816728; PMCID: PMC2956852.
Complete List of Published Work in MyBibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/1hGUixExFzN/bibliography/43172316/public/?sort=date&direction=as
cending
D. Research Support
Ongoing
1R25 ES025494-01 (Klimecki, PI)
04/02/15 – 03/31/20
NIH/NIEHS
Environmental Health Transformative Undergraduate Experience (E-H-TRUE)
The goal of this NIH research education program proposal is to provide undergraduate research education and
training in the environmental health sciences to 40 undergraduates coming from backgrounds underrepresented in the sciences.
5R03 ES023921
(Klimecki, PI)
05/19/14 –04/30/16
NIH/NIEHS
Arsenic carcinogenicity: Metabolic Disruption Leads to loss of PTEN function
The goal of this project is to test the hypothesis that arsenic carcinogenicity is the result of a disturbance in
glucose metabolism that inactivates the tumor suppressor gene, PTEN.
5P42 ES004940
(Maier,PI)
04/01/15 – 09/29/17
NIH/NIEHS
Hazardous Waste Risk and Remediation in the Southwest
Project 3: Arsenic-induced Pseudohypoxia Drives Malignant Transformation in Lung Cancer
The goal of this Superfund component project is to define the role of hypoxia signaling in arsenic-induced
malignant transformation.
Role: Project PI
5P30 ES06694
(Lau, PI)
04/01/12 – 03/31/17
NIH/NIEHS
Southwest Environmental Health Sciences
Integrative Health Sciences Core
The goal of this core is to provide support services for investigators engaged in translational research related
to potentially harmful environmental toxicant exposures. Dr. Klimecki co-directs a core facility focused on
supporting translational research.
Role: Core Co-Director
CHE-1339597
(Pemberton, PI)
09/15/13 – 08/31/17
NSF
NSMDS: Molecular Design, Synthesis and Characterization of Green Glycolipid Surfactants
The goal of this grant is to synthesize a series of glycolipid surfactants based on rhamnolipid. Dr. Klimecki’s
role is to characterize basic cytotoxicity of these analogs.
Completed
ABRC 91005
(Kimecki, PI)
07/01/11-06/30/13
Arizona Biomedical Research Commission
The Unfolded Protein Response: Mechanism of Inorganic Arsenic Resistance
This grant was focused on identifying the contribution of the unfolded protein response to differential
susceptibility to arsenic cytotoxicity in human lymphoblastoid cell lines as a model of population-level individual
susceptibility.