Program Director/Principal Investigator (Last, First, Middle):
Meyskens, Frank L.
5P30CA062203-17
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
John J. Krolewski
Professor of Pathology &
Laboratory Medicine
eRA COMMONS USER NAME
KROLEWSKI
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Mass. Inst. of Technology, Cambridge, MA
New York Univ. Medical School, New York, NY
New York Univ. Medical Center, New York, NY
DEGREE
(if applicable)
MM/YY
SB-SM
MD-PhD
N/A
06/77
06/84
06/89
FIELD OF STUDY
Life Sciences
Medicine/Biochemistry
Resident/Postdoc
A. Personal Statement.
I trained at MIT and NYU Medical School, receiving an MD-PhD (Biochemistry) in 1984. After completing a
full residency in Anatomic Pathology, followed by a post-doctoral fellowship in cancer biology (with Riccardo
Dalla-Favera) at NYU and Columbia P&S, I was appointed an Assistant and then Associate Professor at
Columbia. In 1998 I became Associate Professor of Pathology at UC Irvine. I am currently Professor of
Pathology and Laboratory Medicine at UC Irvine, an Attending Pathologist at UCI Medical Center and the
Director of the Diagnostic Molecular Pathology Lab, a CLIA certified clinical laboratory specializing in
nucleic acids based diagnostic testing for genetic and neoplastic diseases.
My research activities have been focused on cytokine signaling in response to interferons and more recently
cytokine signals controlling apoptosis in prostate cancer. I have an 18 yr history of NIH funded research
focused on aspects of JAK-STAT interferon signaling. Since 2003, I have moved its focus to mechanism of
apoptotic cell death in normal and neoplastic prostate epithelial cells. The underlying rationale for this work
is to harness apoptosis as a therapy for prostate cancers, especially localized cancers. The normal rodent
prostate is an excellent model for early stage prostate cancer. In collaboration with O. Nalcioglou, we
developed a novel MRI method to quantitate prostate regression/apoptosis in genetically engineered mouse
models. Using these tools, we have determined that TNF and FasL are required for prostate apoptosis and
that down-regulation of the capase-8 inhibitor FLIP may also contribute. We are characterizing the
interactions among these death receptor ligands, TGFß, IGF1 and FLIP in prostate apoptosis and using this
knowledge to formulate potential therapies.
In addition to my investigative and clinical activities I am the director of the Experimental Tissue Resource
(ETR), which provides histology, tissue analysis and tumor banking services to cancer center investigators.
B. Positions and Honors.
Positions and Employment
1989-1990
1990-1997
1997-1998
1998-2009
200919992001-
Associate Research Scientist, Columbia University, College of P&S; New York, NY
Assistant Professor of Pathology, Columbia Univ., College of P&S; New York, NY
Associate Professor of Pathology, Columbia Univ., College of P&S; New York, NY
Associate Professor of Pathology & Laboratory Medicine, UC IRVINE; Irvine, CA
Professor of Pathology & Laboratory Medicine, UC IRVINE; Irvine, CA
Director, Diagnostic Molecular Pathology Clinical Laboratory, UCIMC; Irvine, CA
Director, Experimental Tissue Resource, UC IRVINE NCI funded CFCCC; Irvine, CA
PHS 398/2590 (Rev. 06/09)
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Biographical Sketch Format Page
Program Director/Principal Investigator (Last, First, Middle):
Meyskens, Frank L.
5P30CA062203-17
Other Experience and Professional Memberships:
1995-1996
1996
1996
1998
2002
1997-2003
2003-2006
2004
2005, 07, 08
2006
2005-2009
2006-2009
Ad hoc Study Section Member (Scientific Personnel A), American Cancer Society
Ad hoc Study Section Member (Pathology B Study Section), National Institutes of Health
Ad hoc Site Visit Reviewer, Food & Drug Administration CBER Unit
Ad hoc Reviewer, Veterans Affairs, Merit Review Program
Study Section Member, (RFA: Nutrients in Prostate Cancer), National Institutes of Health
Study Section Member (Tumor Biochem.), American Cancer Soc. (Chair 2003)
Ad hoc Study Section Member, (CAMP), CSR, National Institutes of Health
Ad hoc Study Section Member, (NCI-C), Program Project grants, National Institutes of Health
Study Section Member, (CBY-3, CBY-1) DOD Prostate Cancer Res. Program
Study Section Member, (NCRR), CTSA Planning Grants, National Institutes of Health
Study Section Member, Univ. CA, Cancer Research Coordinating Committee (CRCC)
Study Section Member (CAMP), CSR National Institutes of Health
Honors:
1977
1977-1984
1986-1987
1987-1989
1989-1992
1992-1996
1997
John Asinari Award for Undergraduate Biology Research
NRSA Medical Scientist Traineeship
NRSA Pathobiology Traineeship
American Cancer Soc. Postdoctoral Fellowship
Leukemia Society of America Special Fellowship
Hirschl/Weill-Caulier Career Scientist Award
American Cancer Soc. Jr. Faculty Award (1992-1995); Pluto Society
C. Fifteen (15) selected peer-reviewed publications (from 54 total).
Most relevant to the current application:
1. Nastiuk, K.L., Kim, J. Mann, M. and Krolewski, J.J. (2003). Androgen regulation of FLICE-like inhibitory
protein gene expression in the rat prostate. J. Cellular Physiol., 196:386-393.
http://www.ncbi.nlm.nih.gov/pubmed/12811833
2. Nastiuk, K.L., Liu, M.H., Hamamura, M., Muftuler, T., Nalcioglu, O. and Krolewski, J.J. (2007). In vivo
MRI volumetric measurement of prostate regression and growth in mice. BMC Urol., 7:12.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1945027/pdf/1471-2490-7-12.pdf
3. Nastiuk, K.L., Yoo, K., Lo, K., Su, K., Yeung, P., Kutaka, J., Danielpour, D. and Krolewski, J.J. (2008).
FLICE-like inhibitory protein blocks transforming growth factor ß1-induced caspase activation and
apoptosis in prostate epithelial cells. Mol. Cancer Res., 6:231-242.
http://www.ncbi.nlm.nih.gov/pubmed/18314484
3. Cornforth, A.N., Davis, J.S., Khanifar, E., Nastiuk, K.L. and Krolewski, J.J. (2008). FOXO3a mediates
the androgen-dependent regulation of FLIP and contributes to TRAIL-induced apoptosis of LNCaP cells.
Oncogene, 27:4422-4433.
http://www.ncbi.nlm.nih.gov/pubmed/18391984
4. Nastiuk, K.L. and Krolewski, J.J. (2008). REVIEW: FLIP-ping out – death receptor signaling in the
prostate. Cancer Biol. & Therapy, 7:1171-1179.
http://www.ncbi.nlm.nih.gov/pubmed/18719361
5. Yoo, K., Nastiuk, K.L. and Krolewski, J.J. (2009) Transforming growth factor-ß1 induces apoptosis by
suppressing FLICE-like inhibitory protein in DU-145 prostate epithelial cells. Intl. J. Cancer, 124:834-842
http://www.ncbi.nlm.nih.gov/pubmed/19048627
PHS 398/2590 (Rev. 06/09)
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Program Director/Principal Investigator (Last, First, Middle):
Meyskens, Frank L.
5P30CA062203-17
Additional relevant publications:
1. Davis JS, Nastiuk KL, Krolewski JJ. (2011) TNF Is Necessary for Castration-Induced Prostate
Regression, Whereas TRAIL and FasL Are Dispensable. Mol Endocrinol., 25:611-620.
http://www.ncbi.nlm.nih.gov/pubmed/21292828
2. Krolewski, J.J. and Dalla-Favera, R. (1991). The ltk gene encodes a novel receptor-type protein
tyrosine kinase. EMBO J., 10:2911-2919.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC453005/pdf/emboj00108-0189.pdf
3. Colamonici, O.R., Yan, H., Domanski, P., Handa, R., Smalley, D., Mullersman, J., Witte, M., Krishnan,
K., and Krolewski, J.J. (1994). Direct binding and tyrosine phosphorylation of the type I interferon
receptor alpha-subunit by the p135tyk2 tyrosine kinase. Mol. Cell. Biol., 14: 8133-8142.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC359352/pdf/molcellb00012-0465.pdf
4. Yan, H., Krishnan, K., Greenlund, A.C., Gupta, S., Lim, J.T.E., Schreiber, R.D., Schindler, C. W. and
Krolewski, J.J. (1996). Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking
site for the latent form of the 113 kD STAT2 protein. EMBO J., 15:1064-1074.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC450004/pdf/emboj00005-0112.pdf
5. Yan, H., Krishnan, K., Lim, J.T.E., Contillo, L.G. and Krolewski, J.J. (1996). Molecular characterization
of an interferontransduction. Mol. Cell. Biol., 16:2074-2082.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC231194/?tool=pubmed
6. Yan, H., Piazza, F., Krishnan, K., Pine, R. and Krolewski, J.J. (1998). Definition of the interferonreceptor-binding domain on the TYK2 kinase. J. Biol. Chem., 273:4046-4051.
http://www.jbc.org/content/273/7/4046.full.pdf+html
7. Krishnan, K., Singh, B. and Krolewski, J.J. (1998). Identification of amino acid residues critical for the
Src-homology 2 domainJ. Biol. Chem.,
273:19495-19501.
http://www.jbc.org/content/273/31/19495.full.pdf+html
8. Nastiuk, K.L., Mansuhkani, M., Terry, M.B., Kularatne, P., Rubin, M.A., Melamed, J., Gammon, M.D.,
Ittmann, M.M. and Krolewski, J.J. (1999). Common mutations in BRCA1 and BRCA2 do not contribute
to early prostate cancer in Jewish men. Prostate, 40:172-177.
http://www.ncbi.nlm.nih.gov/pubmed/10398279
9. Nguyen, V.P., Saleh, A.Z.M., Arch, A.E., Yan, H., Piazza, F., Kim, J. and Krolewski, J.J. (2002). Stat2
binding to the interferon alpha receptor 2 (IFNaR2) subunit is not required for interferon-alpha signaling
J. Biol. Chem., 277:9713-9721.
http://www.jbc.org/content/277/12/9713.full.pdf+html
10. Saleh, A.Z.M., Fang, A.T., Arch, A.E., Neupane, D. El Fiky, A. and Krolewski, J.J. (2004). Regulated
proteolysis of the IFNaR2 subunit of the interferon-alpha receptor. Oncogene, 23:7076-7086.
http://www.ncbi.nlm.nih.gov/pubmed/15286706
D. Research Support:
Ongoing Research Support:
5P30CA062203-16 Meyskens (PI)
02/01/09-01/31/14
NIH/NCI
University of California Irvine Cancer Center Support Grant Infrastructure and Research award to support
cancer research at UC Irvine and beyond.
Role: Dr. Krolewski is the Director of the Pathology Research Services Core. He is the administrative
coordinator for a group of departmental faculty and support staff who provide histology, genotyping,
image analysis, tissue banking and laser-capture microscopy services to UCI Chao Family
Comprehensive Cancer Center investigators.
PHS 398/2590 (Rev. 06/09)
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Program Director/Principal Investigator (Last, First, Middle):
Meyskens, Frank L.
5P30CA062203-17
R01 CA151753
Krolewski (PI)
09/01/11-07/31/16
NCI
An Androgen-Regulated Cytokine Network Controls Prostate Apoptosis
The overall goal is determine the mechanisms and physiological relevance of death receptor signaling
during the process of androgen withdrawal induced apoptosis.
Role: PI
Completed Research Support
R01 CA056862
Krolewski (PI)
06/18/92-05/31/11
NCI
Signaling via proteolysis of the interferon receptor
The overall aim is to characterize the regulated intramembrane cleavage of the IFNaR2 receptor and
determine the role of these cleavage events in signaling by type I interferons.
Role: PI
1W81WH0810204-3 Krolewski (PI)
03/15/08-03/14/11
DOD
The role of Tumor Necrosis Factor Signaling in Prostate Apoptosis
Role: PI
PHS 398/2590 (Rev. 06/09)
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