The University of Toledo

Dr. James C. Willey, M.D.
Position - Professor of Medicine and Pathology
E-mail: james.willey2@utoledo.edu

• Determining molecular genetic basis of cancer risk 
• Development of molecular diagnostic tests for better diagnosis and more optimized, individualized treatment of cancer
• Gene regulation in normal and malignant human lung cells
• The Development of standardized, quantitative gene expression measurement technologies, including standardized RT-PCR and standardized immunoPCR.  These novel technologies are protected by patents owned by the University of Toledo and licensed to Accugenomics, Inc. (see below)
  
  These research efforts have been funded by the National Institutes of Health (National Cancer Institute, National Heart Lung and Blood Institute, and National Institute of Environmental Health Sciences), the Third Frontier Fund of the State of Ohio, and the George Isaac Cancer Research Fund

Professional Affiliations and Activities

Professional Affiliations and Activities NIH Study Section Service as Grant Reviewer (Last 2 years):
April, 2010: ZCA1 SRLB-C (M1) B; May, 2010: ZCA1 RPRB-0 (J1) P; Sept., 2010: ZCA1 SRLB-4 (J1) B;
Nov. 2010: January, 2011:ZCA1 RPRB 0 M1 P; February, 2011: NCI-ZCA1 SRLB-5(M1);
October, 2010: PAR1-151 (SPECS); October, 2011: PAR11-151 (SPECS).
Editor-in-Chief, Gene Regulation and Systems Biology (2006-Present)
DA MicroArray Quality Control (MAQC) Consortium Member  (2005-Present)
Chief Scientific and Medical Consultant, Accugenomics, Inc. (2011-Present) http://www.accugenomics.com/index.html

Present Laboratory Personnel

Erin Crawford, M.S.
Laboratory Supervisor

Vrushalee Palsule, M.S.
Technician

Thomas Blomquist, B.S. (M.D./Ph.D. Candidate)

Lauren Stanoszek, B.S. (M.D./Ph.D. Candidate)

Jiyoun Yeo, (Ph.D. Candidate)

Xiaolu Zhang (Ph.D. Candidate)

Lindsey Pierce (Ph.D. Candidate)

James Willey, M.D.
Laboratory Director

Graduated Former Students

D'Anna Mullins, M.D., Ph.D.
Graduated in 2008
Clinical Fellow, Hematology/Oncology,  2011-present
The Ohio State University Medical Center

Yasser Aldhamen, M.S.
Graduated 2007
Ph.D. Graduate School, Michigan State University, 2007-present

Timothy Graves, Ph.D.
Graduated 2006
Post-Doctoral Fellowship with St. Jude’s Hospital in Memphis, 2006-2007
Consultant, IMS Health 2007-present

Michael Harr, Ph.D.
Graduated 2006
Post-Doctoral Fellowship, 2006- 2010
Case Western Reserve University Hematology-Oncology
Research Fellow, 2010- Present
Memorial Sloan-Kettering Cancer Center

Ding Wu, M.S.
Graduated 2000
Sr. Research Technician
University of Chicago

Former Post-Doctoral Fellows

David Weaver, Ph.D., D.D.S., 1995-2002
Director of Genomics Facility, UTMC, 2002-present

Kristy Warner, Ph.D., 2000-2003
Research Laboratory Specialist Lead
University of Michigan School of Dentistry, 2003-present

Clara Jackson, M.D./Ph.D.1996-1997
Medical School, 1997-2001
Medicine/Pediatric Residency, 2001-2005
Internal Medicine/Pediatric Practice Fremont, Ohio, 2006-present

Former MS and BS Lab Members

Charles Knight, M.S., 2002-2005
Gene Express, Inc., Toledo, 2005-2007

Bradley Austermiller, B.S., 2003-2005
Gene Express, Inc., Toledo, 2005-present

Jeff Demuth, M.S., 1995-1998
Proctor and Gamble, Cincinnati, 1998-present

Active NIH Grants

Patents Awarded

United States Patent # 5,639,606
Inventor: Willey, James C. June 17, 1997
Method for quantitative measurement of gene expression using multiplex competitive reverse transcriptase-polymerase chain reaction

United States Patent # 5,643,765
Inventor: Willey, James C. July 1, 1997
Method for quantitative measurement of gene expression using multiplex competitive reverse transcriptase-polymerase chain reaction

United States Patent # 5,876,978
Inventor, Willey, et al. March 2, 1999
Method for quantitative measurement of gene expression using multiplex competitive reverse transcriptase-polymerase chain reaction

U.S. Patent No. # 7,476,502
Inventor, Willey et al, January 1, 2009
Methods and compositions for assaying analytes

U.S. Patent No. # 7,527,930
Inventor, Willey et al, May 5, 2009
Compositions and methods of use of standardized mixtures for determining an amount of a nucleic acid

Patents Pending

Methods And Compositions For Identifying Cancer-Related Biomarkers  20070092893  Willey; James C. ;   et al.  April 26, 2007  

Methods And Compositions For Identifying Biomarkers Useful In Diagnosis And/Or Treatment Of Biological States 20070092892 Willey; James C. ; et al. April 26, 2007 

Methods And Compositions For Identifying Biomarkers Useful In Diagnosis And/Or Treatment Of Biological States 20070092891  Willey; James C. ;   et al.  April 26, 2007  

Methods and compositions for assessing nucleic acids and alleles 20060194216  Willey; James C. ;   et al.  August 31, 2006  

Databases for assessing nucleic acids 20060190192   Willey; James C. ;   et al.  August 24, 2006  

Business methods for assessing nucleic acids 20060188909   Willey; James C. ;   et al.  August 24, 2006   

Compositions and methods of use of standardized mixtures 20060188908  Willey; James C. ;   et al.  August 24, 2006   

Methods and compositions for assessing nucleic acids 20060183144  Willey; James C. ;   et al.  August 17, 2006   

Method and compositions for the diagnosis and treatment of non-small cell lung cancer using gene expression profiles  20050260586   Demuth, Jeffrey P. ;   et al.  November 24, 2005 

Methods and compositions for assaying analytes 20050239116  Willey, James C.  October 27, 2005   

Method for quantitative measurement of gene expression for indentifying individuals at risk for bronchogenic carcinoma 20040197785  Willey, James C. ;   et al.  October 7, 2004

Multiplex standardized reverse transcriptase-polymerase chain reacton method for assessment of gene expression in small biological samples 20030186246 Willey, James C. ;   et al.  October 2, 2003 

Representative Publications

Blomquist, T. Crawford, E.L., Mullins, D., Yoon, Y., Hernandez, D., Khuder, S., Ruppel, P.L., Peters, E., Oldfield, D.J., Austermiller, B., Anders, J.C., and Willey, J.C., Pattern of antioxidant and DNA repair gene expression in normal airway epithelium associated with lung cancer diagnosis, Cancer Research, 69, 8629-8635, 2009.

Blomquist T., Crawford, E. L. and Willey, J.C., Genetic variation at E2F1/YY1 and P53 consensus sites is associated with altered allele-specific expression of ERCC5 (XPG) transcript in normal human bronchial epithelium, Carcinogenesis, 31, 1242-1250, 2010.

MAQC Consortium, The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models, Nature Biotechnology, 28, 827-838, 2010.

Crawford, E. L., Blomquist, T, Mullins, D.N., Yoon, Y., Hernandez, D.R., Al-Bagdhadi,M., Ruiz,J., Hammersley, J., Willey, J.C., CEBPG regulates ERCC5/XPG expression in human bronchial epithelial cells and this regulation is modified by E2F1/YY1 interactions, Carcinogenesis, doi:10.1093/carcin/bgm214, 2007.

Harr, M. W. and Willey, James C. , The interactive transcript abundance index [c-myc*p73•]/[p21*Bcl-2] correlates with baseline level of apoptosis and response to CPT-11 in human bronchogenic carcinoma cell lines, International Journal of Cancer, 1553-1560, 2007 

Peters, EH, Rojas-Caro, S, Brigell, MG, Zahorchak, RJ, des Etages, SA, Ruppel, PL, Knight, CR, Austermiller, B, Graham, MC, Wowk, S, Banks, S, Madabusi, LV, Turk, P, Wilder, D, Kempfer, C, Osborn, TW, Willey, JC, Quantification of Variation in Transcript Abundance in Whole Blood Samples from Healthy Volunteers Using Quality-Controlled Measurement Methods, Clinical Chemistry, 53, 1030-1037, 2007.

Braun DP, Ding JD, Shaheen F, Willey, JC, Rana N, and Dmowski WP. Quantitative Expression of Apoptosis Regulating Genes in Endometrium from Women with and without Endometriosis. Fertil and Steril., 87, 263-8, 2007.

Canales, R.D.*, Luo, Y.*, Willey, J.C.*, et al, (Canales, Luo, Willey Shared lead).  Evaluation of DNA Microarray Results with Alternative Quantitative Technology Platforms, Nature Biotechnology, 24, 1115-1122, 2006. (* equal contributors)

Leming Shi*, Reid, L. H.*, Jones, W. D.*, Shippy, R.*, Warrington, J. A.*, Baker, S. C.*, Collins, P. J.*, de Longueville, F.*, Kawasaki, E. S.*, Lee, K. Y.*, Luo, Y.*, Sun, Y. A.*,

Willey, J. C.* et al, The MicroArray Quality Control (MAQC) project shows inter- and intra-platform reproducibility of gene expression measurements, Nature Biotechnology, 24, 1151-1161, 2006. (*These listed authors were project managers) 

Shippy, R., Wolber, P., Jones, W.D., Jensen, R.V.,  Johnson, C.D., Guo, X., Chudin, E., Fulmer-Smentek, Boysen, S., C., Pine, S.P., Sun Y., Willey, J.C. et al, The use of RNA sample titrations for assessing microarray performance and normalization techniques, Nature Biotechnology, 24, 1123-1131, 2006.

Peters, GJ, van Moorsel, CJA, Lakerveld, B, Smid, K, Noordhuis, P, Comijn, EC, Weaver, D, Willey, JC, Voorn, D, Van der Vijgh, WJF, Pinedo, HM, Effects of gemcitabine on cis-platinum-dna adduct formation and repair in a panel of gemcitabine and cisplatin sensitive or resistant human ovarian cancer cell lines, Int J Oncology, 28, 237-44, 2006.

Sudoa, H, Li-Sucholeiki, X-C, Marcelino, LA, Gruhl, AN, Zarbl, H, Willey, JC, Thilly, WG, Distributions of five common point mutants in the human tracheal-bronchial epithelium, Mutation Research, 596, pages 113-127, 2006.

Graves, TG, Harr, MW, Crawford, EL, Willey, JC, Stable low-level expression of p21WAF1/CIP1in A549 human bronchogenic carcinoma cell line-derived clones down-regulates E2F1 mRNA and restores cell proliferation control, Molecular Cancer, 5, 1, 2006.

Mullins, DN, Crawford, EL, Khuder, SA, Hernandez, D-A, Yoon, Y, Willey, JC, CEBPG transcription factor correlates with antioxidant and DNA repair genes in normal bronchial epithelial cells but not in individuals with bronchogenic carcinoma, BMC Cancer,  5, 141, 2005.

Harr, MW, Graves, TG, Crawford, EL, Warner, KA, Reed, CAM, and Willey, JC, Variation in transcriptional regulation of cyclin dependent kinase inhibitor p21waf1/cip1 among human bronchogenic carcinomas, Molecular Cancer,  4, 23, 2005.

Weaver, DA, Crawford, EL., Warner, KA, Elkhairi, F, Khuder, SA, and Willey, JC, Association of ABCC5, ERCC2,  XPA, and XRCC1 gene expression with cisplatin chemoresistance in non-small cell lung cancer cell lines, Molecular Cancer, 4, 18, 2005.

Willey JC, Crawford EL, Knight CR, Warner KA, Motten CA, Herness EA, Zahorchak RJ, Graves TG., Standardized RT-PCR and the standardized expression measurement center, Methods Mol Biol. 2004, 258, 13-41.

Pagliarulo V, George B, Beil SJ, Groshen S, Laird PW, Cai, J, Willey J, Cote RJ, Datar RH. Related Articles, Links  Sensitivity and reproducibility of standardized-competitive RT-PCR for transcript quantification and its comparison with real time RT-PCR, Mol Cancer, 3, 5, 2004.

Warner KA, Crawford EL, Zaher A, Roshong-Denk SL, Sharief I, Amurao GV, Coombs RJ, Elsamaloty H, Yoon Y, Al-Astal AY, Jboor N, Assaly RA, Graves TG, Knight CR, Harr MW, Sheridan TB, DeMuth JP, Zahorchak RJ, Hammersley JR, Olson DE, and

Willey JC,  The c-myc x E2F-1/p21 Interactive gene expression index augments cytomorphologic diagnosis of lung cancer in fine needle aspirate specimens, Journal of Molecular Diagnostics, 5, 176-83, 2003.

Vondracek M., Weaver D., Sarang Z., Hedberg J.J, Willey J.C. Wärngård L., and Grafström R.C.  Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and Simian virus 40 T antigen-immortalized oral keratinocytes.  Int. J. of Cancer, 99, 776-782, 2002.

Crawford, EL, Warner, KA, Khuder, SA, Zahorchak, RJ, Willey, JC. Multiplex Standardized RT-PCR for expression analysis of many genes in small clinical samples. Biochem.Biophis.Res.Commun.,293,509-516, 2002.

Crawford, E.L., Godfridus, J.P., Noordhuis, P., Rots, M.G., Vondracek, M., Grafström, R.C., Lieuallen, K., Lennon, G., Zahorchak, R.J., Georgeson, M.J., Wali, A., Lechner, J.F., Fan, P.-S., Kahaleh, M.B., Khuder, S.A., Warner, K.A., Weaver, D.A., and Willey, J.C.,  Reproducible gene expression measurement among multiple laboratories obtained in a blinded study using standardized RT (StaRT)-PCR,  Mol. Diagnosis, 6, 217-225, 2001.

Rots, M.G., Willey, J.C., Jansen, G., Van Zantwijk, C.H., Noordhuis, P., DeMuth, J.P, Kuiper, E., Veerman, A.J.P., Pieters, R. and Peters, G.J.  mRNA expression levels of methotrexate resistance-related proteins in childhood leukemia as determined by a standardized competitive template-based RT-PCR method.  Leukemia, 14, 2166-2175, 2000.

Crawford E. L, Khuder S. A., Durham S. J., Frampton, M., Utell, M.A., Thilly W.G., Weaver D.A., Ferencak W.J., Jennings C.A., Hammersley J.R., Olson D.A., Willey J.C.  Normal bronchial epithelial cell expression of glutathione transferase P1, glutathione transferase M3, and glutathione peroxidase is low in subjects with bronchogenic carcinoma. Cancer Res. 60, 1609-18, 2000.

Willey, J.C., Crawford, E.L., Jackson, C.M., Weaver, D.A., Hoban, J.C., Khuder, S.A., and DeMuth, J.P.  Expression measurement of many genes simultaneously by quantitative RT-PCR using standardized mixtures of competitive templates  Amer. J. of Respiratory Cell and Mol. Biology, 19, 16-24, 1998.