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Pulmonary Lab

Dr. James C. Willey, M.D.

Principal Investigator, Pulmonary Lab
Professor of Medicine and Pathology
George Isaac Chair In Cancer Research
Email: james.willey2@utoledo.edu

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"I am a Pulmonary/Critical Care sub-specialist in Internal Medicine with more than 25 years of continuous funding from the National Institutes of Health in translational research.Ìý My Pulmonary/Critical Care training was completed at the National Heart, Lung and Blood Institute and the University of Rochester School of Medicine, Strong Memorial Hospital.Ìý I am currently Professor of Medicine and Pathology, and George Isaac Chair for Cancer Research.Ìý I am actively engaged in care of patients with pulmonary and/or critical care problems and education of medical students, Internal Medicine residents, and Pulmonary Fellows.Ìý My laboratory focuses on characterization of inter-individual genetic variation in risk for lung cancer and COPD.Ìý Towards this goal, we also develop methods to optimize to quality control in next generation sequencing analysis of germline and somatic variants associated with risk for lung cancer and COPD.Ìý Since 2005, my laboratory has participated in United States Food and Drug Administration (FDA) collaborative projects to improve quality control in genetic testing, most recently the Sequencing Quality Control (SEQC) consortium.Ìý Through these FDA consortia, as of 2020 I have co-authored six Nature Biotechnology articles reporting results from these collaborative projects.Ìý Since 2012 my laboratory has been a member of the International Early Lung Cancer Action Program (I-ELCAP) and my laboratory has enrolled subjects into this ground-breaking effort that documented the benefits of low dose CT screening in early detection of lung cancer.Ìý As of 2020, I am an Associate Member of the National Cancer Institute Early Detection Research Network (EDRN).Ìý The goal of the EDRN is to discover, develop, and validate biomarkers that improve early detection of cancer.Ìý As of 2020, I am a site project director in the National Human Genome Research Institute sponsoredÌýGenetic Epidemiology of Lung Cancer Consortium (GELCC).Ìý The goal of the GELCC is to identify hereditary genetic variants associated with lung cancer risk. As of 2020, I am Co-System Director of the Pulmonary System in the University of Toledo College of Medicine medical school curriculum, with responsibility to develop and deliver content to prepare medical students for USMLE Steps 1 and 2."

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Research Interests

• Determining molecular genetic basis of cancer riskÌý
• 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.Ìý 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

Education

University of Vermont, Burlington, VTÌýÌý B.A., 1974, Zoology
Medical College of Ohio, Toledo, OHÌý M.D., 1978, Medicine

Pulmonary Training

1984-1986- Senior Staff Fellow National Heart Lung and Blood Institute: Pulmonary Branch (R.G. Crystal)
1993-1994- Strong Memorial Hospital, University of Rochester (Richard Hyde/Mark Utell)

National Cancer Institute Post-Doctoral Fellowships

1981-1984- Medical Staff Fellow National Cancer Institute; Laboratory of Human Carcinogenesis (C.C. Harris)
1984-1986- Senior Staff Fellow National Heart Lung and Blood Institute: Pulmonary Branch (R.G. Crystal)
1986-1990- Biotechnology Fellow and Expert National Cancer Institute

Specialty Training

1978–1981 Resident - Internal Medicine
Georgetown-VA Internal Medicine Residency Program
VA-Hospital and Georgetown University; Washington, D.C.

Academic Appointments

2002-PresentÌý	Professor of Medicine and Pathology, Pulmonary and Critical Care Division, Dept. of Medicine, University of Toledo (previously Medical College of Ohio).
2001-Present	Professor of Medicine, Pulmonary and Critical Care Division, Dept. of Medicine, University of Toledo.
2000-Present	George Isaac Professor for Cancer Research, University of Toledo.
1994-2000	Associate Professor of Medicine, Pulmonary and Critical Care Division, Dept. of Medicine, University of Toledo.
1990-1994	Assistant Professor of Biophysics and Medicine, Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY
1988-1990	Expert, National Cancer Institute, Laboratory of Human Carcinogenesis, Bethesda, MD
1986-1988	Biotechnology Fellow, National Cancer Institute (NCI), Laboratory of Human Carcinogenesis,Ìý Bethesda, MD
1984-1986	Senior Staff Fellow, National Heart Lung Blood Institute, Pulmonary Branch, Bethesda, MD
1981-1984	Medical Staff Fellow, NCI, Laboratory of Human Carcinogenesis, Bethesda, MD
1979-1981	Resident, Internal Medicine, VA-Georgetown ( Georgetown University and Veterans Administration Hospitals, Administered by VA Hospital), Washington, DCÌý

NIH Study Section Service as Grant Reviewer (Last 2 years):

• 05/17/2018 at NCI
• 03/14/2018 at NCI Meeting 2018/05 ZCA1-RTRB-U-M3 SRO: Byeong-Chel Lee
• 01/25/2018 at NCI Meeting 2018/05 ZCA1-RPRB-0-M1, SRO: David Ransom
• 07/11/2017 at NCI, Meeting 2017/10 ZCA1-RTRB-U-O2 SRO: Byeong-Chel Lee
• 02/07/2017 at NCI, Meeting 2017/05 ZCA1-RPRB-M-M1 SRO: Caron Lyman

Professional Affiliations and Activities

• Early Detection Research Network; Associate Member (2017-present)
• Massive Analysis and Quality Control (MAQC) Society (2017-present)

Present Laboratory Personnel

• Erin Crawford, M.S.
• Daniel Craig, Ph.D. graduate student
• Xiaolu Zhang, Ph.D., Post-Doctoral Fellow
• Rose Zolondek, M.S. graduate student
• James Willey , M.D., Laboratory Director

Graduated Former Students

M.D/Ph.D and Ph.D. Major Research Advisor

Xaiolu Zhang, Ph.D.
Currently: Post-Doctoral Fellow, Department of Medicine, University of Toledo

Diego Morales, M.S. in Bioinformatics
Currently: Bioinformaticist, University of Pennsylvania, Philadelphia, PA

Lauren Stanoszek, M.D./Ph.D. (Willey, Major Advisor)
06/07-06/15; MD/PhD Program, College of Medicine, University of Toledo
07/15-06/19; Pathology Resident, University of Michigan

Jiyoun Yeo, Ph.D. (Willey, Major Advisor)
06/09-06/14; PhD Program, College of Medicine, University of Toledo
07/14-present; Post-Doctoral Fellow (Willey laboratory), College of Medicine, University of Toledo

Thomas Blomquist, M.D./Ph.D. (Willey, Major Advisor)
6/05 – 6/12; MD/PhD Program College of Medicine, University of Toledo
06/12-06/13: Research Assistant Professor, Dept. of Medicine, University of Toledo COM.
07/13-07/17; Pathology Resident, University of Toledo Medical Center.
07/17-Present;ÌýDirector of Molecular Diagnostics, Department of Pathology, College of Medicine, University of Toledo

D'Anna Mullins, M.D., Ph.D. (Willey, Major Advisor)
6/02 – 06/08; MD/PhD Program; College of Medicine, University of Toledo
07/08-06/2011; Internal Medicine Residency, Ohio State University Medical Center (OSUMC)
07/01/2011-06/30/13; Hematology/Oncology Fellowship, OSUMC
06/30/13-present; Hematologist/Oncologist, Licking Memorial Hospital, OH
Clinical Fellow, Hematology/Oncology, 2011-present
The Ohio State University Medical Center
Currently: Hematology/Oncology sub-specialist in practice in Columbus, OH

Timothy Graves, Ph.D.
6/1/00 – 5-31-06; Ph.D. Program, School of Medicine, Medical College of Ohio (now College of Medicine, University of Toledo). Graduated 2006
Post-Doctoral Fellowship with St. Jude's Hospital in Memphis, 2006-2007
Consultant, IMS Health 2007-2014
Presently: Executive Director, SAI MedPartners, LLC

Michael Harr, Ph.D.
8/02 – 8/06; Ph.D. program, School of Medicine, Medical College of Ohio
08/06-01/10; Post-Doctoral Fellow Case Western Reserve University School of Medicine, Cleveland, OH.
01/10-2012; Post-Doctoral Fellow Memorial Sloan Kettering, NYC
2012-present; AgencyLx, LLCGraduated 2006

Masters Program Major Research Advisor

Rose Zolondek, M.S.
09/2015-06/2018

Diego Morales, M.S.
09/2015-12/2017

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

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

Ronald Brown, M.S. graduate student 08/09-08/10
Master's program successfully completed; Boston University
Completed Master's thesis lab work in my laboratory
09/10-2014; Medical School, Wright State Medical School, Dayton, OH.

Anjali Tapadia, M.S./M.D. graduate student 01/10- 08/10
College of Medicine, University of Toledo
Completed Master's thesis work in my laboratory
09/10-06/14; Medical School, University of Toledo College of Medicine

Former Post-Doctoral Fellows
Annas Renno, M.D.; 01/2013-06/2013
Presently: Internal Medicine Resident

Aaron Baugh, M.D., 01/2014—6/2014
Presently: Internal Medicine Resident

Fadi Safi, M.D.
07/12-06/14; Pulmonary Fellow
Research training in my laboratory

Anthony Boulos;
07/13-06/15; Pulmonary Fellow
Research training in my laboratoryDavid Weaver, Ph.D., D.D.S., 1995-2002
Director of Genomics Facility, UTMC, 2002-present

Dawn-Alita Hernandez, M.D.
8/02 – 9/06; Residency and Pulmonary Training; School of Medicine, Medical College of Ohio
Presently: Assistant Professor of Pulmonary and Critical Care Medicine
University of Toledo

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
Wolfgang Schuermann, M.D. Post-doctoral Fellow 5/91 - 12/91
School of Medicine, University of Rochester
Presently: Pulmonary Medicine and Research, Hanover, Germany

Michael Apostolakos, M.D. Post-doctoral Fellow 7/91 - 1/93
School of Medicine, University of Rochester
Presently: Director, Critical Care Unit, Strong Memorial Hospital, Rochester, N.Y.

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
Vrushalee Palsule, M.S., Technician
Presently: University of Florida

Summer Undergraduate Interns (last two years)
2014
Karan Padda, Swarthmore College; Currently: Second year, Emery University School of Medicine
Taylor Arend, Denison College; Currently: First year, University of Toledo College of Medicine

2015
Paige Willey, Swarthmore College; Currently: Senior, Swarthmore College
Thad Woodard, Johns Hopkins University; Currently: Sophomore, Johns Hopkins University

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Current NIH Grant

Project NumberÌý	Project Title	Contact PI/Project Leader	Organization	FY	Admin IC	Funding IC	FY Total Cost by IC	Similar ProjectsÌý
5 U24 CA086368-17	Validation of Lunq Cancer Risk Test (LCRT) Biomarker	WILLEY, JAMES C	UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS	2018-2019	NCI	NCIÌý	$150,000	Ìý

Recently Completed NIH Grants

Project NumberÌý	Project Title	Contact PI/Project Leader	Organization	FY	Admin IC	Funding IC	FY Total Cost by IC	Similar ProjectsÌý
1R01HL108016-01	INHERITED GENETIC RISK FACTORS COMMON TO COPD AND LUNG CANCER	WILLEY, JAMES C	UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS	2011-2016	NHLBI	NHLBI	$551,872
7R21CA132806-03	STANDARDIZED NANOARRAY PCR FOR GENE EXPRESSION PROFILING OF LUNG CANCER Ìý	WILLEY, JAMES CÌý	UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS Ìý	2009-2014	NCIÌý	NCI Ìý	$153,845Ìý
5R21CA138397-02	IMPLEMENTATION OF INNOVATIVE RNA SAMPLE QUALITY CONTROL METHODS	WILLEY, JAMES C	UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS	2011-2014	NCI	NCI	$190,982
5RC2CA148572-02	VALIDATION OF A MULTI-GENE TEST FOR LUNG CANCER RISK	WILLEY, JAMES C	UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS	2010-2014	NCI	NCI	$850,365

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Patent Activity

Patent citations: 222

US Patent # US9528161
Issued 2016. Inventor: James C. Willey
Materials and methods for quality-controlled two-color RT-QPCR diagnostic testing of formalin fixed embedded and/or fresh-frozen samples

US Patent # US9683261
Issued 2017; Inventor: James C. Willey
Standardized mixtures for assessing amounts of target nucleic acids in a sample, and kits therefore.

No. WO2014082032 A1.
Allowed Feb. 12; 2018.
Entitled: Methods for standardized sequencing of nucleic acids and uses thereof.

Patents Applications Pending (Filed in last five years)

• 2015/0292,001 ÌýSubmitted: 2015 Methods for Standardized Sequencing of Nucleic Acids and Uses Thereof
• 2015/0225,798 ÌýSubmitted: 2015 Materials and Methods for Quality-Controlled Two-Color RT-QPCR Diagnostic Testing of Formalin Fixed Embedded and/or Fresh-Frozen Samples
• 02015/0184,240 ÌýSubmitted: 2015 Compositions of Standardized Mixtures and Kits Therefor
• 02014/0287,422Ìý Submitted: 2014 Method for Selecting a Treatment for Non-Small Cell Lung Cancer Using Gene Expression Profiles
• 02013/0143,207Ìý Submitted: 2013 METHODS AND COMPOSITIONS FOR IDENTIFYING BIOMARKERS USEFUL IN CHARACTERIZING BIOLOGICAL STATES
• 02012/0322,071 Submitted: 2012Ìý METHOD FOR QUANTITATIVE MEASUREMENT OF GENE EXPRESSION FOR INDENTIFYING INDIVIDUALS AT RISK FOR BRONCHOGENIC CARCINOMA
• 02010/0184,029 Submitted: 2010 METHODS AND COMPOSITIONS FOR IDENTIFYING BIOMARKERS USEFUL IN CHARACTERIZING BIOLOGICAL STATESÌý

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Representative Publications

RNAseq analysis of bronchial epithelial cells to identify COPD-associated genes and SNPs.
Yeo J, Morales DA, Chen T, Crawford EL, Zhang X, Blomquist TM, Levin AM, Massion PP, Arenberg DA, Midthun DE, Mazzone PJ, Nathan SD, Wainz RJ, Nana-Sinkam P, Willey PFS, Arend TJ, Padda K, Qiu S, Federov A, Hernandez DR, Hammersley JR, Yoon Y, Safi F, Khuder SA, Willey JC.
BMC Pulm Med. 2018 Mar 5;18(1):42. doi: 10.1186/s12890-018-0603-y.
PMID: 29506519 Free PMC Article

Baseline and annual repeat rounds of screening: implications for optimal regimens of screening.
Henschke CI, Salvatore M, Cham M, Powell CA, DiFabrizio L, Flores R, Kaufman A, Eber C, Yip R, Yankelevitz DF; International Early Lung Cancer Action Program Investigators.
Eur Radiol. 2018 Mar;28(3):1085-1094. doi: 10.1007/s00330-017-5029-z. Epub 2017 Oct 5. Erratum in: Eur Radiol. 2018 Feb 13;:.
PMID: 28983713

A lung cancer risk classifier comprising genome maintenance genes measured in normal bronchial epithelial cells.
Yeo J, Crawford EL, Zhang X, Khuder S, Chen T, Levin A, Blomquist TM, Willey JC.
BMC Cancer. 2017 May 2;17(1):301. doi: 10.1186/s12885-017-3287-4.
PMID: 28464886 Free PMC Article

Haplotype and diplotype analyses of variation in ERCC5 transcription cis-regulation in normal bronchial epithelial cells.
Zhang X, Crawford EL, Blomquist TM, Khuder SA, Yeo J, Levin AM, Willey JC.
Physiol Genomics. 2016 Jul 1;48(7):537-43. doi: 10.1152/physiolgenomics.00021.2016. Epub 2016 May 27.
PMID: 27235448 Free PMC Article

Crawford, E.L., Levin, A., Safi, F., Lu, M., Baugh, A., Zhang, X., Yeo, J., Khuder, S. A., Boulos, A. M., Nana-Sinkam, P., Massion, P., Arenberg, D. A., Midthun, D., Mazzone, P. J., Nathan, S. D., Wainz, R., Silvestri, G., Tita, J. and Willey, J. C., Lung cancer risk test trial: study design, participant baseline characteristics, bronchoscopy safety, and establishment of a bio-specimen repository, BMC Pulmonary Medicine, 2016 16:16 Epub 2016 Jan 22. DOI 10.1186/s12890-016-0178-4.

Yankelevitz DF, Yip R, Smith JP, Liang M, Liu Y, Xu DM, Salvatore MM, Wolf AS, Flores RM, Henschke CI; International Early Lung Cancer Action Program Investigators Group (including Willey, J.C.), CT Screening for Lung Cancer: Nonsolid Nodules in Baseline and Annual Repeat Rounds, Radiology, 277, 555-64, 2015 doi: 10.1148/radiol.2015142554. Epub 2015 Jun 23.

Blomquist, T.A., Crawford, E. L., Yeo, J., Zhang,X., Willey, J.C., Control for stochastic sampling variation and qualitative sequencing error in next generation sequencing, Biomolecular Detection and Quantification, online on August 28, 2015.

SEQC/MAQC-III Consortium, (Willey, J.C., co-author), A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequence Quality Control consortium, Nature Biotechnology, 32, 903–914, 2014.

Yeo, J., M.S., Crawford, E.L., M.S., Blomquist, T.M., Stanoszek, L.M., Dannemiller, R.E.,Ìý Jordan, L., Zyrek-Betts, J., M.D., de la Casas, L., Willey, J.C., Use of two-color fluorometric real-time PCR to develop molecular diagnostic tests with intrinsic quality control, PLos ONE, 9 (2),Ìý e89395, 2014.

Blomquist, T.M., Crawford, E.L., Lovett, J.L., Yeo, J., Stanoszek, L.M., Levin, A., Li, J., Lu, M., Shi, L., Muldrew, K., Willey, J.C., Targeted RNA-sequencing with competitive amplicon libraries increases reproducibility and reduces data complexity and cost, PLos ONE, 8 (11): e79120, doi:10.1371/journal.pone.0079120, 2013

Pierce, L.R., Willey, J.C., Palsule, V.V., Yeo, J., Shepherd, B.S., Crawford, E.L., Stepien, Accurate Detection and Quantification of the Fish Viral Hemorrhagic Septicemia virus (VHSv) with a Two-Color Fluorometric Real-Time PCR Assay, C.A., PLoS ONE 8(8): e71851. doi:10.1371/journal.pone.0071851

Cis-acting genetic variation contributes to CCAAT/enhancer binding protein gamma (CEBPG) expression variation in human bronchial epithelial cells, Blomquist, T.M., Brown, R.D., Crawford, E.L., de la Serna, I., Williams, K., Yoon. Y., Hernandez, D-A., and Willey, J.C., Gene Regulation and Systems Biology, Gene Regulation and Systems Biology 2013:7 125-138, 2013.

Pierce, L.R., Willey, J.C., Crawford, E.L., Palsulea, V.V., Leaman, D.W., Faisal, M., Kim, R.K., Shepherd, B.S., Stanoszek, L.M., Stepien, C.A.,*A new StaRT-PCR approach to detect and quantify fish Viral Hemorrhagic Septicemia virus (VHSv): Enhanced quality control with internal standards, Journal of Virological Methods, 189, 129-142, 2013.

Stanoszek, L.M., Crawford, E.L., Blomquist, T.M., Willey, P.F.S., Willey, J.C., RNA quality control methods for optimal BCR-ABL clinical testing in human whole blood samples, Journal of Molecular Pathology, 15, 391-400, 2013

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.

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.

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.

Shi LM, Jones WD, Jensen RV, et al., The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies. BMC Bioinformatics, 9, Suppl. 9:S10, 2008.

Sudo, H., Li-Sucholeiki, X.-C., Marcelino, L.A., Gruhl, A.N., Herrero-Jimenez, P., Zarbl, H., Willey, J.C., Furth, E.E., Coller, H,A., Kurzweil, R.l. Ekstrom, P.O., Morgenthaler, S., Gostjeva, E.V., Thilly, W.G., Fetal-juvenile origins of point mutation clusters in the adult human tracheal-bronchial epithelium: absence of effects of age, gender or smoking status, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 646, 25-40, 2008.

Crawford EL, Blomquist T, Mullins DN, Yoon Y, Hernandez DR, Al-Bagdhadi M, Ruiz J, Hammersley J, Willey JC., CEBPG regulates ERCC5/XPG expression in Human Bronchial Epithelial Cells and this regulation is modified by E2F1/YY1 interactions, Carcinogenesis, 28, 2552-2559, 2007.

Harr, MW and Willey, JC, 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, 30, 1553-60, 2007.