James L. Wittliff, Ph. D.

Professor of Biochemistry & Molecular Genetics

Phone Numbers: 502-852-5216 (Office) & 502-852-5694 (Lab)
Fax Number: 502-852-8008

Email: jim.wittliff@louisville.edu

Mailing Address:
Health Sciences Center, Bldg. A, Room 512A
School of Medicine, University of Louisville
Louisville, KY 40292



Additional Appointments:       

  • Co-founder and Director, Institute for Molecular Diversity & Drug Design (IMD3)
  • Research Professor of Surgery
  • Senior Scientist, James Graham Brown Cancer Center



Education:

  • Undergraduate, Chemical Engineering, Texas Technological College, Lubbock, TX,
  • B. A., Chemistry, The University of Texas at Austin
  • M. S., Biochemistry , Louisiana State University School of Medicine, New Orleans
  • Ph. D., Molecular Biology, The University of Texas at Austin
  • Post-doctoral Trainee, USPHS National Institutes of Arthritis & Metabolic Diseases, Biology Division, Oak Ridge National Laboratory



Laboratory Team Members:

  • Sean T. Butterbaugh, Adjunct Medical Student
  • Adrienne M. Bushau, Adjunct Graduate Student
  • Michael W. Daniels, M.S. Graduate Research Fellow
  • Zohair R. Hameed, Undergraduate Research Fellow
  • Seth B. Sereff, Undergraduate Research Fellow

Staff:

  • Theresa H. (Mitzie) Wittliff, Administrative Assistant

Research Focus:

For almost five decades, the Hormone Receptor Laboratory has investigated the biological properties and cellular roles of estrogen and progestin receptors in several types of human carcinomas with the goal of improving their diagnostics and treatment. For example, as inventor with NEN/DuPont of the 1st FDA approved tests for quantifying levels of estrogen and progestin receptor proteins, our laboratory collaborated with the NSABP to launch Tamoxifen as an adjuvant treatment for breast cancer.  As Director of the Hormone Receptor Laboratory in the Department of Biochemistry & Molecular Biology (now Molecular Genetics) and as a research component of The Institute for Molecular Diversity & Drug Design, our program focuses on mechanisms by which steroid and peptide hormones and their mimics induce target cells to synthesize gene products and regulate biological networks. Our goals include the assessment of environmental and therapeutic estrogen mimics to determine their role in human health. The laboratory is examining the genomics and proteomics of specific cell types isolated by the technology of laser capture microdissection (LCM) to study relationships between gene or protein expression profiles and certain cell phenotypes or host behaviors. In addition to developing novel molecular diagnostics, our studies have deciphered new molecular targets for drug design. Our laboratory with collaborators at Thermo Fisher pioneered the application of LCM for deciphering gene signatures derived from RNA Seq and Next Generation Sequencing of mRNA and miRNA expressed by specific cell types.  Many investigations utilize a unique tissue biorepository, containing thousands of specimens of human cancer biopsies, and an associated comprehensive Database of cancer biomarkers and gene signatures as well as patient characteristics and clinical follow-up.  Our experience in handling and processing of human tissue biopsies for sophisticated microgenomics and proteomics based studies and our decades of developing and using comprehensive databases have been of matchless value for our research collaborations.

Selected Publications:

  • Andres S.A., Bickett, K.E., Alatoum, M.A., Kalbfleisch, T.S., Brock, G.N., Wittliff, J.L. Interaction between smoking history and gene expression levels impacts survival of breast cancer patients. Breast Cancer Res Treat. 152(3):545-56, 2015. doi: 10.1007/s10549-015-3507-z. Epub 2015 Jul 23. PMID:26202054
  • Warner, D., Mukhopadhyay, P., Brock, G.N., Smolenkova, I.A., Seelan, R.S.  Webb, C.L.  Wittliff, J.L., Greene, R.M., Pisano, M.M. Temporal Expression of miRNAs in Laser Capture Microdissected Palate Medial Edge Epithelium from Tgfb3-Null Mouse Fetuses. MicroRNA, 4(1): 64-71, 2015 PMID: 26159804
  • Metzler, M. A., Venkatesh, S. G., Lakshmanan, J., Carenbauer, A. L., Perez, S. M., Andres, S. A., Appana, S., Brock, G. N., Wittliff, J. L., Darling, D.S. A Systems Biology Approach Identifies A Regulatory Network in Parotid Acinar Cell Terminal Differentiation. PLoS ONE 10(4): e0125153. doi:10.1371/journal.pone.0125153, 2015.
  • Wittliff, J.L., Andres, S.A. Estrogens, Their Conjugates and Estrogen Mimics (Five Chapters). Encyclopedia of Toxicology, 3rd Edition. Wexler, Philip (ed.) Elsevier Press. pp 462-484, 2014. DOI: 10.1016/B978-0-12-386454-3.01014-9
  • Wittliff, J.L., Andres, S.A. Progesterone and Progestin Mimics. Encyclopedia of Toxicology, 3rd Edition. Wexler, Philip (ed.) Elsevier Press. pp 1073-1076, 2014. DOI: 10.1016/B978-0-12-386454-3.01071-X
  • Andres S.A., Smolenkova, I.A., Wittliff, J.L. Gender-associated Expression of Tumor Markers and a Small Gene Set in Breast Carcinoma. Breast 23:226-33, 2014 Epub ahead of print March 21, 2014. PMID: 24656773
  • Seelan, R.S., Warner, D.R., Mukhopadhyay, P.M., Andres, S.A., Smolenkova, I.A., Wittliff, J.L., Pisano, M. M., Greene, R.M. Epigenetic Analysis of Laser Capture Microdissected Fetal Epithelia. Anal Biochem 442:68-74, 2013 Epub ahead of print July 30, 2013. PMID: 23911529
  • Kruer, T.L., Cummins, T.D., Powell, D.W., Wittliff, J.L. Characterization of Estrogen Response Element Binding Proteins as Biomarkers of Breast Cancer Behavior. Clin Biochem 46:1739-46, 2013 Epub ahead of print July 16, 2013. PMID: 23868020
  • Andres, S.A., Brock, G.N., Wittliff, J.L. Interrogating Differences in Expression of Targeted Gene Sets to Predict Breast Cancer Outcome. BMC Cancer 13:326-343, 2013. PMID: 23819905
  • Andres, S.A., Wittliff, J.L., Cheng, A. Protein Tyrosine Phosphatase 4A2 Expression Predicts Overall and Disease-free Survival of Human Breast Cancer and is Associated with Estrogen and Progesterone Receptor Status. Horm Cancer 4:208-221, 2013. PMID:23568563
  • Andres, S.A., Bumpus, S.B., Wittliff, J.L. Assessment of Phytoestrogen and Mycoestrogen Recognition by Recombinant Human Estrogen Receptor-α Using Ligand Titration Arrays. Phytochem Anal 24:357-366, 2013. PMID: 23401334
  • Andres, S.A., Wittliff, J.L. Co-expression of Genes with Estrogen Receptor-α and Progesterone Receptor in Human Breast Carcinoma Tissue. Horm Mol Biol Clin Investig 12:377-390, 2012.

Recent Patents & Licenses:

  • Judith L. Erb, James G. Downward, IV, John R. Erb-Downward and James L. Wittliff.  Methods and Apparatus for Measurement of the Effect of Test Compounds on Signal Transduction at the Level of Biological Receptors.  United States Patent No: US 6, 300,082 B1, Issued: October 9, 2001.
  • Judith L. Erb, James G. Downward, IV, John R. Erb-Downward and James L. Wittliff.  Methods and Apparatus for Measurement of the Effect of Test Compounds on Signal Transduction at the Level of Biological Receptors.  United States Patent No: US 20,020,137,055, Issued: September 26, 2002.
  • Judith L. Erb, James G. Downward, IV, John R. Erb-Downward and James L. Wittliff.  Methods and Apparatus for Measurement of the Effect of Test Compounds on Signal Transduction at the Level of Biological Receptors.  United States Letters Patent No: US 6,962,808 November 8, 2005.
  • Mark G. Erlander; Ranelle C. Salunga; Kimberly Stecker and James L. Wittliff  Quantitative Immunohistochemistry for Covalently Modified or Structurally Altered Proteins .  United States Application No. 60/314697, Filing Date August 22, 2001.
  • Mark G. Erlander; Ranelle C. Salunga; Kimberly Stecker and James L. Wittliff  Quantitative Immunohistochemistry (QIHC) .  United States Application No. 10/080435, Filing Date February 22, 2002.
  • Mark G. Erlander, Xiao-Jun Ma, Wei Wang and James L. Wittliff.  Breast Cancer Signatures, United States Patent Application No. 10/795092, Filing Date March 5, 2004.
  • Mark G. Erlander, Xiao-Jun Ma, Wei Wang and James L. Wittliff.  Signatures of ER Status in Breast Cancer, United States Patent Application No. 10/794263, Filing Date March 4, 2004.
  • Mark G. Erlander, Xiao-Jun Ma, Wei Wang and James L. Wittliff.  Breast Cancer Survival and Recurrence.  United States Application No. 10/871869, Filing Date:  June 18, 2004.
  • James L. Wittliff, Exclusive Technology License to Asterand, Inc., Detroit, MI, ULRF Research Disclosure 05036, Method for Creation and Maintenance of a Comprehensive Tumor Marker Database and Associated Biological Specimens for the Discovery of Cancer Diagnostics, Prognostics and Therapeutics, Executed October 28, 2005.
  • James L. Wittliff and Sarah A. Andres.  Methods for Identifying an Increased Likelihood of Recurrence of Breast Cancer.  International Patent Application No. PCT/US2008/006963, date of filing June 3, 2008.
  • James L. Wittliff, Technology License to Xceed Molecular Corp, Toronto, Canada, ULRF Research Disclosure 07048, Gene Expression Profiles Predicting Clinical Behavior of Breast Cancer.  U.S. Provisional Patent Application No. 60/933,091, date of filing June 4, 2007 (James L. Wittliff & Sarah A. Andres).
  • James L. Wittliff and D. Alan Kerr II.  Methods of Predicting Disease-Free and Overall Survival of Estrogen Receptor Positive Breast Cancer.  U.S. Provisional Patent Application No. 61/105,297, date of filing October 14, 2008.
  • James L. Wittliff and Sarah A. Andres.  Methods for Identifying an Increased Likelihood of Recurrence of Breast Cancer.  U.S. Patent Application No. 12/630.212, date of filing December 3, 2009.
  • James L. Wittliff and Sarah A. Andres.  Methods for Optimizing Treatment of Breast Cancer.  U.S. Patent Application No. 12/832,474, date of filing July 8, 2010.

 

Clinical Laboratory Licenses

  • 1976-present, Founder/Director, Hormone Receptor Laboratory, University of Louisville
  • Commonwealth of Kentucky (State License #200078 Endocrinology & Chemistry)
  • Health Care Financing Administration (Federal License – CLIA #18D0648476, Endocrinology)
  • 1984-present, Fellow of the National Academy of Clinical Biochemistry (FACB/AACC), Clinical Laboratory Medicine
  • 2011-present, Fellow of the American Society for Clinical Pathology


Recent Awards & Honors:

  • 2013 Inaugural Poster Award for Excellence in Research, Personalized Medicine Division,
                  American Association for Clinical Chemistry, Houston, TX

  • 2014  Morton K. Schwartz Award for Significant Contributions in Cancer Research Diagnostics

                   American Association for Clinical Chemistry

  • 2014  Poster Award for Excellence in Research, Molecular Pathology Division

             American Association for Clinical Chemistry, Chicago, IL