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Douglas S. Darling

Name: Douglas S. Darling, Ph. D. 

Title:
   Professor

Current Position: Director, UofL Oral Biology Graduate Program

See: http://louisville.edu/dental/oralbiology 

Professor, Department of Oral Health and Rehabilitation, UofL School of Dentistry

Phone: 502-852-5508

E-mail: douglas.darling@louisville.edu 

Background:

University

Degree

Year(s)

George Washington University, Washington, D.C.

B.S.

1977

University of Washington, Seattle, WA 

Ph. D.

1983

University of Chicago Medical School, Chicago, IL

Postdoc

1983-87

Harvard University + Howard Hughes Medical Institute, Boston, MA 

Postdoc

1987-92    

 

Academic Appointments and Center Memberships:

Professor, Department of Oral Health and Rehabilitation, School of Dentistry
Department of Biochemistry and Molecular Biology, School of Medicine
Center for Oral Health and Systemic Disease

Center for Genetics and Molecular Medicine

Institute for Molecular Diversity and Drug Design (IMD3)

Birth Defects Center


Research Interests and Current Projects
Understanding the differentiation of salivary cells is a necessary step to enable the restoration of diseased or destroyed parotid salivary tissue. We are using gene expression arrays of differentiating salivary glands to identify networks that cause terminal differentiation. We study the relation between changes of microRNAs and mRNAs during differentiation.  Computer modeling is expected to have the capacity to test the relative importance of specific pathways within the networks, allowing validation by laboratory work. 

Separately, our laboratory is interested in the regulation of gene transcription in eucaryotic cells. Current projects investigate the role of ZEB and related genes in early development, and the molecular interactions that underlie those roles.  We focus on development of the eye, which has specific defects in ZEB1-mutant mice that mimic birth defects in some human babies.  In addition, we are studying the expression of ZEB1 in oral cancer.


Teaching Activities
Introduction to Oral Biology Research, (OBIO 601) 
Oral Health Seminars, (OBIO 605)
Pathomedicine,  (IDSC 821-34)


Service (last three years)
Editorial Board, Oral Health and Dental Management (Omics Group)

NIH NIDCR Special Grants Review Committee, 2014

Austrian Science Fund, Cell and Molecular Biology, Reviewer, 2012

NIH NIDCR ZDE1 MH (14) RFA Special Review Panel, 2012 
NIH CSR ZRG1 MOSS-C (02) S - Musculoskeletal, Oral and Skin, 2010 
Portuguese Foundation for Science and Technology, Ad Hoc Reviewer, 2009 
NIH CSR ZRG1 MOSS-E (02)M, ODCS Member Conflict Special Panel, 2009 
UofL Office of Research Integrity, Associate Research Integrity Ombudsperson 2010-2014
Center for Environmental Genomics and Integrative Biology (CEGIB), 2006 - 2011
CEGIB Internal Advisory Board (Executive Committee)  
ULSD Research Committee


Publications (last 5 years)

1.    Yongqing Liu, Fei Ye, Qiutang Li, Shigeo Tamiya, Douglas S. Darling, Henry J. Kaplan, and Douglas C. Dean (2009) Zeb1 Represses Mitf and Regulates Pigment Synthesis, Cell Proliferation, and Epithelial Morphology. Invest. Ophthalmol. Vis. Sci., 50: 5080 - 5088.  doi:10.1167/iovs.08-2911

2.    U. Wellner, J. Schubert, U.C. Burk, O. Schmalhofer, F. Zhu1, A. Sonntag, B. Waldvogel, C. Vannier, D.S. Darling, A.z. Hausen, V.G. Brunton, J. Morton, O. Sansom, J. Schüler, M.P. Stemmler, C. Herzberger, U. Hopt, T. Keck, S. Brabletz, T. Brabletz.  (2009) The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nature Cell Biology, 11(12): 1487-95.  PMID: 19935649

3.    JZ Jin, M Tan, DR Warner, DS Darling, Y Higashi, T Gridley, and J Ding. (2010)
Mesenchymal cell remodeling during mouse secondary palate reorientation.
Dev Dyn, 239(7): 2110-2117, PMC2919369.

4.    Kenney, P. A., Wszolek, M. F., Rieger-Christ, K. M., Neto, B. S., Gould, J. J., Harty, N. J., Mosquera, J. M., Zeheb, R., Loda, M., Darling, D. S., Libertino, J. A. and Summerhayes, I. C. (2010) Novel ZEB1 expression in bladder tumorigenesis. BJU International, 107(4): 656-63.  doi: 10.1111/j.1464-410X.2010.09489.x    

5.    SG Venkatesh, D Goyal, AL Carenbauer, and DS Darling. (2011) Parotid secretory protein binds Phosphatidylinositol (3,4)bisphosphate. J. Dental Research, 90(9): 1085 – 1090.  DOI 10.1177/0022034511410699  

6.    AP Putzke, AP Ventura, AM Bailey, C Akture, J Opoku-Ansah, M Celiktas, MS Hwang, DS Darling, IM Coleman, PS Nelson, HM Nguyen, E Corey, M Tewari, C Morrissey, RL Vessella, and BS Knudsen. (2011) Metastatic progression of prostate cancer and E-cadherin. Regulation by Zeb1 and SRC family kinases.  Am. J. Pathol., 179(1): 400-10. PMID: 21703419

7.    Shinya Ohashi, Mitsuteru Natsuizaka, Seiji Naganuma, Shingo Kagawa, Sotai Kimura, Hiroshi Itoh, Ross A. Kalman, Momo Nakagawa, Douglas S. Darling, Devraj Basu, Phyllis A. Gimotty, Andres J. Klein-Szanto, J. Alan Diehl, Meenhard Herlyn, and Hiroshi Nakagawa. (2011) A NOTCH3-Mediated Squamous Cell Differentiation Program Limits Expansion of EMT-Competent Cells That Express the ZEB Transcription Factors.  
Cancer Research, 71: 6836 - 6847;  DOI:10.1158/0008-5472.CAN-11-0846.

8.    R. Hertzano, R.Elkon, K. Kurima, A. Morrisson, S.L. Chan, M. Sallin, A. Biedlingmaier, D.S. Darling, A.J. Griffith, D.J. Eisenman, S.E. Strome. (2011) Cell type-specific transcriptome analysis reveals a major role for Zeb1 and miR-200b in mouse inner ear morphogenesis.  PLoS Genetics 7(9):e1002309, PMCID: PMC3183091. 

9.    DS Darling, SG Venkatesh, D Goyal and AL Carenbauer (2012). Phosphatidylinositol Bisphosphate Mediated Sorting of Secretory Granule Cargo; Chapter 3 in “Crosstalk and Integration of Membrane Trafficking Pathways,” Dr. Roberto Weigert (Ed.), ISBN: 978-953-51-0515-2, InTech, Available from: http://www.intechopen.com/books/crosstalk-and-integration-of-membrane-trafficking-pathways/phosphatidylinositol-bisphosphate-mediated-sorting-of-secretory-granule-cargo   

10.  E Sanchez-Tillo, Y Liu, O de Barrios, L Siles, L Fanlo, M Cuatrecasas, DS Darling, DC Dean, A Castells, and A Postigo. (2012) EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness.   Cell Mol Life Sci, Oct 2012; 69(20): 3429-56.  PMID: 22945800.

11.  Ester Sánchez-Tilló, Oriol de Barrios, Laura Siles, Pier G. Amendola, Douglas S. Darling, Miriam Cuatrecasas, Antoni Castells, Antonio Postigo. (2013) ZEB1 promotes invasiveness of colorectal carcinoma cells through the opposing regulation of uPA and PAI-1.  Clinical Cancer Research, 19: 1071 – 1082. PMID: 23340304.

12.  Laura Siles, Ester Sánchez-Tilló, Jong-Won Lim, Douglas S. Darling, Kristen L. Kroll, Antonio Postigo. (2013) ZEB1 imposes a temporary stage-dependent inhibition of muscle gene expression and differentiation via CtBP-mediated transcriptional repression.  Molecular Cell Biology, 33: 1368 - 1382. PMID: 23339872, PMCID: PMC3624276. 

13.  Jaejik Kim, Jiaxu Li, Srirangapatnam G. Venkatesh, Douglas S. Darling and Grzegorz A. Rempala. (2013) Model Discrimination in Dynamic Molecular Systems: Application to Parotid De-differentiation Network. Journal of Computational Biology, 20(7):524-39. PMID: 23829652. 

 

 

 

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