Dr Lingen's proposed career development plan consists of multiple rotations through laboratories with novel expertise which will be directly applicable to his proposed research endeavors. The time frames range from 1 month to 3 months and the locations vary from across the country to within the same institution. During the first year, he has made arrangements to visit Dr. Leroy Hood at the University of Washington for 1 month and learn the cDNA microarray technology. During the second year, he will work within the laboratory of Dr. Brian Nickoloff at Loyola University to gain hands-on experience in the development of both retroviruses and adenoviruses that contain his genes of interest. During year 3, he proposes a 3-month rotation through Dr. Lucio Miele's laboratory at Loyola to gain knowledge of how to identify key transcription factors and perform promoter analyses. In year 4, he visits the laboratory of Dr. Elaine Fuchs at the University of Chicago for a 3-month period to generate transgenic mice in which the expression of the transgenes will be under the control of an inducible endothelial cell specific promoter. The final rotation has not been determined, but will remain available for later consideration of state-of-the-art techniques needed. In addition to the above mentioned rotations, Dr. Lingen also plans to participate and lecture in courses related to research ethics at Loyola University. The described research project is identical to the Dr. Lingen's current R01 grant which has been peer-reviewed and funded.
The specific aims are: 1) To characterize in detail the profile of functional retinoic acid receptors expressed in microvascular endothelial cells by performing Northern and Western blots, and by performing electromobility shift assays to determine the functional status of the expressed receptors. 2) To determine which of the expressed retinoic acid receptors are responsible for causing microvascular endothelial cells to become refractory to inducers of angiogenesis by employing receptor selective ligands, and by introducing either dominant negative, wild-type or chimeric retinoic acid receptors into microvascular endothelial cells. 3) To study retinoic acid-mediated inhibition of in vivo angiogenesis by introducing human microvascular endothelial cells containing a retrovirally driven dominant negative, wild-type or chimeric retinoic receptors into mice and observing their incorporation into newly forming vessels.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DE000470-02
Application #
6516356
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Gordon, Sharon M
Project Start
2001-07-01
Project End
2002-10-14
Budget Start
2002-07-01
Budget End
2002-10-14
Support Year
2
Fiscal Year
2002
Total Cost
$40,190
Indirect Cost
Name
Loyola University Chicago
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153
Mankame, Tanmayi P; Zhou, Guolin; Lingen, Mark W (2010) Identification and characterization of the human NOL7 gene promoter. Gene 456:36-44
Cohen, Ezra E W; Zhu, Hongyan; Lingen, Mark W et al. (2009) A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle. Cancer Res 69:65-74
Hasina, Rifat; Whipple, Mark E; Martin, Leslie E et al. (2008) Angiogenic heterogeneity in head and neck squamous cell carcinoma: biological and therapeutic implications. Lab Invest 88:342-53
Singleton, P A; Lingen, M W; Fekete, M J et al. (2006) Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: role of receptor transactivation. Microvasc Res 72:3-11
Hasina, R; Pontier, A L; Fekete, M J et al. (2006) NOL7 is a nucleolar candidate tumor suppressor gene in cervical cancer that modulates the angiogenic phenotype. Oncogene 25:588-98
Cohen, Ezra Eddy Wyssam; Lingen, Mark W; Zhu, Bangmin et al. (2006) Protein kinase C zeta mediates epidermal growth factor-induced growth of head and neck tumor cells by regulating mitogen-activated protein kinase. Cancer Res 66:6296-303
Connell, Philip P; Jayathilaka, Krishanthi; Haraf, Daniel J et al. (2006) Pilot study examining tumor expression of RAD51 and clinical outcomes in human head cancers. Int J Oncol 28:1113-9
Hasina, Rifat; Lingen, Mark W (2004) Head and neck cancer: the pursuit of molecular diagnostic markers. Semin Oncol 31:718-25
Nickoloff, Brian J; Lingen, Mark W; Chang, Bey-Dih et al. (2004) Tumor suppressor maspin is up-regulated during keratinocyte senescence, exerting a paracrine antiangiogenic activity. Cancer Res 64:2956-61
Petro, B J; Tan, R C; Tyner, A L et al. (2004) Differential expression of the non-receptor tyrosine kinase BRK in oral squamous cell carcinoma and normal oral epithelium. Oral Oncol 40:1040-7

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