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Lucio Miele, MD, PhD
Professor
Department of Pathology
Director, Breast Cancer Basic Science Program
Cancer Immunology Research Program
Cardinal Bernardin Cancer Center
(888) LUHS-888 |
Cell Differentiation Switches In Tumor Biology, Diagnosis, And Treatment
Dr. Miele’s laboratory studies a group of molecules that control cell differentiation in various tumors. The laboratory investigates:
- the functions of these molecules in tumor biology and
- their possible uses as targets for novel therapeutic and diagnostic agents. The design and development of such agents is one of Dr. Miele’s areas of expertise. The main focus is on Notch gene products.
Notch genes encode membrane receptors that control cell fate determination in many cell types during development and postnatal life. Notch receptors have been shown to be upregulated in various cancers and pre-neoplastic lesions. In the uterine cervix, for example, Notch-1 is upregulated in CIN 3 lesions and in carcinomas but not in CIN 1-2 lesions. Additionally, in both squamous and adenocarcinomas, but not in CIN 3 lesions, Notch-1 is uniformly detectable in the nucleus. This suggests that overexpression of Notch-1 identifies premalignant cells and that nuclear Notch-1 is a feature of fully transformed cells. Similar findings have been reported in colon adenocarcinomas and lung squamous carcinomas. In vitro, transformed cells of many embryonic lineages overexpress Notch-1 and other Notch-related genes. Dr. Miele’s laboratory has recently discovered that upregulated Notch-1 in transformed cells protects them from apoptotic cell death. Dr. Miele’s laboratory is now investigating the mechanism of this effect in vitro and in vivo and collaborates with faculty in the Department of Pathology and with leading laboratories in other academic institutions in a systematic effort to study the expression of Notch and Notch-related proteins in human malignancies.
Additional scientific interests of Dr. Miele include proteins of the uteroglobin family (UG). These are secretory molecules produced by mucosal epithelia which inhibit phospholipase A2 and block several aspects of the neoplastic phenotype, including growth and extracellular matrix invasion in prostate and lung cancer cells.
Dr. Miele has made significant contributions to molecular pharmacology, deciphering the basis for plasmid-mediated multi-antibiotic resistance in Gram-negative bacteria as a Ph.D. student, then developing a class of potent immunomodulatory biologics as a fellow at NIH. As a principal investigator, he has developed several Notch-inhibitory agents, both biological and traditional pharmaceutics, which have remarkable anti-cancer activity in vitro and in vivo, and is developing clinical applications for the use of Notch inhibitors. He has authored more than 90 publications in molecular pharmacology.
Dr. Miele is a chartered member of the Drug Discovery and Molecular Pharmacology Study Section of NIH, as well as the DOD Breast Cancer Cell Biology Study Section, and frequently participates in or chairs NIH Special Emphasis Panels in cancer therapeutics and biomarkers. He is Executive Editor for the Americas of the Journal of Experimental and Clinical Cancer Research, Assistant Editor of Women’s Oncology Reviews, and sits on the Editorial Board of J. Cell Biochem. He routinely referees manuscripts for such journals as the Journal of Clinical Investigation, Cancer Research, Cancer Cell, the Journal of Immunology, Biochemistry, the Biochemical Journal and many others.
Teaching
Dr. Miele participates in teaching in the Biochemistry, Molecular Biology, and Immunology graduate programs.
Graduate Student and Resident Participation
Loyola graduate students, medical students, and house staff are invited to participate in these projects. We use immunocytochemistry, flow cytometry, RT-PCR, genomic PCR, Western blotting, tissue culture, differentiation assays, apoptosis assays, animal models, and other techniques. Interested individuals can contact Dr. Miele directly.
Publications
View a partial list of
Dr. Miele's publications through the National Library of
Medicine's PubMed online database. |
