National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Department of Health

University of Illinois

The United States of America As Represented by the Secretary of

The United States of America

National Institutes of Health

Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences

Michael M Gottesman

Ira H Pastan

Kazumitsu Ueda

Igor B Roninson

Christopher J Michejda

Thomas J Pohida

Nadya Tarasova

Nicole Y Morgan

Christine A Hrycyna

Gergely Szakács

Susannah Gal

Chandan Das

Ashley A Jaeger

Spencer Smith

Philip G McQueen

Hanan Galski

Randall H Pursley

Glenn Merlino

Joseph A Ludwig

Matthew D Hall

Jennifer L Hellawell

Henry M Fales

Noeris K Salam

The present disclosure is directed to embodiments of microstructured membranes, methods of fabricating microstructured membranes, bioreactors housing microstructured membranes, and methods of using bioreactors and microstructured membranes. In some embodiments, the present disclosure allows culturing of cellular tissues in an environment which more accurately resembles a native environment. In some more specific embodiments, the present disclosure allows culturing of tumor cells on a membrane having a microfabricated pattern which mimics a native vasculature system.

Microfabricated polymeric vessel mimetics

ATP-binding cassette (ABC) transporters generally contain a number of transmembrane helices. The present invention provides synthetic peptides derived from these transmembrane helices. The peptides inhibit ABC transporter function, presumably by disrupting the structure of the ABC transporter. Negatively charged residues are added at the extracellular terminus to promote correct orientation of the peptide in the membrane, and residues considered to aid solubility may be added at that terminus to increase solubility. Exemplary ABC transporters that can be inhibited by these peptides include MDR1, MRP1, MRP2 and BCRP. The invention further provides nucleic acids encoding the peptides, expression cassettes comprising the nucleic acids, and host cells expressing the expression cassettes. The invention further provides a simple and inexpensive assay for determining whether a potential chemotherapeutic agent can inhibit the activity of P-gly-coprotein.

Inhibition of ABC transporters by transmembrane domain analogs

The present invention provides for vectors carrying a cDNA containing the entire coding region of the human multidrug resistance gene (MDR1) and for a method for introducing MDR1 cDNA into cells thereby inducing a multidrug resistant phenotype.

Methods of inducing multidrug resistance using human MDR1 cDNA

Vectors carrying MDR1 cDNA which confer multidrug resistance on

Transgenic animals expressing a multidrug resistance cDNA

A cloned cDNA containing complete coding sequence for the expression of a protein with all properties of the precursor to human procathepsin L is described. All of the protein's major domains, including the pre, pro, and carboxyterminal extensions are represented in the full length cDNA sequence of the present invention.

Cloned cDNA for human procathepsin l.

Genomic and cDNA clones of human genes which are selectively amplified or overexpressed in multidrug-resistant human tumor cells were isolated. Such clones may be used as probes in diagnostic tests to detect chemotherapy-resistant tumor cells and to predict tumor response to chemotherapy. The complete nucleotide sequence of the coding region of the human mdr1 gene and the complete corresponding amino acid sequence are disclosed.

Compositions for clones containing DNA sequences associated with

Gene therapy utilizing an MDR1 linked fusion coding sequence has been disclosed. ADA activity has been introduced into cells using MDR1 linked fusion gene.

Gene therapy using gene fusions for genetic or acquired disorders

Growing community of inventors

Bethesda, MD, United States of America

Michael M Gottesman