Ronald F Mckay

US Patent:

20030211605, Nov 13, 2003

Filed:

Apr 8, 2003

Appl. No.:

10/258975

Inventors:

Sang-Hun Lee - Seoul, KR
Nadya Lumelsky - Washington DC, US
Lorenz Studer - New York NY, US
Ronald McKay - Bethesda MD, US
Jonathan Auerbach - Bethesda MD, US
Jong-Hoon Kim - Rockville MD, US

International Classification:

C12N005/08

US Classification:

435/368000

Abstract:

The invention provides a method of culturing cells. The method generally includes live stages: (1) expansion of ES cells; (2) generation of embryoid bodies; (3) selection of CNS precursor cells; (4) expansion of CNS precursor cells; and (5) differentiation of CNS precursor cells. During the expansion phase, the CNS precursor cells are cultured in a media which includes at least one neurologic agent such as bFGF, SHH, and FGF-8. The expanded CNS precursors are differentiated by withdrawal of at least one neurologic agent, typically, bFGF. Preferably, the differentiation media includes ascorbic acid. The method of the invention can be used to culture a variety of cells, preferably neuronal cells, including, but not limited to dopaminergic neuron cells, cholinergic neuronal cells and serotonergic neuron cells. The invention also provides a method for treating a neurological disorder, such as Parkinson's disease, a method of introducing a gene product into a brain of a patient, and an assay for neurologically active substances. The invention further provides a cell culture which includes differentiated neuron cells, of which at least about 20 % of the differentiated neurons are dopaminergic neurons.

US Patent:

20040121460, Jun 24, 2004

Filed:

Dec 8, 2003

Appl. No.:

10/470030

Inventors:

Nadya Lumelsky - Washington DC, US
Oliver Blondel - Bethesda MD, US
Ronald McKay - Bethesda MD, US
Jong-Hoon Kim - Rockville MD, US

International Classification:

C12N005/06
C12N005/08

US Classification:

435/366000, 435/354000

Abstract:

A method is provided for differentiating embryonic stem cells to endocrine cells. The method includes generating embryoid bodies from a culture of undifferentiated embryonic stem cells, selecting endocrine precursor cells, expanding the endocrine precursor cells by culturing endocrine cells in an expansion medium that comprises a growth factor, and differentiating the expanded endocrine precursor cells in a differentiation media to differentiated endocrine cells produced by this method are also provided. Artificial islets are disclosed, as well as method for using the pancreatic endocrine cells and the artificial islets.

US Patent:

20040126876, Jul 1, 2004

Filed:

Dec 30, 2002

Appl. No.:

10/334565

Inventors:

Rea Ravin - Rockville MD, US
James Sullivan - Bowie MD, US
Ronald McKay - Bethesda MD, US

Assignee:

United States of America, represented by the Secretary, Department of Health and Human Services

International Classification:

C12M001/22

US Classification:

435/288300, 435/293100, 435/303100, 359/398000

Abstract:

Featured is a long-term cell culture system being configured and arranged so as to be capable of monitoring the dynamic processes that occur during proliferation and differentiation of stem cells such as central nervous system (CNS) stem cells/embryonic stem cells. In particular aspects, the system allows monitoring of such dynamic processes continually and to focally manipulate the cells by focal application of growth factors such as BMP, CNTF and other growth factors. Preferred systems are capable of electrical recording from the cells.

US Patent:

20060009379, Jan 12, 2006

Filed:

Oct 1, 2003

Appl. No.:

10/530340

Inventors:

Robert Tsai - SILVER SPRING MD, US
Ronald McKay - Bethesda MD, US

Assignee:

THE GOVERNMENT OF THE UNITED STATES OF AMERICAN AS REPRESENTED BY THE DEPT. OF HEALTH AND HUMAN SVC - ROCKVILLE MD

International Classification:

A61K 38/17

US Classification:

514012000

Abstract:

An isolated nucleostemin polypeptide is disclosed herein. The nucleostemin polypeptide includes an amino acid sequence at least 85% identical to SEQ ID NO: 2. In several examples, the polypeptide regulates cell differentiation, cell proliferation, or both. Nucleic acids encoding these polypeptides, vectors including the nucleic acids, and host cells transfected with these nucleic acids are also disclosed. Methods for inducing differentiation, inhibiting proliferation, and inducing senescence of a cell by altering the level of a nucleostemin polypeptide including an amino acid sequence at least 80% identical to SEQ ID NO: 2 are also disclosed. Methods for screening for agents that affect proliferation, differentiation, or senescence of cells are also disclosed.

US Patent:

20080242594, Oct 2, 2008

Filed:

Sep 7, 2006

Appl. No.:

12/066075

Inventors:

Ronald D.G. McKay - Bethesda MD, US

International Classification:

A61K 38/28
C12N 5/02
C12N 5/08
G01N 33/574
G01N 33/53
A61K 38/18

US Classification:

514 3, 435375, 435366, 514 12, 435 71, 435 723

Abstract:

It is disclosed herein that STAT3 phosphorylated at serine 727 is a key regulator of proliferation and survival of stem cells and precursor cells. Methods for increasing the survival and proliferation of stem cells and/or precursor are disclosed herein. In one embodiment, the method includes contacting a mammalian stem cell mammalian precursor cell with a JAK inhibitor, a p38 inhibitor, or both. Methods are also disclosed for increasing the survival and proliferation of neuronal precursor cells in a subject. The method includes administering a therapeutically effective amount of a Notch ligand and a growth factor. Methods are also disclosed for identifying an agent that increases the proliferation of stem cells and/or precursor cells. The method includes contacting a stem cell or a precursor cell with an agent of interest, wherein the stem cell or the precursor cell expresses STAT3; and determining the phosphorylation status of serine 727 of STAT3 in the cell. Phosphorylation of serine 727 indicates that the agent increases the survival and/or proliferation of stem cells and/or precursor cells. An isolated population of cells is disclosed, wherein the cells express nestin and STAT3, wherein serine 727 of STAT3 is phosphorylated.

US Patent:

20110105393, May 5, 2011

Filed:

Aug 14, 2008

Appl. No.:

12/673576

Inventors:

Andreas Androutsellis-Theotokis - Athens, GR
Ronald D.G. McKay - Bethesda MD, US

International Classification:

A61K 38/28
C12N 5/071
C12N 5/0797
A61K 38/18
A61P 25/28
A61P 25/16
A61P 25/00

US Classification:

514 65, 435375, 514 76, 514 91

Abstract:

Methods are disclosed herein for increasing the number of stem cells or precursor cells. The number of stem cells can be increased by increasing survival and/or cell proliferation of the cells. The methods include contacting the cells with an effective amount of a Notch ligand, an effective amount of a growth factor, and an effective amount of angiopoietin-2 (Ang-2). In several embodiments, the methods include contacting the cells with an effective amount of a Jak inhibitor. In several non-limiting examples, the growth factor is insulin or glial derived neurotrophic factor (GDNF), or a combination thereof. In additional non-limiting examples, the Notch ligand is Delta. The cells can be in vivo or in vitro. Methods are also disclosed here for the treatment of a neurodegenerative disorder or spinal cord injury in a subject. In several non-limiting examples, the subject has Parkinson's disease or Alzheimer's disease.