George R. Stark, Ph.D.

Staff

Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Location:NE2-306
starkg@ccf.org
Phone: (216) 444-6062
Fax: (216) 444-0512



We use a lentiviral vector to insert a strong promoter near genes in human cells, generating specific cell clones that over-express specific proteins, changing their properties in ways that we can select. This methodology has very broad applications.We have used it to block the constitutive activation of NFkB by over-expressing a novel negative regulator that modifies a key lysine methylation site on the p65 subunit. We have extended our studies of the lysine methylation of p65 to similar modifications of STATs. We also use promoter insertion to over-express proteins that mediate resistance to a variety of chemotherapeutic drugs, for example, the over-expression of kinesins mediates resistance to taxanes. STAT1 and STAT3, activated by phosphorylation in response to interferons and IL-6, respectively, also drive gene expression in their un-phosphorylated forms, which are strongly induced by these cytokines. Un-phosphorylated STAT1 prolongs the expression of a subset of interferon-induced genes to prolong the antiviral response. These proteins also mediate the resistance of cancer cells to DNA damaging therapies, suggesting that blocking the response to endogenous interferon in cancers may sensitize them to such therapies.

In other words ...

Our cells are instructed on how to behave by a large number of external signals, which come from contact with neighboring cells, from signaling molecules that enter the circulation from elsewhere in the body to affect distant cells, and from signaling molecules that alert us to the presence of invading organisms (viruses, bacteria, fungi, parasites). The signals are conveyed from the outside of the cell to the inside by specialized receptors on the cell surface.  Responses to signals result in changes in cellular functions, for example, by increasing the level of antiviral proteins in response to an infection. These changes are carried out by increasing the amounts of specific proteins or by changing their properties.  We study the details of these complex interactions in innate immunity and in cancer.


HyeonJoo  Cheon Ph.D.
HyeonJoo Cheon Ph.D.
Project Staff

Location:NE2-252
Phone:(216) 445-9769
cheonh@ccf.org
Fax:(216) 444-0512
laboratory

Claire  Coleman B.S.
Claire Coleman B.S.
Research Technologist

Location:NB4-252
Phone:(216) 445-9769
colemac3@ccf.org
Fax:(216) 445-6269
laboratory

Sarmishtha  De Ph.D.
Sarmishtha De Ph.D.
Project Staff

Location:NE2-252
Phone:(216) 445-9769
des2@ccf.org
Fax:(216) 444-0512
laboratory

Elise  Holvey-Bates B.S.
Elise Holvey-Bates B.S.
Senior Research Technologist

Location:NE2-252
Phone:(216) 445-9769
holveye@ccf.org
Fax:(216) 444-0512
laboratory

Anna  Kondratova Ph.D.
Anna Kondratova Ph.D.
Research Associate

Location:NE2-251
Phone:(216) 445-9769
kondraa@ccf.org
Fax:(216) 444-0512
laboratory

Jing  Nan Ph.D.
Jing Nan Ph.D.
Postdoctoral Fellow

Location:NE2-252
Phone:(216) 445-9769
nanj@ccf.org
Fax:(216) 444-0512
laboratory

Anette H. van Boxel-Dezaire Ph.D.
Anette H. Van Boxel-Dezaire Ph.D.
Project Staff

Location:NE2-101
Phone:(216) 445-4478
vanboxa@ccf.org
Fax:(216) 444-0512
laboratory

Yuxin  Wang Ph.D.
Yuxin Wang Ph.D.
Research Associate

Location:NE2-252
Phone:(216) 445-9769
wangy7@ccf.org
Fax:(216) 444-0512
laboratory

Samantha  Wightman M.S.
Samantha Wightman M.S.
Graduate Student

Location:NE2-252
Phone:(216) 445-9769
wightms@ccf.org
Fax:(216) 445-0512
laboratory


Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancer. Tan MH, De S, Bebek G, Orloff MS, Wesolowski R, Downs-Kelly E, Budd GT, Stark GR, Eng C. Breast Cancer Res Treat. 2012 Feb;131(3):849-58. PMID:21479552

Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes. Yang J, Huang J, Dasgupta M, Sears N, Miyagi M, Wang B, Chance MR, Chen X, Du Y, Wang Y, An L, Wang Q, Lu T, Zhang X, Wang Z, Stark GR. Proc Natl Acad Sci USA. 2010 Dec 14;107(50):21499-504. PMID:21098664

Regulation of NF-kappaB by NSD1/FBXL11-dependent reversible lysine methylation of p65. Lu T, Jackson MW, Wang B, Yang M, Chance MR, Miyagi M, Gudkov AV, Stark GR. Proc Natl Acad Sci USA. 2010 Jan 5;107(1):46-51. PMID:20080798

Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes. Cheon H, Stark GR. Proc Natl Acad Sci USA. 2009 Jun 9;106(23):9373-8. PMID:19478064