Search Result Details

Back to Search Results

This page shows the details of why an item matched the keywords from your search.

Search Results

Kowalik, Timothy

One or more keywords matched the following properties of Kowalik, Timothy

Property	Value
overview	Academic Background Timothy Kowalik received his B.S. degree in Biology and Mathematics from Belmont Abbey College in 1982. He received his M.S. (1986) and his Ph.D. (1989) in Molecular Biology and Virology from Utah State University. Dr. Kowalik did postdoctoral research on virus-cell interactions from 1990-1993 at the Lineberger Cancer Center of the University of North Carolina. From 1993-1996, he continued his postdoctoral studies in the Department of Genetics at Duke University Medical Center where he analyzed the relationship between the cell cycle and apoptosis. During his postdoctoral training, Dr. Kowalik was a Fellow of the Damon Runyon-Walter Winchell Cancer Research Fund and a Leukemia Society of America Special Fellow. In 1996, Dr. Kowalik joined the Department of Molecular Genetics and Microbiology at the University of Massachusetts Medical School where he is an associate professor. Cell activation and DNA viruses Research in my laboratory centers around the regulation of cellular proliferation control especially from the perspective of an infecting virus. To maximize yields, small DNA tumor viruses encode activities which trick infected cells into proliferative states. This is often achieved by subverting normal homeostatic controls resulting in infected cells progressing into S phase. For small DNA viruses, this entails inactivating the Rb and p53 tumor suppressors. Rb inactivation results in the activation of the E2F transcription factor family which induces expression of genes involved in nucleotide and DNA biosynthesis. Genetic and biochemical studies have demonstrated that Rb inactivation and induction of E2F transcriptional activity normally occur in late G1 and are central to the progression of cells through G1 and into S phase. Using recombinant adenovirus technology, we are presently examining the paradoxical relationship between growth activation by E2F1 overexpression and the resultant p53-dependent apoptotic cell death. We are also studying the consequences of Rb and p53 targeting by large DNA tumor viruses including members of the herpesvirus family.
Rotation Projects	Rotation Projects Identify the region on E2F1 responsible for p53-mediated apoptosis. We know that a transcriptionally functional E2F1 is required for apoptosis signaling. We also know that E2F2 does not induce apoptosis in our system. Therefore, domains on E2F1 and E2F2 will be swapped to determine which E2F1 domain is responsible for apoptosis signaling. Role of nuclear kinases in E2F1 mediated apoptosis. Our recent efforts have revealed that E2F1 expression leads to the phosphorylation of p53 and this modification correlates with apoptosis. There are several candidate kinases that need to be analyzed for their contribution to p53 phosphorylation. A dominant negative approach will be used in this project to identify which kinase(s) contribute to the E2F1 signal to p53. Role of CMV IE proteins in proliferation. We have found that both IE1 and IE2 target different Rb family members. IE2 binds to Rb and IE1 interacts with p107. We now know that IE2 is a strong inducer of S phase but IE1 can only significantly modulate proliferation in cells lacking p53. We are interested in knowing why p53 can prevent IE1 from inducing S phase. Mechanism of p53 accumulation by CMV. It has recently been shown that CMV infection results in an accumulation of p53. We have recently found that IE1 expression also leads to p53 accumulation. We wish to determine the steps leading to p53 accumulation and the consequences of this event.

Property

Value

overview

Academic Background

Timothy Kowalik received his B.S. degree in Biology and Mathematics from Belmont Abbey College in 1982. He received his M.S. (1986) and his Ph.D. (1989) in Molecular Biology and Virology from Utah State University. Dr. Kowalik did postdoctoral research on virus-cell interactions from 1990-1993 at the Lineberger Cancer Center of the University of North Carolina. From 1993-1996, he continued his postdoctoral studies in the Department of Genetics at Duke University Medical Center where he analyzed the relationship between the cell cycle and apoptosis. During his postdoctoral training, Dr. Kowalik was a Fellow of the Damon Runyon-Walter Winchell Cancer Research Fund and a Leukemia Society of America Special Fellow. In 1996, Dr. Kowalik joined the Department of Molecular Genetics and Microbiology at the University of Massachusetts Medical School where he is an associate professor.

Cell activation and DNA viruses

Research in my laboratory centers around the regulation of cellular proliferation control especially from the perspective of an infecting virus. To maximize yields, small DNA tumor viruses encode activities which trick infected cells into proliferative states. This is often achieved by subverting normal homeostatic controls resulting in infected cells progressing into S phase. For small DNA viruses, this entails inactivating the Rb and p53 tumor suppressors. Rb inactivation results in the activation of the E2F transcription factor family which induces expression of genes involved in nucleotide and DNA biosynthesis. Genetic and biochemical studies have demonstrated that Rb inactivation and induction of E2F transcriptional activity normally occur in late G1 and are central to the progression of cells through G1 and into S phase.

Using recombinant adenovirus technology, we are presently examining the paradoxical relationship between growth activation by E2F1 overexpression and the resultant p53-dependent apoptotic cell death. We are also studying the consequences of Rb and p53 targeting by large DNA tumor viruses including members of the herpesvirus family.

Rotation Projects

Identify the region on E2F1 responsible for p53-mediated apoptosis. We know that a transcriptionally functional E2F1 is required for apoptosis signaling. We also know that E2F2 does not induce apoptosis in our system. Therefore, domains on E2F1 and E2F2 will be swapped to determine which E2F1 domain is responsible for apoptosis signaling.

Role of nuclear kinases in E2F1 mediated apoptosis. Our recent efforts have revealed that E2F1 expression leads to the phosphorylation of p53 and this modification correlates with apoptosis. There are several candidate kinases that need to be analyzed for their contribution to p53 phosphorylation. A dominant negative approach will be used in this project to identify which kinase(s) contribute to the E2F1 signal to p53.

Role of CMV IE proteins in proliferation. We have found that both IE1 and IE2 target different Rb family members. IE2 binds to Rb and IE1 interacts with p107. We now know that IE2 is a strong inducer of S phase but IE1 can only significantly modulate proliferation in cells lacking p53. We are interested in knowing why p53 can prevent IE1 from inducing S phase.

Mechanism of p53 accumulation by CMV. It has recently been shown that CMV infection results in an accumulation of p53. We have recently found that IE1 expression also leads to p53 accumulation. We wish to determine the steps leading to p53 accumulation and the consequences of this event.

One or more keywords matched the following items that are connected to Kowalik, Timothy

Item Type	Name
Academic Article	Active RB elicits late G1/S inhibition.
Academic Article	The APC tumor suppressor controls entry into S-phase through its ability to regulate the cyclin D/RB pathway.
Academic Article	Human cytomegalovirus IE1-72 activates ataxia telangiectasia mutated kinase and a p53/p21-mediated growth arrest response.
Academic Article	Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2.
Academic Article	Role of human cytomegalovirus immediate-early proteins in cell growth control.
Academic Article	miR-17 and miR-20a temper an E2F1-induced G1 checkpoint to regulate cell cycle progression.
Academic Article	Compensation of BRG-1 function by Brm: insight into the role of the core SWI-SNF subunits in retinoblastoma tumor suppressor signaling.
Academic Article	Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes.
Academic Article	E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis.
Concept	S Phase
Concept	Cell Division
Concept	G1 Phase

Search Criteria

Cell Division