Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Johnson, Gail V.W."). Showing records 1 – 3 of 3 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters

1. Eom, Tae-Yeon. Regulation of neural precursor cell apoptosis and proliferation by glycogen synthase kinase-3.

Degree: PhD, 2009, University of Alabama – Birmingham

Neurogenesis is a crucial process for development, plasticity, and regenerative capacity of the developing and adult brain. Impairment of neurogenesis has been implicated in the etiology of psychiatric disorders. Although substantial studies have shown that therapeutic interventions enhance neurogenesis, much less is known about what factors impair neurogenesis. Thus, the present work examined if glycogen synthase kinase-3 (GSK3) has a role in impaired neurogenesis, focusing on apoptosis and proliferation of neural precursor cells (NPCs). This investigation found that GSK3 promotes apoptotic signaling in cultured NPCs subjected to two insults, trophic factor withdrawal and genotoxic stress. Both stimuli activated GSK3, Bax, and caspase-3. Pharmacological inhibition of GSK3 activity reduced Bax and caspase-3 activation in both bax+/+ and bax-/- NPCs. GSK3[beta] interacted with p53 after DNA damage in NPCs. This study also investigated the role of hyperactive GSK3 on NPC proliferation in the adult hippocampus using homozygous S21A/S9A-GSK3[alpha]/[beta] knockin mice. In vivo measurements of BrdU positive cells showed a drastic 40 % impairment of proliferation in GSK3 knockin mice. Impaired neurogenesis observed in vivo was not due to direct effects of hyperactive GSK3 in NPCs because proliferation in vitro was equivalent in NPCs from both GSK3 knockin and wild-type mice, suggesting in vivo deficiency in GSK3 knockin mice of an external promoter of NPC proliferation. Measurements of two neurotrophins demonstrated less vascular endothelial growth factor, but not brain-derived neurotrophic factor, in the hippocampus of GSK3 knockin mice than wild-type mice, suggesting insufficient support molecules in vivo in GSK3 knockin mice impairs neurogenesis. Chronic administration of lithium and fluoxetine, which increase inhibitory serine-phosphorylation of wild-type GSK3, increased NPC proliferation in wild-type, but not GSK3 knockin, mice. Overall, this study reveals that GSK3 may be a crucial modulator of apoptosis and proliferation of NPCs. NPCs are sensitive to loss of trophic factors and genotoxic stress, and GSK3 inhibitors are capable of enhancing NPC survival. Blocked inhibitory control of GSK3 impairs NPC proliferation in the adult hippocampus and the capacity of therapeutic drugs to stimulate neurogenesis, likely through deficient environmental factors that support neurogenesis, which may contribute to psychiatric diseases and responses to therapeutic drugs.

vii, 126 p. : ill., digital, PDF file

Cell Biology

Joint Health Sciences

GSK3 Neural Precursor Cell Apoptosis Proliferation Neurogenesis P53

UNRESTRICTED

Advisors/Committee Members: Jope, Richard S., Bijur, Gautam<br>Johnson, Gail V.W.<br>Roth, Kevin A.<br>Serra, Rosa.

Subjects/Keywords: Apoptosis<; br>; Glycogen Synthase Kinase 3  – metabolism<; br>; Mice, Inbred C57BL<; br>; Mice, Knockout<; br>; Mice, Transgenic<; br>; Neurons  – cytology<; br>; Phosphorylation

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Eom, T. (2009). Regulation of neural precursor cell apoptosis and proliferation by glycogen synthase kinase-3. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,390

Chicago Manual of Style (16th Edition):

Eom, Tae-Yeon. “Regulation of neural precursor cell apoptosis and proliferation by glycogen synthase kinase-3.” 2009. Doctoral Dissertation, University of Alabama – Birmingham. Accessed November 17, 2019. http://contentdm.mhsl.uab.edu/u?/etd,390.

MLA Handbook (7th Edition):

Eom, Tae-Yeon. “Regulation of neural precursor cell apoptosis and proliferation by glycogen synthase kinase-3.” 2009. Web. 17 Nov 2019.

Vancouver:

Eom T. Regulation of neural precursor cell apoptosis and proliferation by glycogen synthase kinase-3. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2009. [cited 2019 Nov 17]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,390.

Council of Science Editors:

Eom T. Regulation of neural precursor cell apoptosis and proliferation by glycogen synthase kinase-3. [Doctoral Dissertation]. University of Alabama – Birmingham; 2009. Available from: http://contentdm.mhsl.uab.edu/u?/etd,390

2. Sun, Mianen. The role of DDX3 in regulating apoptosis, p53 and Snail.

Degree: PhD, 2008, University of Alabama – Birmingham

Cancer is a common disease that causes high rates of lethality. Resistance to cancer therapy is one major obstacle for producing an effective cancer treatment. Clarifying mechanisms of cancer development, such as resistance to apoptosis and metastasis, can provide important information for developing effective cancer treatment strategies. In the present study, DDX3 was demonstrated to have effects on both responses to cancer treatment and cancer development. DDX3 together with glycogen synthase kinase-3 (GSK-3) was found to impede death receptor-induced apoptosis, which is important because death receptors are activated by some cancer treatments. Additionally, DDX3 was shown to regulate two proteins critical in cancer, p53 and Snail. Extrinsic apoptotic signaling induced by death receptors, especially TRAIL-R2, is a new method of anti-tumor therapy. However, 50% of cancer cells develop resistance to this therapy (LeBlanc and Ashkenazi 2003). Thus, finding mechanisms that regulate this extrinsic apoptosis pathway is important to overcome this resistance. In this study, we found that DDX3 associates with GSK3 and cellular inhibitor of apoptosis protein (cIAP- 1) to form a complex that binds to death receptors to inhibit activation of the apoptosis cascade. Blocking the actions of DDX3 or GSK3 potentiated apoptosis induced by stimulation of four different death receptors in several types of cells. Thus, DDX3 and GSK3 are regulatory proteins bound to the death receptor that counterbalance apoptotic signaling upon death receptor stimulation. Targeting DDX3 or GSK3 could be a useful therapy in combinations with stimulation of death receptors for resistant cancer treatment. DDX3 was also found to stabilize p53, an important tumor suppressor gene, and Snail, an essential protein for promoting metastasis. The association of DDX3 with p53 and with Snail may contribute to reducing their nuclear export and subsequent degradation, therefore causing their nuclear retention and accumulation. Overall, this study uncovers novel actions of DDX3 affecting both cancer progression and treatment. These results provide a new potential target to overcome resistance to cancer therapy and to develop more specific and powerful therapeutic strategies.

1 online resource (vii, 100 p. : ill., digital, PDF file)

Cell Biology;

Joint Health Sciences;

DDX3 GSK3 apoptosis p53 Snail

UNRESTRICTED

Advisors/Committee Members: Jope, Richard S., Johnson, Gail V.W.<br>, Li, Xiaohua<br>, Wilson, Scott<br>, Zhou, Tong.

Subjects/Keywords: Apoptosis<; br>; Genes, p53<; br. Glycogen Synthase Kinase 3  – metabolism<; br>; Inhibitor of Apoptosis Proteins  – metabolism<; br>; Protein Kinase Inhibitors  – pharmacology<; br>; Receptors, Death Domain  – metabolism

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Sun, M. (2008). The role of DDX3 in regulating apoptosis, p53 and Snail. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,827

Chicago Manual of Style (16th Edition):

Sun, Mianen. “The role of DDX3 in regulating apoptosis, p53 and Snail.” 2008. Doctoral Dissertation, University of Alabama – Birmingham. Accessed November 17, 2019. http://contentdm.mhsl.uab.edu/u?/etd,827.

MLA Handbook (7th Edition):

Sun, Mianen. “The role of DDX3 in regulating apoptosis, p53 and Snail.” 2008. Web. 17 Nov 2019.

Vancouver:

Sun M. The role of DDX3 in regulating apoptosis, p53 and Snail. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2008. [cited 2019 Nov 17]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,827.

Council of Science Editors:

Sun M. The role of DDX3 in regulating apoptosis, p53 and Snail. [Doctoral Dissertation]. University of Alabama – Birmingham; 2008. Available from: http://contentdm.mhsl.uab.edu/u?/etd,827

3. Beagle, Brandon Richard. Canonical Wnt signaling by the proteolytic processing of LRP6.

Degree: PhD, 2010, University of Alabama – Birmingham

Low density Lipoprotein receptor Related 6 (LRP6) functions as an essential coreceptor for Wnt/β-catenin signaling as pathway activation, reflected by cytosolic β- catenin stabilization and TCF/LEF-1 transactivation, requires Glycogen Synthase Kinase 3β (GSK3β)-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane anchored LRP6 intracellular domain. Additionally, LRP6 undergoes a proteolytic cleavage event resulting in the formation of a soluble LRP6 intracellular domain (LRP6-ICD). LRP6-ICD can function within the Wnt/β-catenin pathway by interacting with GSK3β and attenuating the phosphorylation of GSK3β substrates such as cytosolic β-catenin as well as stimulate TCF/LEF-1 activity. However, LRP6-ICD’s role(s) within the Wnt/β-catenin pathway and the mechanism(s) that govern LRP6-ICD activity are not clear. The cytosolic function of LRP6-ICD has been examined, but its possible function in the nucleus remains unexplored. A better understanding of LRP6- ICD biology will improve our understanding of the regulation of the Wnt/β-catenin pathway. The objective for the first part of the project was to determine if LRP6-ICD requires GSK3β-mediated phosphorylation of its PPP(S/T)P motifs to function within the Wnt/β-catenin pathway, similar to LRP6. Results show LRP6-ICD is functionally distinct from LRP6 as LRP6-ICD functions within the pathway in the absence of PPP(S/T)P phosphorylation and functions as a pathway modulatory protein not as a primary activating component. We also showed LRP6-ICD modulates the pathway by functioning as a true GSK3β effector protein capable of directly attenuating GSK3β kinase activity. In the second part, we analyzed a potential role for LRP6-ICD in the nucleus. Our findings showed LRP6-ICD is a nucleocytoplasmic protein that differentially regulates Wnt/β-catenin pathway activity depending upon its localization and proteinprotein interaction. We validated the hypothesis that cytosolic LRP6-ICD positively modulates Wnt/β-catenin activity through GSK3β and enhanced cytosolic β-catenin stabilization. Surprisingly, nuclear LRP6-ICD negatively modulates the pathway by interacting with and attenuating Amino-terminal Enhancer of Split (AES), a positive Wnt/β-catenin modulatory protein. To summarize, our studies reveal that LRP6-ICD differentially modulates the Wnt/β-catenin pathway in a context and localization dependent manner. Our studies also provide further insight concerning the growing role modulatory proteins play in the Wnt/β-catenin pathway and mechanistic diversity of the pathway.

1 online resource (xi, 139 p. : ill., digital, PDF file)

Cell Biology;

Joint Health Sciences;

LRP6 LRP6-ICD AES Beta-catenin GSK3

UNRESTRICTED

Advisors/Committee Members: Johnson, Gail V.W., Benveniste, Etty<br>, Frank, Stuart J.<br>, Lesort, Mathieu<br>, Murphy-Ullrich, Joanne E..

Subjects/Keywords: beta Catenin  – metabolism<; br>; Glycogen Synthase Kinase 3  – metabolism<; br>; LDL-Receptor Related Proteins  – metabolism<; br>; Lymphoid Enhancer-Binding Factor 1  – metabolism<; br>; Repressor Proteins  – metabolism<; br>; Transcription Factors  – metabolism<; br>; Wnt Proteins  – metabolism

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Beagle, B. R. (2010). Canonical Wnt signaling by the proteolytic processing of LRP6. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,857

Chicago Manual of Style (16th Edition):

Beagle, Brandon Richard. “Canonical Wnt signaling by the proteolytic processing of LRP6.” 2010. Doctoral Dissertation, University of Alabama – Birmingham. Accessed November 17, 2019. http://contentdm.mhsl.uab.edu/u?/etd,857.

MLA Handbook (7th Edition):

Beagle, Brandon Richard. “Canonical Wnt signaling by the proteolytic processing of LRP6.” 2010. Web. 17 Nov 2019.

Vancouver:

Beagle BR. Canonical Wnt signaling by the proteolytic processing of LRP6. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2010. [cited 2019 Nov 17]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,857.

Council of Science Editors:

Beagle BR. Canonical Wnt signaling by the proteolytic processing of LRP6. [Doctoral Dissertation]. University of Alabama – Birmingham; 2010. Available from: http://contentdm.mhsl.uab.edu/u?/etd,857

.