Postdoctoral Trainees in the Department of Cell and Developmental Biology
U-3218 MRB III Nashville, TN 37232-8240
(615)322-2134 , fax (615)343-4539
Ahmed, Syed Mukhtar - Macara Lab
Epithelial cells are the foundation for the majority of organs in the mammalian body. These cells have distinctive apical-basal polarity, which is essential to differentiate the inside from outside within the epithelium. However, during several instances of cancers, cell polarity is occasionally deregulated leading to their dissemination to distant secondary sites, otherwise known as metastasis. Partition defective (Par) and associated proteins, including atypical PKCs (aPKC), play crucial roles at controlling the process of epithelial morphogenesis, by organizing epithelial cell membranes into apical and basolateral domains and orienting mitosis in the plane of the epithelial sheet. Previously, the Macara lab found that aPKC interaction with Par3 is essential for the former’s delivery to the apical cortex. Disruption of Par3 in the presence of oncogenic Notch or Ras in mammary cells promotes tumour invasion into the interstitial matrix and metastasis. Additionally, disruption of Par3 also mislocalizes aPKC from the apical surface to the cytosol. As aPKC is a core component of the Par complex and plays a pivotal role in precluding basolateral proteins from accumulating at the apical domain, its mislocalization is thought to be a contributing factor in promoting tumourigenesis such as that of the breast and ovary. My goal is to understand the underlying molecular mechanisms via which disruption of the Par polarity complex results in signalling defects that can induce metastasis. syed.m.ahmed@Vanderbilt.Edu
The isolation and characterization of human embryonic stem cells (hESCs), in recent years, has offered a promising chance at the development of a cell-based replacement therapy for diabetes. At the moment, however, current protocols are severely deficient, only producing small quantities of immature β-cells from hESCs. The goal of my research project is to investigate the underlying mechanism and signals associated with the transition of progenitor cells in the trunk epithelium through an Ngn3hi state toward β-cell specification. Results from this project will provide translationally applicable information that will improve our ability to generate β-cells from human embryonic stem cells as a means to develop more effective treatments for diabetes.
Binshtin, Elad M - Melanie Ohi Lab
Section 1.10.33 of "de Finibus Bonorum et Malorum", written by Cicero in 45 BC
"At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas molestias excepturi sint occaecati cupiditate non provident, similique sunt in culpa qui officia deserunt mollitia animi, id est laborum et dolorum fuga. Et harum quidem rerum facilis est et expedita distinctio. Nam libero tempore, cum soluta nobis est eligendi optio cumque nihil impedit quo minus id quod maxime placeat facere possimus, omnis voluptas assumenda est, omnis dolor repellendus. Temporibus autem quibusdam et aut officiis debitis aut rerum necessitatibus saepe eveniet ut et voluptates repudiandae sint et molestiae non recusandae. Itaque earum rerum hic tenetur a sapiente delectus, ut aut reiciendis voluptatibus maiores alias consequatur aut perferendis doloribus asperiores repellat." elad.binshtein@Vanderbilt.Edu
Cicero 45 BC
" At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas molestias excepturi sint occaecati cupiditate non provident, similique sunt in culpa qui officia deserunt mollitia animi, id est laborum et dolorum fuga. Et harum quidem rerum facilis est et expedita distinctio. Nam libero tempore, cum soluta nobis est eligendi optio cumque nihil impedit quo minus id quod maxime placeat facere possimus, omnis voluptas assumenda est, omnis dolor repellendus. Temporibus autem quibusdam et aut officiis debitis aut rerum necessitatibus saepe eveniet ut et voluptates repudiandae sint et molestiae non recusandae. Itaque earum rerum hic tenetur a sapiente delectus, ut aut reiciendis voluptatibus maiores alias consequatur aut perferendis doloribus asperiores repellat."
Crawley, Scott - Tyska Lab
Intestinal enterocytes possess an apical array of densely packed microvilli known as the enterocyte brush border. Microvilli are so tightly packed in fully differentiated enterocytes that no free space remains between adjacent structures. The functional consequence of this arrangement is an immense capacity for housing membrane-associated nutrient processing and host defense machinery required for maintaining gut homeostasis. Despite being positioned at a critical physiological interface in the intestinal tract, there is little information on the how the brush border is formed. The goal of my research is to begin to elucidate the molecular mechanisms underlying assembly of the enterocyte brush border, specially focussing on the role that extracellular adhesion molecules from the protocadherin family play in regulating proper brush border formation. My research will contribute towards our understanding of the molecules and pathways that may be perturbed in GI diseases characterized by loss of brush border microvilli. william.s.crawley@Vanderbilt.Edu
Du, Yaqing - P. Ohi Lab
During mitosis, microtubule (MT) dynamics drive bipolar spindle formation and power chromosome movements. MT dynamics are heavily regulated by many cellular factors, including Kinesin-8 motors. Kif18A, one of three human Kinesin-8s, controls MT plus end dynamics and by doing so, promotes the equatorial positioning of chromosomes within the mitotic spindle prior to anaphase. My current studies focus on the activities and regulation of Kinesin-8s during cell division.
Huo, Yongliang - Macara LabSection 1.10.33 of "de Finibus Bonorum et Malorum", written by Cicero in 45 BC"
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas molestias excepturi sint occaecati cupiditate non provident, similique sunt in culpa qui officia deserunt mollitia animi, id est laborum et dolorum fuga. Et harum quidem rerum facilis est et expedita distinctio. Nam libero tempore, cum soluta nobis est eligendi optio cumque nihil impedit quo minus id quod maxime placeat facere possimus, omnis voluptas assumenda est, omnis dolor repellendus. Temporibus autem quibusdam et aut officiis debitis aut rerum necessitatibus saepe eveniet ut et voluptates repudiandae sint et molestiae non recusandae. Itaque earum rerum hic tenetur a sapiente delectus, ut aut reiciendis voluptatibus maiores alias consequatur aut perferendis doloribus asperiores repellat." yongliang.huo@Vanderbilt.Edu
Jao, Li-En - Wente Lab
Recently mRNA export factor Gle1 is causally linked to a severe motoneuron disease named lethal congenital contracture syndrome 1 (LCCS1). Using yeast and human cultured cell systems, considerable progress has been made in elucidating the molecular functions of Gle1, including its roles in mRNA nuclear export and translation. However, it is still entirely unclear how Gle1 functions in the context of a multicellular organism and how the gle1 mutations lead to LCCS1. My research is to use the zebrafish as the model system to investigate the link between Gle1 dysfunction and LCCS1 pathogenesis, with the focus on motoneuron development.
Le Guelte, Armelle - Macara Lab
The murine mammary gland is a fascinating and powerful model for the study of adult stem cells. Remarkably, one mammary stem cell is able to reconstitute an entire mammary gland, but the identity of the stem cell has remained uncertain because of the absence of validated stem cell markers. However, the transgenic mouse 11.5kb-GFP reproducibly expresses GFP in cap cells that function as multipotent mammary stem cells. A major unanswered question is whether mammary stem cells generate diverse progeny by asymmetric cell division, or through stochastic population asymmetry. It is also not known whether the polarity proteins identified in Drosophila stem cells play similar roles in mammalian stem cells. I propose to use GFP-tagged mammary stem cells to solve these important, long-standing questions, using a combination of in vivo and in vitro approaches, and live cell imaging.
Lord, Christopher - Wente - Lab
Nuclear pore complexes (NPCs) maintain a semipermeable barrier that allows passive diffusion of small molecules and regulated transport of large cargos through the nuclear envelope. While NPCs have been extensively studied, exactly how they are formed largely remains unclear. Earlier research in the Wente lab revealed production of new NPCs is dependent on the small GTPase Ran and the karyopherin Kap95. My work focuses on elucidating how these and other proteins contribute to NPC formation as well as the cellular effects of compromised permeability in the yeast Saccharomyces cerevisiae. email@example.com
Natalizio, Barbara J.- Wente Lab, Postdoctoral Representative
Eukaryotic gene expression requires the export of mRNA from the nucleus to the cytoplasm. Under conditions of heat shock stress, changes in gene expression occur that result from nuclear retention of non heat shock-induced mRNA as well as from transcriptional upregulation and export of heat shock-induced mRNA. It remains unclear as to how heat shock-induced mRNA export occurs as previous studies have shown that several key factors necessary for normal mRNA export are dispensable for heat shock mRNA export. The focus of my research project is to further characterize the molecular mechanisms underlying mRNA export during heat-shock induced stress using S. cerevisiae as a model system.
My overarching goals are to dissect the relevant genetic regulatory networks, and their interplay with spatiotemporally dynamic intercellular signaling processes, in regulating the processes of pancreas specification, lineage diversification as it interacts with the morphogenetic processes of building the organ, and particularly the b-cell differentiation program. The knowledge obtained from these studies will improve our understanding of the transcriptional regulatory hierarchies that direct the formation of b-cells, thus, could be applied to in vitro directed differentiation of human embryonic stem cells to mature b-cells for transplantation into type I diabetes patients.
Cytokinesis is the last step of cell division, in which cellular cleavage occurs. The cytokinetic process is tightly regulated by concerted phosphorylations and dephosphorylations to ensure the proper division of mother and daughter cell. Failures of cytokinesis can lead to genetic and chromosomal instabilities, a causative event in carcinogenesis. In the fission yeast, Schizosaccharomyces pombe, cytokinesis is coupled with mitotic exit via the spindle pole body-localized essential kinase signaling cascade, termed the septation initiation network (SIN). I am particularly interested in the phosphoregulation of the SIN regulatory components Byr4 and Cdc14 as well as the multisubunit SIN-inhibitory phosphatase, SIP, a conserved PP2A-striatin recently identified in S. pombe by our laboratory. nicole.rachfall@Vanderbilt.Edu
My research is directed at determining the epigenetic mechanisms that interact with the intrinsic transcriptional programs and govern the formation and behavior of various progenitor populations in the developing pancreas. The knowledge obtained will have direct implications with respect to how specific cell populations induce and undergo critical progenitor cell fate decisions,such as tip-trunk lineage allocation. There will also be a direct translational relevance, because we will learn how to enhance progenitor cell specification, and ultimately β-cell formation, from human embryonic stem cells for cellular diabetes therapy. firstname.lastname@example.org
Spears, Erick - Hann Lab
The most well described function of the oncoprotein c-Myc is as a transcription factor involved in upregulation of genes involved in stimulating mitosis. The promoter regions of canonical c-Myc target genes contain an E-box motif, CACGTG, to which c-Myc binds directly. Recently, data from this lab has indicated that c-Myc can stimulate the expression of genes that do not contain this standard E-box element, non-canonical target genes. Also, a subset of genes has been shown to be repressed, instead of activated, by c-Myc. My interests lie in these non-canonical and repressed c-Myc targets. Using molecular and cell biology techniques I aim to elucidate the mechanisms of non-canonical activation and repression by c-Myc and to assess the effects of these targets on c-Myc-specific cellular phenotypes, specifically those involved in the development and progression of cancers.
Wallace, Heather - L. Lee Lab
Regulation of cell division is critical for the proper development of multi-cellular organisms. no poles (nopo) encodes a predicted E3 ubiquitin ligase that is important for cell cycle progression during Drosophila embryogenesis. A screen for NOPO interactors in our lab has identified the Y-family of DNA polymerases, which are involved in translesion synthesis, as potential targets of NOPO. The focus of my research is to understand the role of ubiquitylation by NOPO in the regulation of Y-family polymerases. heather.wallace@Vanderbilt.Edu
Matrix Metalloproteinase are important regulators of development, immune response and disease processes. My research interests lie in studying the variety of substrates that MMPs are cleaving and the significance of these events in development using Drosophila melanogaster as a model. Our lab has previously identified a trans-membrane protein NijA, when cleaved and released by MMP1, regulates cell adhesion. I am currently working on delineation of the pathway that is triggered by NijA. Our study helps to better understand the physiological function of MMP, which is critical in utilizing MMP as therapeutic targets. xiaoxi.wang@Vanderbilt.Edu
Wenzel, Sabine - Tansey Lab
The 26S proteasome is a large multi-functional complex designated to destroy proteins targeted for proteolysis by ubiquitylation. While it is well established that the ubiquitin-proteasome system catalyzes the turnover of transcriptional machinery components in eukaryotes, recent findings indicate a direct role of the proteasome in gene expression and its association with actively transcribed genes. My current project aims to uncover the role of the proteasome during transcription and to decipher the mechanisms of proteasome recruitment to chromatin in yeast. Since recent reports indicate that proteasome subassemblies might function through a non-proteolytic mechanism during gene expression, my studies also focus on the proteolytic as well as potential non-proteolytic function of the 26S proteasome. sabine.a.wenzel@Vanderbilt.Edu
Better identification of pancreatic multipotent progenitor cells, and determination of how they transition to endocrine-based progenitors will improve in vitro ES cell differentiation protocols, and are therefore high relevance to the therapeutic control of beta cell regeneration. As a nexus for gene regulatory networks controlling progenitors and beta cell differentiation, Pdx1’s spatiotemporal expression lead to context-dependent interpretations by different progenitors. My research focuses on the in vivo dissection of Pdx1 function, including (1) Requirement and sufficiency of Pdx1 in multipoent and endocrine-biased progenitor cells, and (2) Roles of cis-regulation of Pdx1 via conserved mammal-specific Area II. yuping.yang@Vanderbilt.Edu
Oncogenic c-Myc plays an essential role in the control of cell proliferation, transformation and apoptosis. The p53-dependent pathway that mediates c-Myc-induced apoptosis is well documented. However, there is accumulating evidence that both c-Myc and ARF have pro-apoptotic activities that are independent of p53. The aim of my research project is to investigate the noncanonical mechanism regulating ARF-dependent c-Myc-induced apoptosis independent of p53. qin.zhang@Vanderbilt.Edu
The goal of my project is to integrate the current advances in the field of the cytoskeleton research with the process of animal development & disease. Currently, I investigate:
(1). the function of Golgi-derived microtubules in the regulation of insulin secretion in pancreatic beta cells,
(2). involvement of the cytoskeleton in lithium nephrotoxicity. xiaodong.zhu@Vanderbilt.Edu