Tina Gumienny

Texas Woman's University · Department of Biology

Generating specific, robust protective responses to different bacteria is vital for animal survival. Here, we address the role of transforming growth factor β (TGF-β) member DBL-1 in regulating signature host defense responses in Caenorhabditis elegans to human opportunistic Gram-negative and Gram-positive pathogens. Canonical DBL-1 signaling is re...

Aging is a complex and highly regulated process of interwoven signaling mechanisms. As an ancient transcriptional regulator of thermal adaptation and protein homeostasis, the Heat Shock Factor, HSF-1, has evolved functions within the nervous system to control age progression; however, the molecular details and signaling dynamics by which HSF-1 modu...

Innate immunity in animals is orchestrated by multiple cell signaling pathways, including the TGF-β; superfamily pathway. While the role of TGF-β signaling in innate immunity has been clearly identified, the requirement for this pathway in generating specific, robust responses to different bacterial challenges has not been characterized. Here, we a...

Animals counter specific environmental challenges with a combination of broad and tailored host responses. One protein family enlisted in the innate immune response includes the saposin-like antimicrobial proteins. We investigated the expression of a Caenorhabditis elegans saposin-like gene, spp-9, in response to different stresses. spp-9 expressio...

Cellular responsiveness to environment, including changes in extracellular matrix (ECM), is critical for normal processes such as development and wound healing, but can go awry, as in oncogenesis and fibrosis. One type of molecular pathway contributing to this responsiveness is the BMP signaling pathway. Due to their broad and potent functions, BMP...

Bone morphogenetic protein (BMP) signaling pathways control many developmental and homeostatic processes, including cell size and extracellular matrix remodeling. An understanding of how this pathway is itself controlled remains incomplete. To identify novel regulators of BMP signaling, we performed a forward genetic screen in C. elegans for genes...

Cellular responsiveness to environmental cues, including changes in extracellular matrix (ECM), is critical for normal processes such as development and wound healing, but can go awry, as in oncogenesis and fibrosis. One type of molecular pathway allowing this responsiveness is the bone morphogenetic protein (BMP) signaling pathway. Due to their br...

Regulation of Extracellular Matrix in C. elegans: Lessons in Sweating the Small Stuff - Volume 24 Supplement - R.D. Schultz, E.A. Ellis, T.L. Gumienny

Programmed cell death, which occurs through a conserved core molecular pathway, is important for fundamental developmental and homeostatic processes. The human iron–sulfur binding protein NAF-1/CISD2 binds to Bcl-2 and its disruption in cells leads to an increase in apoptosis. Other members of the CDGSH iron sulfur domain (CISD) family include mito...

Mitogen-activated protein kinases (MAPK) are critical mediators of cellular responses to pathogens and are activated in response to infection, but investigation is difficult in multi-cell hosts due to developmental lethality of mutations. Mycobacterium marinum (Mm) is an established model for tuberculosis, a disease afflicting nearly one-third of t...

Figure S3. Survival of TP12 after bacterial infection.

Figure S4. Pathological changes in TP12 C. elegans infected with bacteria.

Figure S9. The C. elegans tol‐1, dbl‐1, and daf‐16 Pathways Do Not Impact Mycobacterial Infection.

Figure S16. Pathological changes in vhp‐1 Mutant C. elegans infected with bacteria.

Figure S5. Bacterial load in C. elegans (N2) determined by plating for CFU.

Figure S8. Pathological changes in pmk‐1 Mutant C. elegans infected with bacteria.

Figure S15. Role of C. elegans vhp‐1 in mycobacterial infection.

Figure S1. Pathological changes in wild‐type (N2) C. elegans infected with bacteria.

Figure S2. Morphological characteristics of C. elegans (TP12) infected with E. coli (OP50).

Figure S6 . C. elegans Infected with complemented MIM of M. marinum.

Figure S14. Pathological changes in skn‐1 Mutant C. elegans infected with bacteria

Table S1. Macrophage infection mutants (MIMs) of M. marinum. Table S2. List of C. elegans RNAi constructs and mutant strains. Table S3. Primers used for confirmation of C. elegans mutants and RNAi knock‐down.

Figure S7. Impact of C. elegans pmk‐1 on infection with mycobacteria.

Figure S10. Pathological changes in tol‐1 Mutant C. elegans infected with bacteria.

Figure S11. Pathological changes in dbl‐1 Mutant C. elegans infected with bacteria.

Figure S12. Pathological changes in daf‐16 Mutant C. elegans infected with bacteria.

Figure S13. Role of C. elegans skn‐1 in mycobacterial infection.

div class="title">Novel Regulated Secretion Mechanism For a Nerve-Secreted Cell Signaling Molecule in C. elegans - Volume 21 Issue S3 - R.D. Schultz, K. Beifuss, S. Bageshwar, E.A. Ellis, T.L. Gumienny

In mammals, Bone Morphogenetic Protein (BMP) pathway signaling is important for the growth and homeostasis of extracellular matrix, including basement membrane remodeling, scarring, and bone growth. A conserved BMP member in Caenorhabditis elegans, DBL-1, regulates body length in a dose-sensitive manner. Loss of DBL-1 pathway signaling also results...

of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.

of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.

Transforming Growth Factor-β (TGF-β) superfamily ligands regulate many aspects of cell identity, function, and survival in multicellular animals. Genes encoding five TGF-β family members are present in the genome of C. elegans. Two of the ligands, DBL-1 and DAF-7, signal through a canonical receptor-Smad signaling pathway; while a third ligand, UNC...

Regulated intercellular signaling is critical for the normal development and maintenance of multicellular organisms. Glypicans have been shown to regulate signaling by TGFβs, hedgehogs and Wnts, in several cellular contexts. Glypicans comprise a conserved family of heparan sulfated, glycosylphosphatidylinositol (GPI)-linked extracellular proteins....

Glypicans are multifunctional proteoglycans with regulatory roles in several intercellular signaling pathways. Here, we examine the functional requirements for glypican regulation of bone morphogenetic protein (BMP)-mediated body length in C. elegans. We provide evidence that two parts of C. elegans glypican LON-2 can independently inhibit BMP sign...

Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.

C. elegans has proven to be a valuable model system for the discovery and functional characterization of many genes and gene pathways. More sophisticated tools and resources for studies in this system are facilitating continued discovery of genes with more subtle phenotypes or roles. Here we present a generalized protocol we adapted for identifying...

The cuticle of C. elegans is a highly resistant structure that surrounds the exterior of the animal(1-4). The cuticle not only protects the animal from the environment, but also determines body shape and plays a role in motility(4-6). Several layers secreted by epidermal cells comprise the cuticle, including an outermost lipid layer(7). Circumferen...

Data Summary of regulated genes. The number of regulated genes scored at confidence intervals of 95%, 99% and 99.9%.

Genes highly regulated at the 95% confidence interval. The 99.9% most highly up- and down-regulated are annotated according to WormBase Release WS211. Other annotations primarily come from the Affymetrix microarray spreadsheet. Some manual cross-referencing was required from the Dauer Metabolic Database http://dauerdb.org/ to correlate labels from...

Protein synthesis and degradation genes highly regulated at 95% confidence or above. A summary list of protein synthesis and degradation genes regulated by the Sma/Mab pathway at the 95% confidence level.

Comparisons with similar microarray experiments. A summary list of comparisons among similar microarray experiments. Mochii et al refers to reference [36], Liang et al refers to reference [37], and Mallo et al refers to reference [5].

Structural Genes highly regulated at 95% confidence or above. A summary list of structural genes regulated by the Sma/Mab pathway at the 95% confidence level.

Bone morphogenetic proteins (BMPs) are members of the conserved transforming growth factor beta (TGFbeta superfamily, and play many developmental and homeostatic roles. In C. elegans, a BMP-like pathway, the DBL-1 pathway, controls body size and is involved in innate immunity. How these functions are carried out, though, and what most of the downst...

SMA-10 does not bind BMP ligands. HepG2 cells were transfected with either HA-tagged DAF-4, the control vector, or HA-tagged SMA-10 and incubated with 0.5 nM 125I-BMP2. Lysates were collected and immunoprecipitated with HA antibody. Samples were split and separated on SDS-PAGE gels and scanned for visualization of 125I-BMP2 or immunoblotted with HA...

sma-10 cDNA rescues Body Size sma-10(lf) Mutants. Body lengths of staged one-day adult hermaphrodites were measured. sma-10(wk66) animals were non-transgenic siblings of sma-10(wk66); texEx195 animals. The p value is the probability that the null hypothesis, that the mean body length of the transgenic line is the same as the sma-10(wk66) mean body...

Author Summary Bone morphogenetic protein (BMP) family members, small secreted signaling molecules, play diverse roles in development and homeostasis. Uncontrolled BMP signaling results in a variety of disorders and diseases. BMPs signal to receiving cells through two receptor types, which act together to propagate the BMP signal within cells. To u...

Bone morphogenetic protein (BMP) pathways are required for a wide variety of developmental and homeostatic decisions, and mutations in signaling components are associated with several diseases. An important aspect of BMP control is the extracellular regulation of these pathways. We show that LON-2 negatively regulates a BMP-like signaling pathway t...

Cell size is an important determinant of body size. While the genetic mechanisms of cell size regulation have been well studied in yeast, this process has only recently been addressed in multicellular organisms. One recent report by Wang et al. (2002) shows that in the nematode C. elegans, the TGFβ-like pathway acts in the hypodermis to regulate ce...

The transforming growth factor beta (TGF-beta) superfamily of paracrine and autocrine signaling molecules regulates a vast array of developmental and homeostatic processes and is itself exquisitely regulated. The misregulation of these molecules often results in cancer and other diseases. Here, we focus on new research that explores how TGF-beta su...

The transforming growth factor β (TGF-β) superfamily of paracrine and autocrine signaling molecules regulates a vast array of developmental and homeostatic processes and is itself exquisitely regulated. The misregulation of these molecules often results in cancer and other diseases. Here, we focus on new research that explores how TGF-β superfamily...

In Caenorhabditis elegans, two well-characterized TGF beta signaling cascades have been identified: the Small/Male tail abnormal (Sma/Mab) and Dauer formation (Daf) pathways. The Sma/Mab pathway regulates body size morphogenesis and male tail development. The ligand of the pathway, dbl-1, transmits its signal through two receptor serine threonine k...

The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs crkII, dock180, and rac1, mediate cytoskeletal rearrangements during phagocytosis of apoptotic cells and cell motility. Here, we describe an additional member of this signaling pathway, ced-12, and its mammalian homologs, elmo1 and elmo2. In C. elegans, CED-12 is required f...

Apoptotic cell death in the nematode C. elegans culminates with the removal of the dying cells from the organism. This removal is brought forth through a rapid and specific engulfment of the doomed cell by one of its neighbors. Over half a dozen genes have been identified that function in this process in the worm. Many of these engulfment genes hav...

Apoptotic cell death in the nematode C. elegans culminates with the removal of the dying cells from the organism. This removal is brought forth through a rapid and specific engulfment of the doomed cell by one of its neighbors. Over half a dozen genes have been identified that function in this process in the worm. Many of these engulfment genes hav...

Similar to mammalian excitotoxic cell death, necrotic-like cell death (NCD) in Caenorhabditis elegans can be initiated by hyperactive ion channels. Here we investigate the requirements for genes that execute and regulate programmed cell death (PCD) in necrotic-like neuronal death caused by a toxic MEC-4 channel. Neither the kinetics of necrosis ons...

Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites,...

Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites,...

Programmed cell death plays a vital role in the life of an organism. The developing organism is shaped not only by its cells, but also by the cells it removes through programmed cell death. Programmed cell death also helps regulate homeostasis in a growing number of tissues; the disruption of this pathway can prevent the culling of potentially dang...

Thesis (Ph. D.)--State University of New York at Stony Brook, 2000. Includes bibliographical references.