Alumni Dissertations

 

Alumni Dissertations

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  • THE CHARACTERIZATION OF Pb2+ TOXICITY IN RAT NEURAL DEVELOPMENT: AN ASSESSMENT OF Pb2+ EFFECTS ON THE GABA SHIFT IN NEURAL NETWORKS AND IMPLICATIONS FOR LEARNING AND MEMORY DISRUPTION

    Author:
    Lorenz Neuwirth
    Year of Dissertation:
    2014
    Program:
    Biology
    Advisor:
    Abdeslem El Idrissi
    Abstract:

    The toxic effects of Pb2+ on the developing rat nervous system has been investigated to assess early developmental GABAergic disruption and its implications with altering inhibitory learning and memory. This goal was achieved using a multi-systems approach: blood lead levels (clinical physiology), qRT-PCR (molecular genetics), brain and primary neuronal culture immunology (immunohistochemical and cellular approaches), physiological cellular components (synaptosomes and protein expression) and finally through learning and memory assessment with GABA mimetic drug manipulations in the intact animal (behavioral pharmacology). The influence of a 956ppm Pb2+ gestational diet (i.e. from birth to sacrifice) resulted in pup mean blood lead levels (BLLs measured in ìg/dL) (Range 28-47) and Dams (Range 33-51) respectively. In contrast, control pups and dams were Pb2+ negative. These ages were selected to determine neurodevelopmental trajectories of the GABA-shift from excitation-to-inhibition postnatally in our model. qRT-PCR studies evinced a delay in mRNA expression regulating GAD 80, 65, CACAN â3, GABAAR and were differentially regulated cortex and hippocampus as a function of age in response to Pb2+. Brain slice immunohistochemistry revealed an early shift of KCC2 expression in both cortex and hippocampus. Notably, these alterations were differentially regulated by age, brain region and subcellular circuitry within structures (i.e. DG vs. CA3). Neuronal cultures revealed that in response to Pb2+ at low micro molar concentrations induced VSCC-â3 nuclear translocation and GABAAR upregulation. KCC2 expression was inhibiting in cultures by Pb2+. Synaptosomal effects of Pb2+ revealed altered glutamate accumulation and handling with increased spontaneous and decreased evoked release in significantly modulated by Pb exposure suggesting altered brain synaptogenesis. Pb2+ exposure resulted in increased binding suggesting post synaptic modification in cortex and hippocampus increasing brain excitability. Behaviorally, Pb2+ exposure resulted in increased anxiety, impulsivity, stress, and disrupted learning and memory regulated by inhibitory circuits that were recovered with taurine, a GABAAR agonist, administration. Specifically, Pb2+ disrupted contextual and auditory associative learning. Taken together, these results suggest that Pb2+ interferes with early VSCCs and GABAAR synergistic action that establishes GABAergic neural networks and in turn produces increased brain excitability and over reactivity as a consequence of reduced inhibition.

  • The Diversity and Evolution of Transposable Elements in the Genome of The Lizard Anolis carolinensis

    Author:
    Peter Novick
    Year of Dissertation:
    2010
    Program:
    Biology
    Advisor:
    Stephane Boissinot
    Abstract:

    Eukaryotic genomes are littered with repetitive DNA sequences called transposable elements (TEs). Though once considered "junk DNA," these elements can greatly impact their host genomes by influencing genome size, providing novel proteins and promoter sequences, as well as disrupting gene function or causing chromosomal rearrangements. However, the impact TEs have on their host's genome depends on their abundance and diversity, which differ greatly among vertebrate genomes. The genome of teleostean fish contain a very diverse community of elements that are represented only by recent inserts found in very low copy number (<100). On the other hand, most mammalian genomes have a very low diversity of TEs dominated by L1 retrotransposons, yet elements in mammals accumulate to reach extraordinary copy numbers (>100,000). This difference accounts, for the most part, for the difference in genome size between these two groups. Until recently, we did not have a good model to study the transition from the small repeat-poor genome of fish to the larger repeat-rich genome of mammals. The first non-avian reptile genome sequence, the lizard Anolis carolinensis (the North American green anole), bridges the large phylogenetic gap between fish and mammals and provides a better understanding of early amniotes genomic evolution. We performed the first comprehensive analysis of TEs in the anole genome. We found that the anole genome contains an extraordinary diversity of active TEs. This genome contains several concurrently active clades of non-LTR retrotransposons (CR1, L1, L2, RTE, and R4) each represented by multiple families. The vast majority of insertions are very young, suggesting that most elements do not reach fixation and when they do, they decay rapidly. In addition the anole genome is inhabited by multiple superfamilies of DNA transposons (hAT, Helitron, Maverick and Chapaev), some of which were laterally transferred to the anole. We conclude that the genomic landscape of the lizard is strikingly similar to the one of fish and shows little resemblance to mammalian genomes.

  • The Diversity and Evolution of Transposable Elements in the Genome of The Lizard Anolis carolinensis

    Author:
    Peter Novick
    Year of Dissertation:
    2010
    Program:
    Biology
    Advisor:
    Stephane Boissinot
    Abstract:

    Eukaryotic genomes are littered with repetitive DNA sequences called transposable elements (TEs). Though once considered "junk DNA," these elements can greatly impact their host genomes by influencing genome size, providing novel proteins and promoter sequences, as well as disrupting gene function or causing chromosomal rearrangements. However, the impact TEs have on their host's genome depends on their abundance and diversity, which differ greatly among vertebrate genomes. The genome of teleostean fish contain a very diverse community of elements that are represented only by recent inserts found in very low copy number (<100). On the other hand, most mammalian genomes have a very low diversity of TEs dominated by L1 retrotransposons, yet elements in mammals accumulate to reach extraordinary copy numbers (>100,000). This difference accounts, for the most part, for the difference in genome size between these two groups. Until recently, we did not have a good model to study the transition from the small repeat-poor genome of fish to the larger repeat-rich genome of mammals. The first non-avian reptile genome sequence, the lizard Anolis carolinensis (the North American green anole), bridges the large phylogenetic gap between fish and mammals and provides a better understanding of early amniotes genomic evolution. We performed the first comprehensive analysis of TEs in the anole genome. We found that the anole genome contains an extraordinary diversity of active TEs. This genome contains several concurrently active clades of non-LTR retrotransposons (CR1, L1, L2, RTE, and R4) each represented by multiple families. The vast majority of insertions are very young, suggesting that most elements do not reach fixation and when they do, they decay rapidly. In addition the anole genome is inhabited by multiple superfamilies of DNA transposons (hAT, Helitron, Maverick and Chapaev), some of which were laterally transferred to the anole. We conclude that the genomic landscape of the lizard is strikingly similar to the one of fish and shows little resemblance to mammalian genomes.

  • BIODIVERSITY, TAXONOMY AND SYSTEMATICS OF NEW WORLD FRESHWATER LEECHES (ANNELIDA: HIRUDINEA) WITH PARTICULAR EMPHASIS ON GLOSSIPHONIID LEECHES AND THEIR BACTERIAL ENDOSYMBIONTS

    Author:
    Alejandro Oceguera-Figueroa
    Year of Dissertation:
    2011
    Program:
    Biology
    Advisor:
    Mark Siddall
    Abstract:

    The phylum Annelida Lamarck, 1809 includes segmented worms such as leeches, earthworms, lugworms, sandworms and clamworms that inhabit almost all possible environments and places of the world. Leeches (Class Hirudinea) represents only one group of around 680 species out of the approximately 16,500 described species of Annelida. The class Hirudinea has been divided in two groups based on their mouthparts. The order Rhynchobdellida, a paraphyletic assemblage, includes species with a large and eversible proboscis and the order Arhynchobdellida that includes species with a muscular pharynx with or without jaws. Both orders include organisms specialized to feed on vertebrate blood. This study includes the description of eight species of leeches new to science that belong to three families (Glossiphoniidae, Macrobdellidae and Praobdellidae). The phylogenetic relationships of species of three families (Glossiphoniidae, Macrobdellidae and Praobdellidae) and one suborder (Erpobdelliformes) were investigated using molecular and morphological data and a suite of phylogenetic methods (Parsimony, Maximum Likelihood and Bayesain Inference). The description of the new species Tyrannobdella rex (Praobdellidae) and Oxyptychus bora (Macrobdellidae) are discussed in the context of their placement in phylogenies. The phylogenetic study of Erpobdelliformes includes the comparison of alternative classification schemes. Based on the results, the phylogenetic position of the terrestrial and macrophagous Orobdella octonaria (Gastrostomobdellidae) within the Erpobdelliformes is established for the first time. The phylogenetic relationships of the proboscis-bearing species of the genera Haementeria, Helobdella and Placobdella were investigated using a combination of nuclear and mitochondrial markers and Parsimony and Bayesian Inference methods. In addition to the monophyly of Haementeria, Helobdella and Placobdella, the 3 genera formed a monophyletic group notwithstanding their different feeding preferences. The correlation with phylogeny and some morphological traits is shown. These include, eyespot morphology, annulation patterns, shape of the ovisacs, sensory organs on the dorsal surface and presence of bacteriomes. Species of Haementeria and Placobdella have specialized organs called bacteriomes associated with their salivary complex that harbor symbiotic proteobacteria. Using DNA bacterial sequences (16S rRNA), the exclusive association of Haementeria spp. with gammaproteobacteria and Placobdella spp. with alphaproteobacteria is shown. Using pyrosequencing technology, the nucleotide sequences of a DNA sample extracted from the bacteriomes of Placobdella parasitica were analyzed. A total of 1,053,345 DNA fragments were obtained and assembled. Leech and symbiont DNA fragments were separated using Blast tools and 50 bacterial and Helobdella robusta genomes for reference. Finally, the so-called DNA barcoding protocol is discussed and some recommendations were given to increase the information content of the database (Bold system). In addition, DNA barcoding protocol was used to estimate the diversity of species of Helobdella from Mexico.

  • Medicinal Plants of Northern Thailand for the Treatment of Cognitive Impairment in the Elderly

    Author:
    Lisa Offringa
    Year of Dissertation:
    2013
    Program:
    Biology
    Advisor:
    Michael Balick
    Abstract:

    Dementia is a progressive neurological disease affecting memory and behavior. The diagnosis of dementia is increasing exponentially worldwide and with it the potential risk for a severe social and economic burden of caring for an increasing debilitated elderly population. Cognitive impairment, and especially memory loss, can be the first indication of dementia. This study documents the treatment of cognitive impairment in the elderly by Thai traditional healers in northern Thailand using medicinal plants. Interviews were conducted from 2008-2012 to investigate the etiology of dementia in Thai Traditional Medicine and identify plants used to treat memory loss in the pharmacopeia of northern Thailand. Multi-plant herbal formulas from ancient manuscripts of the Lanna Kingdom were obtained from Thai traditional healers. These formulas were analyzed through ethnobotanical inquiry for plant species with potential bioactivity against memory loss in the elderly. Crude extracts of eleven selected plant species were screened through four in vitro bioassays to measure their general antioxidant activity, total phenolic content and acetylcholinesterase inhibition activity. Of these eleven species, five plants exhibited high levels of acetylcholinesterase inhibition activity: Cinnamomum bejolghota (Buch-Ham.) Sweet, Dracaena loureiroi Gagnep., Diospyros decandra Lour., Jasminum sambac (L.) Aiton., and Eurycoma longifolia Jack. One plant, Cinnamomum bejolghota demonstrated high activity in all four in vitro bioassays. Three different doses of an ethanol extract of Cinnamomum bejolghota were evaluated for their memory enhancing ability on in vivo rat behavioral models and enzymatic marker tests on their brain tissue. Results from the Morris Water Maze navigation task showed that the two highest dosages of the extract produced significant memory improvement after two weeks of treatment. Enzymatic marker analyses in three portions of the rats' brains associated with memory formation, the hippocampus, striatum and cortex, showed significant acetylcholinesterase inhibition activity thereby increasing acetylcholine levels in these parts of the brain. This study identified a plant with memory enhancing activity that, with further study, could help to alleviate the suffering of those afflicted with age-related memory decline. Ethnopharmacological studies support the viability of traditional medicine to treat diseases that are relevant in modern society.

  • The Non-canonical Growth Activating Functions of HIghly Expressed Mdm2-C

    Author:
    Danielle Okoro
    Year of Dissertation:
    2013
    Program:
    Biology
    Advisor:
    Jill Bargonettil
    Abstract:

    Mdm2 is an oncoprotein that regulates the tumor suppressor protein, p53 via the Mdm2 canonical pathway. The pathway involves p53 protein degradation and transcriptional repression. Mdm2 is often found over-expressed in cancers. In the presence of Mdm2 over-expression, the activity of p53 is frequently attenuated and the protein levels remain paradoxically high. Cancers with Mdm2 over-expression also over-express mdm2 splice variant transcripts. There are over forty identified spliced variants of mdm2. Therefore, we hypothesized that in the presence of Mdm2 over-expression, a different form of Mdm2 protein exists that does not function in the Mdm2 canonical pathway. In this study, the functions of an Mdm2 isoform, Mdm2-C, were investigated. We observed that Mdm2 over-expressing cells have high basal levels of mdm2-C transcript. We have cloned and expressed mdm2-C in vitro. We created an Mdm2-C specific antibody, Mdm2 C410, to the splice junction of exons four and ten (Mdm2 C410) and validated the C410 antibody using in vitro translated full-length Mdm2 compared to Mdm2-C. The Mdm2 C410 antibody did not detect Mdm2-FL. We saw that different human cancer cell lines, liposarcoma and breast cancer tissues, over-expressed endogenous Mdm2-C protein. We also observed that there was an estrogen-dependent increase in endogenous Mdm2-C protein in ER+ mdm2 SNP309 breast cancer cells that was p53-independent. In addition, the exogenous expression of Mdm2-C in human p53-null cancer cells showed that Mdm2-C does not function in the Mdm2 canonical pathway. Immunofluorescence utilizing the Mdm2 C410 antibody displayed that Mdm2-C was localized to the cytoplasm and nucleolus in a speckled pattern that might be integral to its cellular functions. We observed that the over-expression of Mdm2-C in the presence or absence of p53 in human and mouse cell lines promoted cell growth. Furthermore, the partial down regulation of mdm2-C via siRNA in mutant p53 G/G mdm2SNP309 breast cancer cells, T47D resulted in increased cell death. Thus suggesting that unlike other Mdm2 isoforms and full-length Mdm2, Mdm2-C has distinct roles in cell survival and p53-independent Mdm2 molecular pathways. Here we report the first identification of an endogenous tumor-associated splice variant Mdm2 protein, and document that Mdm2-C functions through a non-canonical growth activation pathway that is p53-independent.

  • Genetic, Morphological, and Ecological Relationships Among Populations of the Clam Shrimp, Caenestheriella gynecia.

    Author:
    Jonelle Orridge
    Year of Dissertation:
    2011
    Program:
    Biology
    Advisor:
    John Waldman
    Abstract:

    Little is known about the ecology of the clam shrimp, Caenestheriella gynecia. Caenestheriella gynecia was first discovered in 1939 in a single pool in Oxford, Ohio. Schmidt and Kiviat (2007) reported four new localities of C. gynecia in New York and New Jersey, three within the Hudson Valley of New York and one in northeastern New Jersey. Caenestheriella gynecia may have originated from a very small founder population due possibly to unusual dispersal vectors from its natural range to the west, in Ohio. Egg samples and hatched individuals were obtained from all study sites and specimens were raised in the lab to estimate several growth and survivorship traits. In the field, puddle habitats were observed between the months of May and August where water quality parameters (i.e., dissolved oxygen, temperature, conductivity and pH, and nutrient composition) were recorded. Genetic comparisons across the study sites were made using nuclear DNA sequencing and random amplified polymorphic DNA (RAPD) analysis. The results of this study presented a wide range in the hydro-chemical and physical characteristics of the ephemeral pools in which C. gynecia seem to tolerate. Morphologically, New Jersey and Massachusetts populations possessed meristics counts within the range of those discovered by Mattox in 1950. However, I recommend the placement of the New York population within the Cyzicus genus as their meristic measurements fell outside the range for Caenestheriella. RAPD results revealed the presence of more than one clone in puddles containing C. gynecia although mtDNA sequencing did not reveal any genetic variation within or among populations. The lack of males within C. gynecia's population and low levels of genetic variability support the clonal nature of a strictly parthenogenetic species. These investigations provide a substantial extension of fundamental knowledge of this poorly understood species.

  • FUNCTIONAL EVOLUTION OF THE APETALA1/FRUITFULL GENE LINEAGE

    Author:
    Natalia Pabon Mora
    Year of Dissertation:
    2012
    Program:
    Biology
    Advisor:
    Amy Litt
    Abstract:

    Several MADS-box gene lineages involved in flower development have undergone duplications that correlate with the diversification of large groups of flowering plants. In the APETALA1 gene lineage, a major duplication coincides with the origin of the core eudicots, resulting in the euFUL and the euAP1 clades. Arabidopsis FRUITFULL (FUL) and APETALA1 (AP1) function redundantly in specifying floral meristem identity, but function independently in sepal and petal identity (AP1) and in proper fruit development and determinacy (FUL). Many of these functions are largely conserved in other core-eudicot euAP1 and euFUL genes, but notably the role of APETALA1 as an "A-function" (sepal and petal identity) gene is thought to be Brassicaceae-specific. Understanding how functional divergence of the core-eudicot duplicates occurred requires a careful examination of the function of pre-duplication (FUL-like) genes. Using Virus Induced Gene Silencing (VIGS), it is shown that FUL-like genes in Papaver somniferum (opium poppy) and Eschscholzia californica (California poppy) function in axillary meristem growth and in floral meristem and sepal identity, and play a key role in fruit development. Interestingly, in opium poppy, these genes also control flowering time and petal identity, suggesting that AP1/FUL homologs might have been independently recruited in petal organ identity. In contrast, it is shown that the Aquilegia coerulea FUL-like homolog does not appear to play a role in flower or fruit development and instead has been recruited in leaf morphogenesis. In general the FUL-like gene functional repertoire encompasses all roles previously described for the core-eudicot euAP1 and euFUL genes, and subfunctionalization can be postulated as the functional outcome after the major AP1/FUL gene lineage duplication event. However, these results also point to significant functional variability of FUL-like genes within Ranunculales, most likely due to gene duplication and loss, as well as changes of FUL-like protein partners in different taxa.

  • Role of Toll-NF-kB Signaling in Inflammation and Immune Homeostasis in Drosophila melanogaster

    Author:
    Indira Paddibhatla
    Year of Dissertation:
    2011
    Program:
    Biology
    Advisor:
    Shubha Govind
    Abstract:

    Inflammation is defined as a localized reaction in response to injury or tissue destruction. It serves to contain or sequester the causative agent. Fundamentally important to human health, inflammation and its aberrant regulation underlie many diseases including cancer, diabetes and heart disease. Like humans, fruit flies respond to infection by coordinating complex defense responses. Parasitic wasps are natural enemies of Drosophila and attack larvae or pupae. They inject one or more eggs, each approximately 100 mm in size, into the hemocoel of the fly larva. Oviposition results either in the development of the wasp larva that gradually eats the Drosophila host tissue, or the host's blood cells encapsulate the wasp egg. In the latter scenario, circulating host blood cells surround the wasp egg and inhibit its development. In addition to the activation and aggregation of the host blood cells in response to wasp attack, infected larvae also activate gene expression in the fat body. A number of antimicrobial peptides and other immune-related proteins are secreted into the hemolymph. The humoral arm is activated within the first couple of hours of infection, although the significance of this activation is not understood. It is also not clear how the encapsulation reaction is so tightly controlled or how it is terminated. Previous studies from our laboratory have focused on the role of Toll-NF-kB signaling in hematopoiesis. Larvae deficient in either IkB/cactus or the SUMO-conjugating enzyme, Ubc9, exhibit hematopoietic defects (overproliferation and abnormal differentiation of the blood cells) accompanied with aggregation and microtumor formation. These mutants also express antimicrobial peptides such as Drosomycin from the fat body even in the absence of infection. Given that both the humoral and cellular immune systems of these mutants are hyperactive, we hypothesized that changes induced after wasp infection represent acute inflammation, and these effects become chronic in cactus or Ubc9 mutants. Studies in the first chapter explore the cellular and molecular parallels between wasp-induced gene expression and encapsulation versus constitutive gene expression and encapsulation (in microtumors) of Ubc9 mutants. We show that several core components (including SPE, Toll, and cactus) of the Toll-Dorsal pathway are activated in each case. However, while gene expression after wasp infection shows acute phase profile (activation followed by downregulation), expression in mutants remains high. We show that the cytokine Spätzle (the Toll ligand) is expressed in the immune cells, hemocytes and the fat body. Spätzle protein levels are higher after wasp infection and in Ubc9 mutants. Misexpression of either SPE or Spz protein in immune tissues of wild type larvae leads to blood cell proliferation, differentiation, infiltration of the fat body tissue and melanized microtumors. We propose a pro-inflammaotry role for SPE/Spätzle whose downregulation is essential for limiting acute inflammation. Accordingly, loss of spz suppresses Ubc9- defects and loss of SPE in the immune cells fails to encapsulate the parasitic egg. In contrast to the pro-inflammatory role of SPE/Spz, SUMO conjugating enzyme, Ubc9, and IkB homologue, Cactus, are anti-inflammatory agents. RNAi knockdown of Ubc9, or even Uba2/Aos1 subunits of SUMO activating enzymes leads to systemic chronic inflammation. Affected animals activate Drosomycin in the fat body in the absence of infection. Blood cells infiltrate the fat body and these changes are accompanied with microtumor development. Extensive staining of fat body and blood cells reveals that while cactus transcription and protein levels increase after infection, Ubc9 mutants cannot sustain normal cytoplasmic levels of Cactus protein. These studies demonstrate the existence of a sumoylation dependent Ubc9/IkB modulated immune homeostasis mechanism that balances the pro- and anti-inflammatory factors in the hosts. This study on Drosophila inflammatory responses complements the existing mammalian models for cancer inflammation. Knowledge gained from our system should be highly relevant in developing novel strategies for medical and agricultural pest control.

  • Role of Toll-NF-kB Signaling in Inflammation and Immune Homeostasis in Drosophila melanogaster

    Author:
    Indira Paddibhatla
    Year of Dissertation:
    2011
    Program:
    Biology
    Advisor:
    Shubha Govind
    Abstract:

    Inflammation is defined as a localized reaction in response to injury or tissue destruction. It serves to contain or sequester the causative agent. Fundamentally important to human health, inflammation and its aberrant regulation underlie many diseases including cancer, diabetes and heart disease. Like humans, fruit flies respond to infection by coordinating complex defense responses. Parasitic wasps are natural enemies of Drosophila and attack larvae or pupae. They inject one or more eggs, each approximately 100 mm in size, into the hemocoel of the fly larva. Oviposition results either in the development of the wasp larva that gradually eats the Drosophila host tissue, or the host's blood cells encapsulate the wasp egg. In the latter scenario, circulating host blood cells surround the wasp egg and inhibit its development. In addition to the activation and aggregation of the host blood cells in response to wasp attack, infected larvae also activate gene expression in the fat body. A number of antimicrobial peptides and other immune-related proteins are secreted into the hemolymph. The humoral arm is activated within the first couple of hours of infection, although the significance of this activation is not understood. It is also not clear how the encapsulation reaction is so tightly controlled or how it is terminated. Previous studies from our laboratory have focused on the role of Toll-NF-kB signaling in hematopoiesis. Larvae deficient in either IkB/cactus or the SUMO-conjugating enzyme, Ubc9, exhibit hematopoietic defects (overproliferation and abnormal differentiation of the blood cells) accompanied with aggregation and microtumor formation. These mutants also express antimicrobial peptides such as Drosomycin from the fat body even in the absence of infection. Given that both the humoral and cellular immune systems of these mutants are hyperactive, we hypothesized that changes induced after wasp infection represent acute inflammation, and these effects become chronic in cactus or Ubc9 mutants. Studies in the first chapter explore the cellular and molecular parallels between wasp-induced gene expression and encapsulation versus constitutive gene expression and encapsulation (in microtumors) of Ubc9 mutants. We show that several core components (including SPE, Toll, and cactus) of the Toll-Dorsal pathway are activated in each case. However, while gene expression after wasp infection shows acute phase profile (activation followed by downregulation), expression in mutants remains high. We show that the cytokine Spätzle (the Toll ligand) is expressed in the immune cells, hemocytes and the fat body. Spätzle protein levels are higher after wasp infection and in Ubc9 mutants. Misexpression of either SPE or Spz protein in immune tissues of wild type larvae leads to blood cell proliferation, differentiation, infiltration of the fat body tissue and melanized microtumors. We propose a pro-inflammaotry role for SPE/Spätzle whose downregulation is essential for limiting acute inflammation. Accordingly, loss of spz suppresses Ubc9- defects and loss of SPE in the immune cells fails to encapsulate the parasitic egg. In contrast to the pro-inflammatory role of SPE/Spz, SUMO conjugating enzyme, Ubc9, and IkB homologue, Cactus, are anti-inflammatory agents. RNAi knockdown of Ubc9, or even Uba2/Aos1 subunits of SUMO activating enzymes leads to systemic chronic inflammation. Affected animals activate Drosomycin in the fat body in the absence of infection. Blood cells infiltrate the fat body and these changes are accompanied with microtumor development. Extensive staining of fat body and blood cells reveals that while cactus transcription and protein levels increase after infection, Ubc9 mutants cannot sustain normal cytoplasmic levels of Cactus protein. These studies demonstrate the existence of a sumoylation dependent Ubc9/IkB modulated immune homeostasis mechanism that balances the pro- and anti-inflammatory factors in the hosts. This study on Drosophila inflammatory responses complements the existing mammalian models for cancer inflammation. Knowledge gained from our system should be highly relevant in developing novel strategies for medical and agricultural pest control.