Cell and Developmental Biology Commons^™

Increasing Glutathione Levels By A Novel Posttranslational Mechanism Inhibits Neuronal Hyperexcitability, Ashwini Sri Hari, Rajeswari Banerji, Li-Ping Liang, Ruth E Fulton, Christopher Quoc Huynh, Timothy Fabisiak, Pallavi Bhuyan Mcelroy, James R Roede, Manisha Patel

Faculty, Staff and Students Publications

Glutathione (GSH) depletion, and impaired redox homeostasis have been observed in experimental animal models and patients with epilepsy. Pleiotropic strategies that elevate GSH levels via transcriptional regulation have been shown to significantly decrease oxidative stress and seizure frequency, increase seizure threshold, and rescue certain cognitive deficits. Whether elevation of GSH per se alters neuronal hyperexcitability remains unanswered. We previously showed that thiols such as dimercaprol (DMP) elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting GSH biosynthetic enzyme. Here, we asked if elevation of cellular GSH by DMP altered neuronal hyperexcitability in-vitro and in-vivo. Treatment of …

Sigma1 Regulates Lipid Droplet-Mediated Redox Homeostasis Required For Prostate Cancer Proliferation, Halley Oyer, Alexandra Steck, Charles Longen, Sanjana Venkat, Konuralp Bayrak, Eleanor Munger, Dan Fu, Paola Castagnino, Christina Sanders, Nathalia Tancler, My Mai, Justin Myers, Matthew Schiewer, Nan Chen, Elahe Mostaghel, Felix Kim

Department of Urology Faculty Papers

UNLABELLED: Lipid droplets (LD) are dynamic organelles that serve as hubs of cellular metabolic processes. Emerging evidence shows that LDs also play a critical role in maintaining redox homeostasis and can mitigate lipid oxidative stress. In multiple cancers, including prostate cancer, LD accumulation is associated with cancer aggressiveness, therapy resistance, and poor clinical outcome. Prostate cancer arises as an androgen receptor (AR)-driven disease. Among its myriad roles, AR mediates the biosynthesis of LDs, induces autophagy, and modulates cellular oxidative stress in a tightly regulated cycle that promotes cell proliferation. The factors regulating the interplay of these metabolic processes downstream of …

Simian Immunodeficiency Virus-Infected Rhesus Macaques With Aids Co-Develop Cardiovascular Pathology And Encephalitis, Kevin S. White, Joshua A. Walker, John Wang, Patrick Autissier, Andrew D. Miller, Nadia N. Abuelezan, Rachel Burrack, Qingsheng Li, Woong-Ki Kim, Kenneth C. Williams

Nebraska Center for Virology: Faculty Publications

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/ macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently …

Tak1 And Tbk1 Are Differentially Required By Gmp- And Lmpp-Like Leukemia Stem Cells, Austin P. Runde, Joseph Michael Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Allan Youmaran, Mattias Lenz, Rohit Thalla, Wei Wei, Peter Breslin S.J., Jiwang Zhang

School of Medicine

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow. Aside from the M3 subtype (PML-RARA⁺), AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a 2-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine. Despite 60-70% of patients achieving complete remission (CR), at least half of CR-achieving patients …

Co-Infection And Co-Localization Of Kaposi Sarcoma-Associated Herpesvirus And Epstein-Barr Virus In Hiv-Associated Kaposi Sarcoma: A Case Report, Peter Julius, Guobin Guobin, Stepfanie Siyumbwa, Jane Musumali, For Yue Tso, Owen Ngalamika, Trevor Kaile, Fred Maate, Phyllis Moonga, John T. West, Peter Angeletti, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi sarcoma (KS), a multifocal vascular neoplasm frequently observed in HIVpositive individuals, primarily affects the skin, mucous membranes, visceral organs, and lymph nodes. KS is associated primarily with Kaposi sarcomaassociated herpesvirus (KSHV) infection. In this case report, we present a rare occurrence of co-infection and co-localization of KSHV and Epstein-Barr virus (EBV) in KS arising from the conjunctiva, which, to our knowledge, has not been reported previously. Immunohistochemistry (IHC), DNA polymerase chain reaction (PCR), and EBV-encoded RNA in situ hybridization (EBER-ISH) were utilized to demonstrate the presence of KSHV and EBV infection in the ocular KS lesion. Nearly all KSHV-positive …

Using Hyperosmotic Shock To Study The Cell Wall Of Myxococcus Xanthus, Ian Sabol

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

No abstract provided.

Effects Of Growth Rate On Peptidoglycan Crosslink Density Of E. Coli Using Fluorescent Labeling, Morgan Olszewski

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Peptidoglycan (PG) is a polymer composed of polysaccharides and crosslinked peptide chains found in bacterial cell walls. It helps to protect the cell from environmental stress and maintain cell morphology throughout its life cycle and further generations. The PG is made up of two sugars, N-acetyl muramic acid (NAM) and N-acetyl glucosamine (NAG). NAM and NAG are connected by glycosidic linkages to form repeated chains. The chains are formed in layers, which are interconnected via a polypeptide stem linked by a peptide bridge. During cell growth, continuous turnover of existing PG occurs by severing existing crosslinks, inserting new PG into …

A Single-Dose Intramuscular Immunization Of Pigs With Lipid Nanoparticle Dna Vaccines Based On The Hemagglutinin Antigen Confers Complete Protection Against Challenge Infection With The Homologous Influenza Virus Strain, The N. Nguyen, Sushmita Kumari, Sarah Vitosh-Sillman, Jayeshbhai Chaudhari, Danh C. Lai, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The Influenza A virus of swine (IAV-S) is highly prevalent and causes significant economic losses to swine producers. Due to the highly variable and rapidly evolving nature of the virus, it is critical to develop a safe and versatile vaccine platform that allows for frequent updates of the vaccine immunogens to cope with the emergence of new viral strains. The main objective of this study was to assess the feasibility of using lipid nanoparticles (LNPs) as nanocarriers for delivering DNA plasmid encoding the viral hemagglutinin (HA) gene in pigs. The intramuscular administration of a single dose of the LNP-DNA vaccines …

Development Of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer, Poornima Devi Shaji, Ana Martinez Bulnes, Nirnoy Dan, Subhash C. Chauhan, Sheema Khan, Murali M. Yallapu

Research Colloquium

Introduction: About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in other cancers but limited response in pancreatic cancer due to desmoplasia and fibrotic tumor microenvironment. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. Due to its high membrane expression, MUC13 may serve as an excellent target …

Molecular Event In Hrp Apoptosis, Laura Valdez

Research Colloquium

Background: Human retinal pericytes (HRP) are contractile cells providing support for endothelial cells of capillaries, essential in the regulation of retinal vasculature. Early stages of DR are characterized by the loss of HRP, leading to angiogenesis. Our preliminary studies identified monocyte-derived macrophages secrete TGF-β1, inducing the expression and secretion of a TGFβ1-Induced, pro-apoptotic BIGH3 protein leading to apoptosis of HRP. Based on a preliminary study in renal cells (unpublished data), CTP with an RGD domain is released from BIGH3 by proteolysis leading to renal cell apoptosis. In the present study, we employed Western Blots to determine if a similar molecular …

Irbp In Diabetic Retinopathy – Cell Culture & Ophthalmic Pathology Studies, Laura Valdez

Research Colloquium

Background: Interphotoreceptor-Retinoid-Binding-Protein (IRBP) is restricted to the subretinal space by the external limiting membrane and RPE zonulae occludens. Its expression is reduced in diabetic retinopathy (DR) and increased expression is protective. Hypoxia decreases viable conelike photoreceptors (661W) but increased VEGF, suggesting a role of photoreceptors in proliferative DR (PDR) (Rodriguez et al, Arch Clin Exp. Ophthal 3:23,2021). Here, we investigated the effects of high glucose and VEGF on IRBP expression by 661W and rod-like Y79 cells and distribution of IRBP and albumin in human globes with PDR and NPDR.

Methods:  661W and Y79 cells were cultured in DMEM or RPMI …

Meiosis In Budding Yeast, G. Valentin Borner, Andreas Hochwagen, Amy J. Macqueen

Biological, Geological, and Environmental Faculty Publications

Meiosis is a specialized cell division program that is essential for sexual reproduction. The two meiotic divisions reduce chromosome number by half, typically generating haploid genomes that are packaged into gametes. To achieve this ploidy reduction, meiosis relies on highly unusual chromosomal processes including the pairing of homologous chromosomes, assembly of the synaptonemal complex, programmed formation of DNA breaks followed by their processing into crossovers, and the segregation of homologous chromosomes during the first meiotic division. These processes are embedded in a carefully orchestrated cell differentiation program with multiple interdependencies between DNA metabolism, chromosome morphogenesis, and waves of gene expression …

Dynamics And Inhibition Of Abc And Rnd Transporters Associated With Multidrug Resistances In Cancer And Pathogenic Bacteria, Hang Zhao

Biological Sciences Theses and Dissertations

The overexpression of efflux transporters is deemed to be one of the important mechanisms that contribute to Multidrug Resistance (MDR). In this dissertation, three transporters of significance were studied, the Breast Cancer Resistance Protein (BCRP/ABCG2) in a variety of cancer cells, the mtrCDE transporter from Neisseria gonorrhoeae, and the acrAB-tolC transporter from Escherichia coli. It is well known that the overexpression of BCRP in cancer cells results in these cells being resistant to the effects of many chemotherapeutics. This results in multidrug resistance for this cancer because of the fact that BCRP can transport many different types of …

Using Crispr To Generate Integrated Ssa4-Gfp Reporter Strains, Emma Norman, Rebecca Adams

Science University Research Symposium (SURS)

Using CRISPR to Generate Integrated Ssa4-GFP Reporter Strains

Emma Norman, Rebecca Adams, PhD

Proteins play critical roles in numerous cellular processes. In order to synthesize these important molecules in eukaryotes, DNA is first transcribed into an intermediate molecule, mRNA, in the nucleus. The export of mRNA from its origin in the nucleus to the site of protein production, the cytoplasm, is an integral step in protein synthesis. When a cell is subjected to stress, such as heat shock, most mRNA export is halted, as export proteins are inactivated, and cellular machinery is redirected towards recovery. However, particular transcripts, including the …

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …

Modified Vaccine Vectors To Understand Adjuvant Functions Of Listeria During Chronic Schistosomiasis, Stephanie K. Norwood

Biological Sciences Theses & Dissertations

Vaccination is one of the most effective strategies employed to prevent infectious diseases. Successful vaccination is dependent upon the induction of a specific, robust, and prolonged immune response. One of the major challenges faced by vaccine development is vaccine failure due to host-related factors that can modulate the immune system, which leads to non-responsiveness to vaccinations. The generation of new vaccine strategies is imperative to combat these effects. Live bacterial vectors are one approach used as they can elicit humoral immunity, cellular immunity, or both. Listeria monocytogenes is a Gram positive, intracellular pathogen that is an effective bacterial vaccine vector …

College Of Natural Sciences Newsletter, September - October 2023, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message
Page 2 New Faculty an Staff for the Fall 2023 Semester
Page 3 Awards
Page 4 Student Ambassadors in CNS
Page 5 Meet our Jacks
Page 6-8 Events
Page 9-11 Media Coverage of CNS
Page 12-13 Spring 2023 Dean's List
Page 14 Open PRAIRIE Data

Pulsed Electric Field Ablation: Mechanisms Of Differential Cell Sensitivity And Methods To Mitigate Neuromuscular Excitation, Emily Gudvangen

Biomedical Engineering Theses & Dissertations

Ablation therapies aim to destroy tumors while maintaining minimal damage to surrounding healthy tissue. Pulsed electric field (PEF) ablation targets the cell membrane during the destruction of tissues, which consequently spares extracellular structures such as ducts and blood vessels, leaving the framework for tissue regeneration. However, the utility of PEF is limited by neuromuscular excitation, causing pain and involuntary muscle contraction. To identify PEF protocols that efficiently ablate tissue while minimizing neuromuscular stimulation, various PEF protocols differing in pulse duration, shape, and repetition rate were tested. The ratio of cell death and nerve excitation thresholds, which determines the range of …

Distinct Camp Signaling Microdomains Differentially Regulate Melanosomal Ph And Pigmentation, Maftuna Yusupova, Dalee Zhou, Jaewon You, Jeydi Gonzalez-Guzman, Megha B. Ghanta, Hong Pu, Zalfa Abdel-Malek, Qiuying Chen, Steven S. Gross, John August D'Orazio, Shosuke Ito, Kazumasa Wakamatsu, Melissa L. Harris, Jonathan H. Zippin

Markey Cancer Center Faculty Publications

cAMP signaling is a well-established regulator of melanin synthesis. Two distinct cAMP signaling pathways—the transmembrane adenylyl cyclase pathway, activated primarily by the MC1R, and the soluble adenylyl cyclase (sAC) pathway—affect melanin synthesis. The sAC pathway affects melanin synthesis by regulating melanosomal pH, and the MC1R pathway affects melanin synthesis by regulating gene expression and post-translational modifications. However, whether MC1R genotype affects melanosomal pH is poorly understood. We now report that loss of function MC1R does not affect melanosomal pH. Thus, sAC signaling appears to be the only cAMP signaling pathway that regulates melanosomal pH. We also addressed whether MC1R genotype …

Inhibition Of Mitochondrial Fission Activates Glycogen Synthesis To Support Cell Survival In Colon Cancer, Sumati Raj Hasani, Lyndsay E. A. Young, Warren Van Nort, Moumita Banerjee, Dylan R. Rivas, Jinhwan Kim, Xiaopeng Xiong, Ramon C. Sun, Matthew S. Gentry, Hiromi Sesaki, Tianyan Gao

Markey Cancer Center Faculty Publications

Metabolic reprogramming has been recognized as one of the major mechanisms that fuel tumor initiation and progression. Our previous studies demonstrate that activation of Drp1 promotes fatty acid oxidation and downstream Wnt signaling. Here we investigate the role of Drp1 in regulating glycogen metabolism in colon cancer. Knockdown of Drp1 decreases mitochondrial respiration without increasing glycolysis. Analysis of cellular metabolites reveals that the levels of glucose-6-phosphate, a precursor for glycogenesis, are significantly elevated whereas pyruvate and other TCA cycle metabolites remain unchanged in Drp1 knockdown cells. Additionally, silencing Drp1 activates AMPK to stimulate the expression glycogen synthase 1 (GYS1) mRNA …

Phosphatidic Acid Binding To Patched Contributes To The Inhibition Of Smoothened And Hedgehog Signaling In Drosophila Wing Development, Jie Zhang, Yajuan Liu, Chi Wang, Craig W. Vander Kooi, Jianhang Jia

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling controls growth and patterning during embryonic development and homeostasis in adult tissues. Hh binding to the receptor Patched (Ptc) elicits intracellular signaling by relieving Ptc-mediated inhibition of the transmembrane protein Smoothened (Smo). We uncovered a role for the lipid phosphatidic acid (PA) in the regulation of the Hh pathway in Drosophila melanogaster. Deleting the Ptc C-terminal tail or mutating the predicted PA-binding sites within it prevented Ptc from inhibiting Smo in wing discs and in cultured cells. The C-terminal tail of Ptc directly interacted with PA in vitro, an association that was reduced by Hh, and increased …

Regulated Translocation Of Neutral Sphingomyelinase-2 To The Plasma Membrane Drives Insulin Resistance In Steatotic Hepatocytes, Salim S. El-Amouri, Alexander A. Karakashian, Erhard Bieberich, Mariana N. Nikolova‑Karakashian

Markey Cancer Center Faculty Publications

Abstract Obesity-associated diabetes is linked to the accumulation of ceramide in various organs, including the liver. The exact mechanisms by which ceramide contributes to diabetic pathology are unclear, but one proposed scenario is that ceramide accumulation may inhibit insulin signaling pathways. It is unknown however whether the excess ceramide is generated proximal to the insulin receptor, that is, at the plasma membrane (PM), where it could affect the insulin signaling pathway directly, or the onset of insulin resistance is due to ceramide- induced mitochondrial dysfunction and/or lipotoxicity. Using hepatic cell lines and primary cultures, gain- and loss- of function approach, …

Stat3 Modulates Cd4+ T Mitochondrial Dynamics And Function In Aging, Emelia Zukowski, Marco Sannella, Jack Donato Rockhold, Gabriella Kalantar, Jingting Yu, Sara Santacruz-Calvo, Madison K. Kuhn, Nasun Hah, Ling Ouyang, Tzu-Wen Wang, Lyanne Murphy, Heather Marszalkowski, Kaleigh Gibney, Micah J. Drummond, Elizabeth A. Proctor, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Markey Cancer Center Faculty Publications

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and …

Early Development Of C3ar1-Targeting Chimeric Antigen Receptor T Cells For The Treatment Of Glioblastoma Multiforme, Cameron Fraser

Electronic Theses, Projects, and Dissertations

Glioblastoma multiforme is the most aggressive type of glioma, demonstrating extremely low long-term survival despite modern therapies. Chimeric antigen receptor T cells have shown extreme levels of success in the treatment of B cell lymphomas through persistent anti-tumor activity. Prior research has demonstrated the therapeutic potential in targeting the C3a-C3aR1 pathway as it acts in an autocrine loop, maintaining the proliferation and survival of cancer stem cells within the tumor. Here, we reorient the treatment to target C3aR1 for the treatment of glioblastoma multiforme. In order to achieve this, Jurkat immortalized T cells will express various chimeric antigen receptor designs …

Integrating Clinical Cancer And Ptm Proteomics Data Identifies A Mechanism Of Ack1 Kinase Activation, Eranga R. Balasooriya, Deshan Madhusanka, Tania P. López-Palacios, Riley J. Eastmond, Dasun Jayatunge, Jake J. Owen, Jack S. Gashler, Christina M. Egbert, Chanaka Bulathsinghalage, Lu Liu, Stephen R. Piccolo, Joshua L. Andersen

Faculty Publications

Beyond the most common oncogenes activated by mutation (mut-drivers), there likely exists a variety of low-frequency mut-drivers, each of which is a possible frontier for targeted therapy. To identify new and understudied mut-drivers, we developed a machine learning (ML) model that integrates curated clinical cancer data and posttranslational modification (PTM) proteomics databases. We applied the approach to 62,746 patient cancers spanning 84 cancer types and predicted 3,964 oncogenic mutations across 1,148 genes, many of which disrupt PTMs of known and unknown function. The list of putative mut-drivers includes established drivers and others with poorly understood roles in cancer. This ML …

Potent Bile Acid Microbial Metabolites Modulate Clostridium Perfringens Virulence, Tahrir Jatli Alenezi, Ying Fu, Bilal Alrubaye, Thamer Alanazi, Ayidh Almansour, Hong Wang, Xiaolun Sun

Poultry Science Faculty Publications and Presentations

Clostridium perfringens is a versatile pathogen, inducing diseases in the skin, intestine (such as chicken necrotic enteritis (NE)), and other organs. The classical sign of NE is the foul smell gas in the ballooned small intestine. We hypothesized that deoxycholic acid (DCA) reduced NE by inhibiting C. perfringens virulence signaling pathways. To evaluate the hypothesis, C. perfringens strains CP1 and wild-type (WT) HN13 and its mutants were cultured with different bile acids, including DCA and isoallolithocholic acid (isoalloLCA). Growth, hydrogen sulfide (H₂S) production, and virulence gene expression were measured. Notably, isoalloLCA was more potent in reducing growth, H …

Existing Evidence For Influenza B Virus Adaptations To Drive Replication In Humans As The Primary Host, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Influenza B virus (IBV) is one of the two major types of influenza viruses that circulate each year. Unlike influenza A viruses, IBV does not harbor pandemic potential due to its lack of historical circulation in non-human hosts. Many studies and reviews have highlighted important factors for host determination of influenza A viruses. However, much less is known about the factors driving IBV replication in humans. We hypothesize that similar factors influence the host restriction of IBV. Here, we compile and review the current understanding of host factors crucial for the various stages of the IBV viral replication cycle. While …

Understanding An Inflammatory Pathway In Diabetic Retinopathy, Reanna R. Rodriguez

Research Symposium

Diabetic Retinopathy (DR) is the leading cause of blindness in the U.S. However, not much is known of its molecular pathway and how it attributes to increases in inflammatory response in the eye. One avenue we will investigate is the transforming growth factor beta (TGFB) signaling pathway and its effect of vascular endothelial growth factor (VEGF) secretion and cell viability. VEGF is the hallmark that exacerbates DR progression in prolonged diabetes. Some major concern that have arisen are the underlying effects of oxidants and antioxidants in elevating VEGF secretion in diabetes. In attempt to learn more, we evaluated how an …

Trimeric Complex Interactions Of Antp-Tbp With Tfiieb And Exd Are Involved In The Genetic Control Of Drosophila Melanogaster, Gustavo Jiménez Mejía, Ruben De Jesus Montalvo Mendez, Claudia Dalila Altamirano Torres, Diana Reséndez Pérez

Research Symposium

Background: Homeoproteins are transcriptional factors (TFs) that shape animal body axes during development. These TFs are highly conserved and represent one of the most fascinating groups of regulatory molecules. Reports shown the multiplicity of interactions in hox proteins, as complexes trimeric involved to transcriptional activity. The study of trimeric complexes in Hox interactome will allow the better understanding of Hox genetic regulation during embryonic development.

Methodology: Using a new combination BiFCFRET approach performed in HEK293, the quantification was performed by FRETTY of ImageJ. Fly crosses were incubated at 25ºC on standard yeast-agar-cornmeal medium. Embryo cuticle preparations were carried out according …

Tc-Ptp Overexpression Attenuates Skin Cancer Formation During Environmental Skin Carcinogenesis, Zahidur Rahmann, Carson Bogatto, Serena Olivarez, Dae Joon Kim

Research Symposium

Background: T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, has been shown to function as a tumor suppressor during skin carcinogenesis.

Methods: we generated a novel epidermal specific TC-PTP-overexpressing (K5HA.Ptpn2) mouse model to show that TC-PTP contributes to the attenuation of chemically induced skin carcinogenesis through the synergistic regulation of STAT1, STAT3, STAT5, and PI3K/AKT signaling.

Results: We found overexpression of TC-PTP increased epidermal sensitivity to DMBA-induced apoptosis and it decreased TPA-mediated hyperproliferation, coinciding with reduced epidermal thickness. Inhibition of STAT1, STAT3, STAT5 or AKT reversed the effects of TC-PTP overexpression on epidermal survival and proliferation. Mice overexpressing TC-PTP in …