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School of Medicine Faculty Publications

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Full-Text Articles in Medical Pathology

Induction Of Brain Tumors By The Archetype Strain Of Human Neurotropic Jcpyv In A Transgenic Mouse Model, Luis Del Valle, Kamel Khalili Jan 2021

Induction Of Brain Tumors By The Archetype Strain Of Human Neurotropic Jcpyv In A Transgenic Mouse Model, Luis Del Valle, Kamel Khalili

School of Medicine Faculty Publications

JC Virus (JCPyV), a member of the Polyomaviridiæ family, is a human neurotropic virus with world-wide distribution. JCPyV is the established opportunistic infectious agent of progressive multifocal leukoencephalopathy, a fatal demyelinating disease, which results from the cytolytic infection of oligodendrocytes. Mutations in the regulatory region of JCPyV determine the different viral strains. Mad-1 the strain associated with PML contains two 98 base pair repeats, whereas the archetype strain (CY), which is the transmissible form of JCPyV, contains only one 98 tandem with two insertions of 62 and 23 base pairs respectively. The oncogenicity of JCPyV has been suspected since direct …

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Role Of Interleukin-1 Family Members And Signaling Pathways In Kshv Pathogenesis, Lindsey Barrett, Jungang Chen, Lu Dai, Karlie Plaisance-Bonstaff, Luis Del Valle, Zhiqiang Qin Oct 2020

Role Of Interleukin-1 Family Members And Signaling Pathways In Kshv Pathogenesis, Lindsey Barrett, Jungang Chen, Lu Dai, Karlie Plaisance-Bonstaff, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

No abstract provided.

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Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan Oct 2020

Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan

School of Medicine Faculty Publications

Scc4 is an unusual bi-functional protein from Chlamydia trachomatis (CT) that functions as a type III secretion system (T3SS) chaperone and an RNA polymerase (RNAP)-binding protein. Both functions require interactions with protein partners during specific stages of the CT developmental cycle. As a T3SS chaperone, Scc4 binds Scc1 during the late stage of development to form a heterodimer complex, which chaperones the essential virulence effector, CopN. During the early-middle stage of development, Scc4 regulates T3SS gene expression by binding the σ66-containing RNAP holoenzyme. In order to study the structure and association mechanism of the Scc4:Scc1 T3SS chaperone complex using nuclear …

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A Hyperpigmented Plaque In A Female Patient, Harel G. Schwartzberg, Alexandra Bourgeois, Amber Souers, Jeremy Atkinson, Pamela Martin Sep 2020

A Hyperpigmented Plaque In A Female Patient, Harel G. Schwartzberg, Alexandra Bourgeois, Amber Souers, Jeremy Atkinson, Pamela Martin

School of Medicine Faculty Publications

No abstract provided.

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Immune-Related Gene Expression And Cytokine Secretion Is Reduced Among African American Colon Cancer Patients, Jenny Paredes, Jovanny Zabaleta, Jone Garai, Ping Ji, Sayed Imtiaz, Marzia Spagnardi, Joussette Alvarado, Li Li, Mubarak Akadri, Kaylene Barrera, Maria Munoz-Sagastibelza, Raavi Gupta, Mohamed Alshal, Maksim Agaronov, Henry Talus, Xuefeng Wang, John M. Carethers, Jennie L. Williams, Laura A. Martello Sep 2020

Immune-Related Gene Expression And Cytokine Secretion Is Reduced Among African American Colon Cancer Patients, Jenny Paredes, Jovanny Zabaleta, Jone Garai, Ping Ji, Sayed Imtiaz, Marzia Spagnardi, Joussette Alvarado, Li Li, Mubarak Akadri, Kaylene Barrera, Maria Munoz-Sagastibelza, Raavi Gupta, Mohamed Alshal, Maksim Agaronov, Henry Talus, Xuefeng Wang, John M. Carethers, Jennie L. Williams, Laura A. Martello

School of Medicine Faculty Publications

Background: Colorectal cancer is the third most deadly cancer among African Americans (AA). When compared to Caucasian Americans (CA), AA present with more advanced disease and lower survival rates. Here, we investigated if differences in tumor immunology could be contributive to disparities observed between these populations. Methods: We examined gene expression of tumor and non-tumor adjacent tissues from AA and CA by whole transcriptome sequencing, and generated scores for immune cell populations by NanoString. In addition, we utilized “The Cancer Genome Atlas” (TCGA) database from AA and CA as a validation cohort. Finally, we measured the secretion of cytokines characteristic …

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Pancreatic Stromal Gremlin 1 Expression During Pancreatic Tumorigenesis, Joy M. Davis, Binglu Cheng, Madeline M. Drake, Qiang Yu, Baibing Yang, Jing Li, Chunhui Liu, Mamoun Younes, Xiurong Zhao, Jennifer M. Bailey, Qiang Shen, Tien C. Ko, Yanna Cao May 2020

Pancreatic Stromal Gremlin 1 Expression During Pancreatic Tumorigenesis, Joy M. Davis, Binglu Cheng, Madeline M. Drake, Qiang Yu, Baibing Yang, Jing Li, Chunhui Liu, Mamoun Younes, Xiurong Zhao, Jennifer M. Bailey, Qiang Shen, Tien C. Ko, Yanna Cao

School of Medicine Faculty Publications

Chronic pancreatitis (CP) is a major risk factor of pancreatic ductal adenocarcinoma (PDAC). How CP promotes pancreatic oncogenesis remains unclear. A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment, composed of activated fibroblasts and macrophages. Macrophages can be characterized as M1 or M2, with tumor-inhibiting or -promoting functions, respectively. We reported that Gremlin 1 (GREM1), a key pro-fibrogenic factor, is upregulated in the stroma of CP. The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC. By mRNA in …

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Photoactivatable Cre Recombinase 3.0 For In Vivo Mouse Applications, Kumi Morikawa, Kazuhiro Furuhashi, Carmen De Sena-Tomas, Alvaro L. Garcia-Garcia, Ramsey Bekdash, Alison D. Klein, Nicholas Gallerani, Hannah E. Yamamoto, Seon Hye E. Park, Grant S. Collins, Fuun Kawano, Moritoshi Sato, Chyuan Sheng Lin, Kimara L. Targoff, Edmund Au, Michael C. Salling, Masayuki Yazawa May 2020

Photoactivatable Cre Recombinase 3.0 For In Vivo Mouse Applications, Kumi Morikawa, Kazuhiro Furuhashi, Carmen De Sena-Tomas, Alvaro L. Garcia-Garcia, Ramsey Bekdash, Alison D. Klein, Nicholas Gallerani, Hannah E. Yamamoto, Seon Hye E. Park, Grant S. Collins, Fuun Kawano, Moritoshi Sato, Chyuan Sheng Lin, Kimara L. Targoff, Edmund Au, Michael C. Salling, Masayuki Yazawa

School of Medicine Faculty Publications

Optogenetic genome engineering tools enable spatiotemporal control of gene expression and provide new insight into biological function. Here, we report the new version of genetically encoded photoactivatable (PA) Cre recombinase, PA-Cre 3.0. To improve PA-Cre technology, we compare light-dimerization tools and optimize for mammalian expression using a CAG promoter, Magnets, and 2A self-cleaving peptide. To prevent background recombination caused by the high sequence similarity in the dimerization domains, we modify the codons for mouse gene targeting and viral production. Overall, these modifications significantly reduce dark leak activity and improve blue-light induction developing our new version, PA-Cre 3.0. As a resource, …

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Targeting Parp-1 With Metronomic Therapy As A New Approach To Modulate Mdsc Function And Enhance Anti-Pd1 Immunotherapy In Colon Cancer, Salome Valentina Ibba, Mohamed Ghonim, Abdelmetalab Tarhuni, Matthew Dean, Hamid Boulares, Augusto Ochoa, Youssef Errami, Ali Elbahraway, Ilyes Benslimane, Dorota Wyczechowska, Luis Del Valle, Amir Al-Khami, Hanh Luu Nov 2019

Targeting Parp-1 With Metronomic Therapy As A New Approach To Modulate Mdsc Function And Enhance Anti-Pd1 Immunotherapy In Colon Cancer, Salome Valentina Ibba, Mohamed Ghonim, Abdelmetalab Tarhuni, Matthew Dean, Hamid Boulares, Augusto Ochoa, Youssef Errami, Ali Elbahraway, Ilyes Benslimane, Dorota Wyczechowska, Luis Del Valle, Amir Al-Khami, Hanh Luu

School of Medicine Faculty Publications

34th Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer - Part 1, November 6 - 10, 2019, National Harbor, MD

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Human Polyomavirus Jcpyv And Its Role In Progressive Multifocal Leukoencephalopathy And Oncogenesis, Luis Del Valle, Sergio Piña-Oviedo Aug 2019

Human Polyomavirus Jcpyv And Its Role In Progressive Multifocal Leukoencephalopathy And Oncogenesis, Luis Del Valle, Sergio Piña-Oviedo

School of Medicine Faculty Publications

The human neurotropic virus JCPyV, a member of the family, is the opportunistic infectious agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease seen in severe immunosuppressive conditions and, during the last decade, in patients undergoing immunotherapy. JCPyV is a ubiquitous pathogen with up to 85% of the adult population word-wide exhibiting antibodies against it. Early experiments demonstrated that direct inoculation of JCPyV into the brain of different species resulted in the development of brain tumors and other neuroectodermal-derived neoplasias. Later, several reports showed the detection of viral sequences in medulloblastomas and glial tumors, as well as expression of the …

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Role Of Eif4g1 In Non-Small Cell Lung Cancer Pathogenesis And Targeted Therapy, Zhiqiang Qin, Lu Dai, Luis Del Valle Jul 2019

Role Of Eif4g1 In Non-Small Cell Lung Cancer Pathogenesis And Targeted Therapy, Zhiqiang Qin, Lu Dai, Luis Del Valle

School of Medicine Faculty Publications

American Association for Cancer Research Annual Meeting 2019, March 29 - April 3, 2019, Atlanta, GA

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Leptin Produced By Obesity-Altered Adipose Stem Cells Promotes Metastasis But Not Tumorigenesis Of Triple-Negative Breast Cancer In Orthotopic Xenograft And Patient-Derived Xenograft Models, Rachel A. Sabol, Annie C. Bowles, Alex Côté, Rachel Wise, Benjamen O'Donnell, Margarite D. Matossian, Fokhrul M. Hossain, Hope E. Burks, Luis Del Valle, Lucio Miele, Bridgette M. Collins-Burow, Matthew E. Burow, Bruce A. Bunnell May 2019

Leptin Produced By Obesity-Altered Adipose Stem Cells Promotes Metastasis But Not Tumorigenesis Of Triple-Negative Breast Cancer In Orthotopic Xenograft And Patient-Derived Xenograft Models, Rachel A. Sabol, Annie C. Bowles, Alex Côté, Rachel Wise, Benjamen O'Donnell, Margarite D. Matossian, Fokhrul M. Hossain, Hope E. Burks, Luis Del Valle, Lucio Miele, Bridgette M. Collins-Burow, Matthew E. Burow, Bruce A. Bunnell

School of Medicine Faculty Publications

BACKGROUND: Breast cancer is the second leading cause of cancer deaths in the USA. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer with high rates of metastasis, tumor recurrence, and resistance to therapeutics. Obesity, defined by a high body mass index (BMI), is an established risk factor for breast cancer. Women with a high BMI have increased incidence and mortality of breast cancer; however, the mechanisms(s) by which obesity promotes tumor progression are not well understood. METHODS: In this study, obesity-altered adipose stem cells (obASCs) were used to evaluate obesity-mediated effects of TNBC. Both in vitro …

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Ribonucleotide Reductase Inhibitor 3-Ap Induces Oncogenic Virus Infected Cell Death And Represses Tumor Growth, Lu Dai, Jungang Chen, Yueyu Cao, Luis Del Valle, Zhiqiang Qin Dec 2018

Ribonucleotide Reductase Inhibitor 3-Ap Induces Oncogenic Virus Infected Cell Death And Represses Tumor Growth, Lu Dai, Jungang Chen, Yueyu Cao, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human malignancies, particularly Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation while still lacking of effective therapeutic options. We recently found that the ribonucleotide reductase (RR) subunit M2 is potentially regulated by the key oncogenic HGF/c-MET pathway in KSHV-related lymphoma cells. One of RR inhibitor, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) effectively induced apoptosis of KSHV+ lymphomas and suppressed tumor progression . In the current study, we found that 3-AP treatment selectively inhibited the proliferation of KSHV-infected endothelial cells, the major cellular components of KS, through inducing DNA …

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Notch Signaling Regulates Mitochondrial Metabolism And Nf-Κb Activity In Triple-Negative Breast Cancer Cells Via Ikkα-Dependent Non-Canonical Pathways, Fokhrul Hossain, Claudia Sorrentino, Deniz A. Ucar, Yin Peng, Margarite Matossian, Dorota Wyczechowska, Judy Crabtree, Jovanny Zabaleta, Silvana Morello, Luis Del Valle, Matthew Burow, Bridgette Collins-Burow, Antonio Pannuti, Lisa M. Minter, Todd E. Golde, Barbara A. Osborne, Lucio Miele Dec 2018

Notch Signaling Regulates Mitochondrial Metabolism And Nf-Κb Activity In Triple-Negative Breast Cancer Cells Via Ikkα-Dependent Non-Canonical Pathways, Fokhrul Hossain, Claudia Sorrentino, Deniz A. Ucar, Yin Peng, Margarite Matossian, Dorota Wyczechowska, Judy Crabtree, Jovanny Zabaleta, Silvana Morello, Luis Del Valle, Matthew Burow, Bridgette Collins-Burow, Antonio Pannuti, Lisa M. Minter, Todd E. Golde, Barbara A. Osborne, Lucio Miele

School of Medicine Faculty Publications

Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival. Treatment of TNBC with PI3K or mTORC1/2 inhibitors results in drug-resistant, Notch-dependent CSC. However, downstream mechanisms and potentially druggable Notch effectors in TNBC CSCs are largely unknown. We studied the role of the AKT pathway and mitochondrial metabolism downstream of Notch signaling in TNBC CSC from cell lines representative of different TNBC molecular subtypes as well as …

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Radiofrequency Renal Denervation Attenuates Kidney Fibrosis In Spontaneously Hypertensive Rats (2267), Juan Gao, Ian Bart Denys, Luis Del Valle, Mihran V. Naljayan, Daniel R. Kapusta Nov 2018

Radiofrequency Renal Denervation Attenuates Kidney Fibrosis In Spontaneously Hypertensive Rats (2267), Juan Gao, Ian Bart Denys, Luis Del Valle, Mihran V. Naljayan, Daniel R. Kapusta

School of Medicine Faculty Publications

No abstract provided.

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Role Of Heme Oxygenase-1 In The Pathogenesis And Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus, Lu Dai, Jing Qiao, David Nguyen, Amanda P. Struckhoff, Lisa Doyle, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Bryan P. Toole, Rolf Renne, Zhiqiang Qin Mar 2016

Role Of Heme Oxygenase-1 In The Pathogenesis And Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus, Lu Dai, Jing Qiao, David Nguyen, Amanda P. Struckhoff, Lisa Doyle, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Bryan P. Toole, Rolf Renne, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation and lack effective therapeutic options. Heme oxygenase-1 (HO-1) has been reported as an important regulator of endothelial cell cycle control, proliferation and angiogenesis. HO-1 has also been found to be highly expressed in KSHV-infected endothelial cells and oral AIDS-KS lesions. We previously demonstrate that the multifunctional glycoprotein CD147 is required for KSHV/LANA-induced endothelial cell invasiveness. During the identification of CD147 controlled downstream genes by microarray analysis, we found that the expression of HO-1 is significantly …

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Cd147 And Downstream Adamtss Promote The Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus Infected Endothelial Cells, Lu Dai, Jimena Trillo-Tinoco, Yihan Chen, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Augusto C. Ochoa, Jovanny Zabaleta, Bryan P. Toole, Zhiqiang Qin Jan 2016

Cd147 And Downstream Adamtss Promote The Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus Infected Endothelial Cells, Lu Dai, Jimena Trillo-Tinoco, Yihan Chen, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Augusto C. Ochoa, Jovanny Zabaleta, Bryan P. Toole, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's sarcoma (KS), which preferentially arise in immunocompromised patients and lack effective therapeutic options. We have previously shown that KSHV or viral protein LANA up-regulates the glycoprotein CD147, thereby inducing primary endothelial cell invasiveness. In the current study, we identify the global network controlled by CD147 in KSHV-infected endothelial cells using Illumina microarray analysis. Among downstream genes, two specific metalloproteases, ADAMTS1 and 9, are strongly expressed in AIDS-KS tissues and contribute to KSHV-infected endothelial cell invasiveness through up-regulation of IL-6 and VEGF. By using a KS-like nude …

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Ceramides Promote Apoptosis For Virus-Infected Lymphoma Cells Through Induction Of Ceramide Synthases And Viral Lytic Gene Expression, Lu Dai, Jimena Trillo-Tinoco, Aiping Bai, Yihan Chen, Jacek Bielawski, Luis Del Valle, Charles D. Smith, Augusto C. Ochoa, Zhiqiang Qin, Chris Parsons Jul 2015

Ceramides Promote Apoptosis For Virus-Infected Lymphoma Cells Through Induction Of Ceramide Synthases And Viral Lytic Gene Expression, Lu Dai, Jimena Trillo-Tinoco, Aiping Bai, Yihan Chen, Jacek Bielawski, Luis Del Valle, Charles D. Smith, Augusto C. Ochoa, Zhiqiang Qin, Chris Parsons

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for several human cancers including primary effusion lymphoma (PEL), a rapidly progressive malignancy arising preferentially in immunocompromised patients. With conventional chemotherapy, PEL continues to portend high mortality, dictating the development of novel therapeutic strategies. Sphingosine kinase 2 (SphK2) represents a key gatekeeper for sphingolipid metabolism, responsible for conversion of ceramides to sphingosine-1-phosphate (S1P). We have previously demonstrated that targeting SphK2 using a novel selective inhibitor, ABC294640, leads to intracellular accumulation of ceramides and induces apoptosis for KSHV-infected PEL cells, while suppressing tumor progression in vivo. In the current study, we sought to …

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Activation Of C-Myc And Cyclin D1 By Jcv T-Antigen And Β-Catenin In Colon Cancer, Michael J. Ripple, Amanda Parker Struckhoff, Jimena Trillo-Tinoco, Li Li, David A. Margolin, Robin Mcgoey, Luis Del Valle Sep 2014

Activation Of C-Myc And Cyclin D1 By Jcv T-Antigen And Β-Catenin In Colon Cancer, Michael J. Ripple, Amanda Parker Struckhoff, Jimena Trillo-Tinoco, Li Li, David A. Margolin, Robin Mcgoey, Luis Del Valle

School of Medicine Faculty Publications

During the last decade, mounting evidence has implicated the human neurotropic virus JC virus in the pathology of colon cancer. However, the mechanisms of JC virus-mediated oncogenesis are still not fully determined. One candidate to mediate these effects is the viral early transcriptional product T-Antigen, which has the ability to inactivate cell cycle regulatory proteins such as p53. In medulloblastomas, T-Antigen has been shown to bind the Wnt signaling pathway protein β-catenin; however, the effects of this interaction on downstream cell cycle regulatory proteins remain unknown. In light of these observations, we investigated the association of T-Antigen and nuclear β-catenin …

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Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin Feb 2014

Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells …

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Icad Deficiency In Human Colon Cancer And Predisposition To Colon Tumorigenesis: Linkage To Apoptosis Resistance And Genomic Instability, Youssef Errami, Hassan Brim, Karine Oumouna-Benachour, Mustapha Oumouna, Amarjit S. Naura, Hogyoung Kim, Jihang Ju, Christian J. Davis, Jong G. Kim, Hassan Ashktorab, Kenneth Fallon, Ming Xu, Jianhua Zhang, Luis Del Valle, A Hamid Boulares Feb 2013

Icad Deficiency In Human Colon Cancer And Predisposition To Colon Tumorigenesis: Linkage To Apoptosis Resistance And Genomic Instability, Youssef Errami, Hassan Brim, Karine Oumouna-Benachour, Mustapha Oumouna, Amarjit S. Naura, Hogyoung Kim, Jihang Ju, Christian J. Davis, Jong G. Kim, Hassan Ashktorab, Kenneth Fallon, Ming Xu, Jianhua Zhang, Luis Del Valle, A Hamid Boulares

School of Medicine Faculty Publications

We previously showed that DNA fragmentation factor, which comprises a caspase-3-activated DNase (CAD) and its inhibitor (ICAD), may influence the rate of cell death by generating PARP-1-activating DNA breaks. Here we tested the hypothesis that ICAD-deficient colon epithelial cells exhibiting resistance to death stimuli may accumulate additional genetic modifications, leading to a tumorigenic phenotype. We show that ICAD deficiency may be associated with colon malignancy in humans. Indeed, an examination of ICAD expression using immunohistochemistry in an array of both colon cancer and normal tissues revealed that ICAD expression levels were severely compromised in the cancerous tissues. Upon DNA damage …

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Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya Nov 2011

Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya

School of Medicine Faculty Publications

Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release …

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Deregulation Of Micrornas By Hiv-1 Vpr Protein Leads To The Development Of Neurocognitive Disorders, Ruma Mukerjee, J Robert Chang, Luis Del Valle, Asen Bagashev, Monika M. Gayed, Randolph B. Lyde, Brian J. Hawkins, Eugen Brailoiu, Eric Cohen, Chris Power, S Ausim Azizi, Benjamin B. Gelman, Bassel E. Sawaya Oct 2011

Deregulation Of Micrornas By Hiv-1 Vpr Protein Leads To The Development Of Neurocognitive Disorders, Ruma Mukerjee, J Robert Chang, Luis Del Valle, Asen Bagashev, Monika M. Gayed, Randolph B. Lyde, Brian J. Hawkins, Eugen Brailoiu, Eric Cohen, Chris Power, S Ausim Azizi, Benjamin B. Gelman, Bassel E. Sawaya

School of Medicine Faculty Publications

Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic …

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Ros Accumulation And Igf-Ir Inhibition Contribute To Fenofibrate/Pparalpha -Mediated Inhibition Of Glioma Cell Motility In Vitro, Justyna Drukala, Katarzyna Urbanska, Anna Wilk, Maja Grabacka, Ewa Wybieralska, Luis Del Valle, Zbigniew Madeja, Krzysztof Reiss Jun 2010

Ros Accumulation And Igf-Ir Inhibition Contribute To Fenofibrate/Pparalpha -Mediated Inhibition Of Glioma Cell Motility In Vitro, Justyna Drukala, Katarzyna Urbanska, Anna Wilk, Maja Grabacka, Ewa Wybieralska, Luis Del Valle, Zbigniew Madeja, Krzysztof Reiss

School of Medicine Faculty Publications

BACKGROUND: Glioblastomas are characterized by rapid cell growth, aggressive CNS infiltration, and are resistant to all known anticancer regimens. Recent studies indicate that fibrates and statins possess anticancer potential. Fenofibrate is a potent agonist of peroxisome proliferator activated receptor alpha (PPARalpha) that can switch energy metabolism from glycolysis to fatty acid beta-oxidation, and has low systemic toxicity. Fenofibrate also attenuates IGF-I-mediated cellular responses, which could be relevant in the process of glioblastoma cell dispersal. METHODS: The effects of fenofibrate on Glioma cell motility, IGF-I receptor (IGF-IR) signaling, PPARalpha activity, reactive oxygen species (ROS) metabolism, mitochondrial potential, and ATP production were …

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