Digital Commons Network^™

Sigma1 Targeting To Suppress Aberrant Androgen Receptor Signaling In Prostate Cancer., Jeffrey D. Thomas, Charles G. Longen, Halley M. Oyer, Nan Chen, Christina M. Maher, Joseph M. Salvino, Blase Kania, Kelsey N. Anderson, William F. Ostrander, Karen E. Knudsen, Felix J. Kim

Department of Cancer Biology Faculty Papers

Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways. We hypothesized that these Sigma1-mediated responses could be exploited to suppress AR protein levels and activity. Here we demonstrate that …

The Transcriptional Regulation Of The Human Angiotensinogen Gene After High-Fat Diet Is Haplotype-Dependent: Novel Insights Into The Gene-Regulatory Networks And Implications For Human Hypertension, A Rana, S Jain, N Puri, M Kaw, N Sirianni, D Eren, Brahma Mopidevi, Anand Kumar

NYMC Faculty Publications

Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have …

Organic Cation Transporter 3 (Oct3) Is Localized To Intracellular And Surface Membranes In Select Glial And Neuronal Cells Within The Basolateral Amygdaloid Complex Of Both Rats And Mice, Paul J. Gasser, Matthew M. Hurley, June Chan, Virginia M. Pickel

Biomedical Sciences Faculty Research and Publications

Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates corticosterone-sensitive uptake of monoamines including norepinephrine, epinephrine, dopamine, histamine and serotonin. OCT3 is expressed widely throughout the amygdaloid complex and other brain regions where monoamines are key regulators of emotional behaviors affected by stress. However, assessing the contribution of OCT3 to the regulation of monoaminergic neurotransmission and monoamine-dependent regulation of behavior requires fundamental information about the subcellular distribution of OCT3 expression. We used immunofluorescence and immuno-electron microscopy to examine the cellular and subcellular distribution of the transporter in the basolateral amygdaloid complex of the rat and mouse brain. …

The Effects Of Moderate Alcohol Consumption And Inflammation On The Hepatic Matrisome And The Renal Cortex Proteome., Christine E. Dolin

Electronic Theses and Dissertations

Background. The association of chronic ethanol (EtOH) consumption with extracellular matrix (ECM) changes in alcoholic liver disease (ALD) is well established in the context of hepatic fibrosis. However, it is becoming increasingly understood that the hepatic ECM responds dynamically to stress well before fibrosis. The term “transitional tissue remodeling” describes qualitative and quantitative ECM changes in response to injury that do not alter the overall architecture of the organ; these ECM changes may contribute to early disease initiation and/or progression. The nature and magnitude of these changes to the ECM are currently poorly understood. In contrast to the liver, EtOH …

Targeting The Glucose Metabolism Of Myeloid-Derived Suppressor Cells (Mdscs) To Stimulate Cancer Immunity., Jaspreet Grewal

Electronic Theses and Dissertations

Myeloid derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells that are significantly increased in cancer patients and correlate with higher stage and poor prognosis. MDSCs negatively modulate anti-tumor immunity, suppress T cell activity, promote angiogenesis and increase the risk of metastasis. In this study, we report that monocytic-MDSCs (M-MDSCs) but polymorphonuclear-MDSCs (PMN-MDSCs) over-express 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases 3 (PFKFB3), an important regulator of glycolysis. Furthermore in the melanoma model, M-MDSCs but not PMN-MDSCs suppressed T cell function which correlated with PFKFB3 over-expression and increased rate of glycolysis. PFKFB3 inhibition with the first-in-class small molecule inhibitor, PFK-158 reversed M-MDSC …

Chat Expression In Chlamydia Muridarum-Infected Female Murine Genital Tract, Hallie Sartain

Undergraduate Honors Theses

Chlamydia trachomatis is the most prevalent agent of bacterial sexually transmitted infections in the world. However, a profuse number of cases are unreported, as the infection is often asymptomatic. Sequelae such as pelvic inflammatory disease, an increased risk of cervical cancer, premature birth, and perinatal infections in pregnant women can occur. Inflammation occurs in the body in response to infection or injury. Although inflammation can lead to some unwanted secondary effects, such as pain, it serves to return the body to homeostasis by restoring injured tissues and eliminating pathogens. One recently identified connection between the central nervous system and the …

Determination Of The Effects That A Previously Uncharacterized Secreted Product From Klebsiella Pneumoniae Has On Citrobacter Freundii And Enterobacter Cloacae Biofilms, Cody M. Hastings

Undergraduate Honors Theses

More so than ever, Multiple Drug Resistant (MDR) bacteria are on the rise due to overuse of antibiotics along with natural selection for adaptations that enhance drug-resistant properties. One particular bacterial family, Enterobacteriaceae, has been problematic, exhibiting several bacterial members that have developed a precipitous resistance to modern antibiotics and are also primary causative agents of nosocomial, or hospital acquired, infections. Citrobacter freundii (CF) and Enterobacter cloacae (ECL) are two species of the Enterobacteriaceae family causing significant medical concern due to their role in producing numerous opportunistic infections such as bacteremia, lower respiratory tract infections, urinary tract infections, and endocarditis. …

Combating Malignant Melanoma With The Multifaceted Soy-Dervied Peptide Lunasin., Christopher Paul Shidal

Electronic Theses and Dissertations

Lunasin is a 44 amino acid peptide that has been shown to have cancer chemopreventative and chemotherapeutic properties. This study investigated the potential utility of Lunasin as a chemotherapeutic in melanomas. Studies showed that Lunasin had little activity against established melanoma cell lines using adherent culture methods; however, Lunasin’s in vitro activity was significantly higher in non-adherent colony-forming assays and oncosphere formation. These results led to the investigation of whether or not Lunasin has selective effects on cancer initiating cells (CIC) that are known to be present in melanomas. It was revealed that Lunasin selectively inhibited the proliferation of high-ALDH …

Elevated Dna Oxidation And Dna Repair Enzyme Expression In Brain White Matter In Major Depressive Disorder, Attila Szebeni, Katalin Szebeni, Timothy P. Diperi, Luke A. Johnson, Craig A. Stockmeier, Jessica D. Crawford, Michelle J. Chandley Health Sciences, Liza J. Hernandez, Katherine C. Burgess, Russell W. Brown, Gregory A. Ordway

ETSU Faculty Works

Background: Pathology of white matter in brains of patients with major depressive disorder (MDD) is well-documented, but the cellular and molecular basis of this pathology are poorly understood.

Methods:Levels of DNA oxidation and gene expression of DNA damage repair enzymes were measured in Brodmann area 10 (BA10) and/or amygdala (uncinate fasciculus) white matter tissue from brains of MDD (n=10) and psychiatrically normal control donors (n=13). DNA oxidation was also measured in BA10 white matter of schizophrenia donors (n=10) and in prefrontal cortical white matter from control rats (n=8) and rats with repeated stress-induced anhedonia (n=8).

Results:DNA oxidation …

Foxo3 Increases Mir-34a To Cause Palmitate-Induced Cholangiocyte Lipoapoptosis., Sathish Kumar Natarajan, Bailey A. Stringham, Ashley M. Mohr, Cody J. Wehrkamp, Sizhao Lu, Mary A. Smith, Dee Harrison-Findik, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

Nonalcoholic steatohepatitis (NASH) patients have elevated plasma saturated free fatty acid levels. These toxic fatty acids can induce liver cell death and our recent results demonstrated that the biliary epithelium may be susceptible to lipotoxicity. Here, we explored the molecular mechanisms of cholangiocyte lipoapoptosis in cell culture and in an animal model of NASH. Treatment of cholangiocytes with palmitate (PA) showed increased caspase 3/7 activity and increased levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3, demonstrating cholangiocyte lipoapoptosis. Interestingly, treatment with PA significantly increased the levels of microRNA miR-34a, a pro-apoptotic microRNA known to be elevated in NASH. …

Characterization Of Novel Cannabinoid Receptor 2-Selective Agonists At The Biochemical And Cellular Levels: Leads For Therapeutic Agents, Ashley M. Hine

Honors Scholar Theses

Putative cannabinoid receptor 2 (CB₂)-selective agonists were identified from a library of commercially available compounds via inhibition of cAMP accumulation in high throughput screening. Binding affinity and receptor subtype selectivity were assessed using heterologous competition binding assays against the known cannabinoid orthosteric ligand CP55940. Test compounds ASX0152383 and CSC003141 preferentially bound to CB₂, with no detection of binding to CB₁ up to 1 mM. CMB038865 exhibited nearly 100-fold selectivity for CB₁ over CB₂, while CZ000026 bound non-preferentially to both receptors in the low micromolar range. To determine the extent of G protein …

Role Of Dendritic Cells In Pathology Of Respiratory Syncytial Virus Infection In Neonates, Bishwas Shrestha

Theses and Dissertations (ETD)

Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis in children. We have shown that neonatal mice respond to primary RSV infection with T helper type 2 (Th2) biased immune responses, which are enhanced following reinfection. Dendritic cells (DCs) including myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) play important roles in driving host responses to RSV infection. mDCs present antigens to help Th cells differentiate, and pDCs protect against viral infection through type I interferons (IFNs). Despite data demonstrating importance of mDCs and pDCs in protection against RSV, it has not been studied in an age appropriate …

Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao

Dissertations and Theses (Open Access)

With recent approvals for therapeutic antibodies that block CTLA4, PD-1 and PD-L1, immune checkpoints have emerged as new targets in cancer therapy. In addition, there is accumulating evidence highlighting the role of cancer-associated immunity in patient response to cytotoxic anticancer agents. Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, it has been shown that PARP inhibitors (PARPis) upregulate PD-L1 expression in multiple cancer cell lines, human xenograft tumors, and syngeneic mouse tumors. Mechanistically, PARPi inactivates …

Cannabinoid Receptor 2 (Cb2) Ligands Downregulate Pro-Inflammatory Markers In Stimulated Primary Human Periodontal Ligament Fibroblasts (Hpdlfs), Ammaar Hasan Abidi

Theses and Dissertations (ETD)

There are approximately 743 million individuals suffering from chronic periodontitis (PD) making it the sixth most prevalent condition worldwide. The affected adult population in the U.S. are nearly 64.7 million and the healthcare costs exceeds $14 billion. Recently, host response to pathogenic infection has been seen critical to the progression of PD and exhibit increase in various inflammatory markers. Marijuana is well known for its recreational usage and is a risk factor for periodontal disease, which is seen as a concern in society for its negative health consequences. However, many medical conditions can benefit from the pharmacological effects of cannabinoids. …

Investigating The Role Of Dispatched In Hedgehog Ligand Transport And Delivery, William Bodeen

Theses and Dissertations (ETD)

During the development of all metazoans, the Hedgehog (Hh) signaling pathway provides instructional cues influencing a variety of cellular processes. The pathway ligand, Hh, is dually lipidated by cholesterol and palmitate, which effectively anchors the molecule to the lipid bilayer of the signal producing cell. To complicate the Hh pathway induction process, the Hh ligand is often produced at a significant distance from the cells it influences. Only one known conserved molecule, Dispatched (Disp), can alleviate the membrane tethering imparted by Hh lipidation. Underscoring the importance of Disp protein during development, knockout animals succumb to lethality at E9.5, an exact …

Therapeutic Effects Of Ormeloxifene In Cervical Cancer Carcinogenesis, Neeraj Chauhan

Theses and Dissertations (ETD)

Cervical cancer (CxCa) remains the fourth leading cause of cancer related deaths among women worldwide. Cervical cancer is mainly (~ 99.7%) derived from high risk Human papillomavirus (HR HPV). HPV E6/E7 are the two main oncoproteins that interfere with p53 and pRb (retinoblastoma) cell cycle regulatory proteins and hinder their efficacy of controlling cell growth. Additionally, PI3K-Akt is a cell survival pathway that is aberrantly expressed in cervical cancer cells. This pathway has a profound role in inhibiting mitochondrial intrinsic apoptotic signaling pathway. Advanced stage cervical cancer is difficult to treat and patients diagnosed with metastatic disease have a poor …

The Role Of Hsf1 Protein Regulation On Neurodegeneration, Eunhee Kim

Theses and Dissertations (ETD)

Cellular protein homeostasis is achieved by a delicate network of molecular chaperones and various proteolytic processes such as ubiquitin–proteasome system (UPS) to avoid a build-up of misfolded protein aggregates. The latter is a common denominator of neurodegeneration. Neurons are found to be particularly vulnerable to toxic stress from aggregation-prone proteins such as α-synuclein. Induction of heat-shock proteins (HSPs), such as through activated heat shock transcription factor 1 (HSF1) via Hsp90 inhibition, is being investigated as a therapeutic option for proteinopathic diseases. HSF1 is a master stress-protective transcription factor which activates genes encoding protein chaperones (e.g. iHsp70) and anti-apoptotic proteins. However, …

The Interaction Of Homoserine Lactones And Paraoxonase 2 Modulates Cell Death Signaling And Cell Proliferation., Aaron Mackallan Neely

Electronic Theses and Dissertations

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Importantly, C12 induces apoptosis …

An Evaluation Of Gabab Receptors On Modulating Neuroinflammation In A Non-Transgenic Animal Model Of Alzheimer's Disease, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and distinct neuropathological hallmarks, including amyloid beta plaques and neurofibrillary tau tangles (NFT). Although the etiology remains to be discovered, several risk factors exist that significantly contribute to developing AD. Diabetes is one of the major risk factors associated with AD and is characterized by disrupted insulin signaling that may contribute to or exacerbate AD pathologies. Furthermore, both disorders result in increased neuroinflammation. Considerable evidence has demonstrated that a chronic inflammatory response, in particular chronic microglia activation, promotes A production as well as the hyperphosphorylation of tau through …

Investigating Localization And Activity-Dependent Translation Of Astrocyte Mrna, Rohan Khazanchi

Senior Honors Papers / Undergraduate Theses

Over the past two and a half years, I have studied fundamental aspects of astrocyte biology by investigating the existence and mechanism of astrocyte local translation peripherally around tripartite synapses consisting of pre- and post-synaptic neuron terminals and an associated astrocyte. Astrocytes are critical components of central nervous system synapses (which are predominately tripartite in nature); thus, it is important to consider how astrocyte dysregulation and dysfunction could contribute to the pathogenesis of diseases of synaptic connectivity such as autism spectrum disorders, Alzheimer’s disease, seizure disorders, and more. Overall, my projects involved the development of novel methods to identify astrocyte-specific …

Bk Channels Mediate Synaptic Plasticity Underlying Habituation In Rats., Tariq Zaman, Cleusa De Oliveira, Mahabba Smoka, Chakravarthi Narla, Michael O Poulter, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, …

Aspergillus Fumigatus Trehalose-Regulatory Subunit Homolog Moonlights To Mediate Cell Wall Homeostasis Through Modulation Of Chitin Synthase Activity, Arsa Thammahong, Alayna K. Caffrey-Card, Sourabh Dhingra, Joshua J. Obar, Robert Cramer

Dartmouth Scholarship

Trehalose biosynthesis is found in fungi but not humans. Proteins involved in trehalose biosynthesis are essential for fungal pathogen virulence in humans and plants through multiple mechanisms. Loss of canonical trehalose biosynthesis genes in the human pathogen Aspergillus fumigatus significantly alters cell wall structure and integrity, though the mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslAand tslB, which encode proteins that contain domains similar to those corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic residues for phosphatase activity. Loss of tslA reduces trehalose content in both conidia and mycelia, impairs cell wall …

Persistent Neurobehavioral Traits In A Mouse Model Of Prenatal Ethanol Exposure, Jill M. Lawrence

Neuroscience Honors Papers

Fetal Alcohol Spectrum Disorders (FASD) effect an estimated 2% of the population, causing a range of symptoms: from craniofacial defects to inhibited cortical growth (May, et al., 2009; Murawski, et al., 2015). Impaired medial forebrain function apparent in FASD is associated with lifelong cognitive behavioral deficits, but these consequences may be avoided with early diagnosis and intervention (Streissguth, et al., 2004). Our goal is to identify early neurobehavioral abnormalities that persist into adulthood that could potentially serve as early indicators for FASD. Mouse models of prenatal ethanol exposure were developed using a voluntary drinking paradigm that introduced a sweetened ethanol …

Chronic Neuropsychological Sequelae In A Patient With Nontumorous Anti-Nmda-Receptor Encephalitis, Dong Y. Han, Lisa M. Mason, Aarti Patel, Zhengqiu Zhou, Sarah Phillips, Siddharth Kapoor

Neurology Faculty Publications

Anti-N-methyl-D-aspartate receptor encephalitis is a neurological, autoimmune disorder tightly conceptualized only as recently as the mid-2000s. It presents itself in a combination of psychiatric, neurological, and autonomic features. We observe a unique case with probable earlier episode (prior to the mid-2000s conceptualization of the disease) and a later relapse, accompanying a comprehensive neuropsychological profile tracked after the relapse and subsequent improvement. Neurocognitive findings revealed residual frontal deficits with mood changes even in the state after plasmapheresis. This case is the first to describe posttreatment cognition in anti-NMDAR encephalitis after probable serial autoimmune episodes.

Filamentous Fungal Carbon Catabolite Repression Supports Metabolic Plasticity And Stress Responses Essential For Disease Progression, Sarah R. Beattie, Kenneth Mark, Arsa Thammahong, Laure Nicolas Annick Ries, Sourabh Dhingra, Alayna Caffrey-Carr, Chao Cheng

Dartmouth Scholarship

Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A. fumigatus requires a carbon catabolite repression (CCR) mediated genetic network to support in vivo fungal fitness and disease progression. While CCR as mediated by the transcriptional repressor CreA is …

The Addition Of Arachidin 1 Or Arachidin 3 To Human Rotavirus-Infected Cells Inhibits Viral Replication And Alters The Apoptotic Cell Death Pathway, Macie N. Mattila, Caleb M. Witcher, Rebekah Napier-Jameson, Hannah N. Lockwood, Josephine Taylor, Beatrice A. Clack, Judith M. Ball, Fabricio Medina Bolivar, Rebecca D. Parr

Undergraduate Research Conference

Rotavirus (RV) infections are a leading cause of severe gastroenteritis in infants and children under the age of five. There are two vaccines available in the United States and one in India that can be administered early in childhood, however they only protect against specific strains1. From our previous work, both arachidin-1 (A1) and arachidin-3 (A3) from peanut (Arachis hypogaea) hairy root cultures significantly inhibit simian RV replication2,3,4. The purpose of this study was to determine if a human intestinal cell line, HT29.f8, infected with a human RV, Wa, was affected by A1 and A3. Cell viability assays were utilized …

Nicotinamide Phosphoribosyltransferase Promotes Pulmonary Vascular Remodeling And Is A Therapeutic Target In Pulmonary Arterial Hypertension., Jiwang Chen, Justin R Sysol, Sunit Singla, Shuangping Zhao, Aya Yamamura, Daniela Valdez-Jasso, Taimur Abbasi, Krystyna M. Shioura, Sakshi Sahni, Vamsi Reddy, Arvind Sridhar, Hui Gao, Jaime Torres, Sara M. Camp, Haiyang Tang, Shui Q. Ye, Suzy Comhair, Raed Dweik, Paul Hassoun, Jason X-J Yuan, Joe G N Garcia, Roberto F. Machado

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pulmonary arterial hypertension is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT) is a cytozyme that regulates intracellular nicotinamide adenine dinucleotide levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation, and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling and that inhibition of NAMPT could attenuate pulmonary hypertension.

METHODS: Plasma, mRNA, and protein levels of NAMPT were measured in the lungs and isolated pulmonary artery endothelial cells from patients with pulmonary arterial hypertension and in the lungs of rodent models of pulmonary hypertension.Nampt+/- mice were …

Constitutive Activation Of Kappa Opioid Receptors At Ventral Tegmental Area Inhibitory Synapses Following Acute Stress., Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer

Pharmacology and Physiology Faculty Publications

Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs. We also …

Proceedings - Wright State University Boonshoft School Of Medicine Ninth Annual Medical Student Research Symposium: Celebrating Medical Student Scholarship, Office Of Research Affairs, Boonshoft School Of Medicine

Medical Student Research Symposium Proceedings

The student abstract booklet is a compilation of abstracts from students' oral and poster presentations at Wright State University's Ninth Annual Boonshoft School of Medicine Medical Student Research Symposium held on April 12, 2017.

Creation Of An Immunodeficient Hla-Transgenic Mouse (Humamice) And Functional Validation Of Human Immunity After Transfer Of Hla-Matched Human Cells, Yang Zeng, Bingrun Liu, Marie-Therese Rubio, Xinyue Wang, David M. Ojcius, Ruoping Tang, Antoine Durrbach, Zhitao Ru, Yusen Zhou, Yu-Chun Lone

All Dugoni School of Dentistry Faculty Articles

Research on human immunology has been hindered by the lack of optimal small animal models, given that the protective immune responses of human and non-human species show significant differences. However, due to ethical constraints[1] and the high cost of clinical trials, it is urgent to improve the current animal models that can mimic faithfully human physiology, particularly the human immune system (HIS). HIS mice had been generated recently by engrafting human hematopoietic stem cells (hHSCs) or human peripheral mononuclear cells (hPBMCs) into highly immuno-deficient mice such as NSG, NOG or NRG mice. However, a major experimental drawback for studies using …