MU-COM Research Day

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MU-COM Research Day is an annual showcase of the the research engagement of the students within the College of Osteopathic Medicine. Content on display are typically poster presentations along with faculty-led discussions of research projects. This event is coordinated by the MU-COM Research Club as well as the Faculty-led Research Club Committee.
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131. Identification of Commercially-Available Antibodies that Block Ligand-Binding by BMPR2

Title Tesim:
Identification of Commercially-Available Antibodies that Block Ligand-Binding by BMPR2
Créateur:
Hum, Julia M., Schoerning, Laura OMSII, Gorrell, Ruthann E., Newby, Jordan B., and Lowery, Jonathan W.
La description:
Osteoporosis, a disease of low bone mineral density, affects 10 million Americans and is a significant health problem and a considerable socioeconomic burden. Current treatments for osteoporosis have significant limitations, necessitating identifying new treatment strategies via building a better understanding of the endogenous mechanisms regulating bone mass. We recently demonstrated that removal of the BMP type 2 receptor, BMPR2, in skeletal progenitor cells of Bmpr2-cKO mice leads to reduced age-related bone loss due to a sustained elevation in bone formation rate. The molecular mechanism underlying this phenotype is being pursued in other work. In the present study, we sought to advance the translational potential of our genetic model by identifying antibodies that neutralize the ligand-binding function of the BMPR2 extracellular domain (BMPR2- ECD). We first established a modified, cell-free immunoprecipitation assay wherein the ligand BMP2 is pulled-down by BMPR2-ECD conjugated to Protein G beads; the unbound BMP2, which is found in the supernatant, is subsequently quantified by ELISA. This yielded a standard assay wherein approximately 2 ug BMPR2-ECD leads to 70% reduction in BMP2 signal. Next, we examined the neutralizing ability of 3F6, which is a mouse monoclonal antibody raised against the ligand-binding region of BMPR2, and found a dose-dependent inhibition of BMPR2-ECD ligand-binding. Given that the commercial availability of this antibody is as an ascites preparation, specificity of this assay was confirmed by demonstrating that ligand-binding activity of BMPR2-ECD is unchanged in the presence of non-specific, negative control ascites. Using these results as a guide, we then evaluated 1F12, which is another mouse monoclonal antibody raised against the ligand-binding region of BMPR2, and found that this antibody is also capable of neutralizing the ligand-binding function of BMPR2-ECD. These results provide proof-of-concept data for future studies evaluating inhibition of BMPR2 function in vivo as a means to reduce age-related bone loss.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
Mot-clé:
Bone Morphogenetic Protein (BMP), Osteoporosis, BMPR2, 3F6 antibody, and bone mineral density (BMD)
date créée:
1/1/2016

132. Identification of Gene Signature Associated with Elevated Bone Formation Rate in Aging Mice

Title Tesim:
Identification of Gene Signature Associated with Elevated Bone Formation Rate in Aging Mice
Créateur:
Hudnall, Aaron, Lowery, Jonathan, and Jackson, Krista
La description:
Osteoporosis is a disease of low bone mass resulting from bone resorption exceeding bone formation that places individuals at enhanced risk for fracture, disability, and death. There is an urgent and unmet need for novel targets in treating osteoporosis, requiring a better understanding of the endogenous mechanisms regulating bone formation. Recent work indicates that deletion of the Bmpr2 gene in skeletal progenitor cells of mice using Prx1-Cre leads to substantially elevated bone mass in young adulthood due to increased bone formation rate. Additionally, unpublished work suggests that the age-related decline in bone mass of female Bmpr2 mutant mice is reduced approximately two-fold compared to control mice and quantification of serum bone turnover markers reveals this is associated with a sustained increase in bone formation to at least 35 weeks of age (but not 55 weeks of age) with no alteration in bone resorption. Collectively, these data raise the possibility that Bmpr2 mutant mice may serve as a novel model for elucidating mechanisms that regulate osteoblast activity in aging mice. We sought to identify the gene signature associated with elevated osteoblast activity using genome-wide transcriptome profiling of marrow-free humerii from control and Bmpr2 mutant mice. Applying stringent criteria comparing individual transcripts to eight well-accepted housekeeping genes (Ppib, Gapdh, Hprt, Tbp, Ppia, GusB, Prkg1, and Ywhaz), and contrasting the results at 35 weeks of age to the transcriptome profile at 55 weeks of age, we constructed a Venn diagram sorting the genes into 15 distinct zones. Bioinformatic analyses on this refined gene set indicates that elevated bone formation rate in Bmpr2 mutant mice correlates with enrichment for genes containing binding sites for transcription factors associated with skeletal homeostasis. Further, several genes corresponding with osteoblast differentiation and activity are up-regulated in Bmpr2 mutant mice at 35 weeks of age.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
Mot-clé:
Osteoporosis, Bmpr2, skeletal homeostasis, gene signature, and elevated osteoblast activity
date créée:
11/10/2017

133. Identify cmy-2 Incompatibility Groups in Salmonella Multidrug Resistance Plasmids

Title Tesim:
Identify cmy-2 Incompatibility Groups in Salmonella Multidrug Resistance Plasmids
Créateur:
Kuehn, Stephen and Akbar, Samina
La description:
Many Gram negative bacteria including Salmonella enterica species exhibit evolving multi-drug resistance coded for on their chromosome and on mobile genetic elements. Salmonella species carrying multi-drug resistance plasmids can potentially disperse the cmy-2 gene conferring β- lactam resistance to new Salmonella species as well as to other enteric bacteria commonly found in the human and animal gut. Objective: This study seeks to identify the numbers and incompatibility types of plasmids carried by six different Salmonella clinical isolates. Design: Raw whole genome and DNA fragment (contig) sequence secondary data analyses were conducted using the Center for Genomic Epidemiology (Lyngby, Denmark) open source internet databases plasmid Multilocus Sequence Typing (pMLST) and Resistance Finder (ResFinder). Method: Nucleic acid sequences were separated into files, labeled by contig, and uploaded to the consensus databases for analysis against known Salmonella resistance genes and plasmid types. Results were returned in table format and identified specific resistance, susceptibility, and incompatibility groups present with greater than 90% homology between known and analyzed DNA sequences. Results: Results of this analysis show that these bacterial strains carry plasmids which confer multi-drug resistance and that multiple incompatibility groups are present across some but not all analyzed Salmonella strains. Conclusions: The researchers continue to analyze the data and have not yet formed conclusions as to their significance. This study will advance our understanding about how bacteria develop multiple antibiotic resistances and could ultimately help design more effective drugs with greater potential to combat and prevent bacterial diseases.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
Mot-clé:
multiple antibiotic resistances, multidrug resistance plasmids, and Salmonella enterica
date créée:
1/1/2016

134. The Importance of Childhood Vaccinations in an Era of Misinformation

Title Tesim:
The Importance of Childhood Vaccinations in an Era of Misinformation
Créateur:
Kinder, Claire
La description:
In recent medical history, vaccinations have facilitated the reduction/eradication of many transmissible diseases (Olusanya et al., 2021). Recently, a growing reluctance of parents to vaccinate their children is a pertinent threat to public health and safety (Garett et al., 2021). Submitted as part of the BMS-515 Public Health and US Healthcare System course for MUCOM Research Day.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
Poster
Mot-clé:
childhood vaccination, misinformation, transmissible diseases, under-vaccination, and data-based health information
date créée:
2023

135. Importance of fatty acid binding protein 4 (FABP4) during Coxiella burnetti intracellular growth in alveolar macrophages

Title Tesim:
Importance of fatty acid binding protein 4 (FABP4) during Coxiella burnetti intracellular growth in alveolar macrophages
Créateur:
Hilaire, Kelsey
La description:
Coxiella burnetti is an obligate intracellular bacterial pathogen that spreads to humans via inhalation, infects alveolar macrophages and causes the worldwide zoonosis known as Q fever. Acutely, Coxiella infection manifests as a mild flu-like illness. However, chronic disease presents as endocarditis which is fatal if untreated. It is often clinically undetected until as many as 20 years post-infection suggesting Coxiella’s ability to manipulate host cell processes to establish long-term survival. Although Coxiella initial-ly infects alveolar macrophages, in endocarditis patients it is found in lipid droplet (LD)-rich foam cells. Our previous studies demonstrate that Coxiella manipulates host lipid storage organelle LD accumulation by releasing bacterial effector proteins via its major virulence factor Type 4 secretion system (T4SS). Further, manipulation of host cell LD homeostasis significantly alters Coxiella intracellular growth suggesting the importance of LDs during Coxiella infection. Our overall goal is to identify host cell proteins Coxiella targets to manipulate host cell LD metabolism. Fatty acid binding protein 4 (FABP4) is a cytoplasmic fatty acid chaperone expressed primarily in adipocytes and macrophag-es. It regulates intracellular lipid accumulation and plays an important role in foam cell formation during atherosclerosis. Since LD metabolism plays an essential role during Coxiella pathogenesis, we hypothesize that Coxiella manipulates FABP4 to promote LD accumulation in Coxiella-infected cells. To address this, we performed quantitative Real Time PCR (qRT-PCR) to determine Fabp4 expression in Coxiella-infected alveo-lar macrophages. Compared to uninfected cells, Fabp4 gene expression significantly increased in Coxiella-infected cells suggesting its importance during bacterial infection of alveolar macrophages. Ongoing studies are determining if Coxiella actively manipu-lates FABP4 gene expression via T4SS effectors. Future studies will identify the role of FABP4 in LD accumulation in Coxiella-infected alveolar macrophages and measure bacterial growth in Fabp4-/- alveolar macrophages.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
date créée:
11/22/2019

136. Importance of lipid droplets to immunosuppression in Coxiella burnetii-infected alveolar macrophages.

Title Tesim:
Importance of lipid droplets to immunosuppression in Coxiella burnetii-infected alveolar macrophages.
Créateur:
Mulye, Minal, Ali, Mahek, and Reed, Kyle
La description:
Coxiella burnetii, the known causative agent of Q fever, is an obligate intracellular bacterium capable of infecting host alveolar macrophages and residing within these cells for several years. While causing mild symptoms at initial infection, C. burnetii retains the ability to survive long-term by disseminating and causing serious complications such as culture-negative endocarditis. Previous studies in endocarditis patients demonstrated that C. burnetii suppresses the host immune response via production of prosta-glandin E2 (PGE2) and modulation of the anti-inflammatory cytokine IL-10 and proin-flammatory nitric oxide (NO). C. burnetii is also found in lipid droplet-rich foam cells suggesting the importance of host cell immune response and lipid metabolism during bacterial infection. Previous studies in our lab revealed that C. burnetii manipulates host cell lipid storage organelles, lipid droplets (LDs) via its type 4 secretion system (T4SS) which secrets effector proteins into the host cell cytoplasm to modulate cellular processes. Further, we observed that breakdown of LDs is essential for C. burnetii growth suggesting the importance of LD-derived lipids during bacterial infection. LD breakdown releases arachidonic acid, a PGE2 precursor. Since PGE2 plays an immu-nosuppressive role during C. burnetii infection, we hypothesize that LD-derived PGE2 production leads to modulation of IL-10 and NO. To assess this, we determined IL-10 and NO production enzyme iNOS gene expression in mouse alveolar macrophages by quantitative Real Time PCR (RT-qPCR). Compared to uninfected cells, iNOS gene expression decreased while IL-10 expression remained unchanged. Further we per-formed ELISA to determine IL-10 protein level and identify the contribution of LDs con-tribute IL-10 production. Compared to uninfected cells, IL-10 production in C. burnetii-infected cells remained unchanged. Surprisingly, compared to untreated cells, blocking LD formation and breakdown with specific inhibitors resulted in increased IL-10 produc-tion. This suggests that LDs play an important role in IL-10 production in C. burnetii-infected cells. However, if IL-10 contributes to immunosuppression is yet to be deter-mined. Ongoing studies are identifying the importance of LDs in NO production. Future studies will determine the changes in the overall cytokine profile in the presence/absence of LD breakdown.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
date créée:
11/22/2019

137. Impulse Oscillometry Pulmonary Function Abnormalities in Sickle Cell Disease

Title Tesim:
Impulse Oscillometry Pulmonary Function Abnormalities in Sickle Cell Disease
Créateur:
Cudjoe, Lorene, Kato, Roberta, Coates, Thomas, and Shah, Payal
La description:
Context: Sickle Cell Disease (SCD) is characterized by an inherited point mutation in the hemoglobin (Hgb) HBB gene, which results in hemoglobin polymerization and red blood cell sickling when not fully oxygenated. Inflammatory responses to intravascular hemolysis may be the cause of abnormal pulmonary function found in sickle cell disease. Objective: Our goal was to determine if Impulse Oscillometry (IOS), a measure of pulmonary function, is a sensitive tool to detect a subpopulation of sickle cell patients at increased risk of sickle cell related complications. Design: We conducted a case control study of subjects with SCD, hemolytic anemia controls with other Hemoglobinopathies and Hereditary Spherocytosis (HS), and Hgb AA/AS controls. Setting: Our study took place at Children’s Hospital of Los Angeles in the outpatient setting. Methods: We collected each subject’s self-reported medical history, and blood samples to measure markers of hemolysis and inflammation. IOS was performed to measure airway reactance (AX) and total airway resistance at an oscillation frequency of 5Hz (R5). Results: 22 SCD, 20 Control, and 19 Hemoglobinopathy and HS subjects were studied. The percentage of abnormal R5 readings were high in all populations with no significant difference between the populations (SCD: 37% Controls: 40% Hemoglobinopathies and HS:32%; p>.05). There was, however, a significant difference in AX between SCD, Controls, and Hemoglobinopathies and HS (p<.05). Conclusion: Our study demonstrates a high rate of pulmonary function abnormalities in sickle cell disease subjects and the control populations. Analysis will be done to determine the relationship between the level of hemolysis amongst the SCD subjects with normal R5 and AX readings compared to SCD with abnormal readings. IOS may be a more sensitive measure of airway obstruction but would need to be correlated with complete spirometry and plethysmography with pre and post bronchodilator pulmonary function testing.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
date créée:
11/9/2018

138. In vitro OMT-like stimulation of dermal fibroblasts reduces pro-inflammatory cytokine expression

Title Tesim:
In vitro OMT-like stimulation of dermal fibroblasts reduces pro-inflammatory cytokine expression
Créateur:
Ogunbekun, Oladipupo, Patel, Sunny, Hum, Julia, Anloague, Aric, Lowery, Jonathan, and Mahoney, Aaron
La description:
Sarcopenia is a disease characterized by degeneration of muscle and strength that puts individuals at increased risk of functional impairment, physical disability, and mortality. The risk of disability is 1.5 to 4.6 times higher in older individuals with sarcopenia than those with normal muscle. Very few DOs utilize OMT in management of gait disorders such as sarcopenia despite studies showing improved mobility in patients after OMT and improved gait in Parkinson’s patients after after OMT. The body’s exquisite ability to sense loading makes it conceivable that mechanical stimulation may lead to anabolic effects on muscle. To investigate this, we first build upon prior work that established an in vitro model system for studying soft tissue OMT-like mechanical stimulation of human dermal fibroblasts. This work demonstrated that injury-like strain of fibroblasts induces the secretion of numerous cytokines; reduces fibroblast proliferation rate; and increases fibroblast apoptosis. Moreover, mechanical stimulation mimicking soft tissue OMT reverses numerous aspects of this phenotype, such as reducing section of pro-inflammatory interleukin (IL)-3 and IL-6, inducing secretion of anti-inflammatory IL-1ra; increasing fibroblast proliferation; and reducing fibroblast apoptosis. Additionally, conditioned medium from fibroblasts subjected to OMT-like mechanical strain promotes differentiation of satellite cells into skeletal muscle myocytes. The utilization of OMT may represent a novel therapy for treating skeletal muscle atrophy in patients who are mobility limited or unable/unwilling to carry out resistance training. In this study, we validate these findings by subjecting human dermal fibroblasts to the same injury-like and OMT-like strains as the previous investigators. Following these strains, the cytokine expression was analyzed using the R&D Human Cytokine Array, the BD Cytometric Bead Array (CBA), and enzyme-linked immunosorbant assays (ELISA). The primary cytokines expressed were interleukins 6 and 8. The CBA showed increased expression in both IL-6 and IL-8 in the injury-like strain when compared to the control and significant decrease in expression for both cytokines in the OMT-like strain when compared to the injury-like strain. These results were validated by the ELISAs. These interleukins are both pro-inflammatory in nature, suggesting that OMT may reduce inflammation following an atrophy-like state.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
date créée:
11/22/2019

139. The Increase of Antibiotic Resistance and its Implications in the Nina Mason Pulliam EcoLab

Title Tesim:
The Increase of Antibiotic Resistance and its Implications in the Nina Mason Pulliam EcoLab
Créateur:
Brown, Stephanie, McReynolds, Madison, Ahmad, Azeem, and Akbar, Samina
Related Url Tesim:
Audio presentation: https://marian.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=71d9d966-271f-4585-93ce-ac730004cb8a
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
Poster
Mot-clé:
Nina Mason Pulliam EcoLab and Antibiotic Resistance
date créée:
2020

140. Indirect vs. Direct Assessment of Cold Induced Vasodilation

Title Tesim:
Indirect vs. Direct Assessment of Cold Induced Vasodilation
Créateur:
Clegg, Patrick, Gerow, Daniel, and Wilson, Thad
La description:
Cold-induced vasodilation (CIVD) is a phenomenon involving a counterintuitive increase in skin blood flow during cold exposure. Although CIVD was first described in 1930, CIVD mechanisms remain unknown. CIVD research has assessed vasodilation via skin temperature rather than direct assessment of skin blood flow. The study objective was to determine if laser-Doppler flux, cutaneous vascular conductance (CVC), or skin erythrocyte concentration provides better assessment of CIVD. Twelve (8 men and 4 women) healthy (via health history and vital signs) subjects’, laser- Doppler flux, erythrocyte concentration, and skin-surface temperature were measured in the index and middle finger of the left hand and index finger of the right hand, while arterial blood pressure (ABP) on a beat-by-beat basis was measured in the right ring finger. The left hand was exposed to: baseline (10 min 22-23°C air), warming (10 min 35°C water), cooling (30 min 8°C water), and recovery (15 min 22-23°C air) and the right hand to 22-23°C air throughout. Temperature CIVD was observed in all participants, with an average of 2.33±0.98 occurrences. Flux and concentration CIVDs were observed in 11 and 9 subjects with an average occurrence rate of 1.67±1.37 and 0.92±1.16, respectively. CVC increased during warming +38.1±11.8% (P=0.006), then decreased during the first 5 min of cooling -54.1±8.4% (P<0.001) but was not different by the end of cooling (P=0.143). Right hand, CVC was not initially altered, but decreased by the end of opposite hand cooling (p=0.008). Left hand index and middle finger values and responses were congruent. Cooling increased ABP by an average of 17.3±0.08% (P<0.001). These data indicate sympatholysis in immersed hand during CIVD that is not observed in the non-immersed hand. Direct measures of skin blood flow and erythrocyte concentration appear to add different aspects to the traditional indirect assessment of CIVD and allow new investigations into CIVD mechanisms.
Declaração de direitos:
http://rightsstatements.org/vocab/InC/1.0/
La langue:
English
Type:
poster
Mot-clé:
skin erythrocyte concentration, laser-Doppler flux, Cold-induced vasodilation (CIVD), and cutaneous vascular conductance (CVC)
date créée:
1/1/2016