Medical Sciences Commons^™

Identifying Co-Factors That Drive Tra-1 Activator Function, Jibran Imtiaz, Yongquan Shen, Ronald Ellis

Rowan-Virtua Research Day

Gli proteins are involved in cell fate determination, proliferation, and patterning in many species and are major effectors of Hedgehog (Hh) signaling. There are three Gli proteins in humans, and mutations or errors in their regulation lead to a variety of developmental disorders or cancer. However, the mechanisms by which they interact with co-factors are poorly understood. We are analyzing co-factors of Gli proteins using TRA-1 in Caenorhabditis nematodes. The TRA-1 zinc fingers are structurally like those of other Gli proteins, and TRA-1 can be cleaved like other Gli proteins to form a repressor. However, its function has changed during …

Mcl-1 Inhibition Modulates Erk-Mediated Resistance In Multiple Myeloma, Omar Al-Odat, Krishne Gowda, Shantu Amin, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Pandey

Rowan-Virtua Research Day

Novel multiple myeloma (MM) treatments have significantly improved over the previous several decades, primarily on account of targeting bone marrow microenvironment (BMM) pathways. However, drug resistance and patient relapse remain major clinical problems. The role of BMM in the upregulation of anti-apoptotic protein Mcl-1 is well documented. The Mcl-1 protein plays a critical role in the progression and acquired drug resistance in MM. The regulation of Mcl-1, a protein characterized by a short half-life, from transcription to degradation is crucial for understanding its role in cell survival. The GSK3β and Erk play important role in the stability of Mcl-1. Also, …

Maldi-Tof Ms Based Proteomic Fingerprinting Of Total Serum Plasma For Somatic Pain Syndromes, Isaiah Pinkerton, Venkateswar Venkataraman

Rowan-Virtua Research Day

There are racial and ethnic disparities regarding pain management within the United States, and that disproportionately affects women of color. There is also a fundamental lack of information regarding the biological mechanism by which pain sensitization and perception occurs, and how it could be affected by both neurologic and somatic pain syndromes.

Methods: Research was performed on principal electronic scientific databases including Google Scholar, PubMed, and Embase with search terms “MALDI-TOF”, “ESI-MS”, “Pain”, and “Biomarkers”, as well as other modifiers to narrow the literature search.

Results: Studies on comparison between MALDI-TOF and other traditional analysis platforms, including Electrospray Ionization (ESI-MS), …

Maackia Amurensis Seed Lectin (Masl) Increases Movement Velocity Of Mice With Tnfα Induced Rheumatoid Arthritis, Amanda A. Greenspan, Kelly L. Hamilton, Alan J. Shienbaum, Bradford Fischer, Andrea Bottaro, Gary S. Goldberg

Rowan-Virtua Research Day

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. The transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN …

Orthologs Of The C. Elegans Heterochronic Genes Have Divergent Functions In C. Briggsae, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

The heterochronic genes of C. elegans comprise the best-studied pathway controlling the timing of tissue and organ formation in an animal. To begin to understand the evolution of this pathway, the significance of each factor, and the relationships among the components, we characterized 11 C. briggsae orthologs of C. elegans heterochronic genes. Using CRISPR/Cas9, we made a variety of alleles and found that several mutant phenotypes differ in significant ways from those of C. elegans. Although most orthologs displayed defects in developmental timing, those phenotypes could differ in which stages they controlled, the penetrance and expressivity of the phenotypes, or …

Is There A Role For Plant-Based “Meat” In Cardiovascular Disease Prevention?, Aziza Jadallah, Usmaan Al-Shehab, Adam Friedman

Rowan-Virtua Research Day

Diet is an established risk factor for cardiovascular disease. The American Heart Association recommends following a whole-food, minimally processed diet emphasizing fruit and vegetables to reduce cardiovascular mortality. Recently, processed plant-based meat substitutes, such as Beyond Meat® and Impossible™ foods have become easily accessible to consumers and are advertised as a healthful addition to a plant-based diet. However, these products are highly processed and contain high amounts of saturated fat and sodium. The purpose of this research is to investigate the effect of processed plant-based meat diets on adverse cardiovascular events compared to animal-based meat diets and minimally processed healthful …

The Role Of Food Accessibility In Weight Loss In A Rat Model Of Parkinson’S Disease, Anjali Kikkisetti, Nicole Charles, Francois Gould

Rowan-Virtua Research Day

Parkinson’s disease (PD) is a neurodegenerative disorder that causes a variety of motor and non-motor symptoms. The goal of this project was to understand whether the weight loss seen with Parkinson’s disease was due to the lack of being able to access the food because of the food placement or because of inability to chew the food due to degeneration of muscles required for chewing food. Both treatment groups, Adjusted Diet and Unadjusted Diet, lost weight after injections started, whereas control weights were stable throughout the experiment. There is no statistically significant difference in weight loss between adjusted and unadjusted …

Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.

Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.

Methods: We selected Western blotting technique to study …

Human Airway Mucociliary Tissue Cultures Chronically Exposed To E-Cigarette Vapors Exhibit Altered Cell Populations And Increased Secretion Of Immunomodulatory Cytokines, Vanessa Pizutelli, Vincent Manna, Shannon Dwyer, Salvatore Caradonna

Rowan-Virtua Research Day

Vape-pens or electronic cigarettes (e-cigarettes) are handheld battery powered devices that use a vape-liquid to produce a vapor that is inhaled by the user. The active ingredients in commercial vape-liquids are commonly nicotine, tetrahydrocannabinol or cannabidiol. A consequence of the rise in e-cigarette usage was the 2019 emergence of a vaping-induced respiratory disease denoted ‘e-cigarette or vaping use-associated lung injury’ (EVALI). One of the suspected causes of EVALI is Vitamin E Acetate (VEA), which was found to be a diluent in certain illicit tetrahydrocannabinol vape-pens, whereas nicotine is commonly diluted in equal parts propylene glycol and vegetable glycerin (PG:VG). The …

A 5-Year Clinical Course Of Phenocopy Syndrome Of Behavioral Variant Frontotemporal Dementia: Case Report And Literature Review, Joseph Melillo, Keyur Patel, Christian White

Rowan-Virtua Research Day

Frontotemporal dementia is a neurocognitive disease which affects language, behavior, or executive functioning. This disease includes a spectrum of presentations which includes multiple variants. The phenocopy syndrome of behavioral variant frontotemporal dementia is one which mimics the behavioral variant of frontotemporal dementia. Patients with this condition show a decline in personality, social conduct and cognitive ability but often display no signs of neurological imaging and exhibit slow progression. This case focuses on a now 70-year-old male who has shown signs of behavioral changes with a slowly progressive clinical course and minimal findings on PET scan, but moderate changes seen on …

Perioperative Ketamine Use For Post Mastectomy Pain, Alessia Cooney, Jaylyn Thompson, Naomi Watkins-Granville

Rowan-Virtua Research Day

PMPS is defined as chronic neuropathic pain following breast cancer procedures in the ipsilateral arm, chest wall, axilla or shoulder.1-3 Approximately 20 to 50% of post mastectomy patients suffer from Post Mastectomy Pain Syndrome (PMPS).1 With more than 3.8 million breast cancer survivors, due to advances in treatment, there is increased importance in findings ways to better manage the quality of life of breast cancer survivors.1,4 Ketamine induces analgesic effects through its non-competitive antagonism of NDMA receptors.5 Low doses of ketamine infusion (20–30 mg x h−1) have been shown to produce analgesia in neuropathic pain states with benefits lasting up …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Long Term Neuroprotective Effects Of Human Adipose-Derived Stem Cells In Neonatal Rats Post Hypoxic Ischemic Encephalopathy, Melissa February, Thomas N. Tulenko, Barry Weinberger, Alla Kushnir

Cooper Rowan Medical Journal

Background: Hypoxemic ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in the neonatal population. Recent research has shown human adipose stem cells (hASCs) to have neuroprotective effects in animal models of HIE. This study tested the hypothesis that neurodevelopmental outcomes would be improved using hASC therapy in term neonatal HIE rat model.

Methods: Seven day old rats underwent left carotid artery ligation followed by 8% oxygen for 120 minutes, or carotid isolation in shams. Forty-eight hours after surgery half of the rats received hASCs and half normal saline (NS) intravenously. Rota-rod and cylinder tests were used to …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley

Graduate School of Biomedical Sciences Theses and Dissertations

Cells are exposed to an enormous amount of diverse extracellular cues but have a limited arsenal of weapons for protecting and maintaining homeostasis. To overcome these restrictions, nature has engineered proteins that have multiple functions. The pleiotropy of using one protein to carry out a variety of functions allows cells to rapidly execute tailored responses to a diverse set of signals. The Cdk8 kinase module (CKM) is a conserved detachable unit of the Mediator complex predominantly known for its role in transcriptional regulation. The CKM is composed of four proteins, the scaffolding proteins Med13 and Med12, as well as the …

Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights …

Investigating The Role Of Vasopressin Receptor 1a Expressing Neurons In Mouse Dorsal Raphe, Tirth Nimishbhai Patel

Theses and Dissertations

Human social interactions heavily impact our physical and mental wellbeing. Arginine-vasopressin (Avp) and serotonin have both been implicated in modulation of social behaviors ranging from affiliation to aggression. In male mice, Avp neurons in the bed nucleus of stria terminalis (BNST) show increased activity during prosocial behavior. BNST sends Avp afferents to the dorsal raphe (DR) in the midbrain, a home to a large portion of serotonin neurons in the mouse brain. Previous data suggests that DR is activated during male prosocial behavior with a female stimulus, and Avp indirectly excites serotonin neurons. We hypothesized that DR contains a population …

Dual Mechanisms Implemented By Lin-28 For Positive Regulation Of Hbl-1 Are Necessary For Proper Development Of Distinct Tissues In Caenorhabditis Elegans, Madeleine Minutillo

Graduate School of Biomedical Sciences Theses and Dissertations

In Caenorhabditis elegans, the heterochronic pathway is comprised of a hierarchy of genes that control the proper timing of developmental events. hbl-1 (Hunchback Like-1) encodes an Ikaros family zinc-finger transcription factor that promotes the L2 stage cell fate events of the hypodermis. The downregulation ofhbl-1 is a crucial step for the transition from the L2 to the L3 stage. There are two known processes through which negative regulation of hbl-1 occurs: suppression of hbl-1 expression by 3 let-7 miRNAs through the hbl-1 3’UTR and inhibition of HBL-1 activity by LIN-46. The mechanisms by which hbl-1 is positively regulated have not …

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …

Cdk8 Kinase Module Modifies Expression Of Specific Translation-Related Proteins Before And After Stress, Brittany Friedson, Katrina Cooper

Rowan-Virtua Research Day

Translation is tightly coupled to growth status. Efficient protein synthesis is necessary for cell growth in nutrient rich environments, while global translation inhibition combined with selective translation of stress-responsive mRNAs helps limit growth in times of stress. Environmental stress cues which inhibit the nutrient-sensing complex TORC1 are known to reduce general translation, but how does the cell alter protein synthesis machinery to adapt to these conditions? A few mechanisms to promote cell survival in nitrogen starvation include post-translational modification and selective degradation of specific mRNA-binding translation factors, as well as inhibition of activators of genes whose products are required for …

Safety And Efficacy Of Silver-Coated Biomaterials In Vivo, Megan Klem, Darien L. Seidman, Rahyan Mahmoud, Manuella Adu, Lei Yu, Jeffrey Hettinger, Renee M Demarest

Rowan-Virtua Research Day

Overtreatment and overuse of antibiotics in healthcare and agricultural settings have contributed to the selective pressure on bacterial strains to develop resistance. Resistance can develop as a result of mutations and subsequent resistance genes that allow bacteria to survive against antibiotics. Novel silver-oxide coatings were developed and were previously demonstrated to prevent adhesion of gram-negative bacteria (Escherichia Coli and Pseudomonas Aeruginosa) to the disc, but did not prevent gram-positive bacterial adherence (Streptococcus Aureus). In order to determine whether the silver-oxide coatings are bacterial static and may be preventing progression to biofilm formation, in vivo analysis of S. Aureus attached to …

The Role Of Corticothalamic Projections (Prelimbic Cortex To Nucleus Reuniens) In Working Memory, Phillip Kumpf, Paul C. Kumpf, S. D. Dunn, Evan Ciacciarelli, T. Gohar, Timothy Sloand, Mark Niedringhaus, Elizabeth West

Rowan-Virtua Research Day

Working memory (WM) is the ability to store information for short periods of time and is used to execute tasks

WM has been understood to work via the medial prefrontal cortex (mPFC) and dorsal hippocampus (dHPC), but they do not directly project to each other

The nucleus reuniens of the thalamus (Re) is a “middle man” between the mPFC and dHPC

There are projections between the prelimbic cortex (PrL) and Re that may be used during WM

To test the connection of the PrL to Re, a delayed nonmatch to position (DNMTP) task was performed

Neuronal Activity Within The Ventral Tegmental Area Is Correlated With Cocaine-Seeking Behavior In Male, But Not Female, Rats, Colton D. Spencer, Nicole M. Hinds, Ireneusz D. Wojtas, Desta M. Pulley, Daniel Manvich

Rowan-Virtua Research Day

The objective of this study was to begin to determine the neurobiological underpinnings of psychosocial stress-induced cocaine seeking. Social defeat stress, achieved using the well-established resident-intruder procedure, is an ecologically-valid psychosocial stressor in rodents that may more closely recapitulate those psychosocial experiences that elicit cocaine craving and relapse in human cocaine users. Our laboratory has developed a model of psychosocial stress-induced relapse in rats in which extinguished cocaine seeking is reinstated by re-exposure to a discrete cue that signals impending social defeat stress. We previously reported that an individual rat’s predilection towards the display of active coping behaviors during prior …

Conservation And Divergence In The Heterochronic Pathway Of C. Elegans And C. Briggsae, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

The heterochronic pathway of Caenorhabditis elegans is exemplary as a mechanism of developmental timing: mutations in genes of this pathway alter the relative timing of diverse developmental events independent of spatial or cell type specific regulation. It is the most thoroughly characterized developmental timing pathway known. Most of the heterochronic genes are conserved across great evolutionary time, and a few homologs seem to have developmental timing roles in certain contexts. The degree to which other organisms have explicit developmental timing mechanisms, and what factors comprise those mechanisms, isn’t generally known.

Developmental pathways evolve even if the resulting morphology remains the …

A Case Report On Causes Of Covid-19 Induced Psychosis And Treatments, Jennifer Pires, Steven Sarner

Rowan-Virtua Research Day

COVID-19 is a viral infection that is caused by an RNA virus in a subfamily of Coronaviridae named severe acute respiratory syndrome (SARS CoV 2). The family also includes severe acute respiratory syndrome coronavirus (SARS CoV) and middle east respiratory syndrome coronavirus (MERS CoV) which have previously been shown to cause respiratory symptoms and psychosis with immunoreactivity to IgG.

A Preliminary Report: The Hippocampus And Surrounding Temporal Cortex Of Patients With Schizophrenia Have Impaired Blood-Brain Barrier, Eric L. Goldwaser, Randel L. Swanson, Edgardo J. Arroyo, Venkat Venkataraman, Mary C. Kosciuk, Robert G. Nagele, L. Elliot Hong, Nimish K. Acharya

Rowan-Virtua Research Day

Schizophrenia (SZ) is one of the most severe forms of mental illness, yet mechanisms remain unclear. A widely established brain finding in SZ is hippocampal atrophy, and a coherent explanation similarly is lacking. Epidemiological evidence suggests increased cerebrovascular and cardiovascular complications in SZ independent of lifestyle and medication, pointing to disease-specific pathology. Endothelial cell contributions to blood-brain barrier (BBB) compromise may influence neurovascular unit and peripheral vascular function, and we hypothesize that downstream functional and structural abnormalities may be explained by impaired BBB.

Case Report: Covid Arm (Covid Vaccine Arm), Joseph Pagano, James Espinosa, Alan Lucerna, Henry Schuitema

Rowan-Virtua Research Day

We report the case of a 38-year-old male physician who was vaccinated with the Pfizer vaccine. He experienced arm pain and swelling on the vaccinated arm as well as systemic symptoms, including fever, chills, headache and weakness. The systemic symptoms improved after the use of oral prednisone. A review of the literature on the COVID vaccine is presented.

The Brodmann Area 39/40 Of The Brain In Alzheimer’S, Mild Cognitive Impairment, And No Cognitive Impairment Subjects At Advanced Age Demonstrate Comparable Levels Of Blood-Brain Barrier Breach, Dhara Rana, Forum Mangrola, Randel L. Swanson, Venkat Venkataraman, David A. Bennett, Zoe Arvanitakis, David Libon, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

• Alzheimer’s disease (AD) is one of the most common form of dementia

• Mild cognitive impairment (MCI), specifically amnestic subtype, more likely to progress to AD

• Pathogenesis Theories:

• o Accumulation of amyloid-beta peptides and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein
• o Blood Brain Barrier (BBB) dysfunction is associated with AD pathogenesis

• Brodmann area 39/40: regions of parietal cortex are responsible for language, spatial cognition, memory retrieval, attention, phonological processing, and emotional processing

• Hypothesis: An increased BBB permeability in Brodmann area 39/40 of AD and age-matched MCI and no cognitive impairment (NCI) subjects

Cyclin C Is Sufficient For Myoblast Differentiation-Induced Mitochondrial Fragmentation, Alicia N. Campbell, Randy Strich

Rowan-Virtua Research Day

One of the largest and most dynamic tissues in the body, skeletal muscle, requires constant regeneration and upkeep. Dysregulation of this regeneration process has been implicated in many neuromuscular diseases and myotonic dystrophies. Regeneration requires the differentiation of myogenic lineages including exiting the cell cycle, gene expression changes, and fusing of myoblasts into multinucleate myotubes. Part of this reconstruction requires the breakdown and repopulation of mitochondrial networks. At the early onset of myoblast differentiation, there is an upregulation of dynamin-related protein, Drp1, and an increase in mitophagy mediated by sequestosome (SQSTM1) removal of mitochondria.

Previously, our lab has shown that …

Examining Levels Of Catecholamine Neurotransmitter Regulatory Proteins Within The Prefrontal Cortex Of Rodents Following Traumatic Brain Injury, Eleni Papadopoulos, Christopher P. Knapp, Claire M. Corbett, Jessica Loweth, Rachel L. Navarra

Rowan-Virtua Research Day

Traumatic brain injury (TBI) resulting from impact to the head can cause long lasting impairments of cognitive processes that lead to increased risk-taking behavior in clinical populations. Our laboratory has recently shown that female, but not age-matched male, rats increase preference for risky choices after multiple experimentally-induced mild TBI’s. Our overarching goal is to understand the neural mechanisms underlying TBI-induced increases in risk-taking behavior.

The prefrontal cortex (PFC) plays a prominent role in risk-based decision making. Sub[1]regions of the PFC include the medial PFC (mPFC), the orbitofrontal cortex (OFC), and the anterior cingulate cortex (ACC), and these sub[1]regions play specific …