Hemic and Immune Systems Commons^™

Identifying Modulators Of Stable Klrg1+Il7ra+ Memory Cd8+ T-Cells, Christina Ocampo Valdez

Honors Projects

Type 1 diabetes (T1D) is an autoimmune disease targeting the insulin-producing beta cells of the pancreas. The discovery of insulin revolutionized the treatment of T1D, but current research into T1D has progressed from disease management to possible prevention or delayed onset of diagnosis. One drug currently in use is teplizumab, an anti-CD3 monoclonal antibody that has been shown to delay the onset of T1D in some, but not all, at-risk individuals. High levels of a subset of peripheral blood CD8+ T cells we call SKIMs (stable KLRG1+ IL7Ra+ memory cells), which include MAIT (mucosal-associated invariant T) cells, have been associated …

Severe Maternal Morbidity According To Sickle Cell Disease Genotype, Tetsuya Kawakita, Natsume Furukawa, Sora A. Jones, Salimah Navaz Gangji

Department of Obstetrics & Gynecology Faculty Publications

Background

Sickle cell disease (SCD) is a genetic hemoglobinopathy that disproportionately affects individuals of African descent and is associated with elevated risks of maternal complications. However, the contribution of specific SCD genotypes to severe maternal morbidity (SMM) and postpartum readmission remains poorly characterized at the population level.

Objective

We sought to examine the association between SCD genotypes-hemoglobin SS (HbSS) disease, hemoglobin SC (HbSC) disease, sickle thalassemia, and sickle cell trait-and SMM, hospital readmission, and related adverse maternal outcomes.

Study design

This was a retrospective cohort study using the Nationwide Readmissions Database from 2016 through 2022, representing over 20 million weighted …

A Comparison Of F/Taf And F/Tdf As Hiv Pre-Exposure Prophylaxis In A Predominantly Cisgender Women Population In East And South Africa: A Randomised, Factorial, Non-Inferiority Trial, Sheena Mccormack, David Dunn, Sylvia Kusemererwa, Patricia Munseri, Nishanta Singh, Wiston William, Gertrude Mutonyi, Henry Bern, Lauriane Goldwirt, Cherry Kingsley, Arne Kkroidl, Christian Holm Hansen, Song Ding, Rachel Kawuma, Mary Amondi, Ubaldo Bahemuka, Deus Buma, Daniel Clutterbuck, Zakir Gaffoor, Angus Jennings, Agricola Joachim, Ayoub Kakande, Berna Kalanzi, Abisai Kisinda, Mabela Matsoso, Thomas Miller, Neetha Mmedsci Morar, Jacqueline Musau, Jane Nabbuto, Ayanda Nzuza, Doreen Pamba, Simona Salomone, Thandiwe Sithole, Edith Tarimo, Kubashni Woeber, Kundai Chinyenze, Glenda Gray, Eligius Lyamuya, Muhammad Bakari, Said Aboud, Lucas Maganga, Gustavo Doncel, Janet Seeley, Jonathan Weber, Pontiano Kaleebu, Julie Fox, Eugene Ruzagira, On Behalf Of The Prepvacc Study Group

CONRAD Publications

Background:

F/TAF was shown to be non-inferior to F/TDF as pre-exposure prophylaxis (PrEP) in men, but approval was not extended to cisgender women. We report the results of PrEPVacc, in which a predominantly female population was randomly allocated to receive daily oral F/TDF or F/TAF for ∼6 months within a HIV-1 prophylactic vaccine trial.

Setting:

Five study sites in three African countries (Uganda, Tanzania, South Africa).

Methods:

The two regimens were compared by the averted infections ratio (AIR) - the proportion of infections averted by F/TAF relative to F/TDF. The counterfactual HIV incidence, an essential component of this metric, was …

Presentation, Diagnosis, And Acute Treatment Of Secondary Hemophagocytic Lymphohistiocytosis: A Case Report, Alexandra Bartholomew, Michael Connick, Catherine Loehr, Shane Sanne

School of Medicine Faculty Publications

Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare, immunologically driven disorder with a high mortality rate. It is typically diagnosed on the basis of clinical and laboratory criteria. We present the case of a 53-year-old woman with multiple previous hospitalizations for fever of unknown origin and fatigue. Her workup ultimately led to a diagnosis of HLH. We discuss the presentation, diagnostic criteria, and clinical treatment of secondary HLH to guide workup and management for future patients affected by this rare disease.

Imaging Hallmarks Of Idiopathic Intracranial Hypertension And Insights Into Pathogenesis, Albalooshy Basimah, Scott Faro, Hsiangkuo Yuan, Kiran Talekar, Prabath Mondel, Enchao Qiu, Joga Chaganti

Department of Radiology Faculty Papers

Idiopathic Intracranial hypertension (IIH), also referred to as pseudotumor cerebri, is a term used to describe increased intracranial pressure in the absence of a known identifiable secondary cause. Despite advancements of neuroimaging techniques, imaging of the pathological underpinnings in the diagnosis of IIH has been limited. Although the causation of IIH has been ascribed to increased Cerebrospinal Fluid production and disordered drainage through the dural sinuses, new evidence shows that the glymphatic system which is an alternate pathway of drainage is likely to play a pivotal role. In this review, we address the pathophysiological underpinnings in the causation of IIH …

Igg4-Related Autoimmune Pancreatitis In Patients With Prior Occupational Exposure: A Case Report And Review Of Risks Concerning Blue-Collared Workers, Zachary A. Coren, Justin Le, Jason Tran, Nicholas Moscardelli, Krish Patel, Joshua Coren

Rowan-Virtua Research Day

Autoimmune pancreatitis (AIP), a manifestation of IgG4-related disease (IgG4-RD), is a rare, often misdiagnosed condition that can closely mimic pancreatic cancer, particularly in its clinical and radiographic presentation. We report the case of a 76-year-old retired plumber who presented with painless jaundice and was initially suspected to have pancreatic cancer based on imaging findings. Subsequent endoscopic evaluation, biopsy, and markedly elevated serum IgG4 levels led to a diagnosis of type 1 AIP. Treatment with corticosteroids resulted in rapid clinical improvement and reduction in IgG4 levels, confirming the diagnosis.

This case highlights the diagnostic challenges of AIP, especially among blue-collar workers …

Sarcoidosis With Isolated Osseous Manifestations Mimicking Metastatic Malignancy, Ahmed Ismail, Ahmed Saleh, Yanis Boumber

Department of Medicine Faculty Publications

Sarcoidosis is an inflammatory disease of unknown etiology that commonly involves multiple organ systems, with the lungs and lymph nodes most frequently affected. Osseous involvement, although recognized, is considered uncommon and often overlooked due to its nonspecific clinical and radiographic features. Patients may be asymptomatic or present with pain, swelling, and functional limitations of the affected limb. Imaging can reveal findings such as bone lesions that mimic malignancy, including lytic or sclerotic changes. Diagnosis relies on histopathological confirmation of non-caseating granulomas. Treatment is directed at symptom relief and preservation of limb function. Here, we present a rare case of isolated …

Csf1r Inhibition Depletes Brain Macrophages And Reduces Brain Virus Burden In Siv-Infected Macaques, Diana G. Bohannon, Laurent D. Zablocki-Thomas, Evan S. Leung, Jinbum K. Dupont, Julian B. Hattler, Jolanta Kowalewska, Miaoyun Zhao, Jiangtao Luo, Marco Salemi, Angela M. Amedee, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

School of Graduate Studies Faculty Publications

Perivascular macrophages (PVMs) and, to a lesser degree, microglia are targets and reservoirs of HIV and simian immunodeficiency virus (SIV) in the brain. Previously, we demonstrated that colony-stimulating factor 1 receptor (CSF1R) in PVMs was upregulated and activated in chronically SIV-infected rhesus macaques with encephalitis, correlating with SIV infection of PVMs. Herein, we investigated the role of CSF1R in the brain during acute SIV infection using BLZ945, a brain-penetrant CSF1R kinase inhibitor. Apart from three uninfected historic controls, nine Indian rhesus macaques were infected acutely with SIVmac251 and divided into three groups (n = 3 each): an untreated control and …

Splenic Artery Aneurysm Masquerading As Chest Pain: A Case Report Of A Rare Clinical Presentation, Emily Forester, Anjeanette Brown

Rowan-Virtua Research Day

Background: Splenic artery aneurysms most commonly present with vague epigastric or left upper quadrant abdominal pain that may radiate to the left shoulder. Chest pain associated with splenic artery aneurysm is an unusual phenomena. This case presents a rare occurrence of a splenic artery aneurysm originally presenting as atypical chest pain. Case Presentation: A 46 year old G3P2 AAF patient with family history of hypertension presented to the ER with pleuritic left chest pain, episodes of shortness of breath, and new onset hypertension. Chest x-ray and ECG were unremarkable. Pertinent labs included a hemoglobin of 10.6 and D-dimer of 4.10. …

Ikaros Expression Drives The Aberrant Metabolic Phenotype Of Macrophages In Chronic Hiv Infection, Cecilia Vittori, Celeste Faia, Dorota Wyczechowska, Amber Trauth, Karlie Plaisance-Bonstaff, Mary Meyaski-Schluter, Krzysztof Reiss, Francesca Peruzzi

School of Medicine Faculty Publications

The increased risk for acquiring secondary illnesses in people living with HIV (PLWH) has been associated with immune dysfunction. We have previously found that circulating monocytes from PLWH display a trained phenotype. Here, we evaluated the metabolic profile of these cells and found increased mitochondrial respiration and glycolysis of monocyte-derived macrophages (MDMs) from PLWH. We additionally found that cART shifted the energy metabolism of MDMs from controls toward increased utilization of mitochondrial respiration. Importantly, both downregulation of IKAROS expression and inhibition of the mTOR pathway reversed the metabolic profile of MDMs from PLWH and cART-treated control-MDMs. Altogether, this study reveals …

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …

Characterization Of Epithelial Growth Factor Transcripts Identified In Crotalus Atrox Venom, Ivan Lopez, Ying Jia

Research Symposium

Epithelial Growth Factor (EGF) is the primary source in regeneration and stimulation of essential fibroblasts cells commonly found in epithelium. Studies have shown that snake venom components are becoming a growing factor in treating illnesses such as cancer, muscular dystrophy, chronic pain, blood pressure, blood clotting, etc. EGF in human cells contains a promising quaternary structure that can bind to snake venom metalloproteinases, proposing a means of activating biochemical responses through protein-protein interactions to regulate unwanted cellular functions. This supports promising research in achieving a greater understanding of regulation along cellular pathways through ligands, increasing the likelihood of targeting unwanted …

Candida-Induced Granulocytic Myeloid-Derived Suppressor Cells Are Protective Against Polymicrobial Sepsis, Shannon Esher Righi, Amanda J. Harriett, Elizabeth A. Lilly, Paul L. Fidel Jr., Mairi C. Noverr

School of Dentistry Faculty Publications

Polymicrobial intra-abdominal infections (IAI) can lead to life-threatening sepsis with significant morbidity and mortality, especially when pathogenic fungi are involved. We have employed an established clinically relevant mouse model of fungal/bacterial IAI and shown that immunization with low-virulence Candida species, that is, Candida dubliniensis, can induce responses that protect against sepsis via the suppression of lethal inflammation. This protection is dependent on long-lived Gr-1(+) polymorphonuclear leukocytes that display characteristics consistent with myeloid-derived suppressor cells (MDSCs) and trained innate immunity. Here we aimed to functionally and phenotypically characterize these protective Gr-1(+) leukocytes. Compared to nonimmunized control mice, we observed increased levels …

Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder

School of Graduate Studies Faculty Publications

Through a process termed clot retraction, platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from Cudrania trucuspidata, Arctium lappa, …

Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang

School of Public Health Faculty Publications

Quitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999-2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40-16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.

Covid-19 Vaccination And Alcohol Consumption: Justification Of Risks, Pavel A. Solopov

Bioelectrics Publications

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two …

Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese

Journal of Patient-Centered Research and Reviews

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer’s or Moderna’s COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics

Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus.

Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3%) seroconverted to positive …

Daclizumab (Zinbryta®): An Emerging Therapy For The Treatment Of Relapsing-Remitting Multiple Sclerosis, Morgan Homan, Sunitha Jones, Michaela Louden, Molly Wheeler, Anh Dao Le, Lindsey Peters

Pharmacy and Wellness Review

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system characterized by the deterioration of the myelin sheath, causing axonal damage which leads to debilitating symptoms. Most therapies for the treatment of MS, including daclizumab, primarily target relapsing-remitting multiple sclerosis (RRMS), a form of MS where patients experience periods of exacerbated symptoms as well as intermittent periods of remission. Daclizumab is a humanized monoclonal antibody that is administered as a once monthly subcutaneous injection. The SELECT trilogy of trials have been instrumental in providing safety and efficacy data for daclizumab. The DECIDE study was the first randomized controlled …

Attenuated Negative Feedback In Monocyte-Derived Macrophages From Persons Living With Hiv: A Role For Ikaros, Celeste Faia, Karlie Plaisance-Bonstaff, Cecilia Vittori, Dorota Wyczechowska, Adam Lassak, Mary Meyaski-Schluter, Krzysztof Reiss, Francesca Peruzzi

School of Medicine Faculty Publications

Persons living with HIV (PLWH) are at higher risk of developing secondary illnesses than their uninfected counterparts, suggestive of a dysfunctional immune system in these individuals. Upon exposure to pathogens, monocytes undergo epigenetic remodeling that results in either a trained or a tolerant phenotype, characterized by hyper-responsiveness or hypo-responsiveness to secondary stimuli, respectively. We utilized CD14+ monocytes from virally suppressed PLWH and healthy controls for in vitro analysis following polarization of these cells toward a pro-inflammatory monocyte-derived macrophage (MDM) phenotype. We found that in PLWH-derived MDMs, pro-inflammatory signals (TNFA, IL6, IL1B, miR-155-5p, and IDO1) dominate over negative feedback signals (NCOR2, …

Bleeding Disorder Referrals To Hematology Clinic: A Single Institution Experience, Zuri Hudson

Research Days

Background: Our center receives hundreds of referrals yearly for bleeding disorder evaluation both due to bleeding symptoms and secondary to routine preoperative laboratory testing. The evaluation for a bleeding disorder can be challenging due to the wide variability of symptoms as well as the need for accurately interpreting lab results. Bhasin et al showed that 4% of patients referred to hematology based on a preoperative coagulation evaluation had a clinically relevant bleeding disorder. Currently there is little published about the referral patterns to pediatric hematology and the outcomes of these referrals.

Objectives/Goal: To characterize our hematology referrals for bleeding disorder …

Ebola: Africa, James Goodwin

Global Issues in Public Health

In this paper, I talk about the Ebola Hemorrhagic Fever. Ebola is a rare virus that spreads through the immune system and can be fatal. Ebola is a pathogen from Africa, specifically West Africa. There has been almost 32,000 cases since 1976. Symptoms include, Fever, Headache, Muscle pain, Fatigue, Diarrhea, Vomiting, Stomach pain, and Bleeding/Bruising. Transmission happens during close or direct contact. World Health Organization has been making efforts to handle outbreaks such as the outbreak in 2014. World Health Organization mobilized and set up relief efforts. Education is a key idea for my thoughts on how we can intervene …

Namibia : Hiv As A National Issue, Elisabeth Vlasak

Global Public Health

Namibia is located on the southwestern coast of Africa, bordering Angola, Botswana, Zambia, South Africa, and the Atlantic Ocean. Namibia has a population of 2,265,000, as of 2016. Namibia has many challenges, including food insecurity and malnutrition, access to health services, unequal distribution of wealth, but HIV/AIDS is one of the country’s leading challenges. It is estimated that the overall adult infection rate of HIV/AIDS is 15.4% and it is the leading cause of death in Namibia. Adults ages 18-24 are the most at-risk for the disease. Some of the major risk factors are declining condom use, misinformation, social stigma, …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Nanotoxicity In Cells Of The Immune System, Jonathan J. Pelc

Science Scholars

Nanoparticles (NPs) provide a new medical approach to drug therapy. As with every new approach, safety precautions need to be taken, and the immediate and long-term effects for many NPs are still unclear. When administering a medical treatment into the human body, the first issue that needs to be addressed is host detection of the medicine and inflammation as a possible result of the treatment. If a new NP treatment causes inflammation before it releases its medicine, that treatment may be ineffective, even damaging to the patient. Small metallic and organic particles have been shown to elicit an inflammatory responses …

Cxcr7 Expression Disrupts Endothelial Cell Homeostasis And Causes Ligand-Dependent Invasion, Jennifer Totonchy, Lisa Clepper, Kevin G. Phillips, Owen J. T. Mccarty, Ashlee V. Moses

Pharmacy Faculty Articles and Research

The homeostatic function of endothelial cells (EC ) is critical for a number of physiological processes including vascular integrity, immunity, and wound healing. Indeed, vascular abnormalities resulting from EC dysfunction contribute to the development and spread of malignancies. The alternative SDF-1/CXCL12 receptor CXCR7 is frequently and specifically highly expressed in tumor-associated vessels. In this study, we investigate whether CXCR7 contributes to vascular dysfunction by specifically examining the effect of CXCR7 expression on EC barrier function and motility. We demonstrate that CXCR7 expression in EC results in redistribution of CD31/PECAM-1 and loss of contact inhibition. Moreover, CXCR7+ EC are deficient in …

Chikungunya Virus Infection Results In Higher And Persistent Viral Replication In Aged Rhesus Macaques Due To Defects In Anti-Viral Immunity, Ilhem Messaoudi, Jennifer Totonchy, Thomas Totonchy, Craig N. Kreklywich, Kristen Haberthur, Laura Springgay, James D. Brien, Michael S. Diamond, Victor R. Defilippis, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes …

Acute Myeloid Leukaemia In Children: Experience At A Tertiary Care Facility Of Pakistan, Zehra Fadoo, Naureen Mushtaq, Saima Alvi, Muhammad Ali

Department of Paediatrics and Child Health

Objective: To document the demographics and outcome of children with Acute Myeloid Leukemia (AML) treated at a tertiary care facility of Pakistan.

Methods: A retrospective study was conducted at Aga Khan University on children (less than 15 years) diagnosed to have AML between January 2000 to May 2007.Total 40 cases were diagnosed out of which 37 charts were available for review.

Results: The average age of presentation was 8.5±4.5 years and 75% were males. The most common presenting feature was fever in 83% followed by bleeding in 41% and pallor in 39%. Initial WBC of > 100,000 was seen in 19% …

Cytomegalovirus Cc Chemokine Promotes Immune Cell Migration, Jennifer Totonchy, Michael Denton, Craig N. Kreklywich, Takeshi Andoh, Jessica M. Osborn, Daniel Chen, Ilhem Messaoudi, Susan L. Orloff, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Cytomegaloviruses manipulate the host chemokine/receptor axis by altering cellular chemokine expression and by encoding multiple chemokines and chemokine receptors. Similar to human cytomegalovirus (HCMV), rat cytomegalovirus (RCMV) encodes multiple CC chemokine-analogous proteins, including r129 (HCMV UL128 homologue) and r131 (HCMV UL130 and MCMV m129/130 homologues). Although these proteins play a role in CMV entry, their function as chemotactic cytokines remains unknown. In the current study, we examined the role of the RCMV chemokine r129 in promoting cellular migration and in accelerating transplant vascular sclerosis (TVS) in our rat heart transplant model. We determined that r129 protein is released into culture …

Hcmv Pus28 Initiates Pro-Migratory Signaling Via Activation Of Pyk2 Kinase, Jennifer Totonchy, Susan Varnum, Ryan Melnychuk, Patricia Smith, Ljiliana Pasa-Tolic, Janani I. Shutthanadan, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Background: Human Cytomegalovirus (HCMV) has been implicated in the acceleration of vascular disease and chronic allograft rejection. Recently, the virus has been associated with glioblastoma and other tumors. We have previously shown that the HCMV-encoded chemokine receptor pUS28 mediates smooth muscle cell (SMC) and macrophage motility and this activity has been implicated in the acceleration of vascular disease. pUS28 induced SMC migration involves the activation of the protein tyrosine kinases (PTKs) Src and Focal adhesion kinase as well as the small GTPase RhoA. The PTK Pyk2 has been shown to play a role in cellular migration and formation of cancer, …

Human Cytomegalovirus Us28: A Functionally Selective Chemokine Binding Receptor, Jennifer Totonchy, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

The Human Cytomegalovirus (HCMV)-encoded chemokine receptor US28 is the most well-characterized of the four chemokine receptor-like molecules found in the HCMV genome. US28 been studied as an important virulence factor for HCMV-mediated vascular disease and, more recently, in models of HCMV-associated malignancy. US28 is a rare multi-chemokine family binding receptor with the ability to bind ligands from two distinct chemokine classes. Ligand binding to US28 activates cell-type and ligand-specific signaling pathways leading to cellular migration, an example receptor functional selectivity. Additionally, US28 has been demonstrated to constitutively activate PLC and NFkB. Understanding the structure/function relationships between US28, its ligands and …