Immunology and Infectious Disease Commons^™

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila R. Kunuthuru, Laura Graham, Harry D. Bear Md, Phd

UROP Posters

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …

B Cells Are Required To Generate Optimal Anti-Melanoma Immunity In Response To Checkpoint Blockade, Shubhra Singh, Jason Roszik, Neeraj Saini, Vipul Kumar Singh, Karishma Bavisi, Zhiqiang Wang, Long T Vien, Zixi Yang, Suprateek Kundu, Richard E Davis, Laura Bover, Adi Diab, Sattva S Neelapu, Willem W Overwijk, Kunal Rai, Manisha Singh

Faculty, Staff and Student Publications

Immunotherapies such as checkpoint blockade therapies are known to enhance anti-melanoma CD8+ T cell immunity, but only a fraction of patients treated with these therapies achieve durable immune response and disease control. It may be that CD8+ T cells need help from other immune cells to generate effective and long-lasting anti-tumor immunity or that CD8+ T cells alone are insufficient for complete tumor regression and cure. Melanoma contains significant numbers of B cells; however, the role of B cells in anti-melanoma immunity is controversial. In this study, B16 melanoma mouse models were used to determine the role of B cells …

Epithelial Immunomodulation By Aerosolized Toll-Like Receptor Agonists Prevents Allergic Inflammation In Airway Mucosa In Mice, David L Goldblatt, Gabriella Valverde Ha, Shradha Wali, Vikram V Kulkarni, Michael K Longmire, Ana M Jaramillo, Rosha P Chittuluru, Adrienne Fouts, Margarita Martinez-Moczygemba, Jonathan T Lei, David P Huston, Michael J Tuvim, Burton F Dickey, Scott E Evans

Faculty, Staff and Student Publications

Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells …

Neoadjuvant Checkpoint Inhibitor Immunotherapy For Resectable Mucosal Melanoma, Joel Ho, Jane Mattei, Michael Tetzlaff, Michelle D Williams, Michael A Davies, Adi Diab, Isabella C Glitza Oliva, Jennifer Mcquade, Sapna P Patel, Hussein Tawbi, Michael K Wong, Sarah B Fisher, Ehab Hanna, Emily Z Keung, Merrick Ross, Roi Weiser, Shirley Y Su, Michael Frumovitz, Larissa A Meyer, Amir Jazaeri, Curtis A Pettaway, B Ashleigh Guadagnolo, Andrew J Bishop, Devarati Mitra, Ahsan Farooqi, Roland Bassett, Silvana Faria, Priyadharsini Nagarajan, Rodabe N Amaria

Faculty, Staff and Student Publications

BACKGROUND: Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM.

METHOD: Under an institutionally approved protocol, we identified adult …

Identification Of A Rickettsial Endosymbiont In A Soft Tick Ornithodoros Turicata Americanus, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Bacterial endosymbionts are abundantly found in both hard and soft ticks. Occidentia massiliensis, a rickettsial endosymbiont, was first identified in the soft tick Ornithodoros sonrai collected from Senegal and later was identified in a hard tick Africaniella transversale. In this study, we noted the presence of Occidentia species, designated as Occidentia-like species, in a soft tick O. turicata americanus. Sequencing and phylogenetic analyses of the two genetic markers, 16S rRNA and groEL confirmed the presence of Occidentia-like species in O. turicata americanus ticks. The Occidentia-like species was noted to be present in all developmental stages …

Evaluation Of Ivermectin Antiviral Activity Against Avian Infectious Bronchitis Virus Using A Chicken Embryo Model, Donald L. Reynolds, E. Barry Simpson

School of Veterinary and Biomedical Sciences: Faculty Publications

Ivermectin is widely used in both animals and humans as an FDA-approved parasiticide. Ivermectin has also been reported to have antiviral activity against several viruses including coronaviruses. There are reports that indicate ivermectin may have some role in diminishing the disease caused by SARS-CoV-2, but the evidence is inconclusive. The objective of this study was to determine if ivermectin was efficacious in inhibiting avian infectious bronchitis virus (IBV, a coronavirus) replication in chicken embryos. Briefly, our approach was to use the Massachusetts vaccine strain of IBV in combination with various doses of ivermectin and then inoculate these preparations into chicken …

Rna Nanovaccine Protects Against White Spot Syndrome Virus In Shrimp, Yashdeep Phanse, Supraja Puttamreddy, Duan Loy, Julia Vela Ramirez, Kathleen A. Ross, Ignacio Alvarez-Castro, Mark Mogler, Scott Broderick, Krishna Rajan, Balaji Narasimhan, Lyric C. Bartholomay

School of Veterinary and Biomedical Sciences: Faculty Publications

In the last 15 years, crustacean fisheries have experienced billions of dollars in economic losses, primarily due to viral diseases caused by such pathogens as white spot syndrome virus (WSSV) in the Pacific white shrimp Litopenaeus vannamei and Asian tiger shrimp Penaeus monodon. To date, no effective measures are available to prevent or control disease outbreaks in these animals, despite their economic importance. Recently, double-stranded RNA-based vaccines have been shown to provide specific and robust protection against WSSV infection in cultured shrimp. However, the limited stability of double-stranded RNA is the most significant hurdle for the field application of these …

Malaria Resilience In South America: Epidemiology, Vector Biology, And Immunology Insights From The Amazonian International Center Of Excellence In Malaria Research Network In Peru And Brazil, Kathrine Torres, Marcelo U. Ferreira, Marcia C. Castro, Ananias A. Escalante, Jan E. Conn, Elizabeth Villasis, Maisa Da Silva Araujo, Gregorio Almeida, Priscila T. Rodrigues, Rodrigo M. Corder, Anderson R.J. Fernandes, Priscila R. Calil, Winni A. Ladeia, Stefano S. Garcia-Castillo, Joaquin Gomez, Lis Ribeiro Do Valle Antonelli, Ricardo T. Gazzinelli, Douglas T. Golenbock, Alejandro Llanos-Cuentas, Dionicia Gamboa, Joseph M. Vinetz

Harold W. Manter Laboratory of Parasitology: Library Materials

The 1990s saw the rapid reemergence of malaria in Amazonia, where it remains an important public health priority in South America. The Amazonian International Center of Excellence in Malaria Research (ICEMR) was designed to take a multidisciplinary approach toward identifying novel malaria control and elimination strategies. Based on geographically and epidemiologically distinct sites in the Northeastern Peruvian and Western Brazilian Amazon regions, synergistic projects integrate malaria epidemiology, vector biology, and immunology. The Amazonian ICEMR’s overarching goal is to understand how human behavior and other sociodemographic features of human reservoirs of transmission— predominantly asymptomatically parasitemic people—interact with the major Amazonian malaria …

Circling The Drain: The Extinction Crisis And The Future Of Humanity, Rodolfo Dirzo, Gerardo Ceballos, Paul R. Ehrlich

Harold W. Manter Laboratory of Parasitology: Library Materials

Humanity has triggered the sixth mass extinction episode since the beginning of the Phanerozoic. The complexity of this extinction crisis is centered on the intersection of two complex adaptive systems: human culture and ecosystem functioning, although the significance of this intersection is not properly appreciated. Human beings are part of biodiversity and elements in a global ecosystem. Civilization, and perhaps even the fate of our species, is utterly dependent on that ecosystem’s proper functioning, which society is increasingly degrading. The crisis seems rooted in three factors. First, relatively few people globally are aware of its existence. Second, most people who …

Will Covid-19 Be Eradicated?, Matthew Kieke

Williams Honors College, Honors Research Projects

In this paper I want to define the meaning of “eradication”, explain the history of various diseases that have been eradicated, and compare and contrast them to covid-19, to answer the question of “Will covid-19 be eradicated”?

Bone Morphogenetic Proteins Shape TReg Cells, Piotr Kraj

Biological Sciences Faculty Publications

The transforming growth factor-β (TGF-β) family includes cytokines controlling cell behavior, differentiation and homeostasis of various tissues including components of the immune system. Despite well recognized importance of TGF-β in controlling T cell functions, the immunomodulatory roles of many other members of the TGF-β cytokine family, especially bone morphogenetic proteins (BMPs), start to emerge. Bone Morphogenic Protein Receptor 1α (BMPR1α) is upregulated by activated effector and Foxp3+ regulatory CD4+ T cells (Treg cells) and modulates functions of both of these cell types. BMPR1α inhibits generation of proinflammatory Th17 cells and sustains peripheral Treg cells. This finding underscores the importance of …

Associations Between Eight Earth Observation-Derived Climate Variables And Enteropathogen Infection: An Independent Participant Data Meta-Analysis Of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics, Josh M. Colston, Benjamin F. Zaithcik, Hamada S. Badr, Eleanor Burnett, Syed Asad Ali, Ajit Rayamajhi, Syed M. Satter, Daniel Eibach, Ralf Krumkamp, M Imran Nisar, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen‐specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens—adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia—was matched by date with hydrometeorological variables from a global Earth observation dataset—precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting …

The Combination Of Tlr7/8 And Tlr4 Adjuvants In An Influenza Vaccine Produce Unique Antigen-Specific Adaptive Immunity And Protect Against Lethal Heterologous Influenza Challenge, Shelby Lynn Cole

Graduate Student Theses, Dissertations, & Professional Papers

Influenza virus infection is a global health concern resulting in death and illness each year, which disproportionally effects high-risk individuals. While there are several approved vaccines for seasonal influenza, there are some limitations to consider: current vaccines provide minimal cross protection against seasonally drifted influenza subtypes, influenza vaccine strains change each year, requiring timely manufacture of a new vaccine. Thus, vaccines capable of inducing a more robust and broadly protective immune response to multiple influenza subtypes remains a critical unmet need. Adjuvants and novel delivery systems are an interesting and promising avenue of exploration for enhancing and broadening seasonal influenza …

Nutritional Status Of Children Living Within Institution-Based Care: A Retrospective Analysis With Funnel Plots And Control Charts For Programme Monitoring, Emily Delacey, Evan Hilberg, Elizabeth Allen, Michael Quiring, Cally J. Tann, Nora Ellen Groce, James Vilus, Ethan A. Bergman, Merzel Demasu-Ay, Hang T. Dam, Marko Kerac

All Faculty Scholarship for the College of Education and Professional Studies

Objectives The aim of this study is to fill a key information gap on the nutrition-related epidemiology of orphaned and vulnerable children living within institution-based care (IBC) across six countries.

Design A retrospective analysis with Shewhart control charts and funnel plots to explore intersite and over time variations in nutritional status.

Setting We conducted a retrospective analysis of records from Holt International’s Child Nutrition Programme from 35 sites in six countries; Mongolia, India, Ethiopia, Vietnam, China and the Philippines.

Participants Deidentified health records from Holt International’s online nutrition screening database included records from 2926 children, 0–18 years old. Data were …

Arginine-Rich Polypeptides Are Potent Inhibitors Of Human Papillomavirus Infection And Powerful Tools To Investigate Viral Attachment And Entry, Jesse Mckay Young

Biomedical Sciences ETDs

HPV is the most common sexually transmitted infection. It is estimated that 80% of sexually active adults will contract an HPV infection. Thus, there is a significant need for low-cost and easily distributable HPV antivirals that can be used alongside vaccines to combat infection. Herein I have identified protamine sulfate (PS) as a potent microbicide against HPV infection. PS was agnostic to genotype and efficacious pre and post HPV exposure. PS application topically reduced HPV internalization by altering epidermal growth factor receptor (EGFR) signaling and suppressed EGFR-stimulated HPV entry. Our preliminary data also suggest that heparin binding epidermal growth factor …

Kshv Susceptibility And Transmission Within Tonsillar Specimens, Farizeh Aalam

Pharmaceutical Sciences (PhD) Dissertations

Despite nearly three decades of research, not much is known regarding the early stages of development for KSHV lymphoproliferative disorders, hindering our ability to develop prophylactic measures or effective treatments. This dissertation will focus on the host and viral factors influencing the magnitude and dynamics of KSHV infection in the human tonsil to pave the way for future interventions directed at limiting person-to-person transmission of KSHV.

To understand the contribution of host factors to KSHV susceptibility in B lymphocytes, we generated a library of 40 tonsillar specimens. Our results indicate that the immunological composition of tonsillar lymphocytes varies across our …

Genital Chlamydia Infection Is Influenced By The Female Sex Hormones Estrogen And Progesterone In Vivo, Amy Gail Gravitte

Electronic Theses and Dissertations

Chlamydia is the most common bacterial sexually transmitted infection in the United States and worldwide. It often goes unnoticed due to lack of symptoms and left untreated it can ascend the female genital tract to cause sequelae like pelvic inflammatory disease and irreversible tubal infertility. In reproductive-aged women, female sex hormones estrogen (E2) and progesterone (P4) concentrations fluctuate during the menstrual cycle and are influenced by hormonal contraceptives and hormone replacement therapy. E2 and P4 influence genital Chlamydia infection in women and mice, but these multifactorial interactions are not entirely mapped out. The complex interplay of E2 and P4 with …

The Alzheimer’S Disease Drug Development Landscape, Pieter Van Bokhoven, Arno De Wilde, Lisa Vermunt, Prisca S. Leferink, Sasja Heetveld, Jeffrey Cummings, Philip Scheltens, Everard G.B. Vijverberg

Brain Health Faculty Research

Background: Alzheimer’s disease (AD) is a devastating neurodegenerative disease leading to dementia. The field has made significant progress over the last 15 years. AD diagnosis has shifted from syndromal, based on signs and symptoms, to a biomarker construct based on the pathological hallmarks of the disease: amyloid β deposition, pathologic tau, and neurodegeneration. Numerous genetic risk factors for sporadic AD have been identified, providing further insight into the molecular underpinnings of the disease. For the last two decades, however, drug development for AD has been proven to be particularly challenging. Here, we provide a unique overview of the drug development …

Enhancing Adoptive Cell Therapy By Augmenting Fitness And Anti-Tumor Function Of Tumor-Infiltrating Lymphocytes, Parin Shah

Dissertations and Theses (Open Access)

The success of immune checkpoint inhibitors (ICIs) has established the importance of cancer immunotherapy in solid cancers, where it has been adopted as one of the standards of care for advanced melanoma and lung cancer. It is currently being investigated to treat other solid cancers. However, a large fraction of patients do not respond to ICIs and relapse. ICI therapy offers an in vivo approach to activate tumor-specific T cells, albeit in some cases, this modality does not create a sufficiently robust anti-tumor response. Thus, ex vivo approaches employing manipulation of immune cells, such as Adoptive Cell Therapy (ACT) using …

Investigation Of Histomoniasis Prevention In Poultry, Lesleigh Beer

Graduate Theses and Dissertations

Histomonas meleagridis is the etiological agent of histomoniasis, also commonly known as blackhead disease. This protozoal disease of poultry is detrimental to turkeys with flock mortalities often reaching 80-100%, although other gallinaceous birds are susceptible. Since the voluntary removal of nitarsone in 2015, the poultry industry is suffering with no approved prophylactics, therapeutics, or vaccines for this disease. The objectives of this dissertation were to evaluate multiple methods for prevention or control of histomoniasis, including dietary chemoprophylaxis and vaccination. Specifically, this research evaluated quinine as a chemoprophylactic candidate (Chapter 3) or live-attenuated H. meleagridis as vaccine candidates (Chapter 4) in …

Moerv29 Promotes Apoplastic Effector Secretion Contributing To Virulence Of The Rice Blast Fungus Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Danyu Shen, Han Chen, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

During plant-pathogenic fungi and host plants interactions, numerous pathogen-derived proteins are secreted resulting in the activation of the unfolded protein response (UPR) pathway. For efficient trafficking of secretory proteins, including those important in disease progression, the cytoplasmic coat protein complex II (COPII) exhibits a multifunctional role whose elucidation remains limited. Here, we discovered that the COPII cargo receptor MoErv29 functions as a target of MoHac1, a previously identified transcription factor of the UPR pathway. In Magnaporthe oryzae, deletion of MoERV29 severely affected the vegetative growth, conidiation and biotrophic invasion of the fungus in susceptible rice hosts. We demonstrated that MoErv29 …

Chemical And Biological Characterization Of The Anticancer Potency Of Salvia Fruticosa In A Model Of Human Malignant Melanoma, Sotiris Kyriakou, Venetia Tragkola, Michael Plioukas, Ioannis Anestopoulos, Paschalina S. Chatzopoulou, Eirini Sarrou, Dimitrios T. Trafalis, Maria V. Deligiorgi, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidi

School of Veterinary and Biomedical Sciences: Faculty Publications

Malignant melanoma is one of the most aggressive types of skin cancer with an increasing incidence worldwide. Thus, the development of innovative therapeutic approaches is of great importance. Salvia fruticosa (SF) is known for its anticancer properties and in this context, we aimed to investigate its potential anti-melanoma activity in an in vitro model of human malignant melanoma. Cytotoxicity was assessed through a colorimetric-based sulforhodamine-B (SRB) assay in primary malignant melanoma (A375), non-malignant melanoma epidermoid carcinoma (A431) and non-tumorigenic melanocyte neighbouring keratinocyte (HaCaT) cells. Among eight (8) different fractions of S. fruticosa extracts (SF1-SF8) tested, SF3 was found to possess …

Sex And The Streets: The Open Secret Of Sexual Abuse Among Pakistan's Two Million Street Children, Amir Humza Sohail, Muhammad Hassaan Arif Maan, Sachal Sohail

Medical College Documents

Background: About two million children live on the streets in Pakistan. Their complicated past and dire living conditions make them susceptible to many psychological and physical problems, including sexual abuse.
Main body: With little research on the topic, the prevalence of sexual intercourse among street children is reported to be as high as 88% in Pakistan. With commercial sex a common practice among the street children, public places such as bus terminals and parks have become foci of prostitution and sexual exploitation. A growing concern is the spread of HIV/AIDS among the affected children due to a general lack of …

Mt10-Cvb3 Vaccine Virus Protects Against Cvb4 Infection By Inducing Cross-Reactive, Antigen-Specific Immune Responses, Ninaad Lasrado, Rajkumar Arumugam, Mahima T. Rasquinha, Meghna Sur, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Group B coxsackieviruses (CVB) containing six serotypes, B1–B6, affect various organs, and multiple serotypes can induce similar diseases such as myocarditis and pancreatitis. Yet, no vaccines are currently available to prevent these infections. Translationally, the derivation of vaccines that offer protection against multiple serotypes is highly desired. In that direction, we recently reported the generation of an attenuated strain of CVB3, termed Mt10, which completely protects against both myocarditis and pancreatitis induced by the homologous wild-type CVB3 strain. Here, we report that the Mt10 vaccine can induce cross-protection against multiple CVB serotypes as demonstrated with CVB4. We note that the …

Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = …

Inheritance Of A Mutation Causing Neuropathy With Splayed Forelimbs In Jersey Cattle, A. Al-Khudhair, D. J. Null, J. B. Cole, C. W. Wolfe, David J. Steffen, P. M. Vanraden

School of Veterinary and Biomedical Sciences: Faculty Publications

A new undesirable genetic factor, neuropathy with splayed forelimbs (JNS), has been identified recently in the Jersey breed. Calves affected with JNS are unable to stand on splayed forelimbs that exhibit significant extensor rigidity and excessive lateral abduction at birth. Affected calves generally are alert at birth but exhibit neurologic symptoms, including spasticity of head and neck and convulsive behavior. Other symptoms reported include dislocated shoulders, congenital craniofacial anomalies, and degenerative myelopathy. Inheritance of an undesirable genetic factor was determined from a study of 16 affected calves reported by Jersey breeders across the United States. All of their pedigrees traced …

Immunometabolic Dysregulation At The Intersection Of Obesity And Covid-19, Collins N. Khwatenge, Marquette Pate, Laura C. Miller, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Obesity prevails worldwide to an increasing effect. For example, up to 42% of American adults are considered obese. Obese individuals are prone to a variety of complications of metabolic disorders including diabetes mellitus, hypertension, cardiovascular disease, and chronic kidney disease. Recent meta-analyses of clinical studies in patient cohorts in the ongoing coronavirus-disease 2019 (COVID-19) pandemic indicate that the presence of obesity and relevant disorders is linked to a more severe prognosis of COVID-19. Given the significance of obesity in COVID-19 progression, we provide a review of host metabolic and immune responses in the immunometabolic dysregulation exaggerated by obesity and the …

Role Of Gut Microbiome In Covid-19: An Insight Into Pathogenesis And Therapeutic Potential, Ikram Hussain, Gabriel Liu Yuan Cher, Muhammad Abbas Abid, Muhammad Bilal Abid

Department of Pathology and Laboratory Medicine

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut-lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a "leaky gut". The intestinal permeability then allows access to …

The Novel Orfv Protein Orfv113 Activates Lpa-P38 Signaling, Sushil Khatiwad, Gustavo Delho, Sabal Chaulagai, Daniel L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA₁). Consistent with its interaction with LPA₁, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OVIA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. …

Covid-19: Tougher On Women?, Aika Dietz

Research Briefs

Women are receiving the worst effects of the COVID-19 recession.