Digital Commons Network^™

Mouse Models Of Chronic Lymphocytic Leukemia And Richter Transformation: What We Have Learnt And What We Are Missing, Maria Teresa Sabrina Bertilaccio, Shih-Shih Chen

Faculty, Staff and Student Publications

Although the chronic lymphocytic leukemia (CLL) treatment landscape has changed dramatically, unmet clinical needs are emerging, as CLL in many patients does not respond, becomes resistant to treatment, relapses during treatment, or transforms into Richter. In the majority of cases, transformation evolves the original leukemia clone into a diffuse large B-cell lymphoma (DLBCL). Richter transformation (RT) represents a dreadful clinical challenge with limited therapeutic opportunities and scarce preclinical tools. CLL cells are well known to highly depend on survival signals provided by the tumor microenvironment (TME). These signals enhance the frequency of immunosuppressive cells with protumor function, including regulatory CD4

A Relay Velocity Model Infers Cell-Dependent Rna Velocity, Shengyu Li, Pengzhi Zhang, Weiqing Chen, Lingqun Ye, Kristopher W Brannan, Nhat-Tu Le, Jun-Ichi Abe, John P Cooke, Guangyu Wang

Faculty, Staff and Student Publications

RNA velocity provides an approach for inferring cellular state transitions from single-cell RNA sequencing (scRNA-seq) data. Conventional RNA velocity models infer universal kinetics from all cells in an scRNA-seq experiment, resulting in unpredictable performance in experiments with multi-stage and/or multi-lineage transition of cell states where the assumption of the same kinetic rates for all cells no longer holds. Here we present cellDancer, a scalable deep neural network that locally infers velocity for each cell from its neighbors and then relays a series of local velocities to provide single-cell resolution inference of velocity kinetics. In the simulation benchmark, cellDancer shows robust …

Neuromuscular Polytrauma Pain Is Resolved By Macrophage Cox-2 Nanoimmunomodulation, Ibdanelo Cortez, Caitlyn M Gaffney, Riddhi Vichare, Caitlin V Crelli, Lu Liu, Eric Lee, Jules Edralin, James M Nichols, Hoang Vu Pham, Syed Mehdi, Jelena M Janjic, Andrew J Shepherd

Faculty, Staff and Student Publications

Soft tissue injuries often involve muscle and peripheral nerves and are qualitatively distinct from single-tissue injuries. Prior research suggests that damaged innervation compromises wound healing. To test this in a traumatic injury context, we developed a novel mouse model of nerve and lower limb polytrauma, which features greater pain hypersensitivity and more sustained macrophage infiltration than either injury in isolation. We also show that macrophages are crucial mediators of pain hypersensitivity in this model by delivering macrophage-targeted nanoemulsions laden with the cyclooxygenase-2 (COX-2) inhibitor celecoxib. This treatment was more effective in males than females, and more effective when delivered 3 …

Candidate Circulating Microrna Biomarkers In Dogs With Chronic Pancreatitis, Susan K Armstrong, Robert W Hunter, Wilna Oosthyuzen, Maciej Parys, Adam G Gow, Silke Salavati Schmitz, James W Dear, Richard J Mellanby

Faculty, Staff and Student Publications

BACKGROUND: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis.

HYPOTHESIS: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers.

ANIMALS: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17).

METHODS: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, …

Toxicity In The Era Of Immune Checkpoint Inhibitor Therapy, Synat Keam, Naimah Turner, Fernanda G Kugeratski, Rene Rico, Jocelynn Colunga-Minutti, Rayansh Poojary, Sayan Alekseev, Anisha B Patel, Yuanteng Jeff Li, Ajay Sheshadri, Monica E Loghin, Karin Woodman, Ashley E Aaroe, Sarah Hamidi, Priyanka Chandrasekhar Iyer, Nicolas L Palaskas, Yinghong Wang, Roza Nurieva

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression. Although irAEs are common, the detailed molecular and immune mechanisms underlying their development are still elusive. To further our understanding …

A Pthrp Gradient Drives Mandibular Condylar Chondrogenesis Via Runx2, C Tsutsumi-Arai, Y Arai, A Tran, M Salinas, Y Nakai, S Orikasa, W Ono, N Ono

Faculty, Staff and Student Publications

The mandibular condylar cartilage (MCC) is an essential component of the temporomandibular joint, which orchestrates the vertical growth of the mandibular ramus through endochondral ossification with distinctive modes of cell differentiation. Parathyroid hormone–related protein (PTHrP) is a master regulator of chondrogenesis; in the long bone epiphyseal growth plate, PTHrP expressed by resting zone chondrocytes promotes chondrocyte proliferation in the adjacent layer. However, how PTHrP regulates chondrogenesis in the MCC remains largely unclear. In this study, we used a Pthrp-mCherry knock-in reporter strain to map the localization of PTHrP+ cells in the MCC and define the function of PTHrP in the …

Independent Regulation Of Piezo1 Activity By Principal And Intercalated Cells Of The Collecting Duct, Kyrylo Pyrshev, Anna Atamanchuk-Stavniichuk, Mariya Kordysh, Oleg Zaika, Viktor N Tomilin, Oleh Pochynyuk

Faculty, Staff and Student Publications

The renal collecting duct is continuously exposed to a wide spectrum of fluid flow rates and osmotic gradients. Expression of a mechanoactivated Piezo1 channel is the most prominent in the collecting duct. However, the status and regulation of Piezo1 in functionally distinct principal and intercalated cells (PCs and ICs) of the collecting duct remain to be determined. We used pharmacological Piezo1 activation to quantify Piezo1-mediated [Ca2+]i influx and single-channel activity separately in PCs and ICs of freshly isolated collecting ducts with fluorescence imaging and electrophysiological tools. We also employed a variety of systemic treatments to examine their consequences on Piezo1 …

The Immunobiology Of Myelodysplastic Neoplasms: A Mini-Review, Shruthi Kannan, Rolando A Vedia, Jeffrey J Molldrem

Faculty, Staff and Student Publications

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing …

Nasal Bots Carry Relevant Titers Of Cwd Prions In Naturally Infected White-Tailed Deer, Paulina Soto, Francisca Bravo-Risi, Carlos Kramm, Nazaret Gamez, Rebeca Benavente, Denise L Bonilla, J Hunter Reed, Mitch Lockwood, Terry R Spraker, Tracy Nichols, Rodrigo Morales

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting farmed and free-ranging cervids. CWD is rapidly expanding across North America and its mechanisms of transmission are not completely understood. Considering that cervids are commonly afflicted by nasal bot flies, we tested the potential of these parasites to transmit CWD. Parasites collected from naturally infected white-tailed deer were evaluated for their prion content using the protein misfolding cyclic amplification (PMCA) technology and bioassays. Here, we describe PMCA seeding activity in nasal bot larvae collected from naturally infected, nonclinical deer. These parasites efficiently infect CWD-susceptible mice in ways suggestive of high infectivity …

Radiation Induced Skin Fibrosis (Risf): Opportunity For Angiotensin Ii-Dependent Intervention, Patricia F. Boothe, Vidya P. Kumar, Yali Kong, Kan Wang, Howard Levinson, David Mu, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. …

Bet Inhibition Reforms The Immune Microenvironment And Alleviates T Cell Dysfunction In Chronic Lymphocytic Leukemia, Audrey L. Smith, Sydney A. Skupa, Alexandria P. Eiken, Timothy E. Reznicek, Elizabeth Schmitz, Nolan Williams, Dalia Y. Moore, Christopher R. D'Angelo, Avyakta Kallam, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Eslam Mohamed, Anna R. Mahr, Paul W. Denton, Ben Powell, Gideon Bollag, M. Jordan Rowley, Dalia El-Gamal

Journal Articles: Oncology and Hematology

Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T cell exhaustion greatly hinder functional antitumor immune responses in chronic lymphocytic leukemia (CLL). Bromodomain and extraterminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent CLL T cell defects. The pan-BET inhibitor OPN-51107 reduced exhaustion-associated cell signatures resulting in improved T cell proliferation and effector function in the Eμ-TCL1 splenic TME. Following BET inhibition (BET-i), TME T cells coexpressed significantly fewer …

Targeted Insertion Of Conditional Expression Cassettes Into The Mouse Genome Using The Modified I-Pitt, Hiromi Miura, Ayaka Nakamura, Aki Kurosaki, Ai Kotani, Masaru Motojima, Keiko Tanaka, Shigeru Kakuta, Sanae Ogiwara, Yuhsuke Ohmi, Hirotaka Komaba, Samantha L. P. Schilit, Cynthia C. Morton, Channabasavaiah B. Gurumurthy, Masato Ohtsuka

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Transgenic (Tg) mice are widely used in biomedical research, and they are typically generated by injecting transgenic DNA cassettes into pronuclei of one-cell stage zygotes. Such animals often show unreliable expression of the transgenic DNA, one of the major reasons for which is random insertion of the transgenes. We previously developed a method called "pronuclear injection-based targeted transgenesis" (PITT), in which DNA constructs are directed to insert at pre-designated genomic loci. PITT was achieved by pre-installing so called landing pad sequences (such as heterotypic LoxP sites or attP sites) to create seed mice and then injecting Cre recombinase or …

Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia

Biological Sciences Faculty Publications

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap− or ΔinlA) or double (lap−ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates …

Assessing The Value And Knowledge Gains From An Online Tick Identification And Tick-Borne Disease Management Course For The Southeastern United States, Catherine A. Lippi, Holly D. Gaff, Alexis L. White, Sadie J. Ryan

Biological Sciences Faculty Publications

Background

Tick-borne diseases are a growing public health threat in the United States. Despite the prevalence and rising burden of tick-borne diseases, there are major gaps in baseline knowledge and surveillance efforts for tick vectors, even among vector control districts and public health agencies. To address this issue, an online tick training course (OTTC) was developed through the Southeastern Center of Excellence in Vector-Borne Diseases (SECOEVBD) to provide a comprehensive knowledge base on ticks, tick-borne diseases, and their management.

Methods

The OTTC consisted of training modules covering topics including tick biology, tick identification, tick-borne diseases, and public health, personal tick …

Half Of Atlantic Reef-Building Corals At Elevated Risk Of Extinction Due To Climate Change And Other Threats, Luis Gutierrez, Beth Polidoro, David Obura, Francoise Cabada-Blanco, Christi Linardich, Emma Pettersson, Paul Pearce-Kelly, Krista Kemppinen, Juan Jose Alvarado, Lorenzo Alvarez-Filip, Anastazia Banaszak, Pilar Casado De Amezua, James Crabbe, Aldo Croquer, Joshua Feingold, Elizabeth Goergen, Stefano Goffredo, Bert Hoeksema, Danwei Huang, Emma Kennedy, Diego Kersting, Marcelo Kitahara, Petar Kružić, Margaret Miller, Flavia Nunes, Juan Pablo Quimbayo, Andrea Rivera-Sosa, Rosa Rodríguez-Martínez, Nadia Santodomingo, Michael Sweet, Mark Vermeij, Estrella Villamizar, Greta Aeby, Khatija Alliji, Daniel Bayley, Elena Couce, Benjamin Cowburn, C. Isabel Nuñez Lendo, Sean Porter, Kaveh Samimi-Namin, Tom Shlesinger, Bryan Wilson

Biological Sciences Faculty Publications

Atlantic reef-building corals and coral reefs continue to experience extensive decline due to increased stressors related to climate change, disease, pollution, and numerous anthropogenic threats. To understand the impact of ocean warming and reef loss on the estimated extinction risk of shallow water Atlantic reef-building scleractinians and milleporids, all 85 valid species were reassessed under the IUCN Red List Categories and Criteria, updating the previous Red List assessment of Atlantic corals published in 2008. For the present assessment, individual species declines were estimated based on the modeled coral cover loss (1989–2019) and projected onset of annual severe bleaching events (2020–2050) …

Abalones At Risk: A Global Red List Assessment Of Haliotis In A Changing Climate, Howard Peters, Gina M. Ralph, Laura Rogers-Bennett

Biological Sciences Faculty Publications

There is increasing awareness that marine invertebrates such as abalones are at risk from the combined stressors of fishing and climate change. Abalones are an important marine fishery resource and of cultural importance to Indigenous and non-Indigenous people. A highly priced marine delicacy, they are inherently vulnerable: individuals are slow-growing and long-lived and successful reproduction requires dense assemblages. However, their global conservation status is poorly understood. Using IUCN Red List methodology, we assessed the extinction risk to all 54 species of abalone (genus Haliotis). Of the 21 fished commercially for human consumption either now and/or in the past, 15 …

A Comprehensive Review Of Advances In Hepatocyte Microencapsulation: Selecting Materials And Preserving Cell Viability, Hailian Wang, Lebin Wen, Fengdi Jiang, Pengyu Ren, Yixin Yang, Siyuan Song, Zhengteng Yang, Yi Wang

Children’s Nutrition Research Center Staff Publications

Liver failure represents a critical medical condition with a traditionally grim prognosis, where treatment options have been notably limited. Historically, liver transplantation has stood as the sole definitive cure, yet the stark disparity between the limited availability of liver donations and the high demand for such organs has significantly hampered its feasibility. This discrepancy has necessitated the exploration of hepatocyte transplantation as a temporary, supportive intervention. In light of this, our review delves into the burgeoning field of hepatocyte transplantation, with a focus on the latest advancements in maintaining hepatocyte function, co-microencapsulation techniques, xenogeneic hepatocyte transplantation, and the selection of …

Combinatorial Atoh1, Gfi1, Pou4f3, And Six1 Gene Transfer Induces Hair Cell Regeneration In The Flat Epithelium Of Mature Guinea Pigs, Yujie Liu, Lin Yang, Sunita Singh, Lisa A Beyer, Diane M Prieskorn, Donald L Swiderski, Andrew K Groves, Yehoash Raphael

Children’s Nutrition Research Center Staff Publications

Flat epithelium (FE) is a condition characterized by the loss of both hair cells (HCs) and supporting cells and the transformation of the organ of Corti into a simple flat or cuboidal epithelium, which can occur after severe cochlear insults. The transcription factors Gfi1, Atoh1, Pou4f3, and Six1 (GAPS) play key roles in HC differentiation and survival in normal ears. Previous work using a single transcription factor, Atoh1, to induce HC regeneration in mature ears in vivo usually produced very few cells and failed to produce HCs in severely damaged organs of Corti, especially those with FE. Studies in vitro …

Advancing Kidney Xenotransplantation With Anesthesia And Surgery – Bridging Preclinical And Clinical Frontiers Challenges And Prospects, Xiaojian Zhang, Hailian Wang, Qin Xie, Yang Zhang, Yixin Yang, Man Yuan, Yuqi Cui, Si-Yuan Song, Jianzhen Lv, Yi Wang

Children’s Nutrition Research Center Staff Publications

Xenotransplantation is emerging as a vital solution to the critical shortage of organs available for transplantation, significantly propelled by advancements in genetic engineering and the development of sophisticated immunosuppressive treatments. Specifically, the transplantation of kidneys from genetically engineered pigs into human patients has made significant progress, offering a potential clinical solution to the shortage of human kidney supply. Recent trials involving the transplantation of these modified porcine kidneys into deceased human bodies have underscored the practicality of this approach, advancing the field towards potential clinical applications. However, numerous challenges remain, especially in the domains of identifying suitable donor-recipient matches and …

Variant Of The Lactase Lct Gene Explains Association Between Milk Intake And Incident Type 2 Diabetes, Kai Luo, Guo-Chong Chen, Yanbo Zhang, Jee-Young Moon, Jiaqian Xing, Brandilyn A Peters, Mykhaylo Usyk, Zheng Wang, Gang Hu, Jun Li, Elizabeth Selvin, Casey M Rebholz, Tao Wang, Carmen R Isasi, Bing Yu, Rob Knight, Eric Boerwinkle, Robert D Burk, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Cow's milk is frequently included in the human diet, but the relationship between milk intake and type 2 diabetes (T2D) remains controversial. Here, using data from the Hispanic Community Health Study/Study of Latinos, we show that in both sexes, higher milk intake is associated with lower risk of T2D in lactase non-persistent (LNP) individuals (determined by a variant of the lactase LCT gene, single nucleotide polymorphism rs4988235 ) but not in lactase persistent individuals. We validate this finding in the UK Biobank. Further analyses reveal that among LNP individuals, higher milk intake is associated with alterations in gut microbiota (for …

Feathers Together (2022) By Caron Levis, Maughn Rollins Gregory

Picture Books

Feathers Together tells the story of a mated couple of white storks who live and migrate together between Croatia and South Africa, until the female is wounded and can no longer fly. An elderly man builds a rooftop nest for them with a walkway for the injured female and cares for her when the male migrates. On one level, this story is standard animal fable that conveys truths and moral values about the human condition. But the book’s afterword, explaining that this is a true story, raises philosophical questions about the emotional lives of wild animals, the ethics of hunting …

Field/Museum: Poems + Studies, Em Bober

Graduate Student Theses, Dissertations, & Professional Papers

Field/Museum: Poems + Studies is a collection interested in curation—collecting, containing, protecting, preserving, and displaying. Each set of poems becomes its own exhibition, employing experimental form and detail studies to preserve the work. Mortality, masculinity, ethics of the museum space, the concept of wildness, science, and family dynamics are scrutinized and studied throughout.

Readers learn that the author’s uncle worked at the Field Museum of Chicago throughout her childhood; so began her intimate relationship with the museum space—a deep fascination with the task of exhibiting. Later in the collection, readers are guided into the field—into a series of place poems …

Fgf5, Evelyn A Carrion, Malcolm M Moses, Richard R Behringer

Faculty, Staff and Student Publications

FGF5 functions as a negative regulator of the hair cycle in mammals. It is expressed in the outer root sheath of hair follicles during the late anagen phase of the hair cycle. It functions as a signaling molecule, mediating the transition of the anagen growth phase to catagen regression phase of the hair cycle. Spontaneous and engineered FGF5 mutations in mammalian animal models result in long hair phenotypes. In humans, inherited FGF5 mutations result in trichomegaly (long eyelashes). Knockdown of fgf5 in zebrafish embryos results in inner ear alterations. Alterations in FGF5 expression are also associated with various human pathologies.

Failure To Mate Enhances Investment In Behaviors That May Promote Mating Reward And Impairs The Ability To Cope With Stressors Via A Subpopulation Of Neuropeptide F Receptor Neurons, Julia Ryvkin, Liora Omesi, Yong-Kyu Kim, Mali Levi, Hadar Pozeilov, Lital Barak-Buchris, Bella Agranovich, Ifat Abramovich, Eyal Gottlieb, Avi Jacob, Dick R Nässel, Ulrike Heberlein, Galit Shohat-Ophir

Faculty, Staff and Student Publications

Living in dynamic environments such as the social domain, where interaction with others determines the reproductive success of individuals, requires the ability to recognize opportunities to obtain natural rewards and cope with challenges that are associated with achieving them. As such, actions that promote survival and reproduction are reinforced by the brain reward system, whereas coping with the challenges associated with obtaining these rewards is mediated by stress-response pathways, the activation of which can impair health and shorten lifespan. While much research has been devoted to understanding mechanisms underlying the way by which natural rewards are processed by the reward …

Editorial: Mathematical Modeling And Computational Predictions In Oncoimmunology, Vladimir A Kuznetsov, Heiko Enderling, Mark Chaplain

Faculty, Staff and Student Publications

No abstract provided.

Epigallocatechin Gallate Regulates The Myeloid-Specific Transcription Factor Pu1 In Macrophages, Manjula Karpurapu, Kavita Kumari Kakarala, Sangwoon Chung, Yunjuan Nie, Amritendu Koley, Patrick Dougherty, John W Christman

Faculty, Staff and Student Publications

Our previous research demonstrated that PU.1 regulates expression of the genes involved in inflammation in macrophages. Selective knockdown of PU.1 in macrophages ameliorated LPS-induced acute lung injury (ALI) in bone marrow chimera mice. Inhibitors that block the transcriptional activity of PU.1 in macrophages have the potential to mitigate the pathophysiology of LPS-induced ALI. However, complete inactivation of PU.1 gene disrupts normal myelopoiesis. Although the green tea polyphenol Epigallocatechin gallate (EGCG) has been shown to regulate inflammatory genes in various cell types, it is not known if EGCG alters the transcriptional activity of PU.1 protein. Using Schrodinger Glide docking, we have …

Editorial: Immunological Aspects Of Emerging And Re-Emerging Zoonoses, Wei Wang, Jingxin Li, Yuejin Liang, Wenping Gong

Faculty, Staff and Student Publications

No abstract provided.

Hormone Regulation Of Corticotropin-Releasing Factor Receptor 1 In The Female Mouse Brain, Rose M De Guzman, Jason S Jacobskind, Zachary J Rosinger, Krystyna A Rybka, Katherine E Parra, Aya L Caballero, Massoud S Sharif, Nicholas J Justice, Damian G Zuloaga

Faculty, Staff and Student Publications

Introduction: Corticotropin-releasing factor receptor 1 (CRFR1) is a key regulator of neuroendocrine and behavioral stress responses. Previous studies have demonstrated that CRFR1 in certain hypothalamic and preoptic brain areas is modified by chronic stress and during the postpartum period in female mice, although the potential hormonal contributors to these changes are unknown.

Methods: This study focused on determining the contributions of hormones associated with stress and the maternal period (glucocorticoids, prolactin, estradiol/progesterone) on CRFR1 levels using a CRFR1-GFP reporter mouse line and immunohistochemistry.

Results: Administration of dexamethasone, an agonist of the glucocorticoid receptor, elevated CRFR1 in the anteroventral periventricular nucleus …

Generation Of Non-Alloreactive Antiviral Central Memory Cd8 Human Veto T Cells For Cell Therapy, Esther Bachar-Lustig, Assaf Lask, Yaki Eidelstein, Noga Or-Geva, Rotem Gidron-Budovsky, Bar Nathansohn-Levy, Matthias Eyrich, Wei-Hsin Liu, Giang Dang, Karla Castro Miranda, Alejandro Ramirez, Indreshpal Kaur, Katayoun Rezvani, Elizabeth Shpall, Richard E Champlin, Arnon Nagler, Avichai Shimoni, Sivan Barnees-Kagan, Yair Reisner

Faculty, Staff and Student Publications

Previous studies in mice demonstrated that CD8 T cells exhibit marked veto activity enhancing engraftment in several models for T cell-depleted bone marrow (TDBM) allografting. To reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic CD8 veto T cells, these studies made use of naive CD8 T cells stimulated against third-party stimulators under cytokine deprivation and subsequent expansion in the presence of IL-15. More recently, it was shown that mouse CD8 veto T cells can be generated by stimulating CD8 memory T cells from ovalbumin immunized mice under cytokine deprivation, using ovalbumin as a third-party antigen. These cells also …

Emerging Therapeutic Options For Follicular-Derived Thyroid Cancer In The Era Of Immunotherapy, Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C Henderson, Maria Puche, Sayan Alekseev, Jocelynn G Colunga-Minutti, Mark E Zafereo, Stephen Y Lai, Sang T Kim, Maria E Cabanillas, Roza Nurieva

Faculty, Staff and Student Publications

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also …