Digital Commons Network^™

Biallelic Borcs8 Variants Cause An Infantile-Onset Neurodegenerative Disorder With Altered Lysosome Dynamics., Raffaella De Pace, Reza Maroofian, Adeline Paimboeuf, Mina Zamani, Maha S. Zaki, Saeid Sadeghian, Reza Azizimalamiri, Hamid Galehdari, Jawaher Zeighami, Chad D. Williamson, Emily Fleming, Dihong Zhou, Jennifer L. Gannon, Isabelle Thiffault, Emmanuel Roze, Mohnish Suri, Giovanni Zifarelli, Peter Bauer, Henry Houlden, Mariasavina Severino, Shunmoogum A. Patten, Emily G. Farrow, Juan S. Bonifacino

Manuscripts, Articles, Book Chapters and Other Papers

BLOC-one-related complex (BORC) is a multiprotein complex composed of eight subunits named BORCS1-8. BORC associates with the cytosolic face of lysosomes, where it sequentially recruits the small GTPase ARL8 and kinesin-1 and -3 microtubule motors to promote anterograde transport of lysosomes toward the peripheral cytoplasm in non-neuronal cells and the distal axon in neurons. The physiological and pathological importance of BORC in humans, however, remains to be determined. Here, we report the identification of compound heterozygous variants [missense c.85T>C (p.Ser29Pro) and frameshift c.71-75dupTGGCC (p.Asn26Trpfs*51)] and homozygous variants [missense c.196A>C (p.Thr66Pro) and c.124T>C (p.Ser42Pro)] in BORCS8 in five …

Modeling Acute Myocardial Infarction And Cardiac Fibrosis Using Human Induced Pluripotent Stem Cell-Derived Multi-Cellular Heart Organoids, Myeongjin Song, Da Bin Choi, Jeong Suk Im, Ye Na Song, Ji Hyun Kim, Hanbyeol Lee, Jieun An, Ami Kim, Hwan Choi, Joon-Chul Kim, Choongseong Han, Young Keul Jeon, Sung Joon Kim, Dong-Hun Woo

Faculty, Staff and Student Publications

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating …

Igwas: Image-Based Genome-Wide Association Of Self-Supervised Deep Phenotyping Of Retina Fundus Images, Ziqian Xie, Tao Zhang, Sangbae Kim, Jiaxiong Lu, Wanheng Zhang, Cheng-Hui Lin, Man-Ru Wu, Alexander Davis, Roomasa Channa, Luca Giancardo, Han Chen, Sui Wang, Rui Chen, Degui Zhi

Faculty, Staff and Student Publications

Existing imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on these phenotypes …

Acetaminophen Influences Musculoskeletal Signaling But Not Adaptations To Endurance Exercise Training, Brandon Roberts, Alyssa Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa Varanoske, Alyssa Kelley, Raymond Walker, Rigoberto Munoz, Alexander Kolb, Jeffery Staab, Marshall Naimo, Ryan Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% …

Colorectal Cancer Murine Models: Initiation To Metastasis, Ramesh Pothuraju, Imran Khan, Maneesh Jain, Michael Bouvet, Mokenge Malafa, Hemant K Roy, Sushil Kumar, Surinder K Batra

Faculty, Staff and Students Publications

Despite significant advancements in prevention and treatment, colorectal cancer (CRC) remains the third leading cause of cancer-related deaths. Animal models, including xenografts, syngeneic, and genetically engineered, have emerged as indispensable tools in cancer research. These models offer a valuable platform to address critical questions regarding molecular pathogenesis and test therapeutic interventions before moving on to clinical trials. Advancements in CRC animal models have also facilitated the advent of personalized and precision medicine. Patient-derived xenografts and genetically engineered mice that mirror features of human tumors allow for tailoring treatments to specific CRC subtypes, improving treatment outcomes and quality of life. To …

Icnirp Statement On Short Wavelength Light Exposure From Indoor Artificial Sources And Human Health, Sharon Miller, Christian Cajochen, Adele Green, John Hanifin, Anke Huss, Ken Karipidis, Sarah Loughran, Gunnhild Oftedal, John O'Hagan, David H Sliney, Rodney Croft, Eric Van Rongen, Nigel Cridland, Guglielmo D'Inzeo, Akimasa Hirata, Carmela Marino, Martin Röösli, Soichi Watanabe

Department of Neuroscience Faculty Papers

Concerns have been raised about the possibility of effects from exposure to short wavelength light (SWL), defined here as 380-550 nm, on human health. The spectral sensitivity of the human circadian timing system peaks at around 480 nm, much shorter than the peak sensitivity of daytime vision (i.e., 555 nm). Some experimental studies have demonstrated effects on the circadian timing system and on sleep from SWL exposure, especially when SWL exposure occurs in the evening or at night. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has identified a lack of consensus among public health officials regarding whether SWL from …

Metabolism, Fibrosis, And Apoptosis: The Effect Of Lipids And Their Derivatives On Keloid Formation, Chen-Yu Li, Ru-Xin Xie, Shi-Wei Zhang, Jiao Yun, Ai Zhong, Ying Cen, Jun-Jie Chen

Faculty, Staff and Student Publications

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA …

Circadian Immunity From Bench To Bedside: A Practical Guide, Huram Mok, Elaine Ostendorf, Alex Ganninger, Avi J. Adler, Guy Hazan, Jeffrey A. Haspel

2020-Current year OA Pubs

The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. The challenge is how to harness these biological rhythms to improve medical interventions. Here, we review recent literature documenting how circadian clocks organize fundamental innate and adaptive immune activities, the immunologic consequences of circadian rhythm and sleep disruption, and persisting knowledge gaps in the field. We then consider the evidence linking circadian rhythms to vaccination, …

A Road Map For The Treatment Of Pediatric Diffuse Midline Glioma, Carl Koschmann, Wajd N Al-Holou, Marta M Alonso, Jamie Anastas, Pratiti Bandopadhayay, Tara Barron, Oren Becher, Rodrigo Cartaxo, Maria G Castro, Chan Chung, Madison Clausen, Derek Dang, Robert Doherty, Ryan Duchatel, Matthew Dun, Mariella Filbin, Andrea Franson, Stefanie Galban, Marc Garcia Moure, Hugh Garton, Pruthvi Gowda, Joana Graca Marques, Cynthia Hawkins, Allison Heath, Esther Hulleman, Sunjong Ji, Chris Jones, Lindsay Kilburn, Cassie Kline, Michael A Koldobskiy, Daniel Lim, Pedro R Lowenstein, Q Richard Lu, Joanna Lum, Stephen Mack, Suresh Magge, Bernard Marini, Donna Martin, Neena Marupudi, Dana Messinger, Rajen Mody, Meredith Morgan, Mateus Mota, Karin Muraszko, Sabine Mueller, Siva Kumar Natarajan, Javad Nazarian, Michael Niculcea, Nicholas Nuechterlein, Hideho Okada, Valerie Opipari, Manjunath P Pai, Sharmistha Pal, Erik Peterson, Timothy Phoenix, John R Prensner, Matthew Pun, G Praveen Raju, Zachary J Reitman, Adam Resnick, David Rogawski, Amanda Saratsis, Stefanie G Sbergio, Mark Souweidane, James M Stafford, Theophilos Tzaridis, Sujatha Venkataraman, Orazio Vittorio, Jack Wadden, Daniel Wahl, Robert J Wechsler-Reya, Viveka Nand Yadav, Xu Zhang, Qiang Zhang, Sriram Venneti

Faculty, Staff and Students Publications

Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) collaboration among researchers, clinicians, and industry to integrate patient-derived data through sharing, transparency, and regulatory considerations; and (3) streamlining clinical efforts including biopsy, CNS-drug delivery, endpoint determination, and response monitoring. We highlight the importance of comprehensive collaboration to advance the understanding, diagnostics, and therapeutics for DMGs.

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 …

Postmortem-Derived Ipsc Models In Substance Use Disorders Research, Emily Frances Mendez, Consuelo Walss-Bass

Faculty, Staff and Student Publications

No abstract provided.

Meta-Analysis Of Postoperative Myocardial Injury As A Predictor Of Mortality After Living Donor Liver Transplantation, Krzysztof Jankowski, Frank W Peacock, Michal Pruc, Teresa Malecka-Massalska, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: The purpose of this study was to perform a systematic review and meta-analysis to investigate postoperative myocardial injury, as expressed by the postoperative concentration of high-sensitivity cardiac troponin I (hs-cTnI) as a predictor of mortality among living donor liver transplantation (LDLT) patients.

METHODS: PubMed, Scopus, Embase and the Cochrane Library were searched through to September 1st 2022. The primary endpoint included in-hospital mortality. Secondary endpoints were 1-year mortality and re-transplantation occurrence. Estimates are expressed as risk ratios (RRs) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with the I² test.

RESULTS: During the search, 2 studies were found …

The Maternal Gut Microbiome In Pregnancy: Implications For The Developing Immune System, Omry Koren, Liza Konnikova, Petter Brodin, Indira U Mysorekar, Maria Carmen Collado

Faculty, Staff and Students Publications

The gut microbiome has important roles in host metabolism and immunity, and microbial dysbiosis affects human physiology and health. Maternal immunity and microbial metabolites during pregnancy, microbial transfer during birth, and transfer of immune factors, microorganisms and metabolites via breastfeeding provide critical sources of early-life microbial and immune training, with important consequences for human health. Only a few studies have directly examined the interactions between the gut microbiome and the immune system during pregnancy, and the subsequent effect on offspring development. In this Review, we aim to describe how the maternal microbiome shapes overall pregnancy-associated maternal, fetal and early neonatal …

Green Synthesis Of Zinc Oxide Nanoparticles From Althaea Officinalis Flower Extract Coated With Chitosan For Potential Healing Effects On Diabetic Wounds By Inhibiting Tnf-Α And Il-6/Il-1Β Signaling Pathways, Sammar Fathy Elhabal, Nashwa Abdelaal, Saeed Abdul Kareem Saeed Al-Zuhairy, Mohamed Fathi Mohamed Elrefai, Ahmed Mohsen Elsaid Hamdan, Mohamed Mansour Khalifa, Sandra Hababeh, Mohammad Ahmad Khasawneh, Gehad M Khamis, Jakline Nelson, Passant M Mohie, Rania A Gad, Amira Rizk, Soad L Kabil, Mohamed Kandeel El-Ashery, Bhaskara R Jasti, Nahla A Elzohairy, Tayseer Elnawawy, Fatma E Hassan, Mohamed A El-Nabarawi

Faculty, Staff and Students Publications

BACKGROUND: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia.

METHOD AND RESULTS: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean …

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery Of Cyclosporine And Dithranol: In-Vitro, Ex-Vivo, And In-Vivo Studies, Sammar Fathy Elhabal, Nashwa Abdelaal, Saeed A S Al-Zuhairy, Mohamed Fathi Mohamed Elrefai, Mohamed Mansour Khalifa, Mohammad Ahmad Khasawneh, Ahmed Mohsen Elsaid Hamdan, Passant M Mohie, Rania A Gad, Soad L Kabil, Mohamed Kandeel El-Ashery, Bhaskara R Jasti, Nahla A Elzohairy, Nehal Elfar, Tayseer Elnawawy, Fatma E Hassan, Mohamed Ahmed El-Nabarawi

Faculty, Staff and Students Publications

PURPOSE: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Yosi Gilad, Ortal Shimon, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of transcription that play key roles in human physiology and pathology. SRCs are particularly important for the regulation of the immune system with major roles in lymphocyte fate determination and function, macrophage activity, regulation of nuclear factor κB (NF-κB) transcriptional activity and other immune system biology. The three members of the p160 SRC family comprise a network of immune-regulatory proteins that can function independently or act in synergy with each other, and compensate for - or moderate - the activity of other SRCs. Recent evidence indicates that the SRCs are key participants in …

Steroid Receptor Coactivators In Treg And Th17 Cell Biology And Function, Yosi Gilad, Ortal Shimon, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of transcription that play key roles in human physiology and pathology. SRCs are particularly important for the regulation of the immune system with major roles in lymphocyte fate determination and function, macrophage activity, regulation of nuclear factor κB (NF-κB) transcriptional activity and other immune system biology. The three members of the p160 SRC family comprise a network of immune-regulatory proteins that can function independently or act in synergy with each other, and compensate for - or moderate - the activity of other SRCs. Recent evidence indicates that the SRCs are key participants in …

Mir-142: A Master Regulator In Hematological Malignancies And Therapeutic Opportunities, Wilson Huang, Doru Paul, George A Calin, Recep Bayraktar

Faculty, Staff and Student Publications

MicroRNAs (miRNAs) are a type of non-coding RNA whose dysregulation is frequently associated with the onset and progression of human cancers. miR-142, an ultra-conserved miRNA with both active -3p and -5p mature strands and wide-ranging physiological targets, has been the subject of countless studies over the years. Due to its preferential expression in hematopoietic cells, miR-142 has been found to be associated with numerous types of lymphomas and leukemias. This review elucidates the multifaceted role of miR-142 in human physiology, its influence on hematopoiesis and hematopoietic cells, and its intriguing involvement in exosome-mediated miR-142 transport. Moreover, we offer a comprehensive …

A Patterned Human Primitive Heart Organoid Model Generated By Pluripotent Stem Cell Self-Organization, Brett Volmert, Chao Zhou, Et Al.

2020-Current year OA Pubs

Pluripotent stem cell-derived organoids can recapitulate significant features of organ development in vitro. We hypothesized that creating human heart organoids by mimicking aspects of in utero gestation (e.g., addition of metabolic and hormonal factors) would lead to higher physiological and anatomical relevance. We find that heart organoids produced using this self-organization-driven developmental induction strategy are remarkably similar transcriptionally and morphologically to age-matched human embryonic hearts. We also show that they recapitulate several aspects of cardiac development, including large atrial and ventricular chambers, proepicardial organ formation, and retinoic acid-mediated anterior-posterior patterning, mimicking the developmental processes found in the post-heart tube stage …

Benefits Of Sharing Neurophysiology Data From The Brain Initiative Research Opportunities In Humans Consortium, Vasiliki Rahimzadeh, Kathryn Maxson Jones, Mary A Majumder, Michael J Kahana, Ueli Rutishauser, Ziv M Williams, Sydney S Cash, Angelique C Paulk, Jie Zheng, Michael S Beauchamp, Jennifer L Collinger, Nader Pouratian, Amy L Mcguire, Sameer A Sheth

Center for Medical Ethics and Health Policy Staff Publications

Sharing human brain data can yield scientific benefits, but because of various disincentives, only a fraction of these data is currently shared. We profile three successful data-sharing experiences from the NIH BRAIN Initiative Research Opportunities in Humans (ROH) Consortium and demonstrate benefits to data producers and to users.

Dominant Negative Variants In Ikzf2 Cause Ichad Syndrome, A New Disorder Characterized By Immunodysregulation, Craniofacial Anomalies, Hearing Impairment, Athelia, And Developmental Delay, Arezoo Mohajeri, Maryam Vaseghi-Shanjani, Jill A Rosenfeld, Gui Xiang Yang, Henry Lu, Mehul Sharma, Susan Lin, Areesha Salman, Meriam Waqas, Mahshid Sababi Azamian, Kim C Worley, Kate L Del Bel, Frederick K Kozak, Ronak Rahmanian, Catherine M Biggs, Kyla J Hildebrand, Seema R Lalani, Sarah K Nicholas, Daryl A Scott, Sara Mostafavi, Clara Van Karnebeek, Erika Henkelman, Jessica Halparin, Connie L Yang, Linlea Armstrong, Undiagnosed Diseases Network, Anna Lehman Care 4 Rare Canada Consortium, Stuart E Turvey

Faculty, Staff and Students Publications

Background:

Helios (encoded by IKZF2), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognized for its role in the development and function of T lymphocytes, particularly the CD4⁺ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans.

Methods:

We performed detailed phenotypic, genomic, and functional investigations on …

Reduction Of Sparc Protects Mice Against Nlrp3 Inflammasome Activation And Obesity, Seungjin Ryu, Olga Spadaro, Sviatoslav Sidorov, Aileen H. Lee, Sonia Caprio, Christopher Morrison, Steven R. Smith, Eric Ravussin, Irina Shchukina, Maxim N. Artyomov, Yun-Hee Youm, Vishwa Deep Dixit

2020-Current year OA Pubs

The comprehensive assessment of long-term effects of reducing intake of energy (CALERIE-II; NCT00427193) clinical trial established that caloric restriction (CR) in humans lowers inflammation. The identity and mechanism of endogenous CR-mimetics that can be deployed to control obesity-associated inflammation and diseases are not well understood. Our studies have found that 2 years of 14% sustained CR in humans inhibits the expression of the matricellular protein, secreted protein acidic and rich in cysteine (SPARC), in adipose tissue. In mice, adipose tissue remodeling caused by weight loss through CR and low-protein diet feeding decreased, while high-fat diet-induced (HFD-induced) obesity increased SPARC expression …

Innately Expressed Estrogen-Related Receptors In The Skeletal Muscle Are Indispensable For Exercise Fitness, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …

Nuclear Receptors As Potential Therapeutic Targets In Peripheral Arterial Disease And Related Myopathy, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …

Seminar: Extracellular Vesicles As Mediators Of Environmental Stress In Human Disease, Vrinda Kalia, Andrea A Baccarelli, Christine Happel, Jonathan A Hollander, Anne Marie Jukic, Kimberly A Mcallister, Ramkumar Menon, Bruce A Merrick, Aleksander Milosavljevic, Lingamanaidu V Ravichandran, Matthew E Roth, Anita Subramanian, Frederick L Tyson, Leroy Worth, Daniel T Shaughnessy

Faculty, Staff and Students Publications

Background: Extracellular vesicles (EVs), membrane-bound particles containing a variety of RNA types, DNA, proteins, and other macromolecules, are now appreciated as an important means of communication between cells and tissues, both in normal cellular physiology and as a potential indicator of cellular stress, environmental exposures, and early disease pathogenesis. Extracellular signaling through EVs is a growing field of research for understanding fundamental mechanisms of health and disease and for the potential for biomarker discovery and therapy development. EVs are also known to play important roles in mediating the effects of exposure to environmental stress.

Objectives: This seminar addresses the application …

Epicutaneous Sensitization To The Phytocannabinoid Β-Caryophyllene Induces Pruritic Inflammation, Saadet Inan, Sara J Ward, Citlalli T Baltazar, Gabrielle A. Peruggia, Elham Javed, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

In recent years, there has been increased accessibility to cannabis for recreational and medicinal use. Incidentally, there has been an increase in reports describing allergic reactions to cannabis including exacerbation of underlying asthma. Recently, multiple protein allergens were discovered in cannabis, yet these fail to explain allergic sensitization in many patients, particularly urticaria and angioedema. Cannabis has a rich chemical profile including cannabinoids and terpenes that possess immunomodulatory potential. We examined whether major cannabinoids of cannabis such as cannabidiol (CBD) and the bicyclic sesquiterpene beta-caryophyllene (β-CP) act as contact sensitizers. The repeated topical application of mice skin with β-CP at …

Multiancestry Analysis Of The Hla Locus In Alzheimer’S And Parkinson’S Diseases Uncovers A Shared Adaptive Immune Response Mediated By Hla-Drb1*04 Subtypes, Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris Jansen, Eric Yu, Aude Nicolas, Itziar De Rojas, Thiago Peixoto Leal, Akinori Miyashita, Céline Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier-Boley, Tatsuhiko Naito, Fahri Küçükali, Seth D Talyansky, Selina Maria Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Alvarez, Beatrice Arosio, Michael E Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, María J Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stéphanie Debette, Jean-François Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Düzel, Daniela Galimberti, Guillermo Garcia-Ribas, José María García-Alberca, Pablo García-González, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grünblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jürgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Lin, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre De Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gael Nicolas, Shumpei Niida, Børge G Nordestgaard, Goran Papenberg, Janne Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A L Pijnenburg, Gerard Piñol-Ripoll, Julius Popp, Laura Molina Porcel, Raquel Puerta, Jordi Pérez-Tur, Innocenzo Rainero, Inez Ramakers, Luis M Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Owen A Ross, Luis Jose Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John Van Swieten, Raquel Sánchez-Valle, Eng-King Tan, Thomas Tegos, Charlotte Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans Verhey, Margda Waern, Jens Wiltfang, Jing Zhang, Eadb, Gr@Ace Study Group, Degesco Consortium, Demgene, Eadi, Gerad, Asian Parkinson’S Disease Genetics Consortium, Henrik Zetterberg, Kaj Blennow, Zihuai He, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Ole A Andreassen, Cornelia Van Duin, Magda Tsolaki, Pascual Sánchez-Juan, Ruth Frikke-Schmidt, Kristel Sleegers, Tatsushi Toda, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje Van Der Flier, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustín Ruiz, Ziv Gan-Or, Jean-Charles Lambert, Michael D Greicius, Emmanuel Mignot

Faculty, Staff and Students Publications

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. …

Integrating Social Determinants Of Health Into Ethical Digital Simulations, Kristin Kostick-Quenet, Vasiliki Rahimzadeh, Sharmila Anandasabapathy, Meghan Hurley, Anika Sonig, Amy Mcguire

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

High-Throughput Bioprinting Of The Nasal Epithelium Using Patient-Derived Nasal Epithelial Cells., I Deniz Derman, Miji Yeo, Diana Cadena, Megan Callender, Mian Horvath, Zengshuo Mo, Ruoyun Xiong, Elizabeth Fleming, Phylip Chen, Mark E Peeples, Karolina Palucka, Julia Oh, Ibrahim T Ozbolat

Faculty Research 2023

Progenitor human nasal epithelial cells (hNECs) are an essential cell source for the reconstruction of the respiratory pseudostratified columnar epithelium composed of multiple cell types in the context of infection studies and disease modeling. Hitherto, manual seeding has been the dominant method for creating nasal epithelial tissue models through biofabrication. However, this approach has limitations in terms of achieving the intricate three-dimensional (3D) structure of the natural nasal epithelium. 3D bioprinting has been utilized to reconstruct various epithelial tissue models, such as cutaneous, intestinal, alveolar, and bronchial epithelium, but there has been no attempt to use of 3D bioprinting technologies …

Human Microbiome Variation Associated With Race And Ethnicity Emerges As Early As 3 Months Of Age, Elizabeth K. Mallott, Alexandra R. Sitarik, Leslie D. Leve, Camille Cioffi, Carlos A. Camargo, Kohei Hasegawa, Seth R. Bordenstein

Public Health Sciences Articles

Human microbiome variation is linked to the incidence, prevalence, and mortality of many diseases and associates with race and ethnicity in the United States. However, the age at which microbiome variability emerges between these groups remains a central gap in knowledge. Here, we identify that gut microbiome variation associated with race and ethnicity arises after 3 months of age and persists through childhood. One-third of the bacterial taxa that vary across caregiver-identified racial categories in children are taxa reported to also vary between adults. Machine learning modeling of childhood microbiomes from 8 cohort studies (2,756 samples from 729 children) distinguishes …