Medical Sciences Commons^™

Prmt Blockade Induces Defective Dna Replication Stress Response And Synergizes With Parp Inhibition, Yang Li, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Travis D Kerr, Deepa Bisht, Yalong Wang, Sharad Awasthi, Babita Kaundal, Siqi Wu, Weiyi Peng, Marc L Mendillo, Yiling Lu, Collene R Jeter, Guang Peng, Jinsong Liu, Shannon N Westin, Anil K Sood, Michael T Lewis, Jishnu Das, S Stephen Yi, Mark T Bedford, Daniel J Mcgrail, Nidhi Sahni

Faculty, Staff and Student Publications

Multiple cancers exhibit aberrant protein arginine methylation by both type I arginine methyltransferases, predominately protein arginine methyltransferase 1 (PRMT1) and to a lesser extent PRMT4, and by type II PRMTs, predominately PRMT5. Here, we perform targeted proteomics following inhibition of PRMT1, PRMT4, and PRMT5 across 12 cancer cell lines. We find that inhibition of type I and II PRMTs suppresses phosphorylated and total ATR in cancer cells. Loss of ATR from PRMT inhibition results in defective DNA replication stress response activation, including from PARP inhibitors. Inhibition of type I and II PRMTs is synergistic with PARP inhibition regardless of homologous …

Drivers Of Chronic Pathology Following Ischemic Stroke: A Descriptive Review, Grant W Goodman, Trang H Do, Chunfeng Tan, Rodney M Ritzel

Faculty, Staff and Student Publications

Stroke is the third leading cause of death and long-term disability in the world. Considered largely a disease of aging, its global economic and healthcare burden is expected to rise as more people survive into advanced age. With recent advances in acute stroke management, including the expansion of time windows for treatment with intravenous thrombolysis and mechanical thrombectomy, we are likely to see an increase in survival rates. It is therefore critically important to understand the complete pathophysiology of ischemic stroke, both in the acute and subacute stages and during the chronic phase in the months and years following an …

Blue-Shift Photoconversion Of Near-Infrared Fluorescent Proteins For Labeling And Tracking In Living Cells And Organisms, Francesca Pennacchietti, Jonatan Alvelid, Rodrigo A Morales, Martina Damenti, Dirk Ollech, Olena S Oliinyk, Daria M Shcherbakova, Eduardo J Villablanca, Vladislav V Verkhusha, Ilaria Testa

Faculty, Staff and Student Publications

Photolabeling of intracellular molecules is an invaluable approach to studying various dynamic processes in living cells with high spatiotemporal precision. Among fluorescent proteins, photoconvertible mechanisms and their products are in the visible spectrum (400-650 nm), limiting their in vivo and multiplexed applications. Here we report the phenomenon of near-infrared to far-red photoconversion in the miRFP family of near infrared fluorescent proteins engineered from bacterial phytochromes. This photoconversion is induced by near-infrared light through a non-linear process, further allowing optical sectioning. Photoconverted miRFP species emit fluorescence at 650 nm enabling photolabeling entirely performed in the near-infrared range. We use miRFPs as …

Interlaboratory Comparison Of Pseudomonas Aeruginosa Phage Susceptibility Testing, Krupa Parmar, Lauren Komarow, Damon W Ellison, Andrey A Filippov, Mikeljon P Nikolich, Joseph R Fackler, Martin Lee, Anjna Nair, Priyesh Agrawal, Pranita D Tamma, Maria Souli, Scott R Evans, Kerryl E Greenwood-Quaintance, Scott A Cunningham, Robin Patel, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

Standardized approaches to phage susceptibility testing (PST) are essential to inform selection of phages for study in patients with bacterial infections. There is no reference standard for assessing bacterial susceptibility to phage. We compared agreement between PST performed at three centers: two centers using a liquid assay standardized between the sites with the third, a plaque assay. Four Pseudomonas aeruginosa phages: PaWRA01ø11 (EPa11), PaWRA01ø39 (EPa39), PaWRA02ø83 (EPa83), PaWRA02ø87 (EPa87), and a cocktail of all four phages were tested against 145 P. aeruginosa isolates. Comparisons were made within measurements at the two sites performing the liquid assay and between these …

Review Of: Pull Through Blessings: The Colorful Tapestry Of Hirschsprung’S Disease—Lisa Sensenig And Helen Zimmerman, Adin Stauffer

Journal of Amish and Plain Anabaptist Studies

Hirschsprung’s Disease (HD) is a genetic condition found in a child born without ganglion cells in part of the intestines. Ganglion cells send signals to intestinal muscles to contract to help pass bowel movements. No signal means no bowel movement, which results in babies not eating, becoming uncomfortable and sleepy, spitting up, and if not treated, eventually dying. [First paragraph.]

Vitamin D Status Of Anabaptist Children In Southwestern Ontario, Canada, Janis A. Randall Simpson, Natalee Miller, Taylor Hartwig, Jane Leach, Melissa Purdy, Emily Roth, Victoria Mok Siue, Cynthia Soulliere, Jacqui Tam, Ann Watt

Journal of Amish and Plain Anabaptist Studies

The objective was to determine vitamin D status of Old Order Anabaptist children in rural Southwestern, Ontario, Canada, given concerns of community healthcare professionals. Fifty-two children (2.5 months - 6.5 years) (56% female) were recruited. Finger prick blood spot (BSp) samples were analyzed for 25-hydroxy (OH) vitamins D2 & D3 (BSp25(OH)D). Three-day food records were evaluated using Dietary Reference Intakes and Canada’s Food Guide (CFG) (Bush, et al. 2007). Compared to national Canadian data: mean BSp25(OH)D concentrations (78±31 nmol/L) were similar; a slightly smaller proportion (0% vs 2%) were at risk of deficiency (<30 nmol/L) or had inadequate status (4% vs 7%) (<40 nmol/L); and 10% vs 1% had BSp25(OH)D higher than 125 nmol/L. BSp25(OH)D was significantly associated (r2=0.358; p=0.001) with total vitamin D intake. From food alone, vitamin D intake was 68±39 IU/day, lower than the Recommended Dietary Allowance (RDA) of 600 IU/day, and intakes were all below the Estimated Average Requirement (EAR) of 400 IU. Even including supplemental vitamin D, 87% were below the EAR (total intake=213±194 IU/day). No children had vitamin D intakes greater than the Upper Limit. Servings of milk and alternates were 1.6±0.8/day (CFG=2/day). Unfortified farm milk was consumed by 88% of children and 89% received a vitamin D supplement. Results were comparable to recent Canadian data suggesting that most children have adequate vitamin D status. Nevertheless, these findings support the need to encourage appropriate vitamin D intake (from food and supplements) to achieve the RDA for Old Order Anabaptist children in these communities. [Abstract by authors.]

Intouch Week Of December 18, 2023, New York Medical College

InTouch

• Future Healers: 2023 Forum Highlights Medical Student Research
• Dr. Mitchell Cairo Awarded $2.6 Million Grant from Department of Defense for Pediatric Cancer Research
• Long COVID Patients at Greater Risk for Anxiety and PTSD New Study Finds
• NYMC Unveils the Portrait and Diploma of Alumnus Meyer J. Simon, M.D. ’25
• NYMC AMWA Chapter Hosts Medical Mavens Workshop
• Student Spotlight: Mentorship Propels Medical Student on Successful Research Path

Editorial; Biophysics Approaches To Investigate Multi-Organ Alcohol-Induced Damage, Janos Paloczi, Youngchan Kim

School of Graduate Studies Faculty Publications

No abstract provided.

The Role Of Point-Of-Care Ultrasound In The Assessment Of Pelvic Urine Leakage And Diagnosis Of Urinoma, Asra Moradkhani, Mona Zangi, Mobin Azami, Mohammad Ghasemi-Rad, Abdolghader Pakniyat

Faculty, Staff and Students Publications

BACKGROUND: Urinoma, a rare condition resulting from urine leakage due to trauma to the kidney, bladder, or urethra, is typically diagnosed using enhanced computed tomography urogram with delayed imaging. This report presents two cases of urinoma likely caused by overdistention of the renal pelvis following excessive fluid intake and the presence of a ureteral stone.

CASE PRESENTATION: We present two cases of 36-year-old and 38-year-old patients who presented with flank pain. point-of-care ultrasound (POCUS) played a pivotal role in identifying perinephric fluid in Morrison's space and the splenorenal space, respectively. These ultrasound findings guided further investigations, leading to definitive diagnoses …

Genetic And Epigenetic Features Of Bilateral Wilms Tumor Predisposition In Patients From The Children’S Oncology Group Aren18b5-Q, Andrew J Murphy, Changde Cheng, Justin Williams, Timothy I Shaw, Emilia M Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay A Renfro, Brett Tornwall, Vicki Huff, Andrew L Hong, Elizabeth A Mullen, Brian Crompton, Jeffrey S Dome, Conrad V Fernandez, James I Geller, Peter F Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M Jablonowski, Andrew M Fleming, Prahalathan Pichavaram, Christopher L Morton, John Easton, Kim E Nichols, Michael R Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P Zambetti, Zhaoming Wang, Andrew M Davidoff, Xiang Chen

Faculty, Staff and Student Publications

Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of …

Pathway Centric Analysis For Single-Cell Rna-Seq And Spatial Transcriptomics Data With Gsdensity, Qingnan Liang, Yuefan Huang, Shan He, Ken Chen

Faculty, Staff and Student Publications

Advances in single-cell technology have enabled molecular dissection of heterogeneous biospecimens at unprecedented scales and resolutions. Cluster-centric approaches are widely applied in analyzing single-cell data, however they have limited power in dissecting and interpreting highly heterogenous, dynamically evolving data. Here, we present GSDensity, a graph-modeling approach that allows users to obtain pathway-centric interpretation and dissection of single-cell and spatial transcriptomics (ST) data without performing clustering. Using pathway gene sets, we show that GSDensity can accurately detect biologically distinct cells and reveal novel cell-pathway associations ignored by existing methods. Moreover, GSDensity, combined with trajectory analysis can identify curated pathways that are …

Tuftelin1 Drives Experimental Pulmonary Fibrosis Progression By Facilitating Stress Fiber Assembly, Caoyuan Niu, Kai Xu, Yanan Hu, Yanling Jia, Yuexia Yang, Xiaoyue Pan, Ruyan Wan, Hui Lian, Qiwen Wang, Juntang Yang, Yajun Li, Ivan Rosas, Lan Wang, Guoying Yu

Children’s Nutrition Research Center Staff Publications

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) with unknown etiology, characterized by sustained damage repair of epithelial cells and abnormal activation of fibroblasts, the underlying mechanism of the disease remains elusive.

Methods: To evaluate the role of Tuftelin1 (TUFT1) in IPF and elucidate its molecular mechanism. We investigated the level of TUFT1 in the IPF and bleomycin-induced mouse models and explored the influence of TUFT1 deficiency on pulmonary fibrosis. Additionally, we explored the effect of TUFT1 on the cytoskeleton and illustrated the relationship between stress fiber and pulmonary fibrosis.

Results: Our results demonstrated a significant …

Shorter Duration Of Dual Antiplatelet Therapy Following Second Generation Drug Eluting Stent Placement, Alexandra Coy, Caitlyn M. Murtha

Physician Assistant Capstones, 2020-current

Heart disease is the leading cause of death in both men and women in The United States. Because advanced heart disease is often treated with percutaneous coronary intervention (PCI) for stent implantation, many patients will be put on dual antiplatelet therapy to prevent adverse effects such as stent thrombosis or restenosis. The purpose of this literature review is to determine if the development of second-generation drug eluting stents allows for a shorter, 6-month, duration of dual antiplatelet therapy (DAPT) versus the currently recommended 12 months. The articles discussed in this review were obtained on PubMed and narrowed using search terms …

Efficacy Of Dry Cupping Therapy As Treatment For Non-Specific Lower Back Pain, Lucas Albrecht, Kelly Ettari

Physician Assistant Capstones, 2020-current

Lower back pain (LBP) is one of the most common conditions affecting adults globally. Non-specific lower back pain (NSLBP) is a diagnosis based on the exclusion of other pathoanatomical causes, and accounts for over 80% of cases of LBP. 1 Current treatments typically involve a multidisciplinary approach. Dry cupping therapy is a noninvasive treatment option that is used to treat musculoskeletal pain. 2 Three studies were analyzed which assess the utility of dry cupping therapy as a treatment modality for non-acute NSLBP; two of the studies were randomized control trials, and the third was a small pilot study. All three …

Assessing Risk For Complications In Acute Hematogenous Osteomyelitis In Children: Validation Of 2 Predictive Scores, Adriana Sarmiento Clemente, J Chase Mcneil, Kristina G Hultén, Jesus G Vallejo, Michael E Scheurer, Sheldon L Kaplan

Faculty, Staff and Students Publications

Background: Acute hematogenous osteomyelitis (AHO) can be associated with severe complications which can be difficult to predict in the clinical setting. The previously published predictive acute complication score ("A-SCORE") and chronic complication score ("C-SCORE") show promise, however, further external validation is needed.

Methods: We performed a retrospective study of 418 children with AHO and analyzed the performance of A-SCORE (variables included bone abscess, fever after 48 h of starting antibiotics, suppurative arthritis, disseminated disease, and delayed source control) to predict risk for acute complicated course (treatment failure, prolonged admission, and/or need for ≥2 bone debridements) and C-SCORE (includes disseminated disease, …

Adult Presentation Of Congenital Tracheooesophageal Fistula Treated As Asthma And Recurrent Respiratory Infections, Natalie A Drucker, Charles S Cox

The Brown Foundation: Institute of Molecular Medicine

No abstract provided.

Lipoprotein(A): Review Of Existing Guidelines And Application For Practicing Clinicians, Daniella Manarang, Kristy Asbell, Michelle Rhea

Doctor of Medical Science (DMSc)

Purpose A growing amount of research has constituted lipoprotein(a) as an independent risk factor for cardiovascular disease. The main objective of this review is to summarize the current guidelines for testing and managing Lp(a) and provide guidance to clinicians on how to practically utilize Lp(a) with what is known today. Methods: EBSCO, PubMed, and Ovid were searched for this review. Search terms included lipoprotein(a), clinical practice, guidelines, screening, and cardiovascular disease. Sources within ten years were obtained to cover recent material. Results: The current literature on the association between Lp(a) and CVD outcomes and up-to-date guidelines on testing and management …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Citrullinated And Malondialdehyde-Acetaldehyde Modified Proteins Promote Cellular Inflammatory And Fibrotic Responses Associated With Rheumatoid Arthritis, Nozima Aripova

Theses & Dissertations

Rheumatoid arthritis (RA) is a systemic, autoimmune disease primarily characterized by perpetual synovial inflammation that results in synovial tissue proliferation and fibrosis (pannus). Although joint involvement is the predominant manifestation of RA, extra-articular features, such as interstitial lung disease (ILD), contribute significantly to the elevated mortality associated with the condition. Post-translational modifications play a significant role in RA and RA-ILD pathogenesis. Circulating anti-citrullinated protein antibodies (ACPAs) are a highly diagnostic tool implicating a potential role for citrullinated antigens in RA and RA-ILD.

Recently, antibodies to malondialdehyde acetaldehyde adducts (MAA) have been markedly elevated in patients with RA and RA-ILD. MAA …

Myod-Skp2 Axis Boosts Tumorigenesis In Fusion Negative Rhabdomyosarcoma By Preventing Differentiation Through P57kip2 Targeting, Silvia Pomella, Matteo Cassandri, Lucrezia D’Archivio, Antonella Porrazzo, Cristina Cossetti, Doris Phelps, Clara Perrone, Michele Pezzella, Antonella Cardinale, Marco Wachtel, Sara Aloisi, David Milewski, Marta Colletti, Prethish Sreenivas, Zoë S. Walters, Giovanni Barillari, Angela Di Giannatale, Giuseppe Maria Milano, Cristiano De Stefanis, Rita Alaggio, Sonia Rodriguez-Rodriguez, Nadia Carlesso, Christopher R. Vakoc, Enrico Velardi, Beat W. Schafer, Ernesto Guccione, Susanne A. Gatz, Lucio Miele

School of Medicine Faculty Publications

Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer. SKP2 in FN-RMS promotes cell cycle progression and prevents differentiation by directly targeting p27Kip1 and p57Kip2, respectively. SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program and strongly affects stemness and tumorigenic …

Variations Of The Trapezius Branch Of The Accessory Nerve: An Anatomic Study, Matthew E Lin, Celeste Kim, Adam Howard, Niels Kokot

Faculty, Staff and Student Publications

Although modified radical neck dissections have increased in popularity to reduce morbidity secondary to intraoperative accessory nerve damage, inadvertent injury still often occurs. As this phenomenon is thought to be due to anatomic variation in the trapezius branch of the accessory nerve, it is imperative to better understand the nuances of these anatomic variations to better inform surgical decision-making. A total of 24 accessory nerves were dissected, exposed, and traced in 15 cadavers. Three aspects of the accessory nerve were identified and recorded: the course of the trapezius branch in relation to the sternocleidomastoid, the number of trapezius branches at …

Lilrb3 Modulates Acute Myeloid Leukemia Progression And Acts As An Effective Target For Car T-Cell Therapy, Sunny Mai, Alan Hodges, Hui-Ming Chen, Jilu Zhang, Yi-Ling Wang, Yongbin Liu, Fumiko Nakatsu, Xiaoxuan Wang, Jing Fang, Yitian Xu, Vitaliy Davidov, Kyeongah Kang, Sai Ravi Pingali, Siddhartha Ganguly, Masataka Suzuki, Marina Konopleva, Brooke Prinzing, Youli Zu, Stephen Gottschalk, Yong Lu, Shu-Hsia Chen, Ping-Ying Pan

Faculty, Staff and Students Publications

Identifying novel cell surface receptors that regulate leukemia cell differentiation and can be targeted to inhibit cellular proliferation is crucial to improve current treatment modalities in acute myeloid leukemia (AML), especially for relapsed or chemotherapy-refractory leukemia. Leukocyte immunoglobulin-like receptor type B (LILRB) is an immunomodulatory receptor originally found to be expressed in myeloid cells. In this study, we found that LILRB receptors can be induced under inflammatory stimuli and chemotherapy treatment conditions. Blockade of LILRB3 inhibited leukemia cell proliferation and leukemia progression. Additionally, treatment with LILRB3 blocking antibodies upregulated myeloid lineage differentiation transcription factors, including PU.1, C/EBP family, and IRF, …

Gatekeeping At Bio, Daniel A Gorelick

Faculty, Staff and Students Publications

No abstract provided.

A Case Of Filgrastim-Induced Neutrophilic Dermatosis Of The Dorsal Hands In A Patient With Felty Syndrome, Tejas P Joshi, Yelena Dokic, Gordana Verstovsek, Theodore Rosen

Faculty, Staff and Students Publications

Neutrophilic dermatosis of the dorsal hands (NDDH) is a variant of Sweet syndrome that presents with erythematous bullae, papules/plaques, or pustules on the dorsal hands. It is most commonly associated with hematologic and solid organ malignancies, though cases of NDDH associated with inflammatory bowel disease, rheumatologic disorders, and medication exposure have also been described in the literature. Felty syndrome is a rare complication of long-standing rheumatoid arthritis characterized by neuropathy, splenomegaly, and neutropenia. Granulocyte colony stimulating factors (e.g., filgrastim) can be utilized to rescue the neutropenia observed in Felty syndrome, but this treatment may subsequently cause Sweet syndrome. Herein, we …

Early Cellular And Molecular Signatures Correlate With Severity Of West Nile Virus Infection, Ho-Joon Lee, Yujiao Zhao, Ira Fleming, Sameet Mehta, Xiaomei Wang, Brent Vander Wyk, Shannon E Ronca, Heather Kang, Chih-Hung Chou, Benoit Fatou, Kinga K Smolen, Ofer Levy, Clary B Clish, Ramnik J Xavier, Hanno Steen, David A Hafler, J Christopher Love, Alex K Shalek, Leying Guan, Kristy O Murray, Steven H Kleinstein, Ruth R Montgomery

Faculty, Staff and Students Publications

Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis. At the acute time point, we detected both elevation of pro-inflammatory markers in innate immune cell types and reduction of regulatory T cell …

Enniatin A Inhibits The Chaperone Hsp90 And Unleashes The Immune System Against Triple-Negative Breast Cancer, Nada H Eisa, Vincent M Crowley, Asif Elahi, Vamsi Krishna Kommalapati, Michael A Serwetnyk, Taoufik Llbiyi, Sumin Lu, Kashish Kainth, Yasmeen Jilani, Daniela Marasco, Abdeljabar El Andaloussi, Sukyeong Lee, Francis T F Tsai, Paulo C Rodriguez, David Munn, Esteban Celis, Hasan Korkaya, Abdessamad Debbab, Brian Blagg, Ahmed Chadli

Faculty, Staff and Students Publications

Low response rates and immune-related adverse events limit the remarkable impact of cancer immunotherapy. To improve clinical outcomes, preclinical studies have shown that combining immunotherapies with N-terminal Hsp90 inhibitors resulted in improved efficacy, even though induction of an extensive heat shock response (HSR) and less than optimal dosing of these inhibitors limited their clinical efficacy as monotherapies. We discovered that the natural product Enniatin A (EnnA) targets Hsp90 and destabilizes its client oncoproteins without inducing an HSR. EnnA triggers immunogenic cell death in triple-negative breast cancer (TNBC) syngeneic mouse models and exhibits superior antitumor activity compared to Hsp90 N-terminal inhibitors. …

Aspirin And Nonaspirin Nonsteroidal Antiinflammatory Drug Use And Occurrence Of Colorectal Adenoma In Black American Women, Lauren E Barber, Kimberly A Bertrand, Shanshan Sheehy, Laura F White, Hemant K Roy, Lynn Rosenberg, Julie R Palmer, Jessica L Petrick

Faculty, Staff and Students Publications

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals …

Targeting Eif4a Triggers An Interferon Response To Synergize With Chemotherapy And Suppress Triple-Negative Breast Cancer, Na Zhao, Elena B Kabotyanski, Alexander B Saltzman, Anna Malovannaya, Xueying Yuan, Lucas C Reineke, Nadia Lieu, Yang Gao, Diego A Pedroza, Sebastian J Calderon, Alex J Smith, Clark Hamor, Kazem Safari, Sara Savage, Bing Zhang, Jianling Zhou, Luisa M Solis, Susan G Hilsenbeck, Cheng Fan, Charles M Perou, Jeffrey M Rosen

Faculty, Staff and Students Publications

Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A with zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages toward an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade. Mechanistic studies revealed that zotatifin reprograms the tumor translational landscape, inhibits the translation of Sox4 …

Plants As Vectors For Environmental Prion Transmission, Christina M Carlson, Samuel Thomas, Matthew W Keating, Paulina Soto, Nicole M Gibbs, Haeyoon Chang, Jamie K Wiepz, Annabel G Austin, Jay R Schneider, Rodrigo Morales, Christopher J Johnson, Joel A Pedersen

Faculty, Staff and Student Publications

Prions cause fatal neurodegenerative diseases and exhibit remarkable durability, which engenders a wide array of potential exposure scenarios. In chronic wasting disease of deer, elk, moose, and reindeer and in scrapie of sheep and goats, prions are transmitted via environmental routes and the ability of plants to accumulate and subsequently transmit prions has been hypothesized, but not previously demonstrated. Here, we establish the ability of several crop and other plant species to take up prions via their roots and translocate them to above-ground tissues from various growth media including soils. We demonstrate that plants can accumulate prions in above-ground tissues …

Gpr84-Mediated Signal Transduction Affects Metabolic Function By Promoting Brown Adipocyte Activity, Xue-Nan Sun, Yu A An, Vivian A Paschoal, Camila O De Souza, May-Yun Wang, Lavanya Vishvanath, Lorena Ma Bueno, Ayanna S Cobb, Joseph A Nieto Carrion, Madison E Ibe, Chao Li, Harrison A Kidd, Shiuhwei Chen, Wenhong Li, Rana K Gupta, Da Young Oh

Faculty, Staff and Student Publications

The G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study has shed light on the pivotal role of GPR84, revealing its robust expression and functional significance within brown adipose tissue (BAT). Mice lacking GPR84 exhibited increased lipid accumulation in BAT, rendering them more susceptible to cold exposure and displaying reduced BAT activity compared with their WT counterparts. Our in vitro experiments with primary brown adipocytes from GPR84-KO mice revealed diminished expression of thermogenic genes …