Medicine and Health Sciences Commons^™

A Protocol To Purify Human Mediator Complex From Freestyle 293-F Cells, Hui-Chi Tang, Kuang-Lei Tsai, Ti-Chun Chao

Faculty, Staff and Student Publications

The Mediator, a multi-subunit protein complex in all eukaryotes, comprises the core mediator (cMED) and the CDK8 kinase module (CKM). As a molecular bridge between transcription factors (TFs) and RNA polymerase II (Pol II), the Mediator plays a critical role in regulating Pol II-dependent transcription. Considering its large size and complex composition, conducting in vitro studies on the Mediator complex is challenging, especially when isolating the intact and homogeneous complex from human cells. Here, we present a method to purify the intact CKM-cMED complex from FreeStyle 293-F cells (293-F cells), which offers advantages for performing large-scale protein purification. To isolate …

Membrane Lipids Augment Cell Envelope Stress Signaling Via The Madrs System To Defend Against Antimicrobial Peptides And Antibiotics In Enterococcus Faecalis, William R Miller, April Nguyen, Kavindra V Singh, Samie Rizvi, Ayesha Khan, Sam G Erickson, Stephanie L Egge, Melissa Cruz, An Q Dinh, Lorena Diaz, Philip C Thornton, Rutan Zhang, Libin Xu, Danielle A Garsin, Yousif Shamoo, Cesar A Arias

Faculty, Staff and Student Publications

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of …

Zika Virus Ns1 Drives Tunneling Nanotube Formation For Mitochondrial Transfer And Stealth Transmission In Trophoblasts, Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan

Faculty, Staff and Students Publications

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity in humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) in placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation is driven exclusively via ZIKV non-structural protein 1 (NS1). Specifically, the N-terminal 1-50 amino acids of membrane-bound ZIKV NS1 are necessary for triggering TNT formation in host cells. Trophoblasts infected with TNT-deficient ZIKV

Oral Inflammation And Microbiome Dysbiosis Exacerbate Chronic Graft-Versus-Host Disease, Yui Kambara, Hideaki Fujiwara, Akira Yamamoto, Kazuyoshi Gotoh, Shuma Tsuji, Mari Kunihiro, Tadashi Oyama, Toshiki Terao, Ayame Sato, Takehiro Tanaka, Daniel Peltier, Keisuke Seike, Hisakazu Nishimori, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Yoshihiko Soga, Pavan Reddy, Yoshinobu Maeda

Faculty, Staff and Students Publications

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated …

Does Adiponectin Inform Cardiovascular Risk In Older Adults?: The Aric Study, Layla A Abushamat, Xiaoming Jia, Lu Xu, Chao Cheng, Chiadi E Ndumele, Caroline Sun, B Gwen Windham, Kunihiro Matsushita, Bing Yu, Vijay Nambi, Biykem Bozkurt, Jane E B Reusch, Casey M Rebholz, Elizabeth Selvin, Christie M Ballantyne, Ron C Hoogeveen

Faculty, Staff and Student Publications

BACKGROUND: Adiponectin, an atheroprotective adipokine, is associated with adverse outcomes in older age. It is unclear whether this is due to overlapping pathophysiological pathways with N-terminal pro-B-type natriuretic peptide (NT-proBNP).

OBJECTIVES: The authors investigated adiponectin's associations with cardiovascular disease (CVD) risk in older adults.

METHODS: Among Atherosclerosis Risk in Communities prospective cohort study participants without baseline CVD at visit 5 (n = 4,729, mean age 75), adiponectin and adiponectin/NT-proBNP category associations with incident CVD events (heart failure [HF], atherosclerotic cardiovascular disease, and death during median follow-up of 5.5 years) and echocardiographic parameters were assessed. Metabolomic signatures of adiponectin/NT-proBNP categories were …

Ischemia And Anatomy In The New 2024 European Guidelines For Chronic Coronary Syndromes: Update And Comparison Of Recommendations, Christian Adrián Caroli

Journal of the Saudi Heart Association

The new 2024 European guideline on chronic coronary syndromes is a pivotal document for clinical practice, updating the evidence and indications after five years, incorporating insights from the paradigm-shifting ISCHEMIA trial. This article explores the evolving role of functional and anatomical testing in assessing coronary artery disease, highlighting the introduction of a new risk probability score based on clinical and risk factors. Additionally, it provides a detailed comparison between these European recommendations and those from the most influential American guidelines, emphasizing key differences in the approach to risk stratification and diagnostic strategies. This comprehensive analysis provides valuable insights for optimizing …

Intraocular Pressure Changes Associated With Psychological Stress Or Anxiety In Both Healthy And Glaucoma-Diagnosed Patients, Triston Crook, Porter Biggs, James Fini, Zane Kingsbury

Annual Research Symposium

No abstract provided.

Retrospective Analysis Of Angiotensin Receptor Blockers And Knee Cartilage Volume In Osteoarthritis: Evidence From The Osteoarthritis Initiative, Parv Kale, Vijay Kale

Annual Research Symposium

No abstract provided.

Takotsubo Cardiomyopathy: A Case Of The Broken Heart, Lilian Huynh, Kaylee Putney

Annual Research Symposium

Takotsubo cardiomyopathy (TC), or "broken heart syndrome," is a rare cardiac condition causing temporary left ventricular dysfunction due to severe stress. Though the exact cause is unclear, it mimics myocardial infarction and can lead to cardiogenic shock. Current treatment lacks specific guidelines and relies on heart failure protocols. We report a case of a patient with TC-induced cardiogenic shock, likely triggered by emotional stress. She required vasopressors, a percutaneous intervention, an Impella device, and guideline-directed medication therapies. This case underscores the significance of establishing guideline optimizations for managing TC and cardiogenic shock.

Evaluation Of Seven Commercially Available Dna Extraction Kits For Ocular Tissues, Jakob Newton, Conrad K. Ashby, Michael Trapnell, Triston Crook, Mark Eisele, Porter Biggs, Prina Patel, Christina Nelson, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

2025 Annual Roseman Research Symposium

Correlation Of Gnas Mutational Status With Oncologic Outcomes In Patients With Resected Intraductal Papillary Mucinous Neoplasms, Julia S. Evans, Kylee Shivok, Hui Hsuan Chen, Eliyahu Gorgov, Wilbur Bowne, Aditi Jain, Phd, Harish Lavu, Charles J. Yeo, Avinoam Nevler

SKMC Student Presentations and Publications

Background: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic lesions that may progress to invasive pancreatic ductal adenocarcinoma (PDAC). IPMN-associated invasive carcinoma (iIPMN) has been associated with more favorable survival outcomes compared to non-iIPMN-derived PDAC. Here, we aim to investigate the genetic landscape of IPMNs to assess their relevance to oncologic outcomes. Methods: This retrospective study used a large single-institution prospectively maintained database. Patients who underwent curative-intent pancreatic resection between 2016 and 2022 with histologically confirmed diagnosis of IPMN were included. Demographic, pathologic, molecular, and oncologic outcome data were recorded. Kaplan–Meier survival analyses were performed. PDAC data from public genetic …

Development Of A Conditional Plasmid For Gene Deletion In Non-Model Fusobacterium Nucleatum Strains, Peng Zhou, Bibek G C, Chenggang Wu

Faculty, Staff and Student Publications

Fusobacterium nucleatum is an opportunistic pathogen with four subspecies: nucleatum (FNN), vincentii (FNV), polymorphum (FNP), and animalis (FNA), each with distinct disease potentials. Research on fusobacterial pathogenesis has mainly focused on the model strain ATCC 23726 from FNN. However, this narrow focus may overlook significant behaviors of other FNN strains and those from other subspecies, given the genetic and phenotypic diversity within F. nucleatum. While ATCC 23726 is highly transformable, most other Fusobacterium strains exhibit low transformation efficiency, complicating traditional gene deletion methods that rely on non-replicating plasmids. To address this, we developed a conditional plasmid system in which …

Early Application Value Of Flexible Laryngoscope Swallowing Function Assessment In Patients After Partial Laryngectomy, Lina Jia, Chenxu Yan, Run Liu, Pengfei He, Ailing Liu, Fei Yang, Hui Huangfu, Sen Zhang

Faculty, Staff and Student Publications

To investigate the influence of early dysphagia on quality of life in patients with partial laryngectomy, and to investigate the application value of Flexible Endoscopic Evaluation of Swallowing (FEES). This study included 30 inpatients who underwent partial laryngectomy due to laryngeal cancer. In the early postoperative period, a comprehensive assessment was conducted on each patient, encompassing Videofluoroscopic Swallowing Study (VFSS), Flexible Endoscopic Evaluation of Swallowing (FEES), and MD Anderson Dysphagia Inventory (MDADI). Each patient underwent two evaluations at different time points following the surgical procedure, all conducted on the same day. The patients' first MDADI assement score after surgery was …

Benefits Of Equilibrium Between Microbiota- And Host-Derived Ligands Of The Aryl Hydrocarbon Receptor After Stroke In Aged Male Mice, Pedram Peesh, Maria P Blasco-Conesa, Ahmad El Hamamy, Romeesa Khan, Gary U Guzman, Parisa Honarpisheh, Eric C Mohan, Grant W Goodman, Justin N Nguyen, Anik Banerjee, Bryce E West, Kyung Ae Ko, Janelle M Korf, Chunfeng Tan, Huihui Fan, Gabriela D Colpo, Hilda Ahnstedt, Lucy Couture, Solji Roh, Julia K Kofler, Jose F Moruno-Manchon, Michael E Maniskas, Jaroslaw Aronowski, Rodney M Ritzel, Juneyoung Lee, Jun Li, Robert M Bryan, Anjali Chauhan, Venugopal Reddy Venna, Louise D Mccullough, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Recent studies have highlighted the crucial role of microglia (MG) and their interactions with the gut microbiome in post-stroke neuroinflammation. The activation of immunoregulatory pathways, including the aryl hydrocarbon receptor (AHR) pathway, is influenced by a dynamic balance of ligands derived from both the host and microbiota. This study aimed to investigate the association between stroke-induced dysbiosis and the resultant imbalance in AHR ligand sources (loss of microbiota-derived [indole-based] and increase of host-derived [kynurenine-based]) after stroke. Microbiota-derived AHR ligands decreased in human plasma and remained low for days following an ischemic stroke highlighting the translational significance. Transient-middle-cerebral-artery-occlusion was performed in …

Assessing The Contribution Of Rare Protein-Coding Germline Variants To Prostate Cancer Risk And Severity In 37,184 Cases, Jonathan Mitchell, Niedzica Camacho, Patrick Shea, Konrad H Stopsack, Vijai Joseph, Oliver S Burren, Ryan S Dhindsa, Abhishek Nag, Jacob E Berchuck, Amanda O'Neill, Ali Abbasi, Anthony W Zoghbi, Jesus Alegre-Díaz, Pablo Kuri-Morales, Jaime Berumen, Roberto Tapia-Conyer, Jonathan Emberson, Jason M Torres, Rory Collins, Quanli Wang, David Goldstein, Athena Matakidou, Carolina Haefliger, Lauren Anderson-Dring, Ruth March, Vaidehi Jobanputra, Brian Dougherty, Keren Carss, Slavé Petrovski, Philip W Kantoff, Kenneth Offit, Lorelei A Mucci, Mark Pomerantz, Margarete A Fabre

Faculty, Staff and Students Publications

To assess the contribution of rare coding germline genetic variants to prostate cancer risk and severity, we perform here a meta-analysis of 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline whole exome or genome sequencing data, and one cohort with imputed array data. At the gene level, our case-control collapsing analysis confirms associations between rare damaging variants in four genes and increased prostate cancer risk: SAMHD1, BRCA2 and ATM at the study-wide significance level (P <  1×10−8), and CHEK2 at the suggestive threshold (P <  2.6×10−6). Our case-only analysis, reveals that rare damaging variants in AOX1 are associated with more aggressive disease (OR = 2.60 [1.75–3.83], …

A Narrative Review Of Barriers To Utilization Of Surgical Risk Assessment Calculators, Jacob Lahti, Kaiya A. Noe, Abigail Veenstra, Sarah Gallitto, Victoria I. De Leon, Thomas C. Varkey, Nimit Agarwal

Annual Research Symposium

Over the last several decades, it has become the desire of surgical and medical teams to decrease risk levels involved for patients undergoing surgery. However, despite the advent of risk assessment calculators to help physicians obtain more accurate and objective judgements for postoperative complications, these tools are underutilized in standard clinical practices in comparison to other methods of risk assessment. This is likely due at least in part to certain barriers that decrease their functionality and ease of use. This review discusses the major barriers to the utilization of current risk calculators so as to allow for a better understanding …

The Effectiveness Of Cochlear Implants On Cognitive Function In Children And Adolescents With Hearing Loss: A Systematic Review, Harshita Sarambale, Joshua Ahdout, Srinija Balabhadra, Yesenia Valle Ramirez, John V. Rider Phd, Otr/L, M. De Armond Mfa, Mslis, S. Koshy-Chenthittayil Phd

Annual Research Symposium

This ongoing research project is a medical student led systematic review on cognitive function in pediatric cochlear implant patients.

Polmacoxib: A Drug Review, Sakeer Hussain, Dr. Subramanian Ramaswamy , Professor, Mahabaleshwar Mamadapur Assistant Professor, Ananthu Ajikumar

International Journal of Health and Allied Sciences

Polmacoxib, a novel nonsteroidal anti-inflammatory drug (NSAID), has shown a promised therapeutic option for the management of osteoarthritis and other inflammatory conditions. This drug review mainly aims to provide a comprehensive overview of polmacoxib, focusing on its pharmacological properties, clinical efficacy, safety profile, and potential therapeutic applications. Polmacoxib is a notable drug due to its dual mechanism of action, combining selective COX-2 inhibition with inhibition of carbonic anhydrase, which may contribute to its enhanced anti-inflammatory and analgesic effects. Being a selective COX-2 inhibitor, it helps minimize gastrointestinal side effects typically caused by conventional nonselective NSAIDs. Data from clinical studies suggest …

Safety And Efficacy Of Different Stent Strategies In Percutaneous Coronary Intervention: A Network Meta-Analysis, Waqas Ullah, Harigopal Sandhyavenu, Syeda Ramsha Zaidi, Mileydis Alonso, Muhammad Atif Khan, Irfan Ullah, Farah Yasmin, Aravind Reddy Polam, Salman Zahid, Arnav Kumar, Ewout Steyerberg, Mohammed Murtaza, Chadi Alraiesm, Jeffrey Rade

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

BACKGROUND: The utility of polymer-permanent, polymer-absorbable, and polymer-free drug-eluting stents (DES) in the context of different eluting drugs in patients undergoing percutaneous coronary intervention (PCI) remains controversial.

OBJECTIVES: The purpose of this study was to compare the efficacy of different DES strategies in post-PCI patients.

METHODS: Digital databases were searched to select all randomized control trials. Different combinations of DES were directly compared with permanent-polymer sirolimus-eluting stents. The primary outcome was major adverse cardiovascular events; a composite of cardiovascular mortality, myocardial infarction (MI), and target vessel revascularization. A network meta-analysis was performed to determine the net relative risk (RR) and …

Biguanides Antithetically Regulate Tumor Properties By The Dose-Dependent Mitochondrial Reprogramming-Driven C-Src Pathway, Jun Hyoung Park, Kwang Hwa Jung, Dongya Jia, Sukjin Yang, Kuldeep S Attri, Songyeon Ahn, Divya Murthy, Tagari Samanta, Debasmita Dutta, Meron Ghidey, Somik Chatterjee, Seung Yeop Han, Diego A Pedroza, Abha Tiwari, Joyce V Lee, Caitlin Davis, Shuting Li, Vasanta Putluri, Chad J Creighton, Nagireddy Putluri, Lacey E Dobrolecki, Michael T Lewis, Jeffrey M Rosen, José N Onuchic, Andrei Goga, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

The biguanide metformin attenuates mitochondrial oxidation and is proposed as an anti-cancer therapy. However, recent clinical studies suggest increased proliferation and fatty acid β-oxidation (FAO) in a subgroup of patients with breast cancer (BC) after metformin therapy. Considering that FAO can activate Src kinase in aggressive triple-negative BC (TNBC), we postulate that low-dose biguanide-driven AMPK-ACC-FAO signaling may activate the Src pathway in TNBC. The low bioavailability of metformin in TNBC xenografts mimics metformin's in vitro low-dose effect. Pharmacological or genetic inhibition of FAO significantly enhances the anti-tumor properties of biguanides. Lower doses of biguanides induce and higher doses suppress Src …

Development And Implementation Of A Personal Virtual Assistant For Patient Engagement And Communication In Postsurgical Cancer Care: Feasibility Cohort Study, Miguel Bargas-Ochoa, Alejandro Zulbaran-Rojas, M G Finco, Anthony B Costales, Areli Flores-Camargo, Rasha O Bara, Manuel Pacheco, Tina Phan, Aleena Khichi, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Cancer-care complexity heightens communication challenges between health care providers and patients, impacting their treatment adherence. This is especially evident upon hospital discharge in patients undergoing surgical procedures. Digital health tools offer potential solutions to address communication challenges seen in current discharge protocols. We aim to explore the usability and acceptability of an interactive health platform among discharged patients who underwent oncology-related procedures.

METHODS: A 4-week exploratory cohort study was conducted. Following hospital discharge, a tablet equipped with an integrated Personal Virtual Assistant (PVA) system was provided to patients who underwent oncology-related procedures. The PVA encompasses automated features that provide …

Trends In Ischemic Stroke Hospitalization And Outcomes In The United States Pre- And Peri-Covid-19 Pandemic: A National Inpatient Sample Study, Alibay Jafarli, Mario Di Napoli, Rachel S Kasper, Jeffrey L Saver, Louise D Mccullough, Setareh Salehi-Omran, Behnam Mansouri, Vasileios Arsenios Lioutas, Mohammed Ismail, Afshin A Divani

Faculty, Staff and Student Publications

Background/Objectives: The COVID-19 pandemic impacted healthcare systems globally, disrupting the management and treatment of acute ischemic stroke (AIS). Understanding how AIS admissions, treatments, and outcomes were affected is critical for improving stroke care in future crises. The objective of this work was to assess the COVID-19 pandemic's impact on AIS admissions, treatment patterns, complications, and patient outcomes in the U.S. from 2016 to 2021, focusing on differences between pre-pandemic (2016-2019) and peri-pandemic (2020-2021) periods.

Methods: This is a retrospective cohort study using the National Inpatient Sample (NIS) database, analyzing weighted discharge records of AIS patients over six years. Data encompass …

Cardiac Screening Findings And Referral Patterns In Male African-American Basketball Players: Analysis Of The Heartbytes Registry, Douglas Corsi, Avinash Saraiya, Maggie Doyle, Vacha Shah, Blaise O'Malley, Grace Qiu, Renee Lanstaff, Imran Masood, Brian Osler, Alexander G. Hajduczok, Drew Johnson, David Shipon

Student Papers, Posters & Projects

Sudden cardiac death (SCD) is the leading medical cause of death in young athletes. Male African American basketball players (MABP) demonstrate particularly elevated risk for SCD. Despite increasing screening and preventative efforts, the incidence of SCD remains elevated in this population. This retrospective analysis of the HeartBytes National Youth Cardiac Registry (2015-2023) aimed to characterize cardiac screening findings, including symptoms, family history, physical exam, and electrocardiogram (ECG) abnormalities in MABP compared to other youth athletes undergoing cardiac screening. We secondarily examined referral patterns based on screening results between the two groups. Of 8,303 individuals screened, 200 MABP were identified. MABP …

Iroc Phantoms Accurately Detect Mlc Delivery Errors, Sharbacha S Edward, Julianne M Pollard-Larkin, Peter A Balter, Rebecca M Howell, Christine B Peterson, Stephen F Kry

Faculty, Staff and Student Publications

Purpose: We evaluated the impact of random and whole-bank multileaf collimator (MLC) delivery errors on dosimetric delivery accuracy in the Imaging and Radiation Oncology Core (IROC) phantom audits, as well as differences in delivery accuracy between the IROC phantom prescription and typical clinical fraction sizes.

Methods and materials: Plans were created for the IROC IMRT head and neck (H&N) and SBRT spine phantoms. MLC leaf errors were introduced into the plans: random shifts between -2 and 2 mm, and whole bank shifts of 0.5, 1, and 2 mm. Plans were recalculated and delivered on a Varian Truebeam, and the log …

Nanrilkefusp Alfa (Sot101), An Il-15 Receptor Βγ Superagonist, As A Single Agent Or With Anti-Pd-1 In Patients With Advanced Cancers, Stephane Champiat, Elena Garralda, Vladimir Galvao, Philippe A Cassier, Carlos Gomez-Roca, Iphigenie Korakis, Peter Grell, Aung Naing, Patricia Lorusso, Romana Mikyskova, Nada Podzimkova, Milan Reinis, Kaissa Ouali, Andreu Schoenenberger, Joachim Kiemle-Kallee, Sascha Tillmanns, Richard Sachse, Ulrich Moebius, Radek Spisek, David Bechard, Lenka Palova Jelinkova, Irena Adkins, Aurelien Marabelle

Faculty, Staff and Student Publications

Nanrilkefusp alfa (nanril; SOT101) is an interleukin (IL)-15 receptor βγ superagonist that stimulates natural killer (NK) and CD8

Single-Cell Analysis Of Neoplastic Plasma Cells Identifies Myeloma Pathobiology Mediators And Potential Targets, Luz Yurany Moreno Rueda, Hua Wang, Keiko Akagi, Minghao Dang, Amishi Vora, Li Qin, Hans C Lee, Krina K Patel, Pei Lin, David E Mery, Fenghuang Zhan, John D Shaughnessy, Qing Yi, Yang Song, Bo Jiang, Maura L Gillison, Sheeba K Thomas, Donna M Weber, Lixia Diao, Jing Wang, Isere Kuiatse, Elisabet E Manasanch, David E Symer, Robert Z Orlowski

Faculty, Staff and Student Publications

Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138+ cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models. Moreover, functional studies show a …

An Integrative Multiparametric Approach Stratifies Putative Distinct Phenotypes Of Blast Phase Chronic Myelomonocytic Leukemia, Kristian Gurashi, Yu-Hung Wang, Fabio M R Amaral, Katherine Spence, Rachel Cant, Chi-Yuan Yao, Chien-Chin Lin, Christopher Wirth, David C Wedge, Guillermo Montalban-Bravo, Simona Colla, Hwei-Fang Tien, Tim C P Somervaille, Kiran Batta, Daniel H Wiseman

Faculty, Staff and Student Publications

Approximately 30% of patients with chronic myelomonocytic leukemia (CMML) undergo transformation to a chemo-refractory blastic phase (BP-CMML). Seeking novel therapeutic approaches, we profiled blast transcriptomes from 42 BP-CMMLs, observing extensive transcriptional heterogeneity and poor alignment to current acute myeloid leukemia (AML) classifications. BP-CMMLs display distinctive transcriptomic profiles, including enrichment for quiescence and variability in drug response signatures. Integrating clinical, immunophenotype, and transcriptome parameters, Random Forest unsupervised clustering distinguishes immature and mature subtypes characterized by differential expression of transcriptional modules, oncogenes, apoptotic regulators, and patterns of surface marker expression. Subtypes differ in predicted response to AML drugs, validated ex vivo in …

Podcasting Towards Togetherness: Utilizing Podcasts To Improve Departmental Camaraderie And Well-Being, Michael Petrauskis, Colleen Gutman, Rosemarie Fernandez

Journal of Wellness

Introduction: Physician burnout is on the rise, and this is of particular concern in emergency medicine. Burnout is associated with medical errors, adverse events, poor professionalism, and litigation. A sense of community can build engagement and mitigate workplace stressors on well-being. Emergency physicians may have trouble connecting due to the nature of shift-work and various practice settings. Communication technology, and particularly podcasting, has the potential to help overcome these barriers and positively impact relatedness and well-being.

Approach: We developed an inward-facing podcast, “The ER Break Room” within the Department of Emergency Medicine at the University of Florida. Through the …

Natural And Bioengineered Extracellular Vesicles In Diagnosis, Monitoring And Treatment Of Cancer, Xin Luo, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) are cell derived nanovesicles which are implicated in both physiological and pathological intercellular communication, including the initiation, progression, and metastasis of cancer. The exchange of biomolecules between stromal cells and cancer cells via EVs can provide a window to monitor cancer development in real time for better diagnostic and interventional strategies. In addition, the process of secretion and internalization of EVs by stromal and cancer cells in the tumor microenvironment (TME) can be exploited for delivering therapeutics. EVs have the potential to provide a targeted, biocompatible, and efficient delivery platform for the treatment of cancer and other …

Mitochondrial Defects And Metabolic Vulnerabilities In Lynch Syndrome-Associated Msh2-Deficient Endometrial Cancer, Mikayla Borthwick Bowen, Brenda Melendez, Qian Zhang, Diana Moreno, Leah Peralta, Wai Kin Chan, Collene Jeter, Lin Tan, M Anna Zal, Philip L Lorenzi, Kenneth Dunner, Richard K Yang, Russell R Broaddus, Joseph Celestino, Nisha Gokul, Elizabeth Whitley, Deena M Scoville, Tae Hoon Kim, Jae-Wook Jeong, Rosemarie Schmandt, Karen Lu, Hyun-Eui Kim, Melinda S Yates

Faculty, Staff and Student Publications

Lynch syndrome (LS), caused by inherited mutations in DNA mismatch repair genes, including MSH2, carries a 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, mechanisms driving LS-associated EC (LS-EC) remain unclear. We investigated MSH2 loss in EC pathogenesis using a mouse model (PR-Cre Msh2LoxP/LoxP, abbreviated Msh2KO), primary cell lines, human tissues, and human EC cells with isogenic MSH2 knockdown. By 8 months, 58% of Msh2KO mice developed endometrial atypical hyperplasia (AH), a precancerous lesion. At 12-16 months, 50% of Msh2KO mice exhibited either AH or ECs with histologic similarities to human LS-ECs. Transcriptomic profiling of EC from Msh2KO …