Medicine and Health Sciences Commons^™

Glutamatergic Regulation Of Mirna-Containing Intraluminal Vesicle Trafficking And Extracellular Vesicle Secretion From Cortical Neurons, Rashed Alananzeh, Jiaqian Wu, Yongjie Yang

Faculty, Staff and Student Publications

Neuronal extracellular vesicles (microvesicles and exosomes) are emerging secreted vesicular signals that play important roles in the CNS. Currently, little is known about how glutamatergic signalling affects the subcellular localisation of exosome precursor intraluminal vesicles (ILVs), microRNA (miR) packaging into ILVs and in vivo spreading of neuronal EVs. By selectively labelling ILVs and exosomes (but not plasma membrane-derived MVs) with GFP-tagged human CD63 (hCD63-GFP) in cortical neurons, we found that glutamate stimulation significantly redistributes subcellular localisation of hCD63-GFP+ ILVs, especially decreasing its co-localisation with multi-vesicular body (MVB) marker Rab7 while substantially promoting EV secretion. Interestingly, glutamate stimulation only modestly alters …

Audiologic Management Of Individuals With Advanced Cochlear Otosclerosis: A Systematic Review, Sophie Silvermintz

Dissertations, Theses, and Capstone Projects

This systematic review evaluates the efficacy and outcomes of cochlear implantation (CI) in adults diagnosed with far-advanced cochlear otosclerosis. This synthesis of audiological outcomes, surgical complexities, and patient-reported quality-of-life (QoL) measures is the first systematic analysis of peer-reviewed studies on this topic. By completing a comprehensive analysis of CI's viability in managing severe-to-profound mixed or sensorineural hearing loss attributed to CO, it is anticipated that CI will be considered an option for persons experiencing the significant communication challenges presented by CO when traditional approaches to management have been ineffective.

Eleven peer-reviewed articles met the inclusion criteria, examining key outcomes including …

Localization Of Music In Perceived Motion In Cochlear Implant Users, Madeleine Beyer

Dissertations, Theses, and Capstone Projects

Spatial perception contributes to music perception and enjoyment, yet it remains understudied in cochlear implant (CI) users. Spatial effects in music are often achieved through panning, a tool which redistributes an audio signal level between or among several outputs, creating a perceived sound localization. CI users typically perform worse than normal hearing (NH) listeners on tasks of horizontal localization and music perception when manipulating the actual location of the sound. However, despite the common use of panning in daily use and consumption of music, no previous studies were conducted to examine how panning impacts the listening experience for CI users. …

Bimodal Hearing Vs. Bilateral Hearing: Presenting A Review Of Existing Literature To Assist Audiologists With Determining The Optimal Hearing Modality, Eliana Dachman

Dissertations, Theses, and Capstone Projects

While guidelines exist for cochlear implant candidates, there are no specific established guidelines for bimodal users who are considering a 2nd cochlear implant. The objective of this paper is to critically review the literature addressing the question of comparative performance outcomes for bimodal hearing (one hearing aid in combination with a cochlear implant) and bilateral cochlear implants (two cochlear implants). The inclusion criteria were publications comparing bimodal and bilateral cochlear implant performance on speech perception, localization, and subjective quality. Fifteen qualifying papers were identified and analyzed. The results indicate that there are possible advantages to bilateral cochlear implants when assessing …

Ao Spine Clinical Practice Recommendations For Diagnosis And Management Of Degenerative Cervical Myelopathy: Evidence Based Decision Making - A Review Of Cutting Edge Recent Literature Related To Degenerative Cervical Myelopathy, Daipayan Guha, Chris J Neal, Benjamin M Davies, Mario Ganau, Jefferson R Wilson, Allan R Martin, Lukas Grassner, Lindsay Tetreault, Vafa Rahimi-Movaghar, Rex Marco, James Harrop, James Guest, Mohammed Ali Alvi, Karlo M Pedro, Brian K Kwon, Charles G Fisher, Shekar N Kurpad

Faculty, Staff and Student Publications

Study Design

Literature review of key topics related to degenerative cervical myelopathy (DCM) with critical appraisal and clinical recommendations.

Objective

This article summarizes several key current topics related to the management of DCM.

Methods

Recent literature related to the management of DCM was reviewed. Four articles were selected and critically appraised. Recommendations were graded as Strong or Conditional.

Results

Article 1: The Relationship Between pre-operative MRI Signal Intensity and outcomes. Conditional recommendation to use diffusion-weighted imaging MR signal changes in the cervical cord to evaluate prognosis following surgical intervention for DCM. Article 2: Efficacy and Safety of Surgery for Mild …

Implementation Of An Opt-Out And Rapid Point-Of-Care Syphilis Testing Program For Pregnant Patients Presenting To The Emergency Department, Jeffrey D Klausner

Faculty, Staff and Student Publications

Background: Adult and congenital syphilis rates are rising in the United States. The aim of this pre- and post-implementation study was to determine whether implementation of an opt-out laboratory-based and rapid syphilis point-of-care testing program in the emergency department (ED) improves the detection and treatment of syphilis during pregnancy in a high-prevalence region.

Methods: This pre- and post-implementation study was conducted at the University of Texas Health Science Center, Houston, TX. During the pre-implementation phase (November 1, 2023-February 29, 2024), pregnant patients presenting to the ED underwent laboratory-based syphilis testing using the reverse algorithm only when clinically indicated. In the …

Advancing The Development Of Trip13 Inhibitors: A High-Throughput Screening Approach, Rae M Sammons, Soma Ghosh, Lacin Yapindi, Eun Jeong Cho, Faye M Johnson

Faculty, Staff and Student Publications

TRIP13, a promising target for cancer therapy, has been identified as a key regulator of the mitotic checkpoint. Overexpression of TRIP13 is associated with poor clinical outcomes in various cancers. Inhibition of TRIP13 has the potential to address therapeutic challenges in cancer, particularly in therapy-resistant and Rb-deficient cancers. Despite the potential therapeutic benefits of TRIP13 inhibition, the development of TRIP13 inhibitors has been hindered by the lack of a robust high-throughput screening (HTS) assay. We developed a luminescence-based biochemical assay for TRIP13 activity to address this challenge using the ADP-Glo detection system. This assay offers high sensitivity, low background signal, …

Aapm Task Group No 249b-Essentials And Guidelines For Clinical Medical Physics Residency Training Programs, Jonathon A Nye, Joseph P Dugas, William D Erwin, David P Gierga, Darryl G Kaurin, Ho-Ling Anthony Liu, Alphonso W Magri, Lynn N Rill, Leah K Schubert, Beth A Schueler, Irina Vergalasova, John Vetter, Brian D Wichman, Amy Shu-Jung Yu, Dandan Zheng

Faculty, Staff and Student Publications

The establishment of guidelines and curriculum standards for medical physics residency training is a critical component of setting expectations and competencies for the profession. Since the last publication of these standards, residency training has become integrated into the eligibility criteria for most medical physics certification bodies. The rapid growth of medical physics requires periodic review of the curriculum to remove outdated approaches, update established knowledge, and add emerging technologies. The goal of this document is to provide a reference standard for residency training program directors, training mentors, and residents to guide creation and/or optimization of their program's curriculum. The document …

International Multidisciplinary Consensus Recommendations On Clinical Application Of Three-Dimensional Visualization In Precision Surgery For Pediatric Liver Tumors, Mary T Austin, Chengli Liu, Hiroki Ishibashi, Karthik K Tappa, Huanmin Wang, Chuandong Sun, Yuntao Ma, Hongwei Xi, Jian Wang, Jianghua Zhan, Kyong Ihn, Mitsuo Shimada, Mingman Zhang, Mary E Brindle, Patrick B Thomas, Shigehisa Fumino, Tao Liu, Thom Lobe, Udo Rolle, Shan Wang, Xiaowen Zhai, Yoshinori Koga, Yoshiaki Kinoshita, Yuzuo Bai, Zhaozhu Li, Zhe Wen, Weikang Pan, Krysta M Sutyak, Pier C Giulianotti

Faculty, Staff and Student Publications

Background: Pediatric liver tumors are predominantly primary malignant tumors, and complete tumor resection with sufficient preservation of liver tissue is crucial for improving prognosis. However, due to the delicate anatomical structure of the pediatric liver and the relatively large size of the tumors, especially in difficult cases, the surgical challenges are substantial. While precision liver surgery are widely applied in clinical practice, pediatric cases require more customized approaches. The application of three-dimensional (3D) visualization technology is crucial for enhancing surgical accuracy, allowing for precise preoperative planning and intraoperative guidance.

Methods: This consensus was collaboratively developed by 36 experts from eight …

Nlrp3 Inflammasome Activation Expands The Immunosuppressive Myeloid Stroma And Antagonizes The Therapeutic Benefit Of Sting Activation In Glioblastoma, Spencer T Lea, Chao-Hsien Chen, Jun Wei, Ivana William, Inés Lopez Del Castillo

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most common and deadly primary brain malignancy and is clinically refractory to immunotherapy. Active NLRP3 inflammasome signaling and IL-1β secretion have been observed in GBM, and NLRP3-driven myeloid-derived suppressor cell (MDSC) recruitment can mediate cancer immune evasion. Agonists of the cytosolic double-stranded DNA-sensing stimulator of IFN gene (STING) pathway can mediate proinflammatory conversion of cancer MDSCs; however, secretion of the NLRP3 products IL-1β and IL-18 has also been observed in certain myeloid populations following STING activation. In this study, we aimed to determine both the potential mechanistic synergy between STING and NLRP3 agonists, and the effects …

Multicancer Early Detection Tests At A Crossroads: Commercial Availability Ahead Of Definitive Evidence, Carmen E Guerra, Jennifer Keating Litton, Carolina E Viswanath, A Mark Fendrick

Faculty, Staff and Student Publications

Multicancer early detection tests (MCEDs), sometimes referred to as liquid biopsies, are tests that can screen for multiple cancers by analyzing blood, urine, and other bodily fluids for biomarkers released by cancer cells. These tests have the potential to change the cancer screening paradigm if they are shown to reduce cancer mortality. However, it is not yet known whether MCEDs reduce mortality. Randomized controlled trials, the gold standard for evaluating cancer screening programs, are currently evaluating the effectiveness of MCEDs. However, because cancer-specific and all-cause mortality are end points that can take years to reach, trials are being designed with …

An Enzyme-Linked Immunosorbent Assay (Elisa)-Based Activity Assay For Amp-Activated Protein Kinase (Ampk), Trezze P Nguyen, Shangze Lyu, Yang Liu

Faculty, Staff and Student Publications

AMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism and other cellular processes. Substantial efforts have been made to develop pharmacological modulators of AMPK activity due to their therapeutic potential against various diseases. Measuring AMPK activity in vitro is a fundamental step for testing AMPK activators and inhibitors. Here, we report an enzyme-linked immunosorbent assay (ELISA)-based AMPK activity assay with simple steps and high sensitivity. This assay offers a robust, in-house alternative to the traditional radioactive methods and other approaches that rely on specialized reagents or commercial kits.

Time To Weight Plateau With Tirzepatide Treatment In The Surmount-1 And Surmount-4 Clinical Trials, Clare J Lee, Adam Stefanski, Julia P Dunn

Faculty, Staff and Student Publications

The rate of weight reduction during obesity treatment declines over time and eventually reaches a weight plateau. We investigated factors associated with time to weight plateau (TTWP) in tirzepatide-treated participants with obesity or overweight in a post-hoc analysis of SURMOUNT-1 and SURMOUNT-4 trials. Participants adherent to tirzepatide treatment and achieving ≥5% weight loss by primary endpoint (week 72 SURMOUNT-1; week 88 SURMOUNT-4) were included. Weight plateau was defined as a weight change < 5% over a 12-week interval and all subsequent 12-week intervals. TTWP was time from randomization to the start of the first 12-week interval. Association between baseline characteristics and TTWP was assessed. Overall, 1438 participants in SURMOUNT-1 and 259 in SURMOUNT-4 were included. Across BMI categories (overweight, class I, II, and III), median TTWP in SURMOUNT-1 was 24.3, 26.0, 36.1, and 36.1 weeks, respectively (p < .05, class II and III vs. overweight). By week 72, 90.2%, 88.9%, 87.6%, and 87.8% of participants in SURMOUNT-1 had reached a weight plateau across respective BMI categories [Correction added on 22 January 2025, after first online publication: The "72%" has been changed to "72" in this version.]. Higher doses of tirzepatide (10/15 mg), younger age, and female sex were more likely to reach a weight plateau later. Results in SURMOUNT-4 were similar. In this post-hoc analysis, most participants reached a weight plateau by week 72. Higher doses of tirzepatide, younger age, and female sex were associated with a longer TTWP. Further research into modifiers of weight reduction phases with tirzepatide may inform treatment decisions for its use in chronic weight management. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT04184622 (SURMOUNT-1) and NCT04660643 (SURMOUNT-4), available at http://www.clinicaltrials.gov/.

New Frontiers: The Intern Experience In A Newly Established Integrated Plastic Surgery Program, Matthew R Greives

Faculty, Staff and Student Publications

The plastic surgery residency pathway has undergone many changes since its inception. The advent of integrated training has largely taken over as the predominant residency model with the addition of a few new programs every year. There is currently a paucity of literature describing the experiences of first-year interns in a new integrated residency program transitioning from the independent model. In this article, we seek to elucidate some of the advantages and difficulties encountered by the initial residents of a newly established integrated program and the steps taken to pave the way for future matched integrated trainees.

Fracture Patterns In Craniofacial Gunshot Wounds: A Seven-Year Experience, Sean P Mckee, Tang Ho

Faculty, Staff and Student Publications

Objective: To characterize facial fracture patterns and understand predictors of surgical repair and LOS with the objective of assisting providers in managing and understanding these complex injuries.

Study design: This is a retrospective cohort chart review study.

Methods: A retrospective review was conducted for patients admitted with gunshot wounds (GSWs) to the head, neck, or face between January 2013 and March 2020 at a level one trauma tertiary care hospital. Univariate and multivariate analysis were performed to identify associations with surgical repair and LOS.

Results: Of the 578 patients with head, neck, or facial GSWs, 204 survived and sustained facial …

Pharmacogenetics Of Plasma Dolutegravir Exposure During 1-Month Rifapentine/Isoniazid Treatment Of Latent Tuberculosis, Yoninah Cramer, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas

Faculty, Staff and Student Publications

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations …

Endovascular Repair Of Type A Dissection Using Thoracic Stent Graft With Innominate Artery Flaring To Correct For Length Mismatch, Thanila A Macedo

Faculty, Staff and Student Publications

Type A aortic dissection is the most common aortic catastrophe posing challenges for endovascular repair owing to the fragile aortic wall, proximity to the aortic valve, coronaries, and supra-aortic trunks. While open surgical repair remains the gold standard, endovascular repair is considered in select high-risk patients who meet anatomical criteria, including more than 10 mm length between sinotubular junction to primary tear, aortic diameter of less than 40 mm, and suitable length between sinotubular junction and innominate artery. This illustrated video and case presentation address a modified technique using stent graft flaring of the innominate artery to adjust for length …

Assessment Of Contextualized Reinforcement Pathology In A Community Sample Of Young Adult Substance Users, Sara Weidberg

Faculty, Staff and Student Publications

Background: Alcohol, tobacco, and cannabis are the most commonly used substances among young populations, often leading to polysubstance use, which correlates with problematic consumption and adverse health outcomes. The contextualized reinforcer pathology (CRP) model explains addictive behaviors through several constructs, including the following: drug demand, delay discounting (DD), and substance-free and substance-related reinforcement. Most previous studies have focused on a single CRP construct and the couse of only two substances. This study aimed to characterize three subgroups of young adults reporting past month use of alcohol only, alcohol + tobacco or cannabis, and alcohol + tobacco + cannabis, in terms …

Psychometrics Of Inflammatory Back Pain Criteria In The Us Population, Michael H Weisman

Faculty, Staff and Student Publications

Objectives: Evaluation of axial spondyloarthritis relies on capturing various inflammatory back pain (IBP) features represented in different criteria. These criteria are likely to be interpreted differently across demographic subpopulations. We examined IBP criteria dimensionality and differential item functioning (DIF) among different age, gender, and race groups using a nationally representative sample.

Methods: We utilised the National Health and Nutrition Examination Survey (NHANES) 2009-2010 dataset, a US nationally representative data collection with demographic weighting. The Arthritis Questionnaire (ARQ) within NHANES included questions from published Calin, European Spondyloarthropathy Study Group, and Berlin criteria (8a and 7b). Confirmatory factor analysis (CFA) was performed …

The Macrophage Sterol Transport Protein Orp2 Promotes Cholesterol Efflux And Prevents Foam Cell Formation And Atherosclerosis, Chenxi Liang, Jinye Tang, Yidan Ma, Lin Liu, Mingqi Zheng, Hongyuan Yang, Mingming Gao

Faculty, Staff and Student Publications

Cholesterol-loaded macrophage foam cells are a key feature of atherosclerotic plaques. Oxysterol-binding protein-related protein 2 (ORP2) facilitates the transport of cholesterol from lysosomes to the plasma membrane in cultured cell lines. However, the role of ORP2 in macrophages and its involvement in atherosclerosis remain unclear. In this study, we found ORP2 expression was reduced in atherosclerotic vessels and in macrophages exposed to oxidized LDL (ox-LDL). Myeloid-specific human ORP2 overexpression (hORP2MOE) mice were generated and crossed with atherosclerotic-prone ApoE−/− mice and then fed a high-fat diet (HFD) to induce atherosclerosis. Our results showed that myeloid-specific hORP2 overexpression significantly reduced the atherosclerotic …

Enhancing Seizure Control In Ultra-Refractory Postencephalitic Epilepsies Using Multinodal Network Neuromodulation, Nitin Tandon

Faculty, Staff and Student Publications

This case series reports the formidable challenge posed by postencephalitic epilepsies, characterized by frequent drug-resistant seizures and neuropsychiatric and cognitive comorbidities. Polypharmacy is frequently required, and surgical resection may not be feasible due to multifocality. Neuromodulation therapies, including Deep Brain Stimulation (DBS) and Responsive Neurostimulation (RNS), offer a potential lifeline. In this case series, we shed light on the intricate landscape of seizure management and neuropsychiatric comorbidities in five individuals with frequent seizures (often weekly) and ultra-refractory epilepsy (defined as resistance to more than six different antiseizure medications, including failed epilepsy surgery) following catastrophic encephalitis. Four out of five patients …

Cardio-Oncology Outcomes In Ultrasound-Assisted Versus Standard Catheter-Directed Thrombolysis For Acute Pulmonary Embolus, Brenden S Ingraham, Abdelrahman Ali, Salman Arain, Konstantinos Charitakis, Mehmet Cilingiroglu, Konstantinos Dean Boudoulas, Jaime Caballero, Konstantinos Marmagkiolis, Cezar Iliescu

Faculty, Staff and Student Publications

No abstract provided.

The Great Mimicker: Forgotten But Not Gone, Auris O Huen

Faculty, Staff and Student Publications

Once subdued after the advent of penicillin, syphilis has re-emerged in recent years, with incidence rates rising in many countries, including the United States. Its reputation as "the great imitator" is well earned due to its widely variable presentation, particularly in its second stage. This contributes to a high rate of delayed diagnosis and misdiagnosis, adding significant burden to patients and the health care system generally. Herein, we present 2 cases in which syphilis was misdiagnosed, leading to unnecessary therapies and delay of symptom clearance until treponemal tests were performed. In the context of recent epidemiologic trends and its notorious …

Perceptions Of The Intensity Of Heart Failure Medications Among Hospitalized Older Adults: A Pilot Qualitative Study, Min Ji Kwak

Faculty, Staff and Student Publications

Background: Guidelines for heart failure (HF) management recommend high target doses for medications. These targets are based on standardized dosing regimens that rarely consider the complex challenges faced by older patients. However, little is known about such challenges perceived by older adults. We assessed older adults' perceived challenges with HF medication utilization, which may guide a more patient-centered definition of the target intensity for HF medications.

Methods: We conducted a pilot qualitative study using one-on-one, semi-structured interviews with older adults. We included patients over the age of 65 years admitted to the acute cardiac care units (cardiac intensive care unit …

Design Of Conquest, A Novel, Randomized, Placebo-Controlled, Phase 2b Platform Clinical Trial To Investigate New Treatments For Patients With Early Active Systemic Sclerosis With Interstitial Lung Disease, Gregory Gordon

Faculty, Staff and Student Publications

Objective: Safe, effective therapies are urgently needed for patients with systemic sclerosis. However, clinical trial recruitment is challenging given the limited number of people with systemic sclerosis and further restrictions imposed by eligibility criteria. Innovative approaches are needed to accelerate development of new therapies. This article describes the rationale and trial design for CONQUEST (NCT06195072), a novel platform clinical trial sponsored by the Scleroderma Research Foundation, a not-for-profit organization.

Methods: CONQUEST is a multicentre, double-blind, randomized, placebo-controlled, Phase 2b platform trial evaluating the efficacy, safety and pharmacodynamics of multiple investigational products to treat early active systemic sclerosis with …

Three-Dimensional Printed Models To Accelerate Resident Surgical Learning Curve For Standard Endoscopic Sinus Surgery Techniques

Faculty, Staff and Student Publications

Background: Endoscopic sinus surgery presents significant visuospatial challenges to surgical trainees. We tested the utility of novel 3D printed models to simulate sinus surgery tasks to improve endoscopic skillsets in resident trainees.

Methods: This was a prospective quality improvement study of 10 ENT residents (PGY1-5). Participants rotated through 4 stations with different 3D simulation training modules designed to enhance endoscopic skillsets in the axial, sagittal and coronal planes (e.g., straight forceps to grasp a bead from a ledge, angled instruments to cannulate openings). Participants completed a self-assessment survey on the subjective sinus surgical skills using a visual analog …

Comparing Stroke Risk Factors Among Sexual Minority Groups In Texas, Brittany Krenek, Samuel Tundealao, Jennifer E S Beauchamp, Sean I Savitz, Irene Tamí-Maury

Faculty, Staff and Student Publications

Background: Knowledge gaps remain on stroke risk and disparities between sexual minority (SM) subgroups. In this study, stroke risk between SM subgroups, specifically gay/bisexual men and lesbian/bisexual women (G/BM and L/BW), was assessed.

Method: Data were collected in June 2022 using a bilingual (English and Spanish) cross-sectional paper-and-pen survey distributed among 183 SM individuals attending the 2022 Houston Pride Parade and Festival, as well as across Texas via phone call or online format. Relevant sociodemographic and stroke risk factors were compared between G/BM and L/BW using chi-square (or Fisher's exact, when appropriate) and two-sample t-tests. Sexual orientation was used to …

A Plain Language Summary Of The Molecular Changes In The Tumors Of People With Braf V600e-Mutant Colorectal Cancer In The Beacon Study, Scott Kopetz, Danielle A Murphy, Jie Pu, Fortunato Ciardiello, Jayesh Desai, Harpreet Singh Wasan, Hedieh Saffari, Xiaosong Zhang, Phineas Hamilton, Tao Xie, Rona Yaeger, Josep Tabernero

Faculty, Staff and Student Publications

What is this summary about?This summary discusses the genetic and molecular changes in tumors of participants with BRAF V600E–mutant metastatic colorectal cancer who were treated with encorafenib plus cetuximab, with or without binimetinib, in the BEACON study.

What were the results?Encorafenib plus cetuximab, with or without binimetinib, reduced the risk of participants dying compared with cetuximab plus chemotherapy, regardless of genetic or molecular colorectal cancer subtypes.The study also found genetic and molecular changes in the participants’ tumors during treatment that were associated with how long they lived.

What do the results of the study mean?The types of …

Cll Cell-Derived Exosomes Alter The Immune And Hematopoietic Systems, Ivo Veletic, David M Harris, Uri Rozovski, Maria Teresa S Bertilaccio, George A Calin, Ping Li, Taghi Manshouri, Rares-Constantin Drula, Ken Furudate, Muharrem Muftuoglu, Anwar Hossain, William G Wierda, Michael J Keating, Zeev Estrov

Faculty, Staff and Student Publications

The origins of immunosuppression, neutropenia, and anemia in patients with chronic lymphocytic leukemia (CLL) are not fully understood. Because in patients with CLL, circulating exosomes, which participate in cell-to-cell interactions, are CLL cell-derived, we examined whether those exosomes contribute to abnormal features of this disease. Our data revealed that CLL cell-derived exosomes engulfed by healthy donors’ monocytes, fibrocytes, and lymphocytes altered target-cell gene and protein expression and suppressed normal hematopoiesis. CLL cell-derived exosomes increased normal monocytes’ CD14 and CD16 expression such that it mimicked the accessory cell profile and upregulated T cells’ checkpoint PD-1 and CD160 protein levels, potentially reducing …

Emerging Technologies Of Single-Cell Multi-Omics, Yi June Kim, Koichi Takahashi

Faculty, Staff and Student Publications

The heterogeneity of the hematopoietic system was largely veiled by traditional bulk sequencing methods, which measure the averaged signals from mixed cellular populations. In contrast, single-cell sequencing has enabled the direct measurement of individual signals from each cell, significantly enhancing our ability to unveil such heterogeneity. Building on these advances, numerous single-cell multi-omics techniques have been developed into high-throughput, routinely accessible platforms, delineating the precise relationships among different layers of the central dogma in molecular biology. These technologies have uncovered the intricate landscape of genetic clonality and transcriptional heterogeneity in both normal and malignant hematopoietic systems, highlighting their roles in …