Medicine and Health Sciences Commons^™

Neuraxial Vs. General Anesthesia In Total Hip Arthroplasty For Femoral Neck Fracture: A Comparison Of Post-Operative Complications, Kevin Xavier Farley, Robert Dean, Mark S. Karadsheh, Drew Douglas Moore

Conference Presentation Abstracts

INTRODUCTION: Rates of complications with differing anesthetic choices has not been directly compared for patients undergoing total hip arthroplasty (THA) for femoral neck fractures. This study sought to directly compare neuraxial vs. general anesthetic use and compare post-operative outcomes for patients undergoing THA for a femoral neck fracture. METHODS: From 2012-2021, the National Surgical Quality Improvement Project (NSQIP) database was used to identify all patients undergoing THA for a femoral neck fracture. Anesthetic type was identified and categorized as neuraxial (spinal, epidural) or general. Demographic and comorbid variables were collected. Days from admission to surgery was also identified. Postoperative complications …

Associations Of Sociodemographic, Clinical Factors And Hla-B Alleles With Enthesitis And Peripheral Arthritis In Patients With Ankylosing Spondylitis, Benjamin Sornrung Naovarat, Lianne Gensler, Michael Ward, Mark Hwang, Amirali Tahanan, Mohammad Hossein Rahbar, Mariko Ishimori, Minjae Lee, Matthew A Brown, Michael H Weisman, John D Reveille

Faculty, Staff and Student Publications

Objectives: Factors associated with peripheral arthritis and enthesitis, especially Achilles tendonitis and plantar fasciitis, were examined in a longitudinal cohort of 1075 patients with ankylosing spondylitis (AS) (also known as radiographic axial spondyloarthritis).

Methods: Patients were derived from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort. Disease activity and functional indices, as well as physical examination and medications used, were measured at every study visit. Univariable and multivariable analyses of the association of peripheral arthritis and enthesitis with clinical, sociodemographic factors were performed. Human leucocyte antigen (HLA)-B alleles were analysed by single-stranded conformational polymorphism analysis.

Results: Those with peripheral …

Epigastric Hernia Containing Incarcerated Gallbladder, Katelyn R. Ward, Melanie Ermler, Kathryn M. Ziegler

Conference Presentation Abstracts

Introduction: Epigastric hernias represent 1.6–3.6% of all abdominal hernias, and usually contain preperitoneal fat and occasionally omentum or small bowel. Rarely, epigastric hernias may contain portions of other organs, such as colon or stomach. We report an unusual case of a patient whose incarcerated epigastric hernia contained her stone-filled gallbladder.over a million performed in the US, and over 20 million worldwide annually. We aim to study and compare interest trends in the US and the World for IHR techniques (open, laparoscopic, robotic) using GT. Methods: The following search topics were analyzed from January 2010 to August 2024 in ‘‘US’’ and …

Left Behind: A Rare Case Of True Gallbladder Sinistroposition And Surgical Implications, Daniel Finn, Jacob Applegarth, Jacob Mesiti, Mario Villalba

Conference Presentation Abstracts

Objectives: Encountering aberrant biliary anatomy is a known risk factor for inadvertent injury while performing biliary surgery. One described anatomic aberrancy, sinistroposition of the gallbladder (also known as ‘‘left sided gallbladder’’), is a rarely seen anatomic abnormality with an incidence of 0.2% to 1.1%. Given the infrequent encounters with this abnormality and its association with other anatomic anomalies, extreme care and caution should be exercised when performing a cholecystectomy in this patient population. Methods: We present the case of a 37-year-old male who presented with abdominal pain and was diagnosed with Tokyo Grade I acute calculous cholecystitis. An ultrasound of …

Psychological Safety And Clinical Reasoning In Athletic Training And Physical Therapy Clinical Education: A Nationwide Survey Of Student Perception, Kelsey J. Robinson, Heather David, Beth Kinslow, Jennifer Austin

Innovations in Health Sciences Education Journal

Psychological safety contributes to effective learning environments in healthcare, where clinical experiences foster the development of clinical reasoning skills needed for accurate patient care decisions. Inadequate clinical reasoning skills may lead to misdiagnosis and inappropriate patient care decisions, resulting in poor outcomes and unnecessary costs. This study examines the effect of psychological safety on clinical reasoning within athletic training and physical therapy clinical experiences. A quantitative, cross-sectional survey assessed perceptions of psychological safety and clinical reasoning among Doctor of Physical Therapy and Master of Athletic Training students and recent graduates. Survey measures indicated good reliability (a = .83 and .85). …

Feasibility, Acceptability, And Satisfaction Of Redcap As A Tool For Interprofessional Education, Ross J. Bindler, Skye Mckennon, Connie M. Remsberg, Jennifer C. Miller, Marian Wilson

Innovations in Health Sciences Education Journal

Interprofessional education (IPE) is an important component of health science training. Ensuring all students have access to necessary information prior to, during, and following simulation-enhanced IPE (Sim-IPE) activities is imperative to ensure a beneficial learning environment and student engagement. Ensuring access to necessary materials can be difficult due to differences in educational resources between institutions. This manuscript will assess the feasibility, acceptability, and satisfaction of using Research Electronic Data Capture (REDCap) as an educational tool for a Sim-IPE activity. After a pilot Sim-IPE activity, data from student evaluations was reviewed. Updates were made including use of REDCap as a universally …

Effects Of Space Flight On Inflammasome Activation In The Brain Of Mice, Upal Roy, Roey Hadad, Angel A. Rodriguez, Alen Saju, Deepa Roy, Mario Gil, Robert W. Keane, Ryan T. Scott, Xiao W. Mao, Juan Pablo De Rivero Vaccari

Health & Biomedical Sciences Faculty Publications

Space flight exposes astronauts to stressors that alter the immune response, rendering them vulnerable to infections and diseases. In this study, we aimed to determine the levels of inflammasome activation in the brains of mice that were housed in the International Space Station (ISS) for 37 days. C57BL/6 mice were launched to the ISS as part of NASA’s Rodent Research 1 Mission on SpaceX-4 CRS-4 Dragon cargo spacecraft from 21 September 2014 to 25 October 2014. Dissected mouse brains from that mission were analyzed by immunoblotting of inflammasome signaling proteins and Electrochemiluminescence Immunoassay (ECLIA) for inflammatory cytokine levels. Our data …

The Dnase Trex1 Is A Substrate Of The Intramembrane Protease Spp With Implications For Disease Pathogenesis, Onur Kerem Tever, Torben Mentrup, Ivan Kingyue Chinn, Hitoshi Ishikuma, Regina Fluhrer, Marc Schmitz, Rebekka Wehner, Rayk Behrendt, Javier Chinen, Bernd Schröder

Faculty, Staff and Students Publications

Signal peptide peptidase (SPP) is an ER-resident aspartyl intramembrane protease cleaving proteins within type II-oriented transmembrane segments. Here, we identified the tail-anchored protein Three prime repair exonuclease 1 (TREX1) as a novel substrate of SPP. Based on its DNase activity, TREX1 removes cytosolic DNA acting as a negative regulator of the DNA-sensing cGAS/STING pathway. TREX1 loss-of-function variants cause Aicardi-Goutières syndrome (AGS), a type I interferonopathy. Cleavage of ER-bound TREX1 by SPP releases a cleavage product into the cytosol. Proteolysis depends on sequence determinants within the transmembrane segment and is modulated by different disease-associated TREX1 variants. The AGS-causing T303P variant greatly …

Impact Of A Three-Week Full Leg Cast Immobilization On Infant Crawling Kinetics And Spatiotemporal Parameters, Mark Daniel Geil

Faculty Articles

Despite its importance in the development of mobility in infants, there is a general lack of quantified data on infant crawling, and a specific lack of understanding of crawling kinetics, which includes the relative weightbearing and force generation among the four limbs. Moreover, because of the difficulty of measurement and study design, there is no longitudinal quantification of the impact of a perturbation to typical development, such as limb immobilization. This study measured kinetic and spatiotemporal outcomes in a typically developing infant prior to a fracture that necessitated a long-leg cast that immobilized the left knee and ankle, while crawling …

The Role Of Electrophysiologic Study In Device Selection For Leadless Atrial Pacing, Joshua R Hirsch, Jordan M Gales, Irakli Giorgberidze, Hamid Afshar

The Texas Heart Institute Journal

The AVEIR DR (Abbott Medical) was the first dual-chamber leadless pacing system approved by the US Food and Drug Administration. Many patients with sinus node dysfunction have physiologically normal atrioventricular conduction, so an atrial-only pacing system may be appropriate for them. Three patients with symptomatic sinus node dysfunction underwent device implantation with electrophysiologic study, including incremental atrial pacing until loss of 1:1 atrioventricular conduction (atrioventricular Wenckebach cycle length) and His-ventricular interval measurement. If the atrioventricular Wenckebach cycle length was no more than 400 milliseconds and the His-ventricular interval measurement was no more than 55 milliseconds, single-chamber atrial implantation was deemed …

Control Of Clostridioides Difficile Virulence And Physiology By The Flagellin Homeostasis Checkpoint Flic-Fliw-Csra In The Absence Of Motility, Duolong Zhu, Katherine J Wozniak, Firas Midani, Shaohui Wang, Xingmin Sun, Robert A Britton

Faculty, Staff and Students Publications

Mutations affecting Clostridioides difficile flagellin (FliC) have been shown to be hypervirulent in animal models and display increased toxin production and alterations in central metabolism. The regulation of flagellin levels in bacteria is governed by a tripartite regulatory network involving fliC, fliW, and csrA, which creates a feedback system to regulate flagella production. Through genomic analysis of C. difficile clade 5 strains (non-motile), we identified they have jettisoned many of the genes required for flagellum biosynthesis yet retain the major flagellin gene fliC and regulatory gene fliW. We therefore investigated the roles of fliC, fliW …

Electrostatic Effects On Tau Nanocondensates, Phoebe S Tsoi, Lathan Lucas, Derek Rhoades, Josephine C Ferreon, Allan Chris M Ferreon

Faculty, Staff and Students Publications

Biomolecular condensates (BMCs) are membrane-less protein compartments with physiological and pathological relevance. The formation of BMCs is driven by a process known as liquid-liquid phase separation (LLPS), a field that has largely focused on the study of micron-sized condensates. However, there have been recent studies showing that proteins that undergo LLPS also form nanometer-sized condensates. These nanometer-sized condensates, or nanocondensates, are distinct from microcondensates and potentially exhibit more relevance in cell biology. The field of nanocondensate research is in its infancy, with limited biophysical studies of these structures. Here, we studied condensate formation and dissolution of wild-type and disease-linked (hyperphosphorylated …

Identifying Distinct Prognostic And Predictive Contributions Of Tumor Epithelium Versus Tumor Microenvironment In Colorectal Cancer, Mingli Yang, Moh'd Khushman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Accumulating evidence has suggested that cancer progression and therapeutic response depend on both tumor epithelium (EPI) and tumor microenvironment (TME). However, the dependency of clinical outcomes on the tumor EPI vs. the TME has neither been clearly defined nor quantified.

METHODS: We classified 2373 colorectal cancer (CRC) tumors into the consensus molecular subtypes (CMS1-4) and generated the 10-gene TME

RESULTS: The TME

CONCLUSIONS: Here we identified a pair of new, distinct 10-gene signatures (the EPI

Innate Immune Sensing Of Rotavirus By Intestinal Epithelial Cells Leads To Diarrhea, Gaopeng Hou, Juhee Son, Maria Florencia Gomez Castro, Takahiro Kawagishi, Avan Antia, Qiru Zeng, Anna L Deveaux, Hinissan P Kohio, Megan T Baldridge, Siyuan Ding, Et Al.

2020-Current year OA Pubs

Diarrhea is the predominant symptom of acute gastroenteritis resulting from enteric infections and a leading cause of death in infants and young children. However, the role of the host response in diarrhea pathogenesis is unclear. Using rotavirus and neonatal mice as a model, we found that oral inoculation of UV-inactivated replication-defective rotavirus consistently induced watery diarrhea by robust activation of cytosolic double-stranded RNA sensing pathways and type III interferon (IFN-λ) secretion. Diarrhea was significantly diminished in mice lacking the IFN-λ receptor. Mechanistically, IFN-λ signaling downregulates the expression of Dra, a chloride and bicarbonate exchanger, which contributes to reduced water absorption. …

Structural Mapping Of Polyclonal Igg Responses To Ha After Influenza Virus Vaccination Or Infection, André Nicolás León, Alesandra J Rodriguez, Sara T Richey, Alba Torrents De La Pena, Rachael M Wolters, Abigail M Jackson, Katherine Webb, C Buddy Creech, Sandra Yoder, Philip A Mudd, James E Crowe, Julianna Han, Andrew B Ward

2020-Current year OA Pubs

Cellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design. Responses …

Outcomes After Isolated Medial Meniscus Posterior Root Repairs Using An Anatomic Transtibial Pullout Technique In Patients Older Than 60 Years: A Matched Cohort Study, Garrett R Jackson, Derrick M Knapik, Zeeshan A Khan, Harkirat Jawanda, Obianuju A Obioha, Daniel J Kaplan, Johnathon R Mccormick, Joan Sugrañes, Anjay Batra, Enzo S Mameri, Nikhil N Verma, Jorge Chahla

2020-Current year OA Pubs

BACKGROUND: Management of isolated medial meniscus posterior root (MMPR) tears is challenging, especially in older patients, where indications for repair must be weighed against potential repair failure and osteoarthritic progression.

PURPOSE: To compare patient-reported outcomes and incidence of failure after anatomic transtibial pullout repair for isolated MMPR tears in patients >60 versus ≤60 years of age.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: Included in the study were patients aged ≥18 years who underwent isolated anatomic transtibial pullout repair using either the single- or double-tunnel technique for MMPR tears at a single institution between January 2016 and September …

Medical School Watercooler Newsletter - March 11, 2025, Lindsay Hughes

Watercooler Newsletter

This is the Tuesday, March 11, 2025 edition of the Frederick P. Whiddon College of Medicine's newsletter -- Watercooler.

Contents include:

• Borchert lab research challenges longstanding view of gene regulation
• Medical students and pediatrics residents present research at regional meeting
• Class 2025 to celebrate Match Day March 21
• First-year medical student to receive a community health leadership award

Two-Dimensional Preoperative Digital Templating Is Less Accurate When Using A Collared Triple Taper Stem Versus A Single Taper Design, Claudio Diaz-Ledezma, Angel X. Xiao, Juan David Lizcano, Erik N. Hansen, Camilo Restrepo, William J. Hozack

Rothman Institute Papers

Background

Collared triple taper stems (CTTS) and single taper stems (STS) have an excellent performance in primary total hip arthroplasty (THA). While 2-dimensional radiographic templating is accurate for STS, data are lacking for CTTS. We hypothesize that CTTS’ more anatomical design in the anteroposterior dimension may lead to inaccurate templating sizing. This study compared templating accuracy of CTTS to a predecessor STS in THA patients.

Methods

106 THA performed with CTTS were compared to 106 THA performed with STS by 2 high-volume surgeons. The stems chosen for comparison were manufactured by the same company, use the same templating software, shared …

Prodrug Activation In Malaria Parasites Mediated By An Imported Erythrocyte Esterase, Acylpeptide Hydrolase (Apeh), Sesh A. Sundararaman, Justin J. Miller, Ellora C. Daley, Kelsey A. O'Brien, Paulina Kasak, Abigail M. Daniels, Rachel L. Edwards, Kenneth M. Heidel, Darean A. Bague, Madeleine A. Wilson, Andrew J. Koelper, Elexi C. Kourtoglou, Alex D. White, Sloan A. August, Georgia A. Apple, Regis W. Rouamba, Anthony J. Durand, John J. Esteb, Florian L. Muller, R. Jeremy Johnson, Geoffrey C. Hoops, Cynthia S. Dowd, Audrey R. Odom John

College of Health Professions Faculty Papers

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency than their parent compounds [R.L. Edwards et al., Sci. Rep. 7, 8400 (2017)]. However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH), is the major activating enzyme of multiple …

Ibrutinib For Therapy Of Steroid-Refractory Chronic Graft-Versus-Host Disease: A Multicenter Real-World Analysis, Joseph Pidala, Iskra Pusic, Et Al.

2020-Current year OA Pubs

To examine the activity of ibrutinib in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after the US Food and Drug Administration approval, we conducted a multicenter retrospective study. Data were standardly collected (N = 270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), gastrointestinal (GI) (26%), lung (27%), liver (19%), genital (7%), and others (4.4%). The National Institutes of Health (NIH) severity was mild in 5.7%, moderate 42%, and severe 53%. Thirty-nine percent had overlap subtype. Karnofsky performance status (KPS) was ≥80% in 72%. The median prednisone was 0.21 mg/kg (0-2.27). Ibrutinib was started at a …

Structural Basis For Dimerization And Activation Of Uvrd-Family Helicases, Ankita Chadda, Binh Nguyen, Timothy M Lohman, Eric A Galburt

2020-Current year OA Pubs

UvrD-family helicases are superfamily 1A motor proteins that function during DNA replication, recombination, repair, and transcription. UvrD family monomers translocate along single-stranded (ss) DNA but need to be activated by dimerization to unwind DNA in the absence of force or accessory factors. However, prior structural studies have only revealed monomeric complexes. Here, we report the first structures of a dimeric UvrD-family helicase,

Odontogenic Infections Resistant To Empiric Therapy, Opportunistic Prevotella, And Metronidazole: A Clinical Case Series And Review Of The Literature, Ned L. Nix, Nicholas T. Zusman, Nejat Düzgüneş

Pacific Faculty Work

Background/Objectives: Treating odontogenic infections of the head, neck, and oral cavity requires surgical and pharmacotherapeutic interventions of single and multi-space infections. Prevotella species can become virulent during post-extraction wound healing at an extraction site, under conditions of excessive plaque, nearby gingivitis, or periodontitis, and in immunocompromised patients. The aims of this narrative review are to describe the pathogenesis of Prevotella species, particularly those resistant to surgery and empiric antibiotic therapy, and to emphasize the need for the identification of specific antibiotic-resistant Prevotella species. Methods: Three clinical cases from the lead author’s private practice were described, in which Prevotella species were …

Exploring The Effects Of Indoor Plants On Executive Function, Jose David Romero Silva, Aj Heritage

Master's Theses & Other Graduate Student Works

The link between greenery in schools and cognitive performance is underexplored, even with evidence of its benefits in other settings. Research indicates that adding green plants to an office can improve mood and lower stress (Bergefurts et al., 2021). This study explored the factors behind the psychological benefits of indoor plants on executive function in college students. The study proposed two competing hypotheses based on Attention Restoration Theory (ART) and Enrichment Theory. Hypothesis I: Based on the Attention Restoration Theory, integrating plants into the classroom benefits students’ executive function by giving them a sense of relief from fatigue. Hypothesis II: …

Exploratory Co-Design On Electronic Health Record Nursing Summaries: Case Study, Suhyun Park, Jenna L Marquard, Robin R Austin, Christie L Martin, David S Pieczkiewicz, Connie W Delaney

The Brown Foundation: Institute of Molecular Medicine

Background: Although electronic health record nursing summaries aim to provide a concise overview of patient data, they often fall short of meeting nurses' information needs, leading to underutilization. This gap arises from a lack of involvement of nurses in the design of health information technologies.

Objective: The purpose of this exploratory co-design case study was to solicit insights from nurses regarding nursing summary design considerations, including key information types and the preferred design prototype.

Methods: We recruited clinical nurses (N=33) from 7 inpatient units at a university hospital in the Midwestern United States using a purposive sampling method. We used …

Treatment Patterns And Outcomes In Follicular Lymphoma With Pod24: An Analysis From The Leo Consortium, Jonathan R Day, Brad S Kahl, Et Al.

2020-Current year OA Pubs

Progression of disease within 24 months of initial immunochemotherapy (POD24) is a negative prognostic factor for patients with follicular lymphoma (FL). There is no standard treatment after POD24. Assembling an academic-based cohort from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence, we evaluated patterns of care and outcomes for 220 patients with FL with POD24 and retained FL histology. Therapy after POD24 was heterogeneous, with no treatment category accounting for >25% of the total. Among patients initially treated with bendamustine-rituximab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was the predominant second-line choice (48%). Among patients initially treated with R-CHOP, …

Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

Members of the Pol A family of DNA polymerases, found across all domains of life, utilize various strategies for DNA strand separation during replication. In higher eukaryotes, mitochondrial DNA polymerase γ relies on the replicative helicase TWINKLE, whereas the yeast ortholog, Mip1, can unwind DNA independently. Using Mip1 as a model, we present a series of high-resolution cryo-EM structures that capture the process of DNA strand displacement. Our data reveal previously unidentified structural elements that facilitate the unwinding of the downstream DNA duplex. Yeast cells harboring Mip1 variants defective in strand displacement exhibit impaired oxidative phosphorylation and loss of mtDNA, …

Alpha-Frequency Stimulation Strengthens Coupling Between Temporal Fluctuations In Alpha Oscillation Power And Default Mode Network Connectivity, Yijia Ma, Joshua A Brown, Chaowen Chen, Mingzhou Ding, Wei Wu, Wen Li

Faculty, Staff and Student Publications

Alpha (8–12 Hz) oscillations and default mode network (DMN) activity dominate the brain's intrinsic activity in the temporal and spatial domains, respectively. They are thought to play crucial roles in the spatiotemporal organization of the complex brain system. Relatedly, both have been implicated, often concurrently, in diverse neuropsychiatric disorders, with accruing electroencephalogram (EEG)/magnetoencephalogram and functional magnetic resonance imaging (fMRI) data linking these two neural activities both at rest and during key cognitive operations. Prominent theories and extant findings thus converge to suggest a mechanistic relationship between alpha oscillations and the DMN. Here, we leveraged simultaneous EEG–fMRI data acquired before and …

Advancing Drug Development In Myelodysplastic Syndromes, Alain Mina, Kathy L Mcgraw, Lea Cunningham, Nina Kim, Emily Y Jen, Katherine R Calvo, Lori A Ehrlich, Peter D Aplan, Guillermo Garcia-Manero, James M Foran, Jacqueline S Garcia, Amer M Zeidan, Amy E Dezern, Rami Komrokji, Mikkael A Sekeres, Bart Scott, Rena Buckstein, Sara Tinsley-Vance, Amit Verma, Tanya Wroblewski, Steven Pavletic, Kelly Norsworthy

Faculty, Staff and Student Publications

Myelodysplastic syndromes/neoplasms (MDSs) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the US Food and Drug Administration, (eg, luspatercept, ivosidenib, decitabine/cedazuridine, and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories, including criteria for risk stratification and eligibility, response definitions, time-to-event end points, transfusion end points, functional assessments, and biomarker development. Strategies to address these challenges …

Avasimibe Abolishes The Efficacy Of Fluvastatin For The Prevention Of Cancer In A Spontaneous Mouse Model Of Breast Cancer, Anjana Bhardwaj, Alexander Koh, Rhea Bhala, Janvi Sandhu, Zhenlin Ju, Leslie Faye Cando, Jing Wang, Isabelle Bedrosian

Faculty, Staff and Student Publications

The cholesterol biosynthesis pathway is upregulated during breast cancer development and progression. Inhibition of the aberrantly upregulated cholesterol pathway by statins reduces breast tumor incidence and burden by 50% in SV40 C3(1) TAg mice, a mouse model of triple negative breast cancer. We hypothesized that fluvastatin's preventive efficacy could be further enhanced by co-targeting the statin-induced restorative feedback pathways that tightly control the cholesterol pathway and are involved in resistance to statins. Acyl-coenzyme A: cholesterol acyltransferase (

Vdac2 And Bak Scarcity In Liver Mitochondria Enables Targeting Hepatocarcinoma While Sparing Hepatocytes, Shamim Naghdi, Piyush Mishra, Soumya S. Roy, David Weaver, Ludivine Walter, Erika Davies, Anil N. Antony, Xuena Lin, Gisela Moehren, Mark A. Feitelson, Christopher A. Reed, Tullia Lindsten, Craig B. Thompson, Hien T. Dang, Jan B. Hoek, Erik S. Knudsen, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity. Exploring potential therapeutic targeting, we find that combinations of activators of the tBid pathway with inhibitors of the Bcl-2 family proteins …