Medical Specialties Commons^™

Structural Characterization Of A Clinically Described Heparin-Like Substance In Plasma Causing Bleeding, Yanlei Yu, Karen Bruzdoski, Vadim Kostousov, Lisa Hensch, Shiu-Ki Hui, Fakiha Siddiqui, Amber Farooqui, Ahmed Kouta, Fuming Zhang, Jawed Fareed, Jun Teruya, Robert J Linhardt

Faculty, Staff and Students Publications

Heparin-like substances (HLS) have been described in various clinical situations, including in settings of liver disease associated with infection, transplant, and metastasis. HLS are generally attributed to circulating glycosaminoglycans. Initial results for this patient showed coagulopathy due to liver disease without HLS. Two weeks after liver transplantation, a 10 year-old female with liver failure patient began to bleed from catheter insertion sites, mouth, and nares and HLS was suspected. The patient subsequently died and these clinical samples resulted in the isolation of a single heparan sulfate (HS) present at high concentrations in the plasma. Analysis of this HS showed it …

Ms211: Obit For Bishop Hearn, Armin Weinberg

Works on Radiation Effects: 1990-2020

Obit for Bishop Hearn in Sept 9, 2020 Houston Chronicle, He was instrumental in asking Armin to help engage in the work supported by AIHA to compliment his Methodist interest in Kazakhstan. Without him the project would not have begun nor ended . Because of him TMH provided multiple years of support that complimented the AIHA funding and allow Armin to bring many other resources to their effort. A truly warm, respectful and supportive leader. See more at Armin Weinberg, PhD Papers and its finding aid.

Structural Insights Of Transcriptionally Active, Full-Length Androgen Receptor Coactivator Complexes, Xinzhe Yu, Ping Yi, Ross A Hamilton, Hong Shen, Muyuan Chen, Charles E Foulds, Michael A Mancini, Steven J Ludtke, Zhao Wang, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptors activate gene transcription by recruiting coactivators to initiate transcription of their target genes. For most nuclear receptors, the ligand-dependent activation function domain-2 (AF-2) is a primary contributor to the nuclear receptor (NR) transcriptional activity. In contrast to other steroid receptors, such as ERα, the activation function of androgen receptor (AR) is largely dependent on its ligand-independent AF-1 located in its N-terminal domain (NTD). It remains unclear why AR utilizes a different AF domain from other receptors despite that NRs share similar domain organizations. Here, we present cryoelectron microscopy (cryo-EM) structures of DNA-bound full-length AR and its complex structure …

Guidance For Contemporary Use Of Biologics In Management Of Chronic Rhinosinusitis With Nasal Polyps: Discussion From A National Institutes Of Health-Sponsored Workshop, Lauren T Roland, Timothy L Smith, Rodney J Schlosser, Zachary M Soler, Anju T Peters, Tanya M Laidlaw, Benjamin S Bleier, Vijay Ramakrishnan, Elina Toskala, David W Kennedy, Amber U Luong

Faculty, Staff and Student Publications

BACKGROUND: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness.

METHODS: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients.

RESULTS: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice.

CONCLUSION: We suggest that physicians …

Long Noncoding Rna H19x Is A Key Mediator Of Tgf-Β-Driven Fibrosi, Elena Pachera, Shervin Assassi, Gloria A Salazar, Mara Stellato, Florian Renoux, Adam Wunderlin, Przemyslaw Blyszczuk, Robert Lafyatis, Fina Kurreeman, Jeska De Vries-Bouwstra, Tobias Messemaker, Carol A Feghali-Bostwick, Gerhard Rogler, Wouter T Van Haaften, Gerard Dijkstra, Fiona Oakley, Maurizio Calcagni, Janine Schniering, Britta Maurer, Jörg Hw Distler, Gabriela Kania, Mojca Frank-Bertoncelj, Oliver Distler

Faculty, Staff and Student Publications

TGF-β is a master regulator of fibrosis, driving the differentiation of fibroblasts into apoptosis-resistant myofibroblasts and sustaining the production of extracellular matrix (ECM) components. Here, we identified the nuclear long noncoding RNA (lncRNA) H19X as a master regulator of TGF-β-driven tissue fibrosis. H19X was consistently upregulated in a wide variety of human fibrotic tissues and diseases and was strongly induced by TGF-β, particularly in fibroblasts and fibroblast-related cells. Functional experiments following H19X silencing revealed that H19X was an obligatory factor for TGF-β-induced ECM synthesis as well as differentiation and survival of ECM-producing myofibroblasts. We showed that H19X regulates DDIT4L gene …

The Impact Of Narratives And Active Video Games On Long-Term Moderate-To-Vigorous Physical Activity: A Randomized Controlled Trial Protocol, Dar Alon, Caio Victor Sousa, Tom Baranowski, Tiago V Barreira, Romina Cabrera-Perez, Kelly Chiu, Austin Fernandez, Amy Fleischman, Shirley Huang, Jungyun Hwang, Melanie C Green, I-Min Lee, Kelly Lee, Sarah Lessard, Lynne L Levitsky, Aika Misawa, Farzad Noubary, Ronald Samuels, Kyung Jin Sun, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: Although physical activity (PA) has been shown in helping prevent and treat obesity, current PA interventions are still not effective in ameliorating the obesity epidemic. Additional forms of PA need to be investigated to improve PA engagement and outcomes. We hypothesize that pairing a narrative (i.e., story) with an active video game (AVG), a less traditional form of PA, will increase participant engagement in PA. This paper presents the rationale, implementation, and pilot results of a study assessing the effect of narrative's impact on PA and a series of other health outcomes.

Objective: This paper presents the rationale, implementation, …

Fat And Fat-Free Mass Index References In Children And Young Adults: Assessments Along Racial And Ethnic Lines, Roman J Shypailo, William W Wong

Children’s Nutrition Research Center Staff Publications

Background: Fat-free mass index (FFMI) and fat mass index (FMI) are superior to BMI and fat percentage in evaluating nutritional status. However, existing references fail to account for racial/ethnic differences in body composition among children.

Objectives: Our goal was to produce age-based normative references for FFMI and FMI in children for specific racial/ethnic groups.

Methods: Body composition, weight, and height were measured in 1122 normal healthy children aged 2-21 y. Bone mineral content measured by DXA, total body water by deuterium dilution, and total body potassium by whole-body γ counting were combined to calculate fat-free mass (FFM) and fat mass …

Comparison Of Sars-Cov-2 Detection From Nasopharyngeal Swab Samples By The Roche Cobas 6800 Sars-Cov-2 Test And A Laboratory-Developed Real-Time Rt-Pcr Test, Elisabet Pujadas, Nnaemeka Ibeh, Matthew M Hernandez, Aneta Waluszko, Tatyana Sidorenko, Vanessa Flores, Biana Shiffrin, Numthip Chiu, Alicia Young-Francois, Michael D Nowak, Alberto E Paniz-Mondolfi, Emilia M Sordillo, Carlos Cordon-Cardo, Jane Houldsworth, Melissa R Gitman

Faculty, Staff and Student Publications

The urgent need to implement and rapidly expand testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has led to the development of multiple assays. How these tests perform relative to one another is poorly understood. We evaluated the concordance between the Roche Diagnostics cobas 6800 SARS-CoV-2 test and a laboratory-developed test (LDT) real-time reverse transcription-polymerase chain reaction based on a modified Centers for Disease Control and Prevention protocol, for the detection of SARS-CoV-2 in samples submitted to the Clinical Laboratories of the Mount Sinai Health System. A total of 1006 nasopharyngeal swabs in universal transport medium from persons under …

Yttrium-90 Selective Internal Radiotherapy As Bridge To Curative Hepatectomy For Recurrent Malignant Solid Pseudopapillary Neoplasm Of Pancreas: Case Report And Review Of Literature, Adam R Dyas, David Thor Johnson, Erin Rubin, Richard D Schulick, Piyush Kumar Sharma

Faculty, Staff and Student Publications

Recurrent malignant solid pseudopapillary neoplasms of the pancreas (SPNP) are rare tumors with unpredictable clinical and histopathological features. There is a lack of consensus regarding utilization of adjuvant modalities in conjunction with or in lieu of curative metastatectomy. We present a remarkable case where Yttrium-90 selective internal radiation therapy (Y-90 SIRT) was successfully utilized to elucidate underlying tumor biology and aid resection of a large multifocal recurrent metastatic SPNP in the right hemi-liver of a 59-year-old female. Thus, in cases where curative metastatectomy remains the treatment goal in management of recurrent and/or metastatic SPNPs, Y-90 SIRT is a safe and …

Extracorporeal Membrane Oxygenation Utility In Postpartum Patients, Bindu Akkanti, Ismael A Salas De Armas, Ayaaz K Sachedina, Jennifer M Sunny, Mahmoud Samy Ahmed, Avaleen Kaur, Kha T Dinh, Rahat Hussain, Sachin Kumar, Sriram Nathan, Marwan Jumean, Manish K Patel, Mehmet H Akay, Jayeshkumar A Patel, Barbi Witz, John Zaki, Igor Banjac, Lisa Janowiak, Igor D Gregoric, Biswajit Kar

Faculty, Staff and Student Publications

Although extracorporeal membrane oxygenation (ECMO) has been used in many different populations, its use in pregnant or postpartum patients has not been widely studied. This article reviews the ECMO experience in this population at a large urban hospital. Electronic medical records for all pregnant or postpartum patients who required ECMO between 2012 and 2019 were retrospectively reviewed. Data on clinical characteristics, outcomes, and complications were gathered. Comparisons between survivors and nonsurvivors were completed. Ten postpartum patients were identified. The patients presented as follows: four with cardiac arrest, one with a massive pulmonary embolism, three with acute respiratory distress syndrome (ARDS), …

Loss Of Uncoupling Protein 3 Attenuates Western Diet-Induced Obesity, Systemic Inflammation, And Insulin Resistance In Rats, Tyler M Lomax, Sadia Ashraf, Gizem Yilmaz, Romain Harmancey

Faculty, Staff and Student Publications

OBJECTIVE: Uncoupling protein 3 (UCP3) is a mitochondrial carrier related to fatty acid metabolism. Although gene variants of UCP3 are associated with human obesity, their contribution to increased adiposity remains unclear. This study investigated the impact that loss of UCP3 has on diet-induced obesity in rats.

METHODS: Male UCP3 knockout rats (ucp3

RESULTS: Loss of UCP3 decreased fat mass gain, white adipocytes size, and systemic inflammation. The ucp3

CONCLUSIONS: Loss of UCP3 partially protects rats from diet-induced obesity. This phenotype is related to induction of a compensatory antioxidant mechanism and prevention of iBAT whitening.

Early Transplantation In Acute On Chronic Liver Failure: Who And When, Nadim Mahmud, Ruben Hernaez, Tiffany Wu, Vinay Sundaram

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Acute on chronic liver failure (ACLF) is a unique syndrome that afflicts patients with chronic liver disease and results in high short-term mortality, > 50% at 28 days in patients with severe ACLF (grade 3, ACLF-3). Given this prognosis, there is an urgent need to understand risk factors for this condition, as well as selection criteria for patients who may benefit from liver transplantation (LT).

RECENT FINDINGS: Several studies have identified risk factors for developing ACLF, including higher model for end-stage liver disease score, anemia, and morbid obesity, as well ACLF mortality, such as infection, increasing organ failures, …

A Conceptual Model For Residents As Teachers In Obstetrics And Gynecology, Bani M Ratan, Jocelyn T Greely, M Diane Jensen, Charlie C Kilpatrick

Faculty, Staff and Students Publications

BACKGROUND: The learning environment in obstetrics and gynecology (OB/GYN) may have intrinsic differences that require modifying existing resident as teacher models for high-quality teaching.

OBJECTIVE: To explore medical students' views of resident teaching on the OB/GYN clerkship in order to develop more effective educators.

METHODS: Between October 2017 and June 2018, we performed medical student focus groups at the end of the 2-month OB/GYN clerkship. Topics discussed included positive and negative teaching interactions with residents, barriers specific to the OB/GYN clerkship, and best methods for resident teaching. Qualitative analysis utilizing 3 reviewers and N-Vivo software were used to identify themes. …

Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy, Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study

Faculty, Staff and Students Publications

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

RESULTS: Of 256 patients treated in the initial trials, 230 participated in …

Mtor-Initiated Metabolic Switch And Degeneration In The Retinal Pigment Epithelium, Young-Mi Go, Jing Zhang, Jolyn Fernandes, Christopher Litwin, Rui Chen, Theodore G Wensel, Dean P Jones, Jiyang Cai, Yan Chen

Faculty, Staff and Students Publications

The retinal pigment epithelium (RPE) is a particularly vulnerable tissue to age-dependent degeneration. Over the life span, the RPE develops an expanded endo-lysosomal compartment to maintain the high efficiency of phagocytosis and degradation of photoreceptor outer segments (POS) necessary for photoreceptor survival. As the assembly and activation of the mechanistic target of rapamycin complex 1 (mTORC1) occur on the lysosome surface, increased lysosome mass with aging leads to higher mTORC1 activity. The functional consequences of hyperactive mTORC1 in the RPE are unclear. In the current study, we used integrated high-resolution metabolomic and genomic approaches to examine mice with RPE-specific deletion …

Characterization Of Retinal Biomechanical Properties Using Brillouin Microscopy, Yogeshwari S Ambekar, Manmohan Singh, Giuliano Scarcelli, Elda M Rueda, Benjamin M Hall, Ross A Poché, Kirill V Larin

Faculty, Staff and Students Publications

SIGNIFICANCE: The retina is critical for vision, and several diseases may alter its biomechanical properties. However, assessing the biomechanical properties of the retina nondestructively is a challenge due to its fragile nature and location within the eye globe. Advancements in Brillouin spectroscopy have provided the means for nondestructive investigations of retina biomechanical properties.

AIM: We assessed the biomechanical properties of mouse retinas using Brillouin microscopy noninvasively and showed the potential of Brillouin microscopy to differentiate the type and layers of retinas based on stiffness.

APPROACH: We used Brillouin microscopy to quantify stiffness of fresh and paraformaldehyde (PFA)-fixed retinas. As further …

Third-Generation Medium Cross-Linked Polyethylene Demonstrates Very Low Wear In Total Hip Arthroplasty, Omid Jalali, Travis Scudday, Marie-Claire Fickenscher, Steven Barnett, Robert Gorab

Faculty, Staff and Students Publications

BACKGROUND: Cross-linked polyethylene (XLPE) liners have shown lower wear rates than conventional polyethylene liners in total hip arthroplasty. The primary aim of our study was to report our most recent analysis of wear rates and clinical outcomes of a third-generation XLPE liner. Secondary aims were to investigate the rate of adverse events related to mechanical failure or oxidation of this liner.

METHODS: A series of 266 total hip arthroplasties using a specific XLPE liner were retrospectively reviewed. Radiographs were examined to determine linear and volumetric wear rates and presence of osteolysis. Clinical outcomes, revision rates, mechanical failures, and risk factors …

Improvement Of Cryo-Em Maps By Density Modification, Thomas C Terwilliger, Steven J Ludtke, Randy J Read, Paul D Adams, Pavel V Afonine

Faculty, Staff and Students Publications

A density-modification procedure for improving maps from single-particle electron cryogenic microscopy (cryo-EM) is presented. The theoretical basis of the method is identical to that of maximum-likelihood density modification, previously used to improve maps from macromolecular X-ray crystallography. Key differences from applications in crystallography are that the errors in Fourier coefficients are largely in the phases in crystallography but in both phases and amplitudes in cryo-EM, and that half-maps with independent errors are available in cryo-EM. These differences lead to a distinct approach for combination of information from starting maps with information obtained in the density-modification process. The density-modification procedure was …

The De Winter Ecg Pattern: Distribution And Morphology Of St Depression, Zhong-Qun Zhan, Yang Li, Li-Hong Han, Kjell C Nikus, Yochai Birnbaum, Adrian Baranchuk

Faculty, Staff and Students Publications

BACKGROUND: The reported positive predictive value (PPV) for the "de Winter ECG pattern" to predict an acute left anterior descending artery (LAD) lesion is inconsistent. Besides, the morphology of upsloping or nonupsloping ST depression (STD) may have different significance of severity and prognostication.

METHODS: We searched the MEDLINE database using "de Winter" or "junctional ST-depression with tall symmetrical T-waves" or "tall T wave" or "STEMI equivalent" as the item up to March 2020. We compared the ECG differences between the different culprit arteries and various morphological STD.

RESULTS: A total of 70 patients with analyzable ECGs were included. In 60 …

Cangrelor: Safe And Effective For Left Ventricular Assist Device Thrombosis, Roopa Rao, Eve Anderson, Mark Jones, Muhamed Safiia, Maya Guglin

The VAD Journal

Pump thrombosis is a devastating complication of left ventricular assist device implantation as it increases the risk of mortality and morbidity. Early and effective treatment is important to prevent the progression of the clot and to avoid the surgical need for pump exchange or heart transplant. The current strategies of intensifying anticoagulation therapy are not consistently effective and carry significant bleeding risks. Cangrelor is a new pharmacological agent that has been utilized as an antiplatelet agent in several cardiac procedures. In this case series, we describe the use of cangrelor for left ventricular assist device thrombosis in five patients. Cangrelor …

Validating Use Of Electronic Health Data To Identify Patients With Urinary Tract Infections In Outpatient Settings, George Germanos, Patrick Light, Roger Zoorob, Jason Salemi, Fareed Khan, Michael Hansen, Kalpana Gupta, Barbara Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

OBJECTIVE: To validate the use of electronic algorithms based on International Classification of Diseases (ICD)-10 codes to identify outpatient visits for urinary tract infections (UTI), one of the most common reasons for antibiotic prescriptions.

METHODS: ICD-10 symptom codes (e.g., dysuria) alone or in addition to UTI diagnosis codes plus prescription of a UTI-relevant antibiotic were used to identify outpatient UTI visits. Chart review (gold standard) was performed by two reviewers to confirm diagnosis of UTI. The positive predictive value (PPV) that the visit was for UTI (based on chart review) was calculated for three different ICD-10 code algorithms using (1) …

Teaching Diagnostic Reasoning To Faculty Using An Assessment For Learning Tool: Training The Trainer, Adam Cohen, Moushumi Sur, Martin Weisse, Kathryn Moffett, Jeffrey Lancaster, Renee Saggio, Geeta Singhal, Satid Thammasitboon

Faculty, Staff and Students Publications

INTRODUCTION: There is a need for a standardized approach to understand and assess clinical reasoning in medical learners. The Assessment of Reasoning Tool was developed based on prevalent theories and frameworks using a multidisciplinary expert panel. As the tool provides a standardized rubric for assessing clinical reasoning, we designed an interactive train-the-trainer workshop for clinical educators and education leaders interested in improving their teaching skills and/or introducing curricula surrounding diagnostic reasoning.

METHODS: In this workshop, participants were exposed to the major domains of diagnostic reasoning and how to apply it to the assessment of a learner's skills. Kolb's experiential learning …

A Survey Of Dermatology Residents And Program Directors Assessing The Transition To Dermatology Residency, Christina Hopkins, Omid Jalali, Danielle Guffey, Harry Dao

Faculty, Staff and Students Publications

The transition from internship to residency is a critical period for trainees. This study investigated factors that influence the transition of residents from postgraduate year 1 (PGY-1) to dermatology residency. In June 2019, a program director–specific survey and a resident-oriented survey were administered via Survey Monkey. An email containing survey hyperlinks was sent via the Association of Professors of Dermatology Listserv to program directors, who were asked to forward the email to their current trainees. A total of 44 dermatology residents and 33 program directors responded. More than 58% of program directors identified a preliminary year in internal medicine as …

Structure And Mechanism Of A Unique Diiron Center In Mammalian Stearoyl-Coa Desaturase, Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou

Faculty, Staff and Students Publications

Stearoyl-CoA desaturase 1 (SCD1) is a membrane-embedded metalloenzyme that catalyzes formation of a double-bond on a saturated acyl-CoA. SCD1 has a diiron center and its proper function requires an electron transport chain composed of NADH (or NADPH), cytochrome b5 reductase (b5R), and cytochrome b5 (cyt b5). Since SCD1 is a key regulator in fat metabolism and is required for survival of cancer cells, there is intense interest in targeting SCD1 for various metabolic diseases and cancers. Crystal structures of human and mouse SCD1 were reported recently, however, both proteins have two zinc ions instead of two iron ions in the …

Saturated Fats And Health: A Reassessment And Proposal For Food-Based Recommendations: Jacc State-Of-The-Art Review, Arne Astrup, Faidon Magkos, Dennis M Bier, J Thomas Brenna, Marcia C De Oliveira Otto, James O Hill, Janet C King, Andrew Mente, Jose M Ordovas, Jeff S Volek, Salim Yusuf, Ronald M Krauss

Children’s Nutrition Research Center Staff Publications

The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL) cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL particles, which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their …

The Ubiquitin Ligase Cullin-1 Associates With Chromatin And Regulates Transcription Of Specific C-Myc Target Genes, Melanie A Sweeney, Polina Iakova, Laure Maneix, Fu-Yuan Shih, Hannah E Cho, Ergun Sahin, Andre Catic

Faculty, Staff and Students Publications

Transcription is regulated through a dynamic interplay of DNA-associated proteins, and the composition of gene-regulatory complexes is subject to continuous adjustments. Protein alterations include post-translational modifications and elimination of individual polypeptides. Spatially and temporally controlled protein removal is, therefore, essential for gene regulation and accounts for the short half-life of many transcription factors. The ubiquitin-proteasome system is responsible for site- and target-specific ubiquitination and protein degradation. Specificity of ubiquitination is conferred by ubiquitin ligases. Cullin-RING complexes, the largest family of ligases, require multi-unit assembly around one of seven cullin proteins. To investigate the direct role of cullins in ubiquitination of …

Modulation Of Lymphocyte Potassium Channel Kv13 By Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin, Seow Theng Ong, Saumya Bajaj, Mark R Tanner, Shih Chieh Chang, Bankala Krishnarjuna, Xuan Rui Ng, Rodrigo A V Morales, Ming Wei Chen, Dahai Luo, Dharmeshkumar Patel, Sabina Yasmin, Jeremy Jun Heng Ng, Zhong Zhuang, Hai M Nguyen, Abbas El Sahili, Julien Lescar, Rahul Patil, Susan A Charman, Edward G Robins, Julian L Goggi, Peng Wen Tan, Pragalath Sadasivam, Boominathan Ramasamy, Siddana V Hartimath, Vikas Dhawan, Janna Bednenko, Paul Colussi, Heike Wulff, Michael W Pennington, Serdar Kuyucak, Raymond S Norton, Christine Beeton, K George Chandy

Faculty, Staff and Students Publications

We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated KV1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to KV1.3, causing current run-down by a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. EgK5 exhibits selectivity for KV1.3 over other channels, receptors, transporters, and enzymes. EgK5 suppresses antigen-triggered proliferation of effector memory T cells, a subset enriched among pathogenic autoreactive T cells in autoimmune disease. PET-CT imaging with 18F-labeled EgK5 shows accumulation of the peptide in large and small joints of rodents. In keeping with its arthrotropism, EgK5 treats disease in a rat …

Targeting Pd-L1 In Non-Small Cell Lung Cancer Using Car T Cells, Ming Liu, Xu Wang, Wei Li, Xinfang Yu, Pedro Flores-Villanueva, Zijun Y Xu-Monette, Ling Li, Mingzhi Zhang, Ken H Young, Xiaodong Ma, Yong Li

Faculty, Staff and Students Publications

Antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the landscape of therapies for non-small cell lung carcinoma (NSCLC); however, the majority of patients do not respond to these agents. In addition, hyperprogressive disease (HPD) develops in a larger portion of NSCLC patients treated with PD-1/PD-L1 inhibitors than in patients treated with standard chemotherapy. The use of chimeric antigen receptor (CAR) T cells has been successful to treat blood cancers but not for solid tumors like NSCLC. In this work, we constructed CAR T cells that target PD-L1 and evaluated their efficacy in NSCLC …

Low Anterior Resection Syndrome, Theresa H Nguyen, Reena V Chokshi

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Low anterior resection syndrome is a highly prevalent condition that can develop after anal sphincter-sparing surgery for rectal cancer and impair quality of life. In this review, we summarize the major features and pathophysiology of this syndrome and discuss treatment approaches.

RECENT FINDINGS: Quality of life correlates significantly with severity of low anterior resection syndrome. Prompt assessment and initiation of therapy are essential to rehabilitating damaged mechanical and neural structures. Anorectal manometry demonstrates a global decrease in sphincteric function postoperatively, though in many patients, function does recover. Transanal irrigation, pelvic floor rehabilitation, and biofeedback are the mainstays …

Metabolism Of Jq1, An Inhibitor Of Bromodomain And Extra Terminal Bromodomain Proteins, In Human And Mouse Liver Microsomes†, Feng Li, Kevin R Mackenzie, Prashi Jain, Conrad Santini, Damian W Young, Martin M Matzuk

Faculty, Staff and Students Publications

JQ1 is a small-molecule inhibitor of the bromodomain and extra terminal (BET) protein family that potently inhibits the bromodomain testis-specific protein (BRDT), which is essential for spermatogenesis. JQ1 treatment produces a reversible contraceptive effect by targeting the activity of BRDT in mouse male germ cells, validating BRDT as a male contraceptive target. Although JQ1 possesses favourable physical properties, it exhibits a short half-life. Because the details of xenobiotic metabolism play important roles in the optimization of drug candidates and in determining the role of metabolism in drug efficacy, we investigated the metabolism of JQ1 in human and mouse liver microsomes. …