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3i Initiative Weekly Updates
Welcome to the 3i Weekly Update, your source for 3i relevant news and events. Please send all items of interest to Nicole.Frank@hsc.utah.edu by the end of the day on Thursdays.
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2/12- 2/19- TUESDAY, FEBRUARY 16, 2021, 2 – 3PM - Neuroscience Program seminar - Dr. Jenny Hsieh - "Stem cell approaches to understand acquired and genetic epilepsies"
- WEDNESDAY, FEBRUARY 17, 2021, 4 – 5PM - Population Health Sciences Seminar - Dr. Shekinah Elmore - "Global" Breast Cancer: Access to Radiotherapy, Patterns of Care, and Patient Experience in sub-Saharan Africa
- WEDNESDAY, FEBRUARY 17, 2021, 7 – 8:30PM - Understanding the Science: The Covid-19 Vaccine
- THURSDAY, FEBRUARY 18, 2021, 8 – 9AM - Pediatric Grand Rounds - "Gillian Abbots Memorial Lecture - The Mental Health Impacts of COVID on Children, Youth, Families... and Us"
- THURSDAY, FEBRUARY 18, 2021, 10:45AM – 12PM - Dr. Wei-chen Chang - "Mechanistic studies and potential application of non-heme iron enzymes in natural product biosynthesis"
- THURSDAY, FEBRUARY 18, 2021, 4 – 5PM - Rising Star in Metabolism - Dr. Javier Garcia Bermudez - "Understanding the role of metabolic plasticity in tumor progression"
- THURSDAY, FEBRUARY 18, 2021, 4 – 5PM - Department of Geology & Geophysics - Dr. Estella Atekwana - "Biogeophysics: Microbial-mediated changes in geophysical signatures"
- MARCH 9, 2021 - Hematopoietic Stem Cells: Biology, Disease, and Therapy
- MARCH 10, 11 PM - Medical Mycology Trainee Seminar Series
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- Utah Cardiac Recovery Symposium
- THURSDAY, MARCH 18 - FRIDAY, MARCH 19 - 3i Initiative Spring 2021 Symposium - FRIDAY, ARPIL 30, 2021, 8:00 AM -5:00 PM
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New/Competing Renewal NIH Awards:
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- NIAID January 2021 Council-Approved Concepts Posted - See the recently approved concepts from NIAID.
- Open Postdoctoral Research Position - The Puri Lab at the University of Utah seeks to hire a postdoctoral research associate to work on a funded project studying the biosynthesis of natural products made by underexplored bacteria. The ideal candidate will have a Ph.D. in Biochemistry, Chemistry, Microbiology, or a related field, and experience with protein expression, purification, and enzymology. Interested applicants should contact Aaron Puri directly (a.puri@utah.edu) with a cover letter, CV, and contact information for 3 references.
- SEAL (Science Excelerator and Leadership) Program Position Open - With this change in mind, the Gregg lab at the University of Utah is transitioning to a new model of science and discovery that caters to professional scientists by launching the SEAL (Science Excelerator and Leadership) Program. We are investigating new ways to take on higher impact scientific problems and make major advances in a shorter period of time. To help with this, the lab will transition to a new name – the Precision Brain Genetics Lab. This name change reflects the focus of the science and important roles of senior investigators in the lab and their capability to obtain independent grants if they wish. Right now, we are seeking to recruit a new SEAL program scientist to the lab at the level of a career track assistant professor, staff scientist or postdoctoral fellow.
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3i Funding Opportunities
Current Federal and Private FOAs applicable to the 3is can be found on the U's pivot page. New FOAs announced this week:
A monthly funding newsletter from PIVOT is sent to 3i investigators on the 2nd Monday of the month. If you have not been receiving the newsletter and would like to be added, please email Nicole.Frank@hsc.utah.edu.
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3i Investigator PublicationsCongratulations to the teams who published this week. If you have a publication that you would like included, please email us.
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NPJ Biofilms Microbiomes. 2021 Feb 05;7(1):14
Authors: Opron K, Begley LA, Erb-Downward JR, Freeman C, Madapoosi S, Alexis NE, Barjaktarevic I, Graham Barr R, Bleecker ER, Bowler RP, Christenson SA, Comellas AP, Cooper CB, Couper DJ, Doerschuk CM, Dransfield MT, Han MK, Hansel NN, Hastie AT, Hoffman EA, Kaner RJ, Krishnan J, O'Neal WK, Ortega VE, Paine R, Peters SP, Michael Wells J, Woodruff PG, Martinez FJ, Curtis JL, Huffnagle GB, Huang YJ
Abstract
Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes. Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment). Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we find that lung bacterial composition associates with several clinical features, in particular bronchodilator responsiveness, peak expiratory flow rate, and forced expiratory flow rate between 25 and 75% of FVC (FEF25-75). Measures of symptom burden (COPD Assessment Test) and functional impairment (six-minute walk distance) also associate with disparate lung microbiota composition. Drivers of these relationships include members of the Streptococcus, Prevotella, Veillonella, Staphylococcus, and Pseudomonas genera. Thus, lung microbiota differences may contribute to airway dysfunction and airway disease in milder COPD.
PMID: 33547327 [PubMed - as supplied by publisher]
Semin Nucl Med. 2021 Feb 02;:
Authors: Minoshima S, Mosci K, Cross D, Thientunyakit T
Abstract
PET imaging with [F-18]FDG has been used extensively for research and clinical applications in dementia. In the brain, [F-18]FDG accumulates around synapses and represents local neuronal activity. Patterns of altered [F-18]FDG uptake reflecting local neuronal dysfunction provide differential diagnostic clues for various dementing disorders. Image interpretation can be accomplished by employing statistical brain mapping techniques. Various guidelines have been published to support the appropriate use of [F-18]FDG PET for clinical dementia workup. PET images with [F-18]FDG demonstrate distinct patterns of decreased uptake for Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) as well as its multiple subtypes such as behavioral variant FTD, primary progressive aphasia (PPA), progressive supranuclear palsy, and corticobasal degeneration to aid in the differential diagnoses. Mixed dementia, not only AD + Vascular Dementia, but also AD + other neurodegenerative disorders, should also be considered when interpreting [F-18]FDG PET images. Brain PET imaging with [F-18]FDG remains a valuable component of dementia workup owing to its relatively low cost, differential diagnostic performance, widespread availability, and physicians' experience over more than 40 years since the initial development.
PMID: 33546814 [PubMed - as supplied by publisher]
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Cancer Cell. 2021 Feb 08;39(2):148-150
Authors: Viswanath P, Welm AL
Abstract
A new study in Nature determines metastatic tropism in xenograft mouse models. This results in a metastasis map for 21 tumor types, the utility of which is demonstrated by identifying lipid metabolism to be uniquely altered in breast cancer cell lines that metastasize to the brain.
PMID: 33561396 [PubMed - as supplied by publisher]
G3 (Bethesda). 2021 Jan 18;11(1):
Authors: Zaworski J, McClung C, Ruse C, Weigele PR, Hendrix RW, Ko CC, Edgar R, Hatfull GF, Casjens SR, Raleigh EA
Abstract
Bacteriophage L, a P22-like phage of Salmonella enterica sv Typhimurium LT2, was important for definition of mosaic organization of the lambdoid phage family and for characterization of restriction-modification systems of Salmonella. We report the complete genome sequences of bacteriophage L cI-40 13-am43 and L cII-101; the deduced sequence of wildtype L is 40,633 bp long with a 47.5% GC content. We compare this sequence with those of P22 and ST64T, and predict 72 Coding Sequences, 2 tRNA genes and 14 intergenic rho-independent transcription terminators. The overall genome organization of L agrees with earlier genetic and physical evidence; for example, no secondary immunity region (immI: ant, arc) or known genes for superinfection exclusion (sieA and sieB) are present. Proteomic analysis confirmed identification of virion proteins, along with low levels of assembly intermediates and host cell envelope proteins. The genome of L is 99.9% identical at the nucleotide level to that reported for phage ST64T, despite isolation on different continents ∼35 years apart. DNA modification by the epigenetic regulator Dam is generally incomplete. Dam modification is also selectively missing in one location, corresponding to the P22 phase-variation-sensitive promoter region of the serotype-converting gtrABC operon. The number of sites for SenLTIII (StySA) action may account for stronger restriction of L (13 sites) than of P22 (3 sites).
PMID: 33561243 [PubMed - as supplied by publisher]
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Cancers (Basel). 2021 Feb 08;13(4):
Authors: Araujo A, Cook LM, Frieling JS, Tan W, Copland JA, Kohli M, Gupta S, Dhillon J, Pow-Sang J, Lynch CC, Basanta D
Abstract
BACKGROUND: Bone metastatic prostate cancer (BMPCa), despite the initial responsiveness to androgen deprivation therapy (ADT), inevitably becomes resistant. Recent clinical trials with upfront treatment of ADT combined with chemotherapy or novel hormonal therapies (NHTs) have extended overall patient survival. These results indicate that there is significant potential for the optimization of standard-of-care therapies to delay the emergence of progressive metastatic disease.
METHODS: Here, we used data extracted from human bone metastatic biopsies pre- and post-abiraterone acetate/prednisone to generate a mathematical model of bone metastatic prostate cancer that can unravel the treatment impact on disease progression. Intra-tumor heterogeneity in regard to ADT and chemotherapy resistance was derived from biopsy data at a cellular level, permitting the model to track the dynamics of resistant phenotypes in response to treatment from biological first-principles without relying on data fitting. These cellular data were mathematically correlated with a clinical proxy for tumor burden, utilizing prostate-specific antigen (PSA) production as an example.
RESULTS: Using this correlation, our model recapitulated the individual patient response to applied treatments in a separate and independent cohort of patients (n = 24), and was able to estimate the initial resistance to the ADT of each patient. Combined with an intervention-decision algorithm informed by patient-specific prediction of initial resistance, we propose to optimize the sequence of treatments for each patient with the goal of delaying the evolution of resistant disease and limit cancer cell growth, offering evidence for an improvement against retrospective data.
CONCLUSIONS: Our results show how minimal but widely available patient information can be used to model and track the progression of BMPCa in real time, offering a clinically relevant insight into the patient-specific evolutionary dynamics of the disease and suggesting new therapeutic options for intervention.
TRIAL REGISTRATION: NCT # 01953640.
FUNDING: Funded by an NCI U01 (NCI) U01CA202958-01 and a Moffitt Team Science Award. CCL and DB were partly funded by an NCI PSON U01 (U01CA244101). AA was partly funded by a Department of Defense Prostate Cancer Research Program (W81XWH-15-1-0184) fellowship. LC was partly funded by a postdoctoral fellowship (PF-13-175-01-CSM) from the American Cancer Society.
PMID: 33567529 [PubMed]
Am J Respir Crit Care Med. 2021 01 15;203(2):211-220
Authors: Richeldi L, Scholand MB, Lynch DA, Colby TV, Myers JL, Groshong SD, Chung JH, Benzaquen S, Nathan SD, Davis JR, Schmidt SL, Hagmeyer L, Sonetti D, Hetzel J, Criner GJ, Case AH, Ramaswamy M, Calero K, Gauhar UA, Patel NM, Lancaster L, Choi Y, Pankratz DG, Walsh PS, Lofaro LR, Huang J, Bhorade SM, Kennedy GC, Martinez FJ, Raghu G
Abstract
Rationale: Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A "molecular diagnosis of UIP" in transbronchial lung biopsy, the Envisia Genomic Classifier, accurately predicted histopathologic UIP.Objectives: We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern.Methods: Ninety-six patients who had diagnostic lung pathology as well as a transbronchial lung biopsy for molecular testing with Envisia Genomic Classifier were included in this analysis. The classifier results were scored against reference pathology. UIP identified on high-resolution computed tomography (HRCT) as documented by features in local radiologists' reports was compared with histopathology.Measurements and Main Results: In 96 patients, the Envisia Classifier achieved a specificity of 92.1% (confidence interval [CI],78.6-98.3%) and a sensitivity of 60.3% (CI, 46.6-73.0%) for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology, with a sensitivity of 34.0% (CI, 21.5-48.3%) and a specificity of 96.9% (CI, 83.8-100%). In conjunction with HRCT patterns of UIP, the Envisia Classifier results identified 24 additional patients with UIP (sensitivity 79.2%; specificity 90.6%).Conclusions: In 96 patients with suspected interstitial lung disease, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an interstitial lung disease (especially IPF) diagnosis without the need for a surgical lung biopsy.
PMID: 32721166 [PubMed - indexed for MEDLINE]
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