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11. Global Regulatory DNA Potentiation by SMARCA4 Propagates to Selective Gene Expression Programs via Domain-Level Remodeling

Author

Lazar, John E., Stehling-Sun, Sandra, Nandakumar, Vivek, Wang, Hao, Chee, Daniel R., Howard, Nicholas P., Acosta, Reyes, Dunn, Douglass, Diegel, Morgan, Neri, Fidencio, Castillo, Andres, Ibarrientos, Sean, Lee, Kristen, Lescano, Ninnia, Van Biber, Ben, Nelson, Jemma, Halow, Jessica, Sandstrom, Richard, Bates, Daniel, Urnov, Fyodor D., Stamatoyannopoulos, John A., and Funnell, Alister P.W.

Published
2020
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13. Global reference mapping of human transcription factor footprints

Author

Vierstra, Jeff, Lazar, John, Sandstrom, Richard, Halow, Jessica, Lee, Kristen, Bates, Daniel, and Diegel, Morgan

Subjects
Binding sites (Biochemistry) -- Identification and classification -- Analysis -- Methods, Human chromosomes -- Identification and classification -- Analysis -- Methods, Transcription factors -- Analysis -- Methods, Chromosome mapping -- Methods -- Analysis, Genome-wide association studies -- Analysis -- Methods, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Combinatorial binding of transcription factors to regulatory DNA underpins gene regulation in all organisms. Genetic variation in regulatory regions has been connected with diseases and diverse phenotypic traits.sup.1, but it remains challenging to distinguish variants that affect regulatory function.sup.2. Genomic DNase I footprinting enables the quantitative, nucleotide-resolution delineation of sites of transcription factor occupancy within native chromatin.sup.3-6. However, only a small fraction of such sites have been precisely resolved on the human genome sequence.sup.6. Here, to enable comprehensive mapping of transcription factor footprints, we produced high-density DNase I cleavage maps from 243 human cell and tissue types and states and integrated these data to delineate about 4.5 million compact genomic elements that encode transcription factor occupancy at nucleotide resolution. We map the fine-scale structure within about 1.6 million DNase I-hypersensitive sites and show that the overwhelming majority are populated by well-spaced sites of single transcription factor-DNA interaction. Cell-context-dependent cis-regulation is chiefly executed by wholesale modulation of accessibility at regulatory DNA rather than by differential transcription factor occupancy within accessible elements. We also show that the enrichment of genetic variants associated with diseases or phenotypic traits in regulatory regions.sup.1,7 is almost entirely attributable to variants within footprints, and that functional variants that affect transcription factor occupancy are nearly evenly partitioned between loss- and gain-of-function alleles. Unexpectedly, we find increased density of human genetic variation within transcription factor footprints, revealing an unappreciated driver of cis-regulatory evolution. Our results provide a framework for both global and nucleotide-precision analyses of gene regulatory mechanisms and functional genetic variation. A high-density DNase I cleavage map from 243 human cell and tissue types provides a genome-wide, nucleotide-resolution map of human transcription factor footprints., Author(s): Jeff Vierstra [sup.1] , John Lazar [sup.1] [sup.2] , Richard Sandstrom [sup.1] , Jessica Halow [sup.1] , Kristen Lee [sup.1] , Daniel Bates [sup.1] , Morgan Diegel [sup.1] , [...]

Published
2020
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19. Utility of erector spinae plane block in thoracic surgery

Author

Pirsaharkhiz, Naghmeh, Comolli, Kelly, Fujiwara, Wakana, Stasiewicz, Susan, Boyer, Jeanne M., Begin, Eileen V., Rubinstein, Adam J., Henderson, Hayley R., Lazar, John F., Watson, Thomas J., Eger, Christopher M., Trankiem, Christine T., Phillips, Debra G., and Khaitan, Puja Gaur

Published
2020
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24. Understanding Why Residents May Inaccurately Log Their Role in Operations: A Look at the 2013 In-Training Examination Survey

Author

Robich, Michael P., Flagg, Andrew, LaPar, Damien J., Odell, David D., Stein, William, Aftab, Muhammad, Berfield, Kathleen S., Eilers, Amanda L., Groth, Shawn S., Lazar, John F., Shah, Asad A., Smith, Danielle A., Stephens, Elizabeth H., Stock, Cameron T., DeNino, Walter F., Tchantchaleishvili, Vakhtang, and Soltesz, Edward G.

Published
2016
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27. Predictors of Career Choice Among Cardiothoracic Surgery Trainees

Author

Tchantchaleishvili, Vakhtang, LaPar, Damien J., Odell, David D., Stein, William, Aftab, Muhammad, Berfield, Kathleen S., Eilers, Amanda L., Groth, Shawn S., Lazar, John F., Robich, Michael P., Shah, Asad A., Smith, Danielle A., Stephens, Elizabeth H., Stock, Cameron T., DeNino, Walter F., and Nguyen, Tom C.

Published
2015
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32. Objective performance indicators of cardiothoracic residents are associated with vascular injury during robotic-assisted lobectomy on porcine models

Author

Lazar, John F., primary, Brown, Kristen, additional, Yousaf, Sadia, additional, Jarc, Anthony, additional, Metchik, Ariana, additional, Henderson, Hayley, additional, Feins, Richard H., additional, Sancheti, Manu S., additional, Lin, Jules, additional, Yang, Stephen, additional, Nesbitt, Jonathan, additional, D’Souza, Desmond, additional, and Oh, Daniel S., additional

Published
2022
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38. Visual abstract – Supplemental material for The Scan, the Needle, or the Knife? National Trends in Diagnosing Stage I Lung Cancer

Author

Lazar, John F., Adnan, Sakib M., Alpert, Naomi, Joshi, Shivam, Abbas, Abbas E., Bhora, Faiz Y., Taioli, Emanuela, and Bakhos, Charles T.

Subjects
FOS: Clinical medicine, 110323 Surgery
Abstract

Supplemental material, sj-pptx-1-inv-10.1177_15569845221140399 for The Scan, the Needle, or the Knife? National Trends in Diagnosing Stage I Lung Cancer by John F. Lazar, Sakib M. Adnan, Naomi Alpert, Shivam Joshi, Abbas E. Abbas, Faiz Y. Bhora, Emanuela Taioli and Charles T. Bakhos in Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery

Published
2022
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42. Smart Working Paradigms in a Hybrid Working era.

Author

Robu, Daniela and Lazar, John B.

Subjects
*DIGITAL transformation, *FINANCIAL technology, *DASHBOARDS (Management information systems), *WORK environment, *TECHNOLOGY Acceptance Model
Abstract

If we observe top companies in any industry, we notice they have one thing in common: innovation. Successful business leaders recognize when the same ideas and methods used before aren't working anymore. Smart, innovative approaches are needed for our hybrid working environment. The ABCD business model shows that present organizations spend the majority of their time on activities related to business administration (A) and doing repetitive work (D). The rest of the time is allocated to dealing with crises (C), and only nominally to improving the ways business is done (B). Digital transformation, competition, and the need for organizations to leverage technology and innovation in the future will 'force' organizations to maintain A, increase B, and (strategize how to) decrease C and D. Two initiatives will be unpacked and common elements will be identified as indicators in improving B. Five ways to change the game and become a human-focused organization that promotes innovation are proposed based on our learnings: People: 1. Encourage a growth mindset of continuous learning, creativity in how problems are solved, and flexibility how work gets done, 2. Encourage innovative thinking; create innovative groups, 3. Build skills, e.g., analytical thinking, innovation, creativity, and initiative, Workplace: 4. Design a psychologically safe culture, where people are included, can learn, have a sense of belonging, are appreciated, and valued for who they are and what they contribute and challenge. Technology: 5. Create an experimentation lab to TRY-TEST-ADAPT in rapid cycles to learn and fail/learn fast or advance the innovation. We are faced with multiple, messy issues that require out-of-the-box thinking and innovative solutions. Capturing lessons learned can build leading indicators that will help improve B. A simulation dashboard that quantifies the change is an innovation tool we plan to develop. [ABSTRACT FROM AUTHOR]

Published
2022
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45. Vulnerability of cholecystokinin-expressing GABAergic interneurons in the unilateral intrahippocampal kainate mouse model of temporal lobe epilepsy

Author

In-Hyun Park, Bret N. Smith, Young-Jin Kang, Ethan M. Clement, Lazar John Greenfield, and Sang-Hun Lee

Subjects
0301 basic medicine, Male, Hippocampus, Gene Expression, Kainate receptor, Biology, Hippocampal formation, Article, Temporal lobe, Lesion, 03 medical and health sciences, Epilepsy, Mice, 0302 clinical medicine, Developmental Neuroscience, Interneurons, medicine, Animals, GABAergic Neurons, CA1 Region, Hippocampal, Cholecystokinin, Kainic Acid, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, nervous system, Neurology, Epilepsy, Temporal Lobe, GABAergic, Female, medicine.symptom, Neuroscience, 030217 neurology & neurosurgery
Abstract

Temporal lobe epilepsy (TLE) is characterized by recurrent spontaneous seizures and behavioral comorbidities. Reduced hippocampal theta oscillations and hyperexcitability that contribute to cognitive deficits and spontaneous seizures are present beyond the sclerotic hippocampus in TLE. However, the mechanisms underlying compromised network oscillations and hyperexcitability observed in circuits remote from the sclerotic hippocampus are largely unknown. Cholecystokinin (CCK)-expressing basket cells (CCKBCs) critically participate in hippocampal theta rhythmogenesis, and regulate neuronal excitability. Thus, we examined whether CCKBCs were vulnerable in nonsclerotic regions of the ventral hippocampus remote from dorsal sclerotic hippocampus using the intrahippocampal kainate (IHK) mouse model of TLE, targeting unilateral dorsal hippocampus. We found a decrease in the number of CCK+ interneurons in ipsilateral ventral CA1 regions from epileptic mice compared to those from sham controls. We also found that the number of boutons from CCK+ interneurons was reduced in the stratum pyramidale, but not in other CA1 layers, of ipsilateral hippocampus in epileptic mice, suggesting that CCKBCs are vulnerable. Electrical recordings showed that synaptic connectivity and strength from surviving CCKBCs to CA1 pyramidal cells (PCs) were similar between epileptic mice and sham controls. In agreement with reduced CCKBC number in TLE, electrical recordings revealed a significant reduction in amplitude and frequency of IPSCs in CA1 PCs evoked by carbachol (commonly used to excite CCK+ interneurons) in ventral CA1 regions from epileptic mice versus sham controls. These findings suggest that loss of CCKBCs beyond the hippocampal lesion may contribute to hyperexcitability and compromised network oscillations in TLE.

Published
2021

49. Su620 CAN CLINICAL COMPLETE RESPONSE PREDICT PATHOLOGIC COMPLETE RESPONSE FOLLOWING NEOADJUVANT CHEMORADIATION FOR ESOPHAGEAL CANCER?

Author

Holliday, Tyler L., primary, Khaitan, Puja G., additional, Carroll, Austin H., additional, Hofstetter, Wayne L., additional, Corsini, Erin M., additional, Zhou, Nicolas, additional, Desale, Sameer, additional, Lazar, John F., additional, Magolis, Marc, additional, Henderson, Hayley R., additional, Malouf, Stefanie C., additional, Hamm, Margaret E., additional, and Watson, Thomas J., additional

Published
2021
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