110 results on '"Philip Chu"'
Search Results
2. Modeling changes in ice dynamics and subsurface thermal structure in Lake Michigan-Huron between 1979 and 2021
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David Cannon, Ayumi Fujisaki-Manome, Jia Wang, James Kessler, and Philip Chu
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Oceanography - Abstract
The world’s largest lakes, including the Laurentian Great Lakes, have experienced significant surface warming and loss of ice cover over the last several decades. Although changing surface conditions have received substantial research interest, changes below the surface remain largely unexplored, despite their importance for turbulent mixing, nutrient cycling, and primary production. In this study, we investigate changes in subsurface thermal structure and timing in Lake Michigan-Huron related to ongoing climate warming. This work utilizes atmospheric reanalysis data to drive the Great Lakes Finite Volume Community Ocean Model (GL-FVCOM), providing three-dimensional hydrodynamic and ice simulations between 1979 and 2021. Results are used to analyze trends in ice and temperature dynamics, revealing significant changes in annually averaged ice cover (− 2.1– − 5.2%/decade), ice thickness (− 0.68 – − 2.0 cm/decade), surface temperature (+ 0.47– + 0.51 $$^\circ{\rm C}$$ ∘ C /decade), and bottom temperature (+ 0.26– + 0.29 $$^\circ{\rm C}$$ ∘ C /decade) over the last 40 years, especially in ecologically important bays (e.g., Green Bay, Saginaw Bay). Significant warming was observed at all depth layers (0–270 m), with warming trends in the epilimnion and hypolimnion that agreed well with recent analysis of observational data in Lake Michigan. Shifting stratification dynamics led to dramatic changes in modelled overturning behavior, and earlier spring turnover dates (− 2.2– − 7.5 days/decade) and later fall turnover dates (+ 2.5– + 6.3 days/decade) led to a net lengthening of the stratified period. This study presents one of the most comprehensive analyses of changes in Great Lakes subsurface temperatures to date, providing important context for future climate modelling and coastal management efforts in the region.
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- 2023
3. To Use the Back-up Cochlear Implant or Not? Using Intra-operative Impedance to Guide Your Decisions
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Nishchay Mehta, Philip Chu, and Catherine S. Birman
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Cochlear Implants ,Otorhinolaryngology ,Electric Impedance ,Humans ,Neurology (clinical) ,Cochlear Implantation ,Sensory Systems ,Cochlea ,Retrospective Studies - Abstract
Intra-operative electrophysiological testing is being increasingly used to determine device functionality. Impedance abnormalities (open or short circuits) measured at time of surgery pose a dilemma: is it likely to resolve or is it a permanent fault? There is little in the literature on how to manage these intraoperative finding and if, at time of surgery, the back-up device should be used.We routinely undertake impedance testing twice intraoperatively, as well as at switch on, 1 and 3 months postoperatively. Retrospective impedance thresholds were analysed for one surgeon's cases between January 2018 and December 2019.There were 235 cochlear implants performed for 217 patients (5,020 electrode contacts) analysed. Thirty-three electrodes had abnormal impedance thresholds on first intraoperative cycle of testing, 76% resolving with the second testing cycle electrode contacts that demonstrated abnormal impedance during both intraoperative test cycles were 16.54 times (95%CI 2.55-107.13, p = 0.003) more likely to be abnormal at three months. Fifty percent resolved by switch on. The intraoperative abnormalities made up 26% of electrode abnormalities seen at 3 months postoperatively.This study demonstrates the utility of 2 cycles of intraoperative impedance testing, with persistently abnormal electrodes having 16 times the likelihood of persistent abnormalities of impedance, and 50% resolution. These persistent intra-operative abnormal electrodes are responsibly for 26% of electrode abnormalities at 3 months. This information is useful for the surgeon when considering use of the backup cochlear implant device.
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- 2022
4. TRIDENT Drill for VIPER and PRIME-1 Missions to the Moon
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Kris Zacny, Philip Chu, Vince Vendiola, Paul Creekmore, Phil Ng, Sam Goldman, Emily Seto, Kathryn Bywaters, Ezra Bailey, Raymond Zheng, Lilly Ware, Ash Rashedi, Phil Beard, Paul Chow, Stella Dearing, Amelia Grossman, Robert Huddleston, Kevin Humphrey, Anchal Jain, David Lakomski, Zach Mank, Gale Paulsen, Sara Martinez, Tom O’Bannon, Aayush Parekh, Jeff Shasho, Alex Wang, Jack Wilson, Helen Xu, Jackie Quinn, Amy Eichenbaum, Janine Captain, and Julie Kleinhenz
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- 2023
5. 304 Off-the-shelf iPSC-derived CAR-T cells containing seven functional edits overcome antigen heterogeneity, improve trafficking, and withstand immunosuppression associated with failed tumor treatment
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Martin Hosking, Soheila Shirinbak, Bishwas Shrestha, Joy Grant, Kyla Omilusik, Hannah Keegan, Demetrio Cardenas, Angela Gentile, Shilpi Chandra, Lorraine Loter, Lexe Linderhof, Nicholas Brookhouser, Stephanie Kennedy, Francisco Martinez, Loraine Campanati, Chris Ecker, Xu Yuan, Karina Palomares, Yi-Shin Lai, Lauren Fong, Yijia Pan, Shohreh Sikaroodi, Mark Jelcic, Philip Chu, Amit Mehta, Layton Smith, Eigen Peralta, Tom Lee, Ramzey Abujarour, Raedun Clarke, and Bob Valamehr
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- 2022
6. 276 Engineering of synthetic chemokine receptors into iPSC-derived CAR-T cells to increase homing and enhance trafficking into solid tumors
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Soheila Shirinbak, Joy Grant, Angela Gentile, Bishwas Shrestha, Philip Chu, Amit Mehta, Yijia Pan, Bjoern Gaertner, Mochtar Pribadi, Joyee Yao, Matthew Denholtz, Alec Witty, Layton Smith, Tom Lee, Eigen Peralta, Martin Hosking, and Bob Valamehr
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- 2022
7. A CD3 Fusion Receptor (CD3-FR) Uniquely Enables Compatibility of Allogeneic CAR-T and -NK Cells with T Cell Engagers to Enhance Antitumor Function and Limit Antigen Escape
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Eigen Peralta, Dan Lu, Mark Landon, Hui-yi Chu, Soo Park, Masanao Tsuda, Trevor Zarecki, Elena Demeester, Matthew Denholtz, Amit Mehta, Earl Avramis, Philip Chu, Jeffrey Chen, Eric Sung, Alec Witty, Tom Lee, and Bahram Valamehr
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
8. Cover Image, Volume 9, Issue 4
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Ayumi Fujisaki‐Manome, David M. Wright, Greg E. Mann, Eric J. Anderson, Philip Chu, Christiane Jablonowski, and Stanley G. Benjamin
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Ecology ,Ocean Engineering ,Management, Monitoring, Policy and Law ,Aquatic Science ,Oceanography ,Water Science and Technology - Published
- 2022
9. Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection
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James Hurley, Johan Skog, Anand Srivastava, Albana B Mihali, Leonardo V. Riella, Karim M. Yatim, Jamil Azzi, Mauricio P. Lima Filho, Bruno T. Aoyama, Juliano B. Alhaddad, Siawosh K. Eskandari, Hazim Allos, James F. Markmann, Kassem Safa, Isadora T. Lape, Vasisht Tadigotla, Anil Chandraker, John Choi, Christine M. Coticchia, Richard N. Formica, Areej Alghamdi, Philip Chu, and Rania El Fekih
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Urinary system ,General Medicine ,030230 surgery ,Gene signature ,medicine.disease ,Exosome ,Transplant rejection ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Clinical Research ,Nephrology ,Internal medicine ,Biopsy ,medicine ,Biomarker (medicine) ,Liquid biopsy ,business ,Kidney transplantation - Abstract
Background Developing a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells' proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection. Methods Using 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets. Results An exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature's negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell-mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature's negative predictive value was 90.6% and its positive predictive value was 77.8%. Conclusions Our findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.
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- 2021
10. High-Throughput/High Content Imaging Screen Identifies Novel Small Molecule Inhibitors and Immunoproteasomes as Therapeutic Targets for Chordoma
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Amrendra K. Ajay, Philip Chu, Poojan Patel, Christa Deban, Chitran Roychowdhury, Radhika Heda, Ahmad Halawi, Anis Saad, Nour Younis, Hao Zhang, Xiuju Jiang, Mahmoud Nasr, Li-Li Hsiao, Gang Lin, and Jamil R. Azzi
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chordoma ,proteasome ,high-throughput screening ,rare disease ,cell proliferation ,Pharmaceutical Science - Abstract
Chordomas account for approximately 1–4% of all malignant bone tumors and 20% of primary tumors of the spinal column. It is a rare disease, with an incidence estimated to be approximately 1 per 1,000,000 people. The underlying causative mechanism of chordoma is unknown, which makes it challenging to treat. Chordomas have been linked to the T-box transcription factor T (TBXT) gene located on chromosome 6. The TBXT gene encodes a protein transcription factor TBXT, or brachyury homolog. Currently, there is no approved targeted therapy for chordoma. Here, we performed a small molecule screening to identify small chemical molecules and therapeutic targets for treating chordoma. We screened 3730 unique compounds and selected 50 potential hits. The top three hits were Ribociclib, Ingenol-3-angelate, and Duvelisib. Among the top 10 hits, we found a novel class of small molecules, including proteasomal inhibitors, as promising molecules that reduce the proliferation of human chordoma cells. Furthermore, we discovered that proteasomal subunits PSMB5 and PSMB8 are increased in human chordoma cell lines U-CH1 and U-CH2, confirming that the proteasome may serve as a molecular target whose specific inhibition may lead to better therapeutic strategies for chordoma.
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- 2023
11. Forecasting lake‐/ <scp>sea‐effect</scp> snowstorms, advancement, and challenges
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Ayumi Fujisaki‐Manome, David M. Wright, Greg E. Mann, Eric J. Anderson, Philip Chu, Christiane Jablonowski, and Stanley G. Benjamin
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Ecology ,Ocean Engineering ,Management, Monitoring, Policy and Law ,Aquatic Science ,Oceanography ,Water Science and Technology - Published
- 2022
12. mTORC1 Inhibition Protects Human Regulatory T Cells From Granzyme-B-Induced Apoptosis
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Siawosh K. Eskandari, Hazim Allos, Basmah S. Al Dulaijan, Gandolina Melhem, Ina Sulkaj, Juliano B. Alhaddad, Anis J. Saad, Christa Deban, Philip Chu, John Y. Choi, Branislav Kollar, Bohdan Pomahac, Leonardo V. Riella, Stefan P. Berger, Jan S. F. Sanders, Judy Lieberman, Li Li, Jamil R. Azzi, Groningen Kidney Center (GKC), and Groningen Institute for Organ Transplantation (GIOT)
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EXPRESSION ,FOXP3 ,Immunology ,Receptors, Antigen, T-Cell ,RAPAMYCIN INHIBITION ,Apoptosis ,Mechanistic Target of Rapamycin Complex 1 ,T-Lymphocytes, Regulatory ,Granzymes ,CALCINEURIN ,Mice ,granzyme B ,grapoptosis ,KINASE ,Immunology and Allergy ,Animals ,Humans ,treg homeostasis ,MODULATION ,MEDIATED SUPPRESSION ,mTORC1 ,rapamycin ,INDUCTION ,PERFORIN ,human tregs ,MAMMALIAN TARGET - Abstract
Regulatory T cells (Tregs) have shown great promise as a means of cellular therapy in a multitude of allo- and auto-immune diseases—due in part to their immunosuppressive potency. Nevertheless, the clinical efficacy of human Tregsin patients has been limited by their poorin vivohomeostasis. To avert apoptosis, Tregsrequire stable antigenic (CD3ζ/T-cell-receptor-mediated), co-stimulatory (CD28-driven), and cytokine (IL-2-dependent) signaling. Notably, this sequence of signals supports an activated Tregphenotype that includes a high expression of granzymes, particularly granzyme B (GrB). Previously, we have shown that aside from the functional effects of GrB in lysing target cells to modulate allo-immunity, GrB can leak out of the intracellular lysosomal granules of host Tregs, initiating pro-apoptotic pathways. Here, we assessed the role of inhibiting mechanistic target of rapamycin complex 1 (mTORC1), a recently favored drug target in the transplant field, in regulating human TregapoptosisviaGrB. Usingex vivomodels of human Tregculture and a humanized mouse model of human skin allotransplantation, we found that by inhibiting mTORC1 using rapamycin, intracytoplasmic expression and functionality of GrB diminished in host Tregs; lowering human Tregapoptosis by in part decreasing the phosphorylation of S6K and c-Jun. These findings support the already clinically validated effects of mTORC1 inhibition in patients, most notably their stabilization of Tregbioactivity andin vivohomeostasis.
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- 2022
13. Pneumatic Sampler (P-Sampler) for the Martian Moons Exploration (MMX)
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Hunter Williams, Tomas Statler, Hirotaka Sawada, Lisa Thomas, Tomohiro Usui, Michael Zolensky, Takane Imada, Masaki Fujimoto, Kris Zacny, Hiroki Kato, Dara Sabahi, Yasutaka Satou, J. Spring, Gale Paulsen, Dylan Van Dyne, Philip Chu, Leonard A. Dudzinski, Robert P. Mueller, and Sherman Lam
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Moons of Mars ,Geology ,MMX ,Astrobiology - Published
- 2021
14. Comparison of Strategies to Conserve Iodinated Intravascular Contrast Media for Computed Tomography During a Shortage
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Matthew S, Davenport, Philip, Chu, Timothy P, Szczykutowicz, and Rebecca, Smith-Bindman
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Health Care Rationing ,Iodine Compounds ,Research Letter ,Contrast Media ,Infusions, Parenteral ,General Medicine ,Tomography, X-Ray Computed - Abstract
This study models the amount of contrast that could be conserved in computed tomographic examinations in the context of the current global shortage of iodinated contrast media.
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- 2022
15. Developing a Speckle Pattern to Evaluate Adhesive Joints Using Digital Image Correlation
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Seyed Fouad Karimian and Tsuchin Philip Chu
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010302 applied physics ,Digital image correlation ,business.industry ,Computer science ,Mechanical Engineering ,Track (disk drive) ,Condensed Matter Physics ,01 natural sciences ,Ultrasonic imaging ,Speckle pattern ,Mechanics of Materials ,0103 physical sciences ,General Materials Science ,Computer vision ,Adhesive ,Artificial intelligence ,business ,010301 acoustics - Abstract
Digital Image Correlation (DIC) is a known Non-Destructive Evaluation (NDE) method used in various industries. DIC requires a randomly produced pattern, known as speckle pattern, to track a...
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- 2019
16. Abstract 5513: Chimeric CD3 fusion receptors expressed on iPSC-derived universal TCR-less CAR-T and -NK cells synergize with bispecific engagers to enhance antitumor activity and limit antigen escape
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Eigen Peralta, Dan Lu, Mark Landon, Hui-Yi Chu, Amit Mehta, Philip Chu, Alec Witty, Tom Lee, and Bahram Valamehr
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Cancer Research ,Oncology - Abstract
Despite success in hematologic malignancies, chimeric antigen receptor (CAR) T cells have been less effective in solid tumors, in part because of the heterogeneous expression of the CAR-specific target antigen (1° Ag) found within the tumor mass. In combination with a CAR, bispecific T cell engagers (BiTEs) can target additional tumor antigens (2° Ag) while engaging CD3 signaling molecules on T cells, providing a unique way to address tumor heterogeneity, mitigate antigen escape and further potentiate durable effector function. However, in generating off-the-shelf universal CAR-T and NK cells, a combination strategy is not feasible as neither modified cell product is compatible to specifically engage with a BiTE. In developing allogeneic CAR-T cells, the T cell receptor (TCR) surface expression must be eliminated to prevent graft versus host disease, but the absence of surface TCR expression leads to loss of surface CD3 expression and BiTE compatibility. Similarly, NK cells naturally lack TCR expression and have no surface CD3 molecules for BiTE engagement. Here we discuss the development of a novel chimeric CD3ε fusion receptor (CD3-CFR) with a modified transmembrane and endodomain enabling surface expression in TCR-less T or NK cells, allowing for a novel combinatorial solution between universal CAR-T or NK cells with BiTEs in an allogeneic setting. CD3-CFR signal transduction was initially investigated in TRAC knockout NFAT reporter (T-KO) Jurkat cells engineered with CD3-CFR and co-cultured with EpCAM+ target cells. When soluble EpCAM-BiTE was added to the co-culture, the observed 6.9-fold increase in NFAT activity indicated successful engagement associated with the interaction of CD3-CFR, target cells and the BiTE. CD3-CFR T-KO Jurkat cells were further modified to secrete the EpCAM-BiTE and showed increased NFAT activity, demonstrating the feasibility of self-secreting BiTE-mediated targeting through CD3-CFR signaling. We next engineered CD3-CFR expressing iPSC-derived CAR-T (iT) cells to show preserved T cell differentiation kinetics and maintained CAR activity against 1° Ag positive targets (>90% cytolysis). Importantly, while CAR-iT cells showed only background lysis of 1° Ag negative tumor cells, CD3-CFR+ CAR-iT cells were able to lyse ~99% of 1° Ag negative tumor cells with the addition of soluble EpCAM-BiTE targeting the 2° Ag. When CD3-CFR+ CAR-iT cells were further engineered to secrete the EpCAM-BiTE, CD3-CFR+ BiTE+ CAR-iT cells demonstrated superior killing of heterogenous tumors compared to CD3-CFR+ BiTE- CAR-iT cells (70% vs. 5% cytolysis). Taken together these data demonstrate for the first time that CD3 expression and BiTE engagement can be combined in a universal iPSC-derived CAR-iT cell product to overcome antigen heterogeneity and enhance efficacy in solid tumor settings. Citation Format: Eigen Peralta, Dan Lu, Mark Landon, Hui-Yi Chu, Amit Mehta, Philip Chu, Alec Witty, Tom Lee, Bahram Valamehr. Chimeric CD3 fusion receptors expressed on iPSC-derived universal TCR-less CAR-T and -NK cells synergize with bispecific engagers to enhance antitumor activity and limit antigen escape [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5513.
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- 2022
17. The Impact of the COVID-19 Pandemic and Telemedicine Implementation on Practice Patterns and Electronic Health Record Utilization in an Academic Rheumatology Practice
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Megan E.B. Clowse, Andrew Johannemann, Lisa G. Criscione-Schreiber, Mithu Maheswaranathan, David L Leverenz, and Philip Chu
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Telemedicine ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Practice patterns ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,medicine.disease ,Rheumatology ,Electronic health record ,Pandemic ,medicine ,Electronic Health Records ,Humans ,Medical emergency ,business ,Pandemics - Published
- 2021
18. Analysis of the frequency of single nucleotide polymorphisms in cytokine genes in patients with New Onset Diabetes After Transplant
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Parasad Nair, Parul Aggarwal, Philip Chu, Tarek Mahmoud, Nashwa Othman, Torki Al-Otaibi, Mohamed Jahromi, Osama Gheith, Jamil Azzi, Medhat A-Halim, Sacha A. De Serres, and Grace Messenger
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Adult ,Male ,0301 basic medicine ,Science ,Adaptive immunity ,030232 urology & nephrology ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Diabetes mellitus genetics ,0302 clinical medicine ,Diabetes complications ,Interferon ,Diabetes mellitus ,Genotype ,Diabetes Mellitus ,medicine ,Humans ,Interferon gamma ,Kidney transplantation ,Multidisciplinary ,business.industry ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Transplantation ,030104 developmental biology ,Immunology ,Cytokines ,Medicine ,Female ,business ,medicine.drug - Abstract
New Onset Diabetes After Transplantation (NODAT) is a serious metabolic complication. While β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis is not well understood. Cytokines are thought to be involved in the inflammation of islet β-cells in diabetes; however, few studies have investigated this hypothesis in NODAT. A total of 309 kidney transplant recipients (KTRs) were included in this study. An association between kidney transplants, and the development of diabetes after transplant (NODAT) was investigated. Comparison was made between KTRs who develop diabetes (NODAT cases) or did not develop diabetes (control), using key cytokines, IL-6 G (− 174)C, macrophage mediator; IL-4 C (− 490)T, T helper (Th)-2 cytokine profile initiator; Th-1 cytokine profile initiator interferon-γ T (+ 874) A gene and TGF β1 C (+ 869) T gene polymorphisms were investigated. The genes were amplified using well-established polymerase chain reaction (PCR) techniques in our laboratory. Compared to the AA and AT genotypes of interferon gamma (IFNG), there was a strong association between the TT genotype of IFNG and NODAT kidney transplant recipients (KTRs) versus non-NODAT KTRs (p = 0.005). The AA genotype of IFNG was found to be predominant in the control group (p = 0.004). Also, significant variations of IL6 G (− 174) C, IL-4 C (− 590) T, interferon-γ T (+ 874) A gene and transforming growth factor β1 C (+ 869) T may contribute to NODAT. Our data is consistent with theTh-1/T-reg pathway of immunity. Further larger pan Arab studies are required to confirm our findings.
- Published
- 2021
19. A Mimic of Ankylosing Spondylitis, Ochronosis: Case Report and Review of the Literature
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Maria C Cuellar, Philip Chu, Teresa K. Tarrant, and Sonali J. Bracken
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musculoskeletal diseases ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Immunology ,Osteoarthritis ,Alkaptonuria ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Immunology and Allergy ,Animals ,Humans ,Spondylitis, Ankylosing ,Homogentisic acid ,030223 otorhinolaryngology ,Homogentisic Acid ,Homogentisate 1,2-dioxygenase ,Sacroiliac joint ,Ankylosing spondylitis ,Ochronosis ,business.industry ,medicine.disease ,Hyperpigmentation ,medicine.anatomical_structure ,030228 respiratory system ,chemistry ,medicine.symptom ,business - Abstract
Ochronosis and alkaptonuria are manifestations of the same condition—a rare autosomal recessive disorder resulting from a constitutional lack of homogentisate 1,2-dioxygenase (HGD) with the consequent accumulation of homogentisic acid (HGA). In ochronosis, HGA undergoes autoxidation as well as enzymatic oxidation to form an ochronotic pigment that accumulates in cartilage and connective tissues. In the beginning, there is homogentisic aciduria and pigmentation of cartilages and other connective tissues. In later years, generalized osteoarthritis of the spine and large joints, termed ochronotic arthropathy, develops. The diagnosis is confirmed by quantitative measurement of HGA in urine and mutation analysis of the HGD gene. One of the differential diagnoses for the skin findings is exogenous ochronosis, a limited hyperpigmentation of skin caused by some chemicals. As for the lumbar spine findings, there can be radiographic similarities with ankylosing spondylitis (AS) including reduced intervertebral disc spaces and loss of lumbar lordosis; however, ochronosis will spare the sacroiliac joint, and the lumbar spine will show dense, wafer-like disk calcification with a vacuum disc phenomenon and broad syndesmophytes. Here, we present a case of a patient with probable ochronosis that was treated many years as ankylosing spondylitis without response, and we provide a review of the current literature on ochronosis pathogenesis, diagnosis, and treatment.
- Published
- 2021
20. Groundwater in Crisis? Addressing Groundwater Challenges in Michigan (USA) as a Template for the Great Lakes
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Alan D. Steinman, Donald G. Uzarski, David P. Lusch, Carol Miller, Patrick Doran, Tom Zimnicki, Philip Chu, Jon Allan, Jeremiah Asher, John Bratton, Don Carpenter, Dave Dempsey, Chad Drummond, John Esch, Anne Garwood, Anna Harrison, Lawrence D. Lemke, Jim Nicholas, Wendy Ogilvie, Brendan O’Leary, Paul Sachs, Paul Seelbach, Teresa Seidel, Amanda Suchy, and John Yellich
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Renewable Energy, Sustainability and the Environment ,Geography, Planning and Development ,Management, Monitoring, Policy and Law - Abstract
Groundwater historically has been a critical but understudied, underfunded, and underappreciated natural resource, although recent challenges associated with both groundwater quantity and quality have raised its profile. This is particularly true in the Laurentian Great Lakes (LGL) region, where the rich abundance of surface water results in the perception of an unlimited water supply but limited attention on groundwater resources. As a consequence, groundwater management recommendations in the LGL have been severely constrained by our lack of information. To address this information gap, a virtual summit was held in June 2021 that included invited participants from local, state, and federal government entities, universities, non-governmental organizations, and private firms in the region. Both technical (e.g., hydrologists, geologists, ecologists) and policy experts were included, and participants were assigned to an agricultural, urban, or coastal wetland breakout group in advance, based on their expertise. The overall goals of this groundwater summit were fourfold: (1) inventory the key (grand) challenges facing groundwater in Michigan; (2) identify the knowledge gaps and scientific needs, as well as policy recommendations, associated with these challenges; (3) construct a set of conceptual models that elucidate these challenges; and (4) develop a list of (tractable) next steps that can be taken to address these challenges. Absent this type of information, the sustainability of this critical resource is imperiled.
- Published
- 2022
21. Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
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Leonardo V. Riella, Peter T. Sage, Juliano B. Alhaddad, Simiao Xu, Hazim Allos, Anil Chandraker, Saif A. Muhsin, Thiago J. Borges, Xiaofei Li, Philip Chu, Songjie Cai, Hengcheng Zhang, John Choi, Jamil Azzi, Ji Miao, Takaharu Ichimura, Siawosh K. Eskandari, and Karim M. Yatim
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Graft Rejection ,Male ,0301 basic medicine ,T-Lymphocytes ,Science ,medicine.medical_treatment ,Population ,Hematopoietic stem cell transplantation ,Article ,Immune tolerance ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Transplant immunology ,Immune Tolerance ,medicine ,Animals ,Transplantation, Homologous ,Myeloid Cells ,education ,Immunosuppression Therapy ,Mice, Inbred BALB C ,education.field_of_study ,Multidisciplinary ,business.industry ,Myeloid-Derived Suppressor Cells ,Graft Survival ,Alloimmunity ,Hematopoietic Stem Cell Transplantation ,Immunosuppression ,Allografts ,Tissue Donors ,Mice, Inbred C57BL ,Transplantation ,030104 developmental biology ,Cancer research ,Myeloid-derived Suppressor Cell ,Heart Transplantation ,Medicine ,Immunotherapy ,business ,030217 neurology & neurosurgery - Abstract
Solid organ transplantation is a lifesaving therapy for patients with end-organ disease. Current immunosuppression protocols are not designed to target antigen-specific alloimmunity and are uncapable of preventing chronic allograft injury. As myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells, we tested whether donor-derived MDSCs can protect heart transplant allografts in an antigen-specific manner. C57BL/6 (H2Kb, I-Ab) recipients pre-treated with BALB/c MDSCs were transplanted with either donor-type (BALB/c, H2Kd, I-Ad) or third-party (C3H, H2Kk, I-Ak) cardiac grafts. Spleens and allografts from C57BL/6 recipients were harvested for immune phenotyping, transcriptomic profiling and functional assays. Single injection of donor-derived MDSCs significantly prolonged the fully MHC mismatched allogeneic cardiac graft survival in a donor-specific fashion. Transcriptomic analysis of allografts harvested from donor-derived MDSCs treated recipients showed down-regulated proinflammatory cytokines. Immune phenotyping showed that the donor MDSCs administration suppressed effector T cells in recipients. Interestingly, significant increase in recipient endogenous CD11b+Gr1+ MDSC population was observed in the group treated with donor-derived MDSCs compared to the control groups. Depletion of this endogenous MDSCs with anti-Gr1 antibody reversed donor MDSCs-mediated allograft protection. Furthermore, we observed that the allogeneic mixed lymphocytes reaction was suppressed in the presence of CD11b+Gr1+ MDSCs in a donor-specific manner. Donor-derived MDSCs prolong cardiac allograft survival in a donor-specific manner via induction of recipient’s endogenous MDSCs.
- Published
- 2020
22. Measures of Sleep in Rheumatologic Diseases: Sleep Quality Patient-Reported Outcomes in Rheumatologic Diseases
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Yo-El Ju, Philip Chu, Alfred H.J. Kim, and Alicia M. Hinze
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medicine.medical_specialty ,Sleep quality ,business.industry ,MEDLINE ,Sleep in non-human animals ,Article ,Rheumatology ,Rheumatic Diseases ,Medicine ,Humans ,Patient Reported Outcome Measures ,business ,Intensive care medicine ,Sleep - Published
- 2020
23. Author response: Cell-type-specific control of basolateral amygdala neuronal circuits via entorhinal cortex-driven feedforward inhibition
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Katharine R. Smith, Serapio M. Baca, Molly M. Huntsman, E Mae Guthman, Ming Ma, Diego Restrepo, Philip Chu, and Joshua D. Garcia
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Feedforward inhibition ,medicine.anatomical_structure ,Neuronal circuits ,Chemistry ,Cell type specific ,medicine ,Entorhinal cortex ,Neuroscience ,Basolateral amygdala - Published
- 2019
24. 138 Synthetic re-direction of TGFβ receptors as a novel strategy to enhance the anti-tumor activity of CAR-T cells in solid tumors
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Eigen Peralta, Kenyon Lyon, Thomas H. Lee, Yijia Pan, Arvin Tam, Alec Witty, Mochtar Pribadi, Hui-yi Chu, Emily Carron, Natalie Navarrete, Bob Valamehr, Amit R. Mehta, Philip Chu, Dan Lu, and Lorraine Loter
- Subjects
Pharmacology ,Cancer Research ,Tumor microenvironment ,biology ,Chemistry ,medicine.medical_treatment ,Immunology ,Cell ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Transforming growth factor beta ,Cell biology ,Cell therapy ,medicine.anatomical_structure ,Cytokine ,Oncology ,Ectodomain ,medicine ,biology.protein ,Molecular Medicine ,Immunology and Allergy ,Receptor ,Cytokine receptor ,RC254-282 - Abstract
BackgroundTransforming growth factor beta (TGFβ) is an immuno-suppressive cytokine present in the tumor microenvironment (TME) that creates considerable challenges for the treatment of solid tumors. Small molecule inhibitors targeting TGFβ exist, but the pleiotropic nature of TGFβ signaling suggests that a more targeted approach is preferential, especially in the context of cellular therapy. We hypothesized that primary T cells and iPSC-derived chimeric antigen receptor-T cells (CAR-iT cells) would benefit not only from blockade of TGFβ signaling, but also from re-direction of the signaling event toward specific cytokine pathways that activate cell function. Here we discuss novel synthetic TGFβ redirector constructs that overcome TME limitations and enhance CAR-iT cell function for improved efficacy in treating solid tumors.MethodsTo identify activation pathways for redirection of TGFβ signaling, we screened a panel of cytokines for their effect on the anti-tumor activity of CAR-iT cells. We then developed synthetic redirector receptors where a TGFBR2 ectodomain was fused to the top selected cytokine receptor endodomains. Redirection of TGFβ signaling was confirmed by phospho-flow of key signaling proteins. Anti-tumor activity of CAR-iT cells expressing these synthetic redirector constructs was tested in serial restimulation assays in the absence of cytokine support and in the presence of recombinant TGFβ (rTGFβ).ResultsA dose-dependent decrease in CAR-iT cell cytolytic capacity in the presence of rTGFβ was observed, with the activity of CAR-iT cells rescued in the presence of unique cytokines. We designed and tested synthetic TGFβ redirector constructs and demonstrated a rTGFβ-dependent increase in pSTAT5 positive cells (2.8-fold over control). The serial stimulation assay was then used to test CAR-iT cells engineered with synthetic TGFβ redirector receptors. After three rounds of restimulation, an increase in tumor cell numbers for non-engineered and dominant negative TGFBR2 CAR-iT cell controls was observed (41-fold and 32-fold increase over base input, respectively). In contrast, the synthetic TGFβ redirector receptor improved the ability of CAR-iT cells to control tumor cell growth with remarkable efficiency, limiting tumor growth to only 1.5-fold over three rounds of restimulation.ConclusionsThese studies demonstrate that a novel synthetic construct comprised of fusion of cytokine endodomains to a TGFBR2 ectodomain can be deployed to hijack the immuno-suppressive signal of TGFβ often found in the TME and activate CAR-iT cells for enhanced anti-tumor activity in solid tumors. Additional studies are underway to assess the temporal expression and activity of these synthetic redirector receptors in various preclinical models which will be further discussed.
- Published
- 2021
25. Coupled ocean-atmosphere forecasting at short and medium time scales
- Author
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Julie Pullen, Shuyi S. Chen, Rui Caldeira, Richard Allard, Philip Chu, Luciano Ponzi Pezzi, Hyodae Seo, Arthur J. Miller, Travis A. Smith, and José Matias Alves
- Subjects
Atmosphere ,010504 meteorology & atmospheric sciences ,010505 oceanography ,Environmental science ,Oceanography ,Atmospheric sciences ,01 natural sciences ,0105 earth and related environmental sciences - Published
- 2017
26. Abstract 1497: A unique strategy to arm iPSC-derived CAR-T cells to perform antibody-directed cellular cytotoxicity to facilitate multi-antigen targeting
- Author
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Shohreh Sikaroodi, Bruce Walcheck, Yijia Pan, Amanda D. Yzaguirre, Martin Hosking, Soheila Shirinbak, Angela Gentile, Jianming Wu, Bahram Valamehr, Mochtar Pribadi, Joy Grant, Philip Chu, Amit R. Mehta, Wen-I Yeh, and Anhco Nguyen
- Subjects
Cancer Research ,Antigen Targeting ,Oncology ,biology ,Chemistry ,biology.protein ,Car t cells ,Antibody ,Cell-mediated cytotoxicity ,Cell biology - Abstract
Although chimeric antigen receptor (CAR)-T cells have been transformational for several liquid tumors, their effectiveness in treating a variety of solid tumors has been limited in part because the heterogeneity of tumor-associated antigens found in many bulky tumors represents a major obstacle to the development and the delivery of effective CAR-T cell therapies in cancer. Here we demonstrate that iPSC-derived CAR-T (CAR-iT) cells are an ideal off-the-shelf approach that can be engineered to perform antibody-dependent cell-mediated cytotoxicity (ADCC) to facilitate multi-antigen targeting with the introduction of various monoclonal antibodies (mAbs). Under this strategy, while the CAR is equipped to predominantly target antigen 1, targeting additional tumor associated antigens through the use of various mAbs can be leveraged through ADCC. To this end, CAR-iT cells were genetically edited at the iPSC stage to uniformly express a novel high-affinity variant (158V), non-cleavable CD16A (hnCD16) Fc receptor to recognize and bind to the Fc fragment of mAbs and facilitate ADCC. When combined with therapeutic mAbs targeting HER2, EGFR, or PDL1, the cytolytic efficacy of hnCD16+ CAR-iT cells was significantly enhanced compared to parental CAR-iT cells in several tumor models, including ovarian, HER2+ breast, and triple-negative breast cancers, underscoring the flexibility of a combined CAR and ADCC – mediated targeting approach. Importantly, although both CD16A and CAR signaling share common CD3ζ pathways, simultaneous activation did not appreciably attenuate the activation and effector function of CAR-iT cells. Moreover, hnCD16+ CAR-iT cells demonstrated enhanced control in an established triple negative breast cancer solid tumor xenograft model. The control of antigenically heterogenous tumors by hnCD16+ CAR-iT cells was also significantly improved when compared to parental CAR-iT cells. To confirm selectivity and avoidance of immunoglobulin interference with functional output, various in vitro cellular cytotoxicity assays were conducted with IgG1 to confirm that hnCD16 requires crosslinking to elicit ADCC while maintaining full potentiation of CAR function. Additional in vitro and in vivo studies are ongoing and will be presented. Collectively, the data demonstrates that CAR-iT cells can be further modified with hnCD16 Fc receptor to elicit ADCC and the combination of CAR and hnCD16 is a unique approach to tackling tumor heterogeneity often found in bulky tumors. Citation Format: Martin Hosking, Soheila Shirinbak, Joy Grant, Wen-I Yeh, Yijia Pan, Mochtar Pribadi, Amit Mehta, Amanda Yzaguirre, Philip Chu, Shohreh Sikaroodi, Angela Gentile, Bruce Walcheck, Jianming Wu, Anhco Nguyen, Bahram Valamehr. A unique strategy to arm iPSC-derived CAR-T cells to perform antibody-directed cellular cytotoxicity to facilitate multi-antigen targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1497.
- Published
- 2021
27. Linear Ion Trap Mass Spectrometer (LITMS) for in situ Astrobiology
- Author
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Xiang Li, Friso H. W. van Amerom, Kris Zacny, Ricardo Arevalo, Philip Chu, William B. Brinckerhoff, Desmond Allen Kaplan, Andrej Grubisic, Ryan M. Danell, and M. Castillo
- Subjects
Spectrum analyzer ,Materials science ,Evolved gas analysis ,010401 analytical chemistry ,Mars Exploration Program ,Mass spectrometry ,01 natural sciences ,0104 chemical sciences ,Characterization (materials science) ,Ion ,Astrobiology ,0103 physical sciences ,Quadrupole ion trap ,010303 astronomy & astrophysics ,Pyrolysis - Abstract
The highly compact Linear Ion Trap Mass Spectrometer (LITMS) combines pyrolysis gas-chromatography/mass spectrometry (GCMS) and Mars-ambient laser desorption mass spectrometry (LDMS) through a single, miniaturized yet highly-capable linear ion trap mass analyzer. The LITMS instrument is based substantially on the Mars Organic Molecule Analyzer - Mass Spectrometer (MOMA-MS) for the 2020 ExoMars mission but features further analytical enhancements. In addition to the core MOMA capabilities, LITMS enhances the instrument performance by including negative ion detection, a dual frequency RF power supply to increase mass range, precision subsampling of drill cores at fine (≤ 1 mm) spatial scales, and pyrolysis of powdered sample for evolved gas analysis (EGA) of organic content and mineral assemblages. LITMS enables in situ characterization of inorganics and organics in individual rock core layers and features. This level of integrated analytical capability is critical to achieve advanced astrobiology objectives on Mars and other planets.
- Published
- 2019
28. PlanetVac Xodiac: Lander Foot Pad Integrated Planetary Sampling System
- Author
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Andrew Peekema, Ian Heidenberger, Nicklaus Traeden, Reuben A. Garcia, J. Spring, Bruce Betts, Kathryn Luczek, Kris Zacny, Philip Chu, and Steven Ford
- Subjects
010504 meteorology & atmospheric sciences ,business.industry ,Sampling (statistics) ,Robotics ,Field tests ,Propulsion ,01 natural sciences ,Takeoff and landing ,Sampling system ,0103 physical sciences ,Environmental science ,Artificial intelligence ,Descent (aeronautics) ,business ,010303 astronomy & astrophysics ,0105 earth and related environmental sciences ,Marine engineering - Abstract
This paper describes the development and testing of the PlanetVac Xodiac sampler by Honeybee Robotics. This iteration of PlanetVac builds on Honeybee's heritage of pneumatic sampling systems and modifies it to function on an Entry, Descent, and Landing (EDL) test bed vehicle. PlanetVac Xodiac was flown on Masten Space Systems Xodiac vehicle in the Mojave Desert of California. The sampler was designed to withstand the high temperatures emitted by the propulsion system plume, as well as the vibration and impact stresses of takeoff and landing. PlanetVac Xodiac not only survived all three end-to-end field tests, it also collected over three times the expected 100g sample in each trial.
- Published
- 2019
29. EMILI: Europan Molecular Indicators of Life Investigation
- Author
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Andrej Grubisic, E. Lalime, William B. Brinckerhoff, J. Spring, Ricardo Arevalo, Ryan M. Danell, M. Casey, M. Castillo, Kris Zacny, Stephanie Getty, Jennifer L. Eigenbrode, Xiang Li, Tori M. Hoehler, F. H. W. van Amerom, and Philip Chu
- Published
- 2018
30. Generation of Multiplexed Engineered, Off-the-Shelf CAR T Cells Uniformly Carrying Multiple Anti-Tumor Modalities to Prevent Tumor Relapse
- Author
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Bahram Valamehr, Samuel LaBarge, Yi-Shin Lai, Mochtar Pribadi, Suzanna Gasparian, Mandal Mili, Alma Gutierrez, Matthew Denholtz, Gloria Hsia, Jason ORourke, May Sumi, Bi-Huei Yang, Cokey Nguyen, Sandeep Kothapally Hanok, Alec Witty, Eric Sung, Amit R. Mehta, Raedun Clarke, Ramzey Abujarour, Eigen Peralta, Emily Carron, Thomas H. Lee, Emily Driver, Angela Gentile, Natalie Navarrete, David J. Robbins, Wen-I Yeh, Philip Chu, Chia-Wei Chang, and Amanda D. Yzaguirre
- Subjects
medicine.medical_treatment ,T cell ,Immunology ,T-cell receptor ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Chimeric antigen receptor ,Cytokine ,medicine.anatomical_structure ,Antigen ,Cancer research ,medicine ,Induced pluripotent stem cell ,Cell bank ,Reprogramming - Abstract
The development of chimeric antigen receptor (CAR) T cell therapeutics is widely recognized as a significant advancement for the treatment of cancer. However, several obstacles currently impede the broad use of CAR T cells, including the inherent process variability, cost of manufacturing, the absolute requirement for precise and uniform genetic editing in the allogeneic setting, and the challenge to keep pace with clonal heterogeneity and tumor growth. Utilizing our previously described induced pluripotent stem cell (iPSC)-derived T (iT) cell platform, we illustrate here the unique ability to address these challenges by creating a consistent CAR iT cell product that can be repeatedly manufactured in large quantities from a renewable iPSC master cell bank that has been engineered to mitigate the occurrence of graft versus host disease (GvHD), antigen escape and tumor relapse. Utilizing our proprietary cellular reprogramming and engineering platform and stage-specific T cell differentiation protocol, we demonstrate that iPSC can be engineered at the single cell level to generate a fully characterized clonal iPSC line, which can then be accessed routinely to yield CAR iT cells in a highly scalable manufacturing process (>100,000 fold expansion). Through bi-allelic targeting of a CAR into the T cell receptor alpha constant (TRAC) region, we generated CAR iT cells with uniform CAR expression (99.0 ± 0.5% CAR+) and complete elimination of T cell receptor (TCR) expression to avoid GvHD in the allogeneic setting. We elected to utilize the 1XX-CAR configuration, which has demonstrated superior anti-tumor performance relative to other CAR designs and when introduced into iT cells displayed enhanced antigen specificity (% specific cytotoxicity at E:T=10:1, antigen positive group: 86.4 ± 7.8; antigen null group: 8.9 ± 3.5). To enhance persistence without reliance on exogenous cytokine support, we engineered signaling-fusion complexes, including IL-7 receptor fusion (RF), into iPSC and studied its impact on iT phenotype, persistence, and efficacy. In vitro, IL-7RF clones demonstrated improved anti-tumor activity in a serial antigen dependent tumor challenge assay (Day 10, relative tumor counts, IL-7RF group: 1.95 ± 0.01; control group: 57.56 ± 4.55, P Collectively, the described studies demonstrate that iPSCs are an ideal cellular source to generate large-quantities of uniformly multi-edited off-the-shelf CAR T cell products that include a best-in-class CAR design, enhanced product modalities, and complete elimination of TCR expression to avoid the potential of GvHD while maintaining high anti-tumor efficacy in allogeneic setting. Disclosures Hsia: Fate Therapeutics Inc.: Current Employment. Clarke:Fate Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Lee:Fate Therapeutics, Inc.: Current Employment. Robbins:Fate Therapeutics, Inc.: Current Employment. Denholtz:Fate Therapeutics, Inc: Current Employment. Hanok:Fate Therapeutics, Inc.: Current Employment. Carron:Fate Therapeutics, Inc.: Current Employment. Navarrete:Fate Therapeutics, Inc.: Current Employment. ORourke:Fate Therapeutics, Inc.: Current Employment. Sung:Fate Therapeutics, Inc.: Current Employment. Gentile:Fate Therapeutics, Inc.: Current Employment. Nguyen:Fate Therapeutics, Inc.: Current Employment. Valamehr:Fate Therapeutics, Inc: Current Employment, Current equity holder in publicly-traded company.
- Published
- 2020
31. Rethinking the River
- Author
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Jessica R. Henkel, Carol Richards, Catherine Fitzpatrick, Ehab A. Meselhe, Elizabeth McCoy, Alyssa Dausman, Gary Brown, Kim de Mutsert, Alexander S. Kolker, Philip Chu, Mead A. Allison, Dubravko Justic, and Barbara A. Kleiss
- Subjects
0106 biological sciences ,010504 meteorology & atmospheric sciences ,010604 marine biology & hydrobiology ,General Earth and Planetary Sciences ,01 natural sciences ,Geology ,0105 earth and related environmental sciences - Abstract
The Mississippi River and its delta and plume provide insights into research-informed approaches to managing river-dominated coastal zones.
- Published
- 2018
32. Cell Type Specific Control of Basolateral Amygdala Plasticity Via Entorhinal Cortex Driven Feedforward Inhibition
- Author
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Philip Chu, Diego Restrepo, E. M. Guthman, Serapio M. Baca, Ming Ma, and Molly M. Huntsman
- Subjects
biology ,fungi ,Hippocampus ,Sensory system ,Entorhinal cortex ,Inhibitory postsynaptic potential ,Cortex (botany) ,medicine.anatomical_structure ,nervous system ,biology.protein ,medicine ,Olfactory Learning ,Neuroscience ,Parvalbumin ,Basolateral amygdala - Abstract
The basolateral amygdala (BLA) plays a vital role in associating sensory stimuli with salient valence information. Excitatory principal neurons (PNs) undergo plastic changes to encode this association; however, local BLA inhibitory interneurons (INs) gate PN plasticity via feedforward inhibition (FFI). Despite literature implicating parvalbumin expressing (PV+) INs in FFI in cortex and hippocampus, prior anatomical experiments in BLA implicate somatostatin expressing (Sst+) INs. The lateral entorhinal cortex (LEC), a brain region carrying olfactory information, projects to BLA where it drives FFI. In the present study, we asked whether LEC input mediates plasticity in BLA and explored the role of interneurons in this circuit. We combined patch clamp electrophysiology, chemogenetics, unsupervised cluster analysis, and predictive modeling and found that a previously unreported subpopulation of fast-spiking Sst+ INs mediate LEC→BLA FFI and gate plasticity. Our study raises the question whether this circuit is involved in plasticity in olfactory learning.
- Published
- 2018
33. The Impact of Perineuronal Net Digestion Using Chondroitinase ABC on the Intrinsic Physiology of Cortical Neurons
- Author
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Usma Khan, Kumarie Budhu, Reena Abraham, Philip Chu, Joshua C. Brumberg, and Natalia V. De Marco García
- Subjects
0301 basic medicine ,Male ,Physiology ,Biology ,Chondroitin ABC Lyase ,Inhibitory postsynaptic potential ,Synaptic Transmission ,Article ,Membrane Potentials ,Tissue Culture Techniques ,03 medical and health sciences ,Bursting ,Mice ,0302 clinical medicine ,Neuroplasticity ,medicine ,Animals ,Neurons ,Neocortex ,General Neuroscience ,Perineuronal net ,Somatosensory Cortex ,Barrel cortex ,Axon initial segment ,Extracellular Matrix ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Excitatory postsynaptic potential ,Female ,030217 neurology & neurosurgery - Abstract
Perineuronal nets (PNNs) are a form of aggregate Extracellular Matrix (ECM) in the brain. Recent evidence suggests that the postnatal deposition of PNNs may play an active role in regulating neuroplasticity and, potentially, neurological disorders. Observations of high levels of PNN expression around somas, proximal dendrites, and axon initial segments of a subtype of neurons have also led to proposals that PNNs may modulate the intrinsic properties of the neurons they ensheathe. While high levels of PNNs are postnatally expressed throughout the neocortex, it is still unclear how they impact the neuronal physiology of the many classes and subtypes of neurons that exist. In this study, we demonstrate that Chondroitinase ABC digestion of PNNs from acute cortical slices from juvenile mice (P28–35) resulted in neuron-specific impacts on intrinsic physiology. Fast spiking (FS) interneurons showed decreased input resistance, resting membrane potential (RMP), reduced action potential (AP) peaks and altered spontaneous synaptic inputs. Low-Threshold Spiking interneurons showed altered rebound depolarizations and decreased frequency of spontaneous synaptic inputs. Putative excitatory neurons; regular spiking, bursting, and doublet phenotypes did not demonstrate any alterations. Our data indicate that chABC-sensitive PNNs may specifically regulate the intrinsic and synaptic physiology of inhibitory interneurons. © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
- Published
- 2017
34. Comparison and analysis of Acoustography with other NDE techniques for foreign object inclusion detection in graphite epoxy composites
- Author
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Anish Poudel, Charles Pergantis, Jaswinder S. Sandhu, Shashi Shrestha, and Tsuchin Philip Chu
- Subjects
Materials science ,business.industry ,Mechanical Engineering ,Ultrasonic testing ,Composite number ,Epoxy ,Composite laminates ,Inspection time ,Industrial and Manufacturing Engineering ,Mechanics of Materials ,visual_art ,Thermography ,Ceramics and Composites ,visual_art.visual_art_medium ,Ultrasonic sensor ,Composite material ,business ,Quality assurance - Abstract
This paper presents the use of a novel through-transmission ultrasonic (TTU) Acoustography non-destructive evaluation (NDE) method to detect foreign object inclusion (FOI) defects in graphite epoxy composite laminates. The study employed three different composite test standards with varied size FOI defects embedded at varying depth within the composite laminates. For validation, Acoustography results were directly compared with conventional immersion TTU testing and infrared thermography (IRT) methods. From results obtained, it was demonstrated that the Signal-to-Noise Ratio (SNR) measurements for Acoustography were more than 6:1 and were in good correlation with immersion TTU and IRT results. The defect sizing ability of TTU Acoustography for FOI defects in graphite epoxy composite laminates were also in strong correlation with immersion TTU and IRT techniques. Finally, for the three laboratory systems employed in this study, typical panel TTU Acoustography inspection time was just about three minutes to scan a 300 mm × 300 mm (11.8″ × 11.8″) area, which was more than three times faster compared to IRT and sixty times faster to conventional immersion TTU C-Scan techniques. This is a very significant finding for the reason that Acoustography is being developed as a faster, more efficient, and affordable alternative to traditional ultrasonic inspection systems for composite manufacturing quality control and quality assurance (QC/QA) and field maintenance of composite structure applications.
- Published
- 2015
35. Barrels XXVII meeting report: Barrels in the monument city
- Author
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Robert Steger, Philip Chu, Adesh Bajnath, and Joshua C. Brumberg
- Subjects
Gerontology ,Afferent Pathways ,History ,Physiology ,Motor commands ,Medial thalamus ,Somatosensory Cortex ,Sensory Systems ,Visual arts ,Vibrissae ,Thursday ,Baltimore ,Animals ,Humans - Abstract
The 27th annual Barrels meeting highlighted the latest advances in this rapidly growing field. The Barrels meeting annually focuses on the role of the posterior medial thalamus in somatosensation, dendritic processing, and the cortical dynamics involved during touch perception. Speakers utilized diverse molecular, physiological, computational techniques to understand the development, sensory processing, and motor commands that are involved with the rodent mystacial vibrissae. The meeting was held Thursday, 13 November through Friday, 14 November 2014 on the Homewood campus of Johns Hopkins University, Baltimore, MD.
- Published
- 2015
36. Non-destructive evaluation of composite repairs by using infrared thermography
- Author
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Keven R. Mitchell, Carl Jacques, Stephen Neidigk, Anish Poudel, and Tsuchin Philip Chu
- Subjects
Air transport ,Materials science ,Nomex honeycomb ,business.industry ,Mechanical Engineering ,Composite number ,Delamination ,Glass fiber ,Composite repairs ,02 engineering and technology ,Structural engineering ,021001 nanoscience & nanotechnology ,01 natural sciences ,010309 optics ,Mechanics of Materials ,Non destructive ,0103 physical sciences ,Thermography ,Materials Chemistry ,Ceramics and Composites ,Composite material ,0210 nano-technology ,business - Abstract
Composite structures are found in modern aircraft designs ranging from air transport to general aviation. Maintenance repair technology varies for each original equipment manufacturer and aircraft type. This research reports on two different composite repair methods commonly used within the composite aviation industry and how they compare when inspected with transient infrared thermography non-destructive evaluation technique. Composite sandwich test coupons made with carbon fiber laminate, nomex honeycomb, and glass fiber laminate were used for this work. Impact damages were generated in the sandwich test coupons and repairs were conducted by following repair procedures of two leading general aviation composite aircraft manufactures. During the repair process, controlled flaws were also induced to simulate bad repairs with weak bond areas, disbonds, and excessive porosity. During transient infrared thermography, several patches were identified that contained wrinkles, porosity, and disbond defects in the repaired panels. The indications were evaluated utilizing the time vs. temperature plot curves and profile data. The porosity indications displayed significant variations compared to the surrounding areas and were subsequently deemed defects as a result of the data.
- Published
- 2015
37. Making It Move: Scripting the Cube
- Author
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Allan Fowler and Philip Chu
- Published
- 2017
38. Using Unity iOS
- Author
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Allan Fowler and Philip Chu
- Published
- 2017
39. The Game GUI
- Author
-
Allan Fowler and Philip Chu
- Published
- 2017
40. Let’s Dance! Animation and Sound
- Author
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Allan Fowler and Philip Chu
- Published
- 2017
41. Let’s Bowl! Advanced Physics
- Author
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Allan Fowler and Philip Chu
- Published
- 2017
42. Handling Device Input
- Author
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Allan Fowler and Philip Chu
- Published
- 2017
43. Getting Started
- Author
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Allan Fowler and Philip Chu
- Published
- 2017
44. Let’s Roll! Physics and Controls
- Author
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Allan Fowler and Philip Chu
- Published
- 2017
45. Presentation: Screens and Icons
- Author
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Allan Fowler and Philip Chu
- Published
- 2017
46. Where to Go from Here?
- Author
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Allan Fowler and Philip Chu
- Published
- 2017
47. Building for Real: Device Testing and App Submission
- Author
-
Allan Fowler and Philip Chu
- Published
- 2017
48. A Unity Tour
- Author
-
Allan Fowler and Philip Chu
- Published
- 2017
49. Making a Scene
- Author
-
Allan Fowler and Philip Chu
- Published
- 2017
50. Optimization
- Author
-
Allan Fowler and Philip Chu
- Published
- 2017
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