9 results on '"Emma R. Hill"'
Search Results
2. Data from FGFR2 Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma
- Author
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Brian M. Wolpin, Nabeel Bardeesy, Vincent Zoete, Antoine Daina, Matthew Meyerson, Ryan B. Corcoran, Andrew D. Cherniack, William C. Hahn, Pasi A. Jänne, Deborah Schrag, Kimmie Ng, Claudio Zanna, Anna Pokorska-Bocci, Geoffrey I. Shapiro, Emma R. Hill, Sarah Denning, Rachel B. Keller, Ryan J. Sullivan, Anne Vaslin Chessex, Franck Brichory, Anuj K. Patel, Jiping Wang, Thomas E. Clancy, Thomas A. Abrams, Atul B. Shinagare, Maureen Loftus, Lauren K. Brais, Lei Shi, Lipika Goyal, Giulia Siravegna, Jonathan A. Nowak, Jason L. Hornick, Isobel J. Fetter, Douglas A. Rubinson, Hersh V. Gupta, Liam F. Spurr, Yvonne Y. Li, Qibiao Wu, Srivatsan Raghavan, and James M. Cleary
- Abstract
We conducted next-generation DNA sequencing on 335 biliary tract cancers and characterized the genomic landscape by anatomic site within the biliary tree. In addition to frequent FGFR2 fusions among patients with intrahepatic cholangiocarcinoma (IHCC), we identified FGFR2 extracellular domain in-frame deletions (EID) in 5 of 178 (2.8%) patients with IHCC, including two patients with FGFR2 p.H167_N173del. Expression of this FGFR2 EID in NIH3T3 cells resulted in constitutive FGFR2 activation, oncogenic transformation, and sensitivity to FGFR inhibitors. Three patients with FGFR2 EIDs were treated with Debio 1347, an oral FGFR1/2/3 inhibitor, and all showed partial responses. One patient developed an acquired L618F FGFR2 kinase domain mutation at disease progression and experienced a further partial response for 17 months to an irreversible FGFR2 inhibitor, futibatinib. Together, these findings reveal FGFR2 EIDs as an alternative mechanism of FGFR2 activation in IHCC that predicts sensitivity to FGFR inhibitors in the clinic.Significance:FGFR2 EIDs are transforming genomic alterations that occur predominantly in patients with IHCC. These FGFR2 EIDs are sensitive to FGFR inhibition in vitro, and patients with these alterations benefited from treatment with FGFR inhibitors in the clinic.This article is highlighted in the In This Issue feature, p. 2355
- Published
- 2023
3. Data from Spatially Resolved Single-Cell Assessment of Pancreatic Cancer Expression Subtypes Reveals Co-expressor Phenotypes and Extensive Intratumoral Heterogeneity
- Author
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Brian M. Wolpin, Jonathan A. Nowak, Andrew J. Aguirre, Alex K. Shalek, William C. Hahn, Aram F. Hezel, Albert C. Koong, Daniel T. Chang, Richard F. Dunne, David C. Linehan, Margaret M. Kozak, Emma R. Hill, Lauren K. Brais, Joseph D. Mancias, Jiping Wang, Thomas E. Clancy, James M. Cleary, Kimberly Perez, Harshabad Singh, Douglas A. Rubinson, Vicente Morales-Oyarvide, Dalia Elganainy, Mai Chan Lau, Kristen E. Lowder, Radha L. Kalekar, Timothy L. Bosse, Annan Yang, Junning Wang, Andrew W. Navia, Chen Yuan, Juha P. Väyrynen, Sara A. Väyrynen, Scott P. Ginebaugh, Kevin S. Kapner, Peter S. Winter, Srivatsan Raghavan, Jinming Zhang, Andressa Dias Costa, and Hannah L. Williams
- Abstract
Pancreatic ductal adenocarcinoma (PDAC) has been classified into classical and basal-like transcriptional subtypes by bulk RNA measurements. However, recent work has uncovered greater complexity to transcriptional subtypes than was initially appreciated using bulk RNA expression profiling. To provide a deeper understanding of PDAC subtypes, we developed a multiplex immunofluorescence (mIF) pipeline that quantifies protein expression of six PDAC subtype markers (CLDN18.2, TFF1, GATA6, KRT17, KRT5, and S100A2) and permits spatially resolved, single-cell interrogation of pancreatic tumors from resection specimens and core needle biopsies. Both primary and metastatic tumors displayed striking intratumoral subtype heterogeneity that was associated with patient outcomes, existed at the scale of individual glands, and was significantly reduced in patient-derived organoid cultures. Tumor cells co-expressing classical and basal markers were present in > 90% of tumors, existed on a basal-classical polarization continuum, and were enriched in tumors containing a greater admixture of basal and classical cell populations. Cell–cell neighbor analyses within tumor glands further suggested that co-expressor cells may represent an intermediate state between expression subtype poles. The extensive intratumoral heterogeneity identified through this clinically applicable mIF pipeline may inform prognosis and treatment selection for patients with PDAC.Significance:A high-throughput pipeline using multiplex immunofluorescence in pancreatic cancer reveals striking expression subtype intratumoral heterogeneity with implications for therapy selection and identifies co-expressor cells that may serve as intermediates during subtype switching.
- Published
- 2023
4. Supplementary Data from Spatially Resolved Single-Cell Assessment of Pancreatic Cancer Expression Subtypes Reveals Co-expressor Phenotypes and Extensive Intratumoral Heterogeneity
- Author
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Brian M. Wolpin, Jonathan A. Nowak, Andrew J. Aguirre, Alex K. Shalek, William C. Hahn, Aram F. Hezel, Albert C. Koong, Daniel T. Chang, Richard F. Dunne, David C. Linehan, Margaret M. Kozak, Emma R. Hill, Lauren K. Brais, Joseph D. Mancias, Jiping Wang, Thomas E. Clancy, James M. Cleary, Kimberly Perez, Harshabad Singh, Douglas A. Rubinson, Vicente Morales-Oyarvide, Dalia Elganainy, Mai Chan Lau, Kristen E. Lowder, Radha L. Kalekar, Timothy L. Bosse, Annan Yang, Junning Wang, Andrew W. Navia, Chen Yuan, Juha P. Väyrynen, Sara A. Väyrynen, Scott P. Ginebaugh, Kevin S. Kapner, Peter S. Winter, Srivatsan Raghavan, Jinming Zhang, Andressa Dias Costa, and Hannah L. Williams
- Abstract
Supplementary Figures
- Published
- 2023
5. Spatially-resolved single-cell assessment of pancreatic cancer expression subtypes reveals co-expressor phenotypes and extensive intra-tumoral heterogeneity
- Author
-
Hannah L. Williams, Andressa Dias Costa, Jinming Zhang, Srivatsan Raghavan, Peter S. Winter, Kevin S. Kapner, Scott P. Ginebaugh, Sara A. Väyrynen, Juha P. Väyrynen, Chen Yuan, Andrew W. Navia, Junning Wang, Annan Yang, Timothy L. Bosse, Radha L. Kalekar, Kristen E. Lowder, Mai Chan Lau, Dalia Elganainy, Vicente Morales-Oyarvide, Douglas A. Rubinson, Harshabad Singh, Kimberly Perez, James M. Cleary, Thomas E. Clancy, Jiping Wang, Joseph D. Mancias, Lauren K. Brais, Emma R. Hill, Margaret M. Kozak, David C. Linehan, Richard F. Dunne, Daniel T. Chang, Albert C. Koong, Aram F. Hezel, William C. Hahn, Alex K. Shalek, Andrew J. Aguirre, Jonathan A. Nowak, and Brian M. Wolpin
- Subjects
Cancer Research ,Oncology - Abstract
Pancreatic ductal adenocarcinoma (PDAC) has been classified into classical and basal-like transcriptional subtypes by bulk RNA measurements. However, recent work has uncovered greater complexity to transcriptional subtypes than was initially appreciated using bulk RNA expression profiling. To provide a deeper understanding of PDAC subtypes, we developed a multiplex immunofluorescence (mIF) pipeline that quantifies protein expression of six PDAC subtype markers (CLDN18.2, TFF1, GATA6, KRT17, KRT5, and S100A2) and permits spatially resolved, single-cell interrogation of pancreatic tumors from resection specimens and core needle biopsies. Both primary and metastatic tumors displayed striking intratumoral subtype heterogeneity that was associated with patient outcomes, existed at the scale of individual glands, and was significantly reduced in patient-derived organoid cultures. Tumor cells co-expressing classical and basal markers were present in > 90% of tumors, existed on a basal-classical polarization continuum, and were enriched in tumors containing a greater admixture of basal and classical cell populations. Cell–cell neighbor analyses within tumor glands further suggested that co-expressor cells may represent an intermediate state between expression subtype poles. The extensive intratumoral heterogeneity identified through this clinically applicable mIF pipeline may inform prognosis and treatment selection for patients with PDAC. Significance: A high-throughput pipeline using multiplex immunofluorescence in pancreatic cancer reveals striking expression subtype intratumoral heterogeneity with implications for therapy selection and identifies co-expressor cells that may serve as intermediates during subtype switching.
- Published
- 2022
6. FGFR2Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma
- Author
-
Giulia Siravegna, Thomas A. Abrams, Isobel J Fetter, Atul B. Shinagare, Kimmie Ng, Sarah L. Denning, William C. Hahn, Maureen Loftus, Anuj K. Patel, Yvonne Y. Li, James M. Cleary, Liam F. Spurr, Srivatsan Raghavan, Ryan J. Sullivan, Douglas A. Rubinson, Matthew Meyerson, Hersh Gupta, Nabeel Bardeesy, Emma R. Hill, Antoine Daina, Brian M. Wolpin, Ryan B. Corcoran, Jiping Wang, Lauren K. Brais, Pasi A. Jänne, Claudio Zanna, Qibiao Wu, Lipika Goyal, Andrew D. Cherniack, Lei Shi, Anne Vaslin Chessex, Jonathan A. Nowak, Anna Pokorska-Bocci, Rachel B. Keller, Thomas E. Clancy, Jason L. Hornick, Vincent Zoete, Geoffrey I. Shapiro, Deborah Schrag, and Franck Brichory
- Subjects
musculoskeletal diseases ,0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Mutation ,integumentary system ,business.industry ,medicine.disease_cause ,Article ,DNA sequencing ,stomatognathic diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Protein kinase domain ,Biliary tract ,Fibroblast growth factor receptor ,030220 oncology & carcinogenesis ,embryonic structures ,Extracellular ,Cancer research ,medicine ,business ,Function (biology) ,Intrahepatic Cholangiocarcinoma - Abstract
We conducted next-generation DNA sequencing on 335 biliary tract cancers and characterized the genomic landscape by anatomic site within the biliary tree. In addition to frequent FGFR2 fusions among patients with intrahepatic cholangiocarcinoma (IHCC), we identified FGFR2 extracellular domain in-frame deletions (EID) in 5 of 178 (2.8%) patients with IHCC, including two patients with FGFR2 p.H167_N173del. Expression of this FGFR2 EID in NIH3T3 cells resulted in constitutive FGFR2 activation, oncogenic transformation, and sensitivity to FGFR inhibitors. Three patients with FGFR2 EIDs were treated with Debio 1347, an oral FGFR1/2/3 inhibitor, and all showed partial responses. One patient developed an acquired L618F FGFR2 kinase domain mutation at disease progression and experienced a further partial response for 17 months to an irreversible FGFR2 inhibitor, futibatinib. Together, these findings reveal FGFR2 EIDs as an alternative mechanism of FGFR2 activation in IHCC that predicts sensitivity to FGFR inhibitors in the clinic.Significance:FGFR2 EIDs are transforming genomic alterations that occur predominantly in patients with IHCC. These FGFR2 EIDs are sensitive to FGFR inhibition in vitro, and patients with these alterations benefited from treatment with FGFR inhibitors in the clinic.This article is highlighted in the In This Issue feature, p. 2355
- Published
- 2021
7. From medical imaging data to 3D printed anatomical models.
- Author
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Thore M Bücking, Emma R Hill, James L Robertson, Efthymios Maneas, Andrew A Plumb, and Daniil I Nikitichev
- Subjects
Medicine ,Science - Abstract
Anatomical models are important training and teaching tools in the clinical environment and are routinely used in medical imaging research. Advances in segmentation algorithms and increased availability of three-dimensional (3D) printers have made it possible to create cost-efficient patient-specific models without expert knowledge. We introduce a general workflow that can be used to convert volumetric medical imaging data (as generated by Computer Tomography (CT)) to 3D printed physical models. This process is broken up into three steps: image segmentation, mesh refinement and 3D printing. To lower the barrier to entry and provide the best options when aiming to 3D print an anatomical model from medical images, we provide an overview of relevant free and open-source image segmentation tools as well as 3D printing technologies. We demonstrate the utility of this streamlined workflow by creating models of ribs, liver, and lung using a Fused Deposition Modelling 3D printer.
- Published
- 2017
- Full Text
- View/download PDF
8. Identification and removal of laser-induced noise in photoacoustic imaging using singular value decomposition
- Author
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Emma R, Hill, Wenfeng, Xia, Matthew J, Clarkson, and Adrien E, Desjardins
- Subjects
ocis:(110.4280) Noise in imaging systems ,ocis:(110.5120) Photoacoustic imaging ,Physics::Medical Physics ,ocis:(100.0100) Image processing ,Article - Abstract
Singular value decomposition (SVD) was used to identify and remove laser-induced noise in photoacoustic images acquired with a clinical ultrasound scanner. This noise, which was prominent in the radiofrequency data acquired in parallel from multiple transducer elements, was induced by the excitation light source. It was modelled by truncating the SVD matrices so that only the first few largest singular value components were retained, and subtracted prior to image reconstruction. The dependency of the signal amplitude and the number of the largest singular value components used for noise modeling was investigated for different photoacoustic source geometries. Validation was performed with simulated data and measured noise, and with photoacoustic images acquired from the human forearm and finger in vivo using L14-5/38 and L40-8/12 linear array clinical imaging probes. The use of only one singular value component was found to be sufficient to achieve near-complete removal of laser-induced noise from reconstructed images. This method has strong potential to increase image quality for a wide range of photoacoustic imaging systems with parallel data acquisition.
- Published
- 2016
9. Interventional multi-spectral photoacoustic imaging in laparoscopic surgery
- Author
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Daniil I. Nikitichev, Paul C. Beard, Adrien E. Desjardins, Kurinchi Selvan Gurusamy, David J. Hawkes, Wenfeng Xia, Brian R. Davidson, and Emma R. Hill
- Subjects
Laparoscopic surgery ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Ultrasound ,Photoacoustic imaging in biomedicine ,Multi spectral ,Light delivery ,01 natural sciences ,030218 nuclear medicine & medical imaging ,Resection ,010309 optics ,03 medical and health sciences ,0302 clinical medicine ,Transducer ,0103 physical sciences ,medicine ,business ,Laparoscopy ,Biomedical engineering - Abstract
Laparoscopic procedures can be an attractive treatment option for liver resection, with a shortened hospital stay and reduced morbidity compared to open surgery. One of the central challenges of this technique is visualisation of concealed structures within the liver, particularly the vasculature and tumourous tissue. As photoacoustic (PA) imaging can provide contrast for haemoglobin in real time, it may be well suited to guiding laparoscopic procedures in order to avoid inadvertent trauma to vascular structures. In this study, a clinical laparoscopic ultrasound probe was used to receive ultrasound for PA imaging and to obtain co-registered B-mode ultrasound (US) images. Pulsed excitation light was delivered to the tissue via a fibre bundle in dark-field mode. Monte Carlo simulations were performed to optimise the light delivery geometry for imaging targets at depths of 1 cm, 2 cm and 3 cm, and 3D-printed mounts were used to position the fibre bundle relative to the transducer according to the simulation results. The performance of the photoacoustic laparoscope system was evaluated with phantoms and tissue models. The clinical potential of hybrid PA/US imaging to improve the guidance of laparoscopic surgery is discussed.
- Published
- 2016
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