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Richard Torres

MD, MS, BS
Associate Professor of Laboratory Medicine

Contact Information

Richard Torres, MD, MS, BS

Mailing Address

  • Laboratory Medicine

    PO Box 208035

    New Haven, CT 06520-8035

    United States

Yale Medicine

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Research Summary

For several years, my research laboratory has worked at the interface of engineering and medicine, applying new advances to important clinical laboratory problems. Specifically, a principal focus of my professional research interest is in translating technological developments in optics and image analysis into practical approaches to problems in diagnostic pathology. The impetus for this work has been the first-hand experience of enormous technical limitations affecting routine practice, for which technology offers exciting opportunities for improvement. The laboratory continually engages clinical practitioners and cutting-edge investigator colleagues to identify which evolving methods, techniques, and approaches can be readily molded into practical tools and have the best opportunities for significant impact on the understanding, diagnosis, and management of disease. We apply new techniques in a range of engineering fields such as rapid prototyping, electronics design, modern machine learning applications, and optics research, complemented by clinical experience which informs the understanding of pathology methods, diagnostic challenges, and clinical relevance. A principal area of research is a new method of tissue preparation and advanced microscopy that seeks to transform the manner in which pathologists render diagnoses for a whole host of diseases, including cancer of all types and renal disease.

Extensive Research Description

The work that we have done over the last decade for the development of a practical technique and instrument for non-destructive three-dimensional histology is of immense potential impact to both human diagnostics and animal studies of pathophysiology of disease. The success has been made possible by focused innovations in a variety of areas. Together with long-time collaborator Michael Levene and in concert with several other groups, we pioneered use of benzyl alcohol/benzyl benzoate (BABB) clearing for multiphoton microscopy. We developed strategies incorporating chemical modificaitons to speed up clearing using BABB, reducing processing time of small samples from days to a few hours. Early on we recognized the utility of a combined nuclear/protein fluorescent dye approach for visual reproduction of common pathology stains and identified the DAPI/eosin combination subsequently adopted by others. We designed and built the fastest high-resolution multiphoton microscope in the world, achieving light-microscopy level quality quickly and at depth, enabling heretofore largely impossible large-scale high-resolution reconstructions of animal tissue for investigative projects as well as practical clinical application for diagnostic pathology. And we have developed specialized efficient software for visualization of these large-scale three dimensional image stacks.

These techniques offer numerous potential advantages over traditional methods in terms of completeness of analysis, preservation of tissue for advanced molecular studies, speed and cost savings, and examination of important parameters such as architecture and abnormal growth, all while maintaining the compatibility with traditional histologic analysis.

We are continuing to both demonstrate the clinical and investigational prowess of the new technologies as well as further develop performance capabilities. Clinical trials of the application of the methods and techniques are well-advanced in prostate cancer and renal disease, and we have begun examining the increased diagnostic capabilities of multiphoton microscopy of bone marrow aspirate specimens for diagnosis and pathophysiology research studies.

Additionally, like other disciplines, we have been exploiting large data initiatives in pathology with are poised to benefit immensely from high quality digital data. Both three-dimensional imaging with digitization of morphologic data and genomic sequencing result in generation of vast amounts of information which require computing management and analysis tools in order to yield utility. Work done with current and former trainees with specialized knowledge of powerful new computing tools for imaging and genomic data management are the source of on-going computing projects. These developments are demonstrating that newest image pattern recognition techniques based on convolutional neural networks and python programming modules can be employed to aid in the accurate characterization of pathology image data. We are extending our data management and analysis techniques to a variety of anatomic and clinical pathology projects.


Coauthors

Research Interests

Bone Marrow Examination; Hematologic Tests; Image Interpretation, Computer-Assisted; Microscopy; Serologic Tests; Immunophenotyping; Imaging, Three-Dimensional; Microscopy, Fluorescence, Multiphoton; Nonlinear Optical Microscopy; Second Harmonic Generation Microscopy

Research Image

Multiphoton clearing histology with multiphoton microscopy (CHiMP) and whole slide imaging comparison.

A, Standard histology physical slide preparation with whole slide imaging (hematoxylin-eosin [H&E]). B, Multiphoton images produced via CHiMP processing, obtained prior to embedding and physical sectioning. Torres et al, Arch Path Lab Med, 2020

Selected Publications

  • Flow cytometric evaluation of peripheral blood for suspected Sézary syndrome or mycosis fungoides: International guidelines for assay characteristics.Horna P, Wang SA, Wolniak KL, Psarra K, Almeida J, Illingworth AJ, Johansson U, Craig FE, Torres R. Flow cytometric evaluation of peripheral blood for suspected Sézary syndrome or mycosis fungoides: International guidelines for assay characteristics. Cytometry. Part B, Clinical Cytometry 2021, 100: 142-155. PMID: 32319723, DOI: 10.1002/cyto.b.21878.
  • Initial Evaluation of Rapid, Direct-to-Digital Prostate Biopsy Pathology.Torres R, Olson E, Homer R, Martin DT, Levene MJ, Perincheri S, Sprenkle PC, Humphrey PA. Initial Evaluation of Rapid, Direct-to-Digital Prostate Biopsy Pathology. Archives Of Pathology & Laboratory Medicine 2021, 145: 583-591. PMID: 32991670, DOI: 10.5858/arpa.2020-0037-OA.
  • International guidelines for the flow cytometric evaluation of peripheral blood for suspected Sézary syndrome or mycosis fungoides: Assay development/optimization, validation, and ongoing quality monitors.Illingworth A, Johansson U, Huang S, Horna P, Wang SA, Almeida J, Wolniak KL, Psarra K, Torres R, Craig FE. International guidelines for the flow cytometric evaluation of peripheral blood for suspected Sézary syndrome or mycosis fungoides: Assay development/optimization, validation, and ongoing quality monitors. Cytometry. Part B, Clinical Cytometry 2021, 100: 156-182. PMID: 33112044, DOI: 10.1002/cyto.b.21963.
  • Evolution of the liver biopsy and its future.Jain D, Torres R, Celli R, Koelmel J, Charkoftaki G, Vasiliou V. Evolution of the liver biopsy and its future. Translational Gastroenterology And Hepatology 2021, 6: 20. PMID: 33824924, PMCID: PMC7829074, DOI: 10.21037/tgh.2020.04.01.
  • Ultrahigh-speed point scanning two-photon microscopy using high dynamic range silicon photomultipliers.Ching-Roa VD, Olson EM, Ibrahim SF, Torres R, Giacomelli MG. Ultrahigh-speed point scanning two-photon microscopy using high dynamic range silicon photomultipliers. Scientific Reports 2021, 11: 5248. PMID: 33664354, PMCID: PMC7933192, DOI: 10.1038/s41598-021-84522-0.
  • Primate model of chronic retinal neovascularization and vascular leakage.Patel C, Goody R, Hu W, Kurian A, James D, Torres R, Christie LA, Hohman T, Lawrence M. Primate model of chronic retinal neovascularization and vascular leakage. Experimental Eye Research 2020, 195: 108031. PMID: 32275921, PMCID: PMC7335215, DOI: 10.1016/j.exer.2020.108031.
  • Double-Edged Spike-Are SARS-CoV-2 Serologic Tests Safe Right Now?Torres R, Rinder HM. Double-Edged Spike-Are SARS-CoV-2 Serologic Tests Safe Right Now? Laboratory Medicine 2020, 51: 236-238. PMID: 32322891, PMCID: PMC7188174, DOI: 10.1093/labmed/lmaa025.
  • Double-Edged Spike.Torres R, Rinder HM. Double-Edged Spike. American Journal Of Clinical Pathology 2020, 153: 709-711. PMID: 32322898, PMCID: PMC7188132, DOI: 10.1093/ajcp/aqaa071.
  • Impact of intra-tumoral heterogeneity detected by next-generation sequencing on acute myeloid leukemia survival.Schulz WL, Rinder HM, Durant TJS, Tormey CA, Torres R, Smith BR, Hager KM, Howe JG, Siddon AJ. Impact of intra-tumoral heterogeneity detected by next-generation sequencing on acute myeloid leukemia survival. Leukemia & Lymphoma 2020, 61: 3269-3271. PMID: 32715805, DOI: 10.1080/10428194.2020.1797016.
  • False-Positive Light Chain Clonal Restriction by Flow Cytometry in Patients Treated With Alemtuzumab: Potential Pitfalls for the Misdiagnosis of B-Cell Neoplasms.Chen PP, Tormey CA, Eisenbarth SC, Torres R, Richardson SS, Rinder HM, Smith BR, Siddon AJ. False-Positive Light Chain Clonal Restriction by Flow Cytometry in Patients Treated With Alemtuzumab: Potential Pitfalls for the Misdiagnosis of B-Cell Neoplasms. American Journal Of Clinical Pathology 2019, 151: 154-163. PMID: 30307483, DOI: 10.1093/ajcp/aqy129.
  • Modified approach to fibrinogen replacement in the setting of dysfibrinogenaemia.Chandler JB, Siddon AJ, Bahel P, Torres R, Rinder HM, Tormey CA. Modified approach to fibrinogen replacement in the setting of dysfibrinogenaemia. Journal Of Clinical Pathology 2019, 72: 177-180. PMID: 30463936, DOI: 10.1136/jclinpath-2018-205438.
  • A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies.Song Y, Rongvaux A, Taylor A, Jiang T, Tebaldi T, Balasubramanian K, Bagale A, Terzi YK, Gbyli R, Wang X, Fu X, Gao Y, Zhao J, Podoltsev N, Xu M, Neparidze N, Wong E, Torres R, Bruscia EM, Kluger Y, Manz MG, Flavell RA, Halene S. A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies. Nature Communications 2019, 10: 366. PMID: 30664659, PMCID: PMC6341122, DOI: 10.1038/s41467-018-08166-x.
  • Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease.Landau SI, Guo X, Velazquez H, Torres R, Olson E, Garcia-Milian R, Moeckel GW, Desir GV, Safirstein R. Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease. Kidney International 2019, 95: 797-814. PMID: 30904067, PMCID: PMC6543531, DOI: 10.1016/j.kint.2018.11.042.
  • AI: What Have You Done for Us Lately?Torres R, Olson E. AI: What Have You Done for Us Lately? Journal Of The American Society Of Nephrology : JASN 2018, 29: 2031-2032. PMID: 29921720, PMCID: PMC6065091, DOI: 10.1681/ASN.2018050566.
  • Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney Disease.Cassini MF, Kakade VR, Kurtz E, Sulkowski P, Glazer P, Torres R, Somlo S, Cantley LG. Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney Disease. Journal Of The American Society Of Nephrology : JASN 2018, 29: 2471-2481. PMID: 30209078, PMCID: PMC6171277, DOI: 10.1681/ASN.2018050518.
  • Very Deep Convolutional Neural Networks for Morphologic Classification of Erythrocytes.Durant TJS, Olson EM, Schulz WL, Torres R. Very Deep Convolutional Neural Networks for Morphologic Classification of Erythrocytes. Clinical Chemistry 2017, 63: 1847-1855. PMID: 28877918, DOI: 10.1373/clinchem.2017.276345.
  • Microbiota control immune regulation in humanized mice.Gülden E, Vudattu NK, Deng S, Preston-Hurlburt P, Mamula M, Reed JC, Mohandas S, Herold BC, Torres R, Vieira SM, Lim B, Herazo-Maya JD, Kriegel M, Goodman AL, Cotsapas C, Herold KC. Microbiota control immune regulation in humanized mice. JCI Insight 2017, 2 PMID: 29093268, PMCID: PMC5752290, DOI: 10.1172/jci.insight.91709.
  • Modelling gas exchange during platelet storage without agitation.Torres R, Tormey CA. Modelling gas exchange during platelet storage without agitation. Vox Sanguinis 2016, 111: 445-448. PMID: 27864979, DOI: 10.1111/vox.12452.
  • Fluid motion and shear forces in platelet storage bags with different modes of agitation.Torres R, Tormey CA, Stack G. Fluid motion and shear forces in platelet storage bags with different modes of agitation. Vox Sanguinis 2016, 111: 209-12. PMID: 27078040, PMCID: PMC4981547, DOI: 10.1111/vox.12409.
  • Multiphoton microscopy with clearing for three dimensional histology of kidney biopsies.Olson E, Levene MJ, Torres R. Multiphoton microscopy with clearing for three dimensional histology of kidney biopsies. Biomedical Optics Express 2016, 7: 3089-96. PMID: 27570700, PMCID: PMC4986816, DOI: 10.1364/BOE.7.003089.
  • Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD.Torres R, Velazquez H, Chang JJ, Levene MJ, Moeckel G, Desir GV, Safirstein R. Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD. Journal Of The American Society Of Nephrology : JASN 2016, 27: 1102-12. PMID: 26303068, PMCID: PMC4814184, DOI: 10.1681/ASN.2015010079.
  • Evaluation of relational and NoSQL database architectures to manage genomic annotations.Schulz WL, Nelson BG, Felker DK, Durant TJ, Torres R. Evaluation of relational and NoSQL database architectures to manage genomic annotations. Journal Of Biomedical Informatics 2016, 64: 288-295. PMID: 27810480, DOI: 10.1016/j.jbi.2016.10.015.
  • Use of application containers and workflows for genomic data analysis.Schulz WL, Durant TJ, Siddon AJ, Torres R. Use of application containers and workflows for genomic data analysis. Journal Of Pathology Informatics 2016, 7: 53. PMID: 28163975, PMCID: PMC5248400, DOI: 10.4103/2153-3539.197197.
  • Computational Approach to Annotating Variants of Unknown Significance in Clinical Next Generation Sequencing.Schulz WL, Tormey CA, Torres R. Computational Approach to Annotating Variants of Unknown Significance in Clinical Next Generation Sequencing. Laboratory Medicine 2015, 46: 285-9. PMID: 26489672, DOI: 10.1309/LMWZH57BRWOPR5RQ.
  • Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/β-catenin Signaling in the Liver.Protiva P, Gong J, Sreekumar B, Torres R, Zhang X, Belinsky GS, Cornwell M, Crawford SE, Iwakiri Y, Chung C. Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/β-catenin Signaling in the Liver. Cellular And Molecular Gastroenterology And Hepatology 2015, 1: 535-549.e14. PMID: 26473164, PMCID: PMC4604042, DOI: 10.1016/j.jcmgh.2015.06.006.
  • Abnormal lymphocytes with "filamentous-like" cytoplasmic inclusions in chronic lymphocytic leukemia.Torres R, Tormey CA. Abnormal lymphocytes with "filamentous-like" cytoplasmic inclusions in chronic lymphocytic leukemia. Blood 2014, 124: 1391. PMID: 25313413, PMCID: PMC4148760, DOI: 10.1182/blood-2014-06-582098.
  • Humanized mice as a model for aberrant responses in human T cell immunotherapy.Vudattu NK, Waldron-Lynch F, Truman LA, Deng S, Preston-Hurlburt P, Torres R, Raycroft MT, Mamula MJ, Herold KC. Humanized mice as a model for aberrant responses in human T cell immunotherapy. Journal Of Immunology (Baltimore, Md. : 1950) 2014, 193: 587-96. PMID: 24943216, PMCID: PMC4123131, DOI: 10.4049/jimmunol.1302455.
  • Lupus anticoagulant testing and anticoagulation do not mix: quantitation of discrepant results and potential approaches to reduce false positives.Chandler JB, Torres R, Rinder HM, Tormey CA. Lupus anticoagulant testing and anticoagulation do not mix: quantitation of discrepant results and potential approaches to reduce false positives. British Journal Of Haematology 2014, 167: 704-7. PMID: 25041401, PMCID: PMC7024602, DOI: 10.1111/bjh.13030.
  • High-resolution, 2- and 3-dimensional imaging of uncut, unembedded tissue biopsy samples.Torres R, Vesuna S, Levene MJ. High-resolution, 2- and 3-dimensional imaging of uncut, unembedded tissue biopsy samples. Archives Of Pathology & Laboratory Medicine 2014, 138: 395-402. PMID: 23829375, DOI: 10.5858/arpa.2013-0094-OA.
  • Integrated fluorescence correlation spectroscopy device for point-of-care clinical applications.Olson E, Torres R, Levene MJ. Integrated fluorescence correlation spectroscopy device for point-of-care clinical applications. Biomedical Optics Express 2013, 4: 1074-82. PMID: 23847733, PMCID: PMC3704089, DOI: 10.1364/BOE.4.001074.
  • Clinical measurement of von Willebrand factor by fluorescence correlation spectroscopy.Torres R, Genzen JR, Levene MJ. Clinical measurement of von Willebrand factor by fluorescence correlation spectroscopy. Clinical Chemistry 2012, 58: 1010-8. PMID: 22451621, PMCID: PMC3733381, DOI: 10.1373/clinchem.2011.179200.
  • Normalized CCND1 expression has prognostic value in mantle cell lymphoma.Siddon AJ, Torres R, Rinder HM, Smith BR, Howe JG, Tormey CA. Normalized CCND1 expression has prognostic value in mantle cell lymphoma. British Journal Of Haematology 2012, 158: 551-3. PMID: 22671703, DOI: 10.1111/j.1365-2141.2012.09181.x.
  • Colonic in situ mantle cell lymphoma.Neto AG, Oroszi G, Protiva P, Rose M, Shafi N, Torres R. Colonic in situ mantle cell lymphoma. Annals Of Diagnostic Pathology 2012, 16: 508-14. PMID: 21840231, DOI: 10.1016/j.anndiagpath.2011.05.001.
  • Multiphoton fluorescence, second harmonic generation, and fluorescence lifetime imaging of whole cleared mouse organs.Vesuna S, Torres R, Levene MJ. Multiphoton fluorescence, second harmonic generation, and fluorescence lifetime imaging of whole cleared mouse organs. Journal Of Biomedical Optics 2011, 16: 106009. PMID: 22029356, DOI: 10.1117/1.3641992.
  • Laboratory testing for von Willebrand disease: toward a mechanism-based classification.Torres R, Fedoriw Y. Laboratory testing for von Willebrand disease: toward a mechanism-based classification. Clinics In Laboratory Medicine 2009, 29: 193-228. PMID: 19665675, PMCID: PMC7184927, DOI: 10.1016/j.cll.2009.06.005.
  • Applications of Digital Microscopy and Densely Connected Convolutional Neural Networks for Automated Quantification of Babesia-Infected Erythrocytes.Durant TJS, Dudgeon SN, McPadden J, Simpson A, Price N, Schulz WL, Torres R, Olson EM. Applications of Digital Microscopy and Densely Connected Convolutional Neural Networks for Automated Quantification of Babesia-Infected Erythrocytes. Clinical Chemistry 2021, 68: 218-229. PMID: 34969114, DOI: 10.1093/clinchem/hvab237.
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