Dr. Lefort is an Assistant Professor in the Department of Surgery, Division of Surgical Research. He received his BS in Biomedical Engineering from Columbia University in 2001 and his Ph.D. in the same field from the University of Rochester in 2007. He completed postdoctoral work in Immunology at the University of Rochester and at La Jolla Institute for Allergy & Immunology.
| Hinman KD, Laforce-Nesbitt SS, Cohen JT, Mundy M, Bliss JM, Horswill AR, Lefort CT. "Bi-fluorescent Staphylococcus aureus infection enables single-cell analysis of intracellular killing in vivo." Frontiers in immunology, vol. 14, 2023, pp. 1089111. |
| Cohen JT, Danise M, Hinman KD, Neumann BM, Johnson R, Wilson ZS, Chorzalska A, Dubielecka PM, Lefort CT. "Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host." Frontiers in Cell and Developmental Biology, vol. 10, 2022, pp. 840894. |
| Guerrero-Fonseca IM, García-Ponce A, Vadillo E, Lartey NL, Vargas-Robles H, Chánez-Paredes S, Castellanos-Martínez R, Nava P, Betanzos A, Neumann BM, Penkala-Auguste K, Lefort CT, Schnoor M. "HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage." European journal of cell biology, vol. 101, no. 2, 2022, pp. 151214. |
| Fredericks AM, East KW, Shi Y, Liu J, Maschietto F, Ayala A, Cioffi WG, Cohen M, Fairbrother WG, Lefort CT, Nau GJ, Levy MM, Wang J, Batista VS, Lisi GP, Monaghan SF. "Identification and mechanistic basis of non-ACE2 blocking neutralizing antibodies from COVID-19 patients with deep RNA sequencing and molecular dynamics simulations." Frontiers in molecular biosciences, vol. 9, 2022, pp. 1080964. |
| Harrington EO, Kumar A, Leandre V, Wilson ZS, Guarino B, Braza J, Lefort CT, Klinger JR. "Natriuretic peptide receptor-C mediates the inhibitory effect of atrial natriuretic peptide on neutrophil recruitment to the lung during acute lung injury." American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 323, no. 4, 2022, pp. L438-L449. |
| LeBlanc BW, Lefort CT. "A Mouse Model of Pseudomonas aeruginosa Pneumonia." Methods in Molecular Biology, vol. 2321, 2021, pp. 53-61. |
| Cohen JT, Danise M, Machan JT, Zhao R, Lefort CT. "Murine Myeloid Progenitors Attenuate Immune Dysfunction Induced by Hemorrhagic Shock." Stem Cell Reports, vol. 16, no. 2, 2021, pp. 324-336. |
| Wilson ZS, Witt H, Hazlett L, Harman M, Neumann BM, Whitman A, Patel M, Ross RS, Franck C, Reichner JS, Lefort CT. "Context-Dependent Role of Vinculin in Neutrophil Adhesion, Motility and Trafficking." Scientific reports, vol. 10, no. 1, 2020, pp. 2142. |
| Demirdjian S, Hopkins D, Cumbal N, Lefort CT, Berwin B. "Distinct Contributions of CD18 Integrins for Binding and Phagocytic Internalization of Pseudomonas aeruginosa." Infection and Immunity, vol. 88, no. 5, 2020. |
| Lee K, Cohen JT, Wilson ZS, Zhao R, Lomas-Neira J, Chung CS, Chen Y, Jamieson AM, Ayala A, Lefort CT. "Hemorrhage Attenuates Neutrophil Recruitment in Response to Secondary Respiratory Infection by Pseudomonas Aeruginosa." SHOCK, vol. 52, no. 5, 2019, pp. 506-512. |
| Wilson ZS, Ahn LB, Serratelli WS, Belley MD, Lomas-Neira J, Sen M, Lefort CT. "Activated β<sub>2</sub> Integrins Restrict Neutrophil Recruitment during Murine Acute Pseudomonal Pneumonia." American Journal of Respiratory Cell and Molecular Biology, vol. 56, no. 5, 2017, pp. 620-627. |
| Bai M, Grieshaber-Bouyer R, Wang J, Schmider AB, Wilson ZS, Zeng L, Halyabar O, Godin MD, Nguyen HN, Levescot A, Cunin P, Lefort CT, Soberman RJ, Nigrovic PA. "CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation." Blood, 2017. |
| Johnson CM, O'Brien XM, Byrd AS, Parisi VE, Loosely AJ, Li W, Witt H, Faridi MH, LeFort CT, Gupta V, Kim M, Reichner JS. "Integrin Cross-Talk Regulates the Human Neutrophil Response to Fungal β-Glucan in the Context of the Extracellular Matrix: A Prominent Role for VLA3 in the Antifungal Response." The Journal of Immunology, vol. 198, no. 1, 2017, pp. 318-334. |
| Ye, Feng, Petrich, Brian G., Anekal, Praju, Lefort, Craig T., Kasirer-Friede, Ana, Shattil, Sanford J., Ruppert, Raphael, Moser, Markus, Fässler, Reinhard, Ginsberg, Mark H. "The Mechanism of Kindlin-Mediated Activation of Integrin αIIbβ3." Current Biology, vol. 23, no. 22, 2013, pp. 2288-2295. |
| Stadtmann, A., Germena, G., Block, H., Boras, M., Rossaint, J., Sundd, P., Lefort, C., Fisher, C. I., Buscher, K., Gelschefarth, B., Urzainqui, A., Gerke, V., Ley, K., Zarbock, A. "The PSGL-1-L-selectin signaling complex regulates neutrophil adhesion under flow." Journal of Experimental Medicine, vol. 210, no. 11, 2013, pp. 2171-2180. |
| Stadtmann, A., Germena, G., Block, H., Boras, M., Rossaint, J., Sundd, P., Lefort, C., Fisher, C. I., Buscher, K., Gelschefarth, B., Urzainqui, A., Gerke, V., Ley, K., Zarbock, A. "The PSGL-1-L-selectin signaling complex regulates neutrophil adhesion under flow." The Journal of Cell Biology, vol. 203, no. 2, 2013, pp. 2032OIA125-2032OIA125. |
| Lefort, C. T., Rossaint, J., Moser, M., Petrich, B. G., Zarbock, A., Monkley, S. J., Critchley, D. R., Ginsberg, M. H., Fassler, R., Ley, K. "Distinct roles for talin-1 and kindlin-3 in LFA-1 extension and affinity regulation." Blood, vol. 119, no. 18, 2012, pp. 4275-4282. |
| Rillahan, Cory D, Antonopoulos, Aristotelis, Lefort, Craig T, Sonon, Roberto, Azadi, Parastoo, Ley, Klaus, Dell, Anne, Haslam, Stuart M, Paulson, James C. "Global metabolic inhibitors of sialyl- and fucosyltransferases remodel the glycome." Nature Chemical Biology, vol. 8, no. 7, 2012, pp. 661-668. |
| Lefort, Craig T., Ley, Klaus. "Neutrophil arrest by LFA-1 activation." Front. Immun., vol. 3, 2012. |
| Tang, J., Zarbock, A., Gomez, I., Wilson, C. L., Lefort, C. T., Stadtmann, A., Bell, B., Huang, L.-C., Ley, K., Raines, E. W. "Adam17-dependent shedding limits early neutrophil influx but does not alter early monocyte recruitment to inflammatory sites." Blood, vol. 118, no. 3, 2011, pp. 786-794. |
| Hu, X., Kang, S., Lefort, C., Kim, M., Jin, M. M. "Combinatorial libraries against libraries for selecting neoepitope activation-specific antibodies." Proceedings of the National Academy of Sciences, vol. 107, no. 14, 2010, pp. 6252-6257. |
| Lefort, Craig T., Kim, Minsoo. "Human T Lymphocyte Isolation, Culture and Analysis of Migration In Vitro." Journal of Visualized Experiments, no. 40, 2010. |
| Lefort, C. T., Wojciechowski, K., Hocking, D. C. "N-cadherin Cell-Cell Adhesion Complexes Are Regulated by Fibronectin Matrix Assembly." Journal of Biological Chemistry, vol. 286, no. 4, 2010, pp. 3149-3160. |
| Hyun, Young-Min, Lefort, Craig T., Kim, Minsoo. "Leukocyte integrins and their ligand interactions." Immunologic research, vol. 45, no. 2-3, 2009, pp. 195-208. |
| Lefort, C. T., Hyun, Y.-M., Schultz, J. B., Law, F.-Y., Waugh, R. E., Knauf, P. A., Kim, M. "Outside-In Signal Transmission by Conformational Changes in Integrin Mac-1." The Journal of Immunology, vol. 183, no. 10, 2009, pp. 6460-6468. |
| Kaba, N. K., Schultz, J., Law, F.-Y., Lefort, C. T., Martel-Gallegos, G., Kim, M., Waugh, R. E., Arreola, J., Knauf, P. A. "Inhibition of Na+/H+ exchanger enhances low pH-induced L-selectin shedding and 2-integrin surface expression in human neutrophils." AJP: Cell Physiology, vol. 295, no. 5, 2008, pp. C1454-C1463. |
During infection or injury, white blood cells (leukocytes) must exit from the circulation to reach sites in the tissue where they are needed to mount an immune response. My lab's focus is on the neutrophil, a type of innate immune cell that is the first to mobilize from the circulation to mount the inflammatory response. The recruitment of neutrophils occurs by a cascade of interactions with the endothelial cell lining of the blood vessel wall that precedes their migration into the tissue. We use biophysical and molecular engineering methods to dissect the mechanisms of neutrophil trafficking and how they engulf and destroy microbes. Our research also uses an innovative cellular tool - conditionally-immortalized neutrophil progenitors - to gain the technical capacity for genetic engineering in order to identify novel aspects of neutrophil function and thereby develop strategies for combating drug-resistant bacterial and fungal infections.
We are also deeply interested in understanding how the neutrophil response is altered in the critically ill. We have found that the systemic response to hemorrhagic shock, as occurs following traumatic injury, renders neutrophils unable to efficiently sense and migrate to sites of infection. At the same time, neutrophils can become prematurely activated under conditions of systemic immune dysfunction and cause damage to host tissues. Our research aims to develop strategies to restore neutrophil function and minimize tissue injury associated with hyperinflammation.
R35GM124911, NIH/NIGMS, 2017-2028: "Selective modulation of neutrophils in critical illness"
R03AI130526, NIH/NIAID, 2017-2018: "A murine model of Pseudomonas aeruginosa pneumonia secondary to hemorrhagic shock"
Oh-Zopfi Pediatric Research Pilot Grant, Women & Infants Hospital, 2017-2018: "A Genetic Screen to Identify Mechanisms of Neutrophil Phagocytosis of Candida"
Pilot Project, CardioPulmonary Vascular Biology COBRE, 2015-2016: "Integrin activation regulates neutrophil trafficking during bacterial pneumonia"
Scientist Development Grant, American Heart Association, 2012-2016: "Mechanisms of LFA-1 Conformational Activation in Neutrophils"
| Year | Degree | Institution |
|---|---|---|
| 2007 | PhD | University of Rochester |
| 2003 | MS | University of Rochester |
| 2001 | BS | Columbia University |
| Name | Title |
|---|---|
| Ayala, Alfred | Professor of Surgery (Research) |
| Franck, Christian | Associate Professor of Engineering |
| Heffernan, Daithi | Associate Professor of Surgery |
| Lomas-Neira, Joanne | Assistant Professor of Surgery (Research) |
| Lu, Qing | Associate Professor of Medicine |
| Monaghan, Sean | Associate Professor of Surgery |
| Reichner, Jonathan | Professor of Surgery (Research) |
