Photo of Steven J. Mentzer,  MD

Steven J. Mentzer, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 732-6703
Fax: (617) 730-2898


smentzer@partners.org

Steven J. Mentzer, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Surgery, Harvard Medical School
  • Professor, Adult Oncology, Dana-Farber Cancer Institute
  • Professor, Surgery, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

In the mammalian immune system, cell migration plays an important role in the host defense against a variety of antigenic challenges. Cell migration is the process that delivers lymphocytes to virally infected tissues, organ allografts, or growing tumors. Understanding the mechanism of lymphocyte homing to the site of antigen challenge offers the potential for regulating this process clinically. For example, it would be desirable to enhance lymphocyte migration into virally infected tissues and malignant tumors, but suppress lymphocyte migration into organ allografts.



In recent years, attempts to define the mechanism of lymphocyte homing to the site of inflammation have focused on cell adhesion molecules. These molecules are expressed on the cell surface and appear to regulate the interaction of lymphocytes with the endothelial cells that line the vessel wall. Our approach has been to study the function of these molecules under physiologic conditions both in vitro and in vivo. Using a video microscopy chamber to simulate flow conditions in the inflammatory microcirculation, we study the contribution of these cell adhesion molecules to lymphocyte movement, adhesion, and locomotion. The regulation of lymphocyte migration can be clarified by selectively inhibiting or augmenting the function of these cell adhesion molecules.



Cell migration to the site of antigen challenge is a process that involves not only lymphocytes and endothelial cells, but complex microhemodynamic forces as well. The forces at the vessel wall appear to be important determinants of whether cells exit the microcirculation or remain in the flow stream. For example, during lymphocytic inflammation, microhemodynamic forces can vary widely as the microcirculation undergoes dramatic structural adaptation. It is possible these structural changes facilitate lymphocyte transmigration. To study the effect of microhemodynamic forces on lymphocyte migration, we track migrating lymphocytes from the efferent lymph to the antigen-stimulated microcirculation. Using fluorescence and dark-field intravital video microscopy, we directly observe the movements of cells in the microcirculation. Defining the molecular and physiologic mechanisms of lymphocyte migration into the inflammatory tissue is leading to new approaches to the inhibition and augmentation of cell migration in vivo.

Publications from Harvard Catalyst Profiles

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  • White AA, Lee DN, Mazzola E, Kucukak S, Polhemus E, Jaklitsch MT, Mentzer SJ, Wee JO, Bueno R, Swanson SJ. Adjuvant therapy following induction therapy and surgery improves survival in N2-positive non-small cell lung cancer. J Surg Oncol 2021; 123:579-586. PubMed
  • Dolan DP, White A, Mazzola E, Lee DN, Gill R, Kucukak S, Bueno R, Jaklitsch MT, Mentzer SJ, Swanson SJ. Outcomes of superior segmentectomy versus lower lobectomy for superior segment Stage I non-small-cell lung cancer are equivalent: An analysis of 196 patients at a single, high volume institution. J Surg Oncol 2021; 123:570-578. PubMed
  • Rodriguez M, Dezube AR, Bravo-Iniguez CE, Fox S, De León LE, Tarascio J, Freyaldenhoven S, Mentzer SJ, Swanson SJ, Bueno R, Rochefort MM, Marshall MB, Jaklitsch MT. Impact of Neoadjuvant Chemoradiation On Adverse Events Following Bronchial Sleeve Resection. Ann Thorac Surg 2020. PubMed
  • White A, Kucukak S, Lee DN, Bueno R, Jaklitsch M, Mentzer S, Sugarbaker D, Wee J, Swanson SJ. Completion pneumonectomy is safe and effective in select patients with recurrent non-small cell lung cancer. J Thorac Dis 2020; 12:217-222. PubMed
  • Ysasi AB, Bennett RD, Wagner W, Valenzuela CD, Servais AB, Tsuda A, Pyne S, Li S, Grimsby J, Pokharel P, Livak KJ, Ackermann M, Blainey PC, Mentzer SJ. Single-Cell Transcriptional Profiling of Cells Derived From Regenerating Alveolar Ducts. Front Med (Lausanne) 2020; 7:112. PubMed
  • Haber S, Holtzman Z, Mentzer SJ, Tsuda A. Why do myofibroblasts preferentially accumulate on the convex surface of the remodeling lung after pneumonectomy? J Theor Biol 2019; 479:90-96. PubMed
  • Valenzuela CD, Wagner WL, Bennett RD, Ysasi AB, Belle J, Molter K, Straub BK, Wang D, Chen Z, Ackermann M, Tsuda A, Mentzer SJ. Extracellular Assembly of the Elastin Cable Line Element in the Developing Lung. Anat Rec (Hoboken) 2017. PubMed
  • Ackermann M, Kim YO, Wagner WL, Schuppan D, Valenzuela CD, Mentzer SJ, Kreuz S, Stiller D, Wollin L, Konerding MA. Effects of nintedanib on the microvascular architecture in a lung fibrosis model. Angiogenesis 2017. PubMed
  • Ackermann M, Mentzer SJ, Roth W, Geisthoff U, Stoelben E. Pulmonary microvascular architecture in hereditary haemorrhagic telangiectasia. Thorax 2017. PubMed
  • Bennett RD, Ysasi AB, Wagner WL, Valenzuela CD, Tsuda A, Pyne S, Li S, Grimsby J, Pokharel P, Livak KJ, Ackermann M, Blainey P, Mentzer SJ. Deformation-induced transitional myofibroblasts contribute to compensatory lung growth. Am J Physiol Lung Cell Mol Physiol 2017; 312:L79-L88. PubMed
  • Cleary JM, Mamon HJ, Szymonifka J, Bueno R, Choi N, Donahue DM, Fidias PM, Gaissert HA, Jaklitsch MT, Kulke MH, Lynch TP, Mentzer SJ, Meyerhardt JA, Swanson RS, Wain J, Fuchs CS, Enzinger PC. Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer. BMC Cancer 2016; 16:468. PubMed
  • Wagner W, Bennett RD, Ackermann M, Ysasi AB, Belle J, Valenzuela CD, Pabst A, Tsuda A, Konerding MA, Mentzer SJ. Elastin Cables Define the Axial Connective Tissue System in the Murine Lung. Anat Rec (Hoboken) 2015. PubMed
  • Mohiuddin K, Haneuse S, Sofer T, Gill R, Jaklitsch MT, Colson YL, Wee J, Bueno R, Mentzer SJ, Sugarbaker DJ, Swanson SJ. Relationship between margin distance and local recurrence among patients undergoing wedge resection for small (≤2 cm) non-small cell lung cancer. J Thorac Cardiovasc Surg 2014; 147:1169-75; discussion 1175-7. PubMed
  • Oxman DA, Issa NC, Marty FM, Patel A, Panizales CZ, Johnson NN, Licona JH, McKenna SS, Frendl G, Mentzer SJ, Jaklitsch MT, Bueno R, Colson Y, Swanson SJ, Sugarbaker DJ, Baden LR. Postoperative antibacterial prophylaxis for the prevention of infectious complications associated with tube thoracostomy in patients undergoing elective general thoracic surgery: a double-blind, placebo-controlled, randomized trial. JAMA Surg 2013. PubMed
  • Chamoto K, Gibney BC, Lee GS, Ackermann M, Konerding MA, Tsuda A, Mentzer SJ. Migration of CD11b+ accessory cells during murine lung regeneration. 2013; 10:267-77. PubMed
  • Gibney BC, Houdek JP, Chamoto K, Lee GS, Ackermann M, Lin M, Collings-Simpson D, Konerding MA, Tsuda A, Mentzer SJ. Mechanostructural adaptations preceding postpneumonectomy lung growth. Exp. Lung Res. 2012; 38:396-405. PubMed
  • Butler JP, Loring SH, Patz S, Tsuda A, Yablonskiy DA, Mentzer SJ. Evidence for adult lung growth in humans. N Engl J Med 2012; 367:244-7. PubMed
  • Lee GS, Filipovic N, Lin M, Gibney BC, Simpson DC, Konerding MA, Tsuda A, Mentzer SJ. Intravascular pillars and pruning in the extraembryonic vessels of chick embryos. Dev Dyn 2011. PubMed
  • Erba P, Ogawa R, Ackermann M, Adini A, Miele LF, Dastouri P, Helm D, Mentzer SJ, D'Amato RJ, Murphy GF, Konerding MA, Orgill DP. Angiogenesis in wounds treated by microdeformational wound therapy. Ann Surg 2011. PubMed
  • Konerding MA, Turhan A, Ravnic DJ, Lin M, Fuchs C, Secomb TW, Tsuda A, Mentzer SJ. Inflammation-Induced Intussusceptive Angiogenesis in Murine Colitis. Anat Rec (Hoboken) 2010; 293:849-57. PubMed
  • Filipovic N, Tsuda A, Lee GS, Miele LF, Lin M, Konerding MA, Mentzer SJ. Computational flow dynamics in a geometric model of intussusceptive angiogenesis. Microvasc Res 2009; 78:286-93. PubMed
  • Caglar HB, Baldini EH, Othus M, Rabin MS, Bueno R, Sugarbaker DJ, Mentzer SJ, Jänne PA, Johnson BE, Allen AM. Outcomes of patients with stage III nonsmall cell lung cancer treated with chemotherapy and radiation with and without surgery. Cancer 2009; 115:4156-66. PubMed
  • Pratt JP, Zeng Q, Ravnic D, Huss H, Rawn J, Mentzer SJ. Hierarchical clustering of monoclonal antibody reactivity patterns in nonhuman species. Cytometry A 2009; 75:734-42. PubMed
  • Miele LF, Turhan A, Lee GS, Lin M, Ravnic D, Tsuda A, Konerding MA, Mentzer SJ. Blood flow patterns spatially associated with platelet aggregates in murine colitis. Anat Rec (Hoboken) 2009; 292:1143-53. PubMed
  • Turhan A,Lin M,Lee GS,Miele LF,Tsuda A,Konerding MA,Mentzer SJ. Vascular microarchitecture of murine colitis-associated lymphoid angiogenesis. Anat Rec (Hoboken) 2009; 292:621-32. PubMed
  • Lee GS,Miele LF,Turhan A,Lin M,Hanidziar D,Konerding MA,Mentzer SJ. Spatial calibration of structured illumination fluorescence microscopy using capillary tissue phantoms. Microsc Res Tech 2009; 72:85-92. PubMed
  • Tsuda A,Turhan A,Konerding M,Ravnic D,Hanidziar D,Lin M,Mentzer SJ. Bimodal oscillation frequencies of blood flow in the inflammatory colon microcirculation. Anat Rec (Hoboken) 2009; 292:65-72. PubMed
  • Turhan A,Tsuda A,Konerding MA,Lin M,Miele L,Lee G,Mentzer SJ. Effect of intraluminal pillars on particle motion in bifurcated microchannels. In Vitro Cell Dev Biol Anim 2008; 44:426-33. PubMed
  • Allen AM, Mentzer SJ, Yeap BY, Soto R, Baldini EH, Rabin MS, Sugarbaker DJ, Bueno R. Pneumonectomy after chemoradiation: the Dana-Farber Cancer Institute/Brigham and Women's Hospital experience. Cancer 2008; 112:1106-13. PubMed
  • Filipovic N, Ravnic D, Kojic M, Mentzer SJ, Haber S, Tsuda A. Interactions of blood cell constituents: experimental investigation and computational modeling by discrete particle dynamics algorithm. Microvasc Res 2008; 75:279-84. PubMed
  • Allen AM, Rabin MS, Reilly JJ, Mentzer SJ. Unresectable adenoid cystic carcinoma of the trachea treated with chemoradiation. J Clin Oncol 2007; 25:5521-3. PubMed
  • Chang MY, Mentzer SJ, Colson YL, Linden PA, Jaklitsch MT, Lipsitz SR, Sugarbaker DJ. Factors predicting poor survival after resection of stage IA non-small cell lung cancer. J Thorac Cardiovasc Surg 2007; 134:850-6. PubMed
  • Ravnic DJ, Konerding MA, Huss HT, Wolloscheck T, Pratt JP, Mentzer SJ. Murine microvideo endoscopy of the colonic microcirculation. J Surg Res 2007; 142:97-103. PubMed
  • Paul S, Kurtz M, Mentzer SJ. Osteomalacia associated with a fibroblast growth factor-23 secreting chest wall tumor. J Thorac Cardiovasc Surg 2007; 134:803-5. PubMed
  • Loring SH, Mentzer SJ, Reilly JJ. Sources of graft restriction after single lung transplantation for emphysema. J Thorac Cardiovasc Surg 2007; 134:204-9. PubMed
  • Zeng QT, Pratt JP, Pak J, Ravnic D, Huss H, Mentzer SJ. Feature-guided clustering of multi-dimensional flow cytometry datasets. J Biomed Inform 2007; 40:325-31. PubMed
  • Mentzer SJ. Optimizing the selection of surgical candidates for lung volume reduction surgery. Semin Thorac Cardiovasc Surg 2007; 19:151-6. PubMed
  • Li Y, Chang Q, Rubin BP, Fletcher CD, Morgan TW, Mentzer SJ, Sugarbaker DJ, Fletcher JA, Xiao S. Insulin receptor activation in solitary fibrous tumours. J Pathol 2007; 211:550-4. PubMed
  • Perrine SP, Hermine O, Small T, Suarez F, O'Reilly R, Boulad F, Fingeroth J, Askin M, Levy A, Mentzer SJ, Di Nicola M, Gianni AM, Klein C, Horwitz S, Faller DV. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood 2007; 109:2571-8. PubMed
  • Linden PA, Bueno R, Mentzer SJ, Zellos L, Lebenthal A, Colson YL, Sugarbaker DJ, Jaklitsch MT. Modified T-tube repair of delayed esophageal perforation results in a low mortality rate similar to that seen with acute perforations. Ann Thorac Surg 2007; 83:1129-33. PubMed
  • Jiang X, Pratt JP, Huss HO, Ravnic DJ, Mentzer SJ. Structural mapping of immunoglobulin subclasses using multiplexed bead flow cytometry. Hybridoma (Larchmt) 2006; 25:133-8. PubMed
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