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Steven James Mentzer, MD
Senior Surgeon, Brigham and Women's Hospital
Professor of Surgery, Harvard Medical School

Brigham and Women's Hospital
Department of Surgery
Thoracic Surgery
75 Francis Street
Boston, MA 02115


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Research Narrative:

 

Adult Tissue Morphogenesis Research Group. Our group investigates the biological processes responsible for the development of organ shape and form (morphogenesis). Although morphogenesis is often studied in a developmental context, our interest is in the acquisition of shape and form in adult tissues. Morphogenesis is a process generally linked to tissue repair and regeneration, but clinically relevant to the understanding of a variety of diseases. In addition, morphogenesis is a fundamental issue in many contemporary approaches to tissue engineering. The process of adult tissue morphogenesis is intriguing because it is self-organized and involves complex structural, cellular and molecular interactions. 

 

A primary focus of our research group is the growth and patterning of new blood vessels (angiogenesis). Blood vessel networks are generated and modified during development, physiologic stresses (exercise) and tissue repair. The mechanisms responsible for vascular patterning include sprouting and intussusceptive angiogenesis. Intussusceptive angiogenesis is a particularly intriguing mechanism of network expansion because it involves the splitting of a single vessel into two lumens. This morphogenetic process allows for the rapid expansion of existing microcirculatory networks without compromising tissue blood flow. Intussusceptive angiogenesis appears to be a primary mechanism for vascular expansion in the lung; it also appears to be a 2 prominent mechanism of tumor-induced angiogenesis. An understanding of the mechanisms of vascular patterning offers the potential for therapies in ischemic diseases (brain, heart and peripheral vascular disease), cancer, wound healing and tissue engineering. 


Lung Regeneration Working Group. An interesting observation in most mammalian species is that removal of one lung (pneumonectomy) leads to the compensatory growth of the remaining lung. The majority of the compensatory growth occurs within a week or two of pneumonectomy and involves a dramatic increase in both lung volumes and the number of airsacs (alveoli). In fact, the lung is nearly back to baseline volume and function by 3 weeks after pneumonectomy. Equally dramatic, the lung undergoes significant angiogenesis; estimates of capillary growth vary, but post-pneumonectomy angiogenesis may involve more than 1km of new vessels within 2 weeks of lung removal. Although not yet demonstrated in humans, the observations in experimental models suggests that “reverse engineering” lung regeneration will provide important clues for understanding human lung repair and regeneration. 


Education:
MD

Publications (Pulled from Harvard Catalyst Profiles):

1. Servais AB, Kienzle A, Ysasi AB, Valenzuela CD, Wagner WL, Tsuda A, Ackermann M, Mentzer SJ. Structural heteropolysaccharides as air-tight sealants of the human pleura. J Biomed Mater Res B Appl Biomater. 2019 Apr; 107(3):799-806.

2. Servais AB, Valenzuela CD, Ysasi AB, Wagner WL, Kienzle A, Loring SH, Tsuda A, Ackermann M, Mentzer SJ. Pressure-decay testing of pleural air leaks in intact murine lungs: evidence for peripheral airway regulation. Physiol Rep. 2018 05; 6(10):e13712.

3. Kienzle A, Servais AB, Ysasi AB, Gibney BC, Valenzuela CD, Wagner WL, Ackermann M, Mentzer SJ. Free-Floating Mesothelial Cells in Pleural Fluid After Lung Surgery. Front Med (Lausanne). 2018; 5:89.

4. Mentzer SJ. The puzzling mechanism of compensatory lung growth. Stem Cell Investig. 2018; 5:8.

5. Servais AB, Valenzuela CD, Kienzle A, Ysasi AB, Wagner WL, Tsuda A, Ackermann M, Mentzer SJ. Functional Mechanics of a Pectin-Based Pleural Sealant after Lung Injury. Tissue Eng Part A. 2018 05; 24(9-10):695-702.

6. Mentzer SJ, Tsuda A, Loring SH. Pleural mechanics and the pathophysiology of air leaks. J Thorac Cardiovasc Surg. 2018 May; 155(5):2182-2189.

7. Gibney BC, Wagner WL, Ysasi AB, Belle JM, Tsuda A, Ackermann M, Mentzer SJ. Structural and functional evidence for the scaffolding effect of alveolar blood vessels. Exp Lung Res. 2017 Nov - Dec; 43(9-10):337-346.

8. White A, Kucukak S, Bueno R, Servais E, Lee DN, Colson Y, Jaklitsch M, McNamee C, Mentzer S, Wee J, Swanson SJ. Pneumonectomy is safe and effective for non-small cell lung cancer following induction therapy. J Thorac Dis. 2017 Nov; 9(11):4447-4453.

9. Ackermann M, Gaumann A, Mentzer SJ, Hinrichs JB, Warnecke G, Hoeper MM, Braubach P, Kuehnel M, Maegel L, Jonigk D. Plexiform Vasculopathy in Chronic Thromboembolic Pulmonary Hypertension. Am J Respir Crit Care Med. 2017 10 15; 196(8):e48-e51.

10. George E, Barile M, Tang A, Wiesel O, Coppolino A, Giannopoulos A, Mentzer S, Jaklitsch M, Hunsaker A, Mitsouras D. Utility and reproducibility of 3-dimensional printed models in pre-operative planning of complex thoracic tumors. J Surg Oncol. 2017 Sep; 116(3):407-415.