The Lammerding Lab

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What squishing cells can tell us about human disease – studying the interplay between cellular structure, mechanics, and function.

Cells in the human body reside in a physically stressful and demanding environment, being continuously exposed to large forces and deformations. Examples include not only contracting skeletal and cardiac muscle cells, bone and cartilage, but also immune cells, stem cells, and metastatic cancer cells that move through tight tissue spaces to reach distant sites in the body. It is now well established that cells respond to such physical challenges with characteristic changes in cellular organization, signaling, and function through a process referred to as ‘mechanotransduction’. The molecular mechanisms by which cells sense their physical environment and translate mechanical stimuli into biochemical signals remains incompletely understood. Nonetheless, it has become abundantly clear that defects in cellular mechanics or mechanotransduction signaling—arising from mutations or altered gene expression—can disturb cellular function and contribute to a large number of human diseases, ranging from muscular dystrophy to heart disease and cancer.

In the Lammerding laboratory, we investigate this intricate interplay between cellular structure, mechanics and function through an interdisciplinary research approach that combines engineering principles, microfabrication, and cell and molecular biology techniques, as well as the development and application of novel experimental assays. Our team is composed of students and postdoctoral researchers with a broad range of backgrounds, including (biomedical) engineering, biology, chemistry and other life sciences, who explore creative solutions to relevant biological and clinical problems. Our research is focused on the nuclear envelope and its interface with the surrounding cytoskeleton, as mutations in nuclear envelope proteins are responsible for more than 10 human diseases, such as muscular dystrophy, dilated cardiomyopathy, and premature aging (Hutchison-Gilford progeria syndrome). Furthermore, abnormal expression of nuclear envelope proteins expression has recently been identified in numerous cancers, often correlating with negative clinical outcomes. Work conducted in the Lammerding lab has already shown that mutations or loss of nuclear envelope proteins such as lamins render cells more sensitive to mechanical stress and also impair mechanotransduction signaling, providing a potential mechanism for the progressive muscle defects in many nuclear envelopathies. Furthermore, we have demonstrated that the deformability of the nucleus, the largest and most rigid cell organelle, constitutes a rate-limiting factor in the ability of cells to migrate through tight spaces, stimulating increased interest in understanding how highly motile cells such as neutrophils and metastatic cancer cells overcome this challenge.

Please check our Research Section for more details.

 Selected Publications

Denais CM, Gilbert RM, Isermann P, McGregor AL, te Lindert M, Weigelin B, Davidson PM, Friedl P, Wolf K, Lammerding J. Nuclear envelope rupture and repair during cancer cell migrationScience. 2016. 352(6283): 353-358.

Davidson PM, Sliz J, Isermann P, Denais C, Lammerding J. Design of a microfluidic device to quantify intra-nuclear deformation during cell migration through confining environments. Integr Biol (Camb). 2015. 30(7): 1534-46.

Dialynas G, Shrestha OK, Ponce JM, Zwerger M, Thiemann DA, Young GH, Moore SA, Yu L, Lammerding J and Wallrath LL. Myopathic lamin mutations cause reductive stress and activate the Nrf2/Keap-1 pathway. PLoS Genetics. 2015. 11(5): e1005231. Published online May 21, 2015.

Ho CY, Jaalouk DE, Vartiainen MK, Lammerding J. Lamin A/C and emerin regulate MKL1/SRF activity by modulating actin dynamics. Nature 2013. 497(7450):507-11.

Isermann P, Lammerding J. Nuclear Mechanics and Mechanotransduction in Health and Disease. Curr Biol 2013. 23(24): R1113-R1121.

Zwerger M, Jaalouk DE, Lombardi ML, Isermann P, Mauermann M, Dialynas G, Herrmann H, Wallrath LL, Lammerding J. Myopathic lamin mutations impair nuclear stability in cells and tissue and disrupt nucleo-cytoskeletal coupling. Hum Mol Gen 2013. 22(12):2335-49

Rowat A, Jaalouk DJ, Zwerger M, Ung WL, Eydelnant IA, Olins D, Olins A, Herrmann H, Weitz DA, Lammerding J. Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions. J Biol Chem 2013. 288(12):8610-8618.

Verstraeten VLRM, Peckham LA, Olive M, Capell BC, Collins FS, Nabel EG, Young SG, Fong LG, Lammerding J. Protein farnesylation inhibitors cause donut-shaped cell nuclei due to a centrosome separation defect. Proc Natl Acad Sci. 2011. 108(12):4997-5002.

Jaalouk DE, Lammerding J. Mechanotransduction gone awry. Nature Reviews Molecular Cell Biology 2009. 10(1):63–73.

 

Jan Lammerding, PhD

Growing up in Germany, Jan Lammerding initially followed a traditionally engineering trajectory. Taking apart everything from cameras and clocks to radios as a kid, he went on to study mechanical engineering at the Rheinisch Westfälische Technische Universität (University of Technology) Aachen, in Aachen, Germany. Given the chance to study abroad through a fellowship from the Deutscher Akademischer Austausch Dienst (DAAD), he spent a year at the Thayer School of Engineering at Dartmouth College, earning a Bachelor of Engineering degree. The interdisciplinary environment at Thayer School reinforced his longstanding interest in combining engineering with biology. After completing his Diplom Ingenieur degree in Germany, he joined the newly founded Biological Engineering program at MIT in the first group of PhD students, designing new techniques to study the biophysical properties of cells in Dr. Roger Kamm’s laboratory.

After he received his Ph.D. from MIT, Jan Lammerding completed a brief post-doctoral training in Dr. Richard Lee’s laboratory at Brigham and Women’s Hospital before ascending through the rank of instructor to the position of Assistant Professor at Harvard Medical School. During that time, he also served as Lecturer in the Department of Biological Engineering at MIT, teaching a class in molecular, cell, and tissue biomechanics in the new Biological Engineering major. Jan’s interests in developing and applying new research approaches to study cellular biology and mechanics, as well as his passion for teaching and working with students, recently drove him to join the Department of Biomedical Engineering and the Weill Institute for Cell and Molecular Biology at Cornell.

Weill Institute for Cell & Molecular Biology
Department of Biomedical Engineering
Cornell University
235 Weill Hall
Ithaca, NY 14853-7202
jan.lammerding@cornell.edu
(607)255-1700 (office)
(607)255-1980 (lab)
(607)255-2472 (fax)

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