Frederick Lanni
Associate Professor
Address:
294C Mellon Institute
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
Phone: 412-268-3460
Education
Ph.D., Harvard University
Postdoctoral Appointment, Syracuse University
Research
The mechanical activities of non-muscle cells drive many processes in embryonic development, tissue maintenance and healing, immune cell migration and function, neuronal circuit formation, and progression of certain diseases. Our understanding of these processes at the multicellular level requires a foundation of knowledge on the behavior of single cells. This research group studies the mechanics of single fibroblasts through experimental comparison of the arrangement of key cytoskeletal and adhesive proteins to the traction patterns generated by the cell. Our fundamental aim is to answer the following questions: What cytoskeletal machinery is assembled by a fibroblast to carry out a native task? Where is that machinery located within the cell, when does it operate, what is its effect under native conditions, and how is it regulated? A key part of our investigation is the growth of cells in a 3D collagen gel which serves as a model tissue-like extracellular matrix (ECM). In our experiments, the gel also serves as an elastic in-situ "strain gauge", the deformations of which can be read out by timelapse optical-sectioning microscopy. Using methods adapted from materials science, strain and other measures of mechanical action can be derived through digital image processing and matched to fluorescence images showing specific cytoskeletal proteins such as actin, alpha-actinin, or zyxin.
We developed and maintain a web site through which researchers anywhere may analyze timelapse image sequences showing ECM deformation caused by a cell (https://dqa.ni.cmu.edu/). In a parallel approach, we are experimenting with molecular methods to analyze activation in cytoskeletal signal-transduction pathways with speed and moderate spatial resolution in single cells. Our secondary aim is to understand the short-term and long-term "rules of engagement" between a fibroblast and its matrix, including neighboring cells. Rules of engagement undoubtedly differ between cell types, and reflect the epigenetic programming that accompanies differentiation. We plan to use this knowledge as a model for understanding and predicting cell responsivity and mechanics in native tissue, and as a design tool in the engineering of tissues.
Publications
Lanni F, Lagree K, Huang MY, Yan L, Woolford CA, Mitchell AP. Clarifying and Imaging Candida albicans Biofilms. J Vis Exp. 2020 Mar 6;(157). doi: 10.3791/60718. PMID: 32202525
Lawless MJ, Pettersson JR, Rule GS, Lanni F, Saxena S. ESR Resolves the C Terminus Structure of the Ligand-free Human Glutathione S-Transferase A1-1. Biophys J. 2018 Feb 6;114(3):592-601. doi: 10.1016/j.bpj.2017.12.016. PMID: 29414705
Lagree K, Desai JV, Finkel JS, Lanni F. Microscopy of fungal biofilms. Curr Opin Microbiol. 2018 Jun;43:100-107. doi: 10.1016/j.mib.2017.12.008. Epub 2018 Feb 4. PMID: 29414442
Pettersson JR, Lanni F, Rule GS. Dual Lifetimes for Complexes between Glutathione-S-transferase (hGSTA1-1) and Product-like Ligands Detected by Single-Molecule Fluorescence Imaging. Biochemistry. 2017 Aug 8;56(31):4073-4083. doi: 10.1021/acs.biochem.7b00030. Epub 2017 Jul 27. PMID: 28677395
Woolford CA, Lagree K, Xu W, Aleynikov T, Adhikari H, Sanchez H, Cullen PJ, Lanni F, Andes DR, Mitchell AP. Bypass of Candida albicans Filamentation/Biofilm Regulators through Diminished Expression of Protein Kinase Cak1. PLoS Genet. 2016 Dec 9;12(12):e1006487. doi: 10.1371/journal.pgen.1006487. PMID: 27935965
Desai JV, Cheng S, Ying T, Nguyen MH, Clancy CJ, Lanni F, Mitchell AP. Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2. Pathogens. 2015 Jul 24;4(3):573-589.
Van PT, Bass V, Shiwarski D, Lanni F, Minden J. High dynamic range proteome imaging with the Structured Illumination Gel Imager. Electrophoresis. 2014 Jun 17.
Youker RT, Bruns JR, Costa SA, Rbaibi Y, Lanni F, Kashlan OB, Teng H, Weisz OA. Multiple motifs regulate apical sorting of p75 via a mechanism that involves dimerization and higher-order oligomerization. Mol Biol Cell. 2013 May 1.
Desai JV, Bruno VM, Ganguly S, Stamper RJ, Mitchell KF, Solis N, Hill EM, Xu W, Filler SG, Andes DR, Fanning S, Lanni F, Mitchell AP. Regulatory Role of Glycerol in Candida albicans Biofilm Formation. MBio. 2013 Apr 9;4(2). pii: e00637-12.
Subramanian S, Woolford CA, Desai JV, Lanni F, Mitchell AP. Cis- and trans-acting localization determinants of pH-response regulator Rim13 in Saccharomyces cerevisiae. Eukaryot Cell. 2012 Aug 3. [Epub ahead of print]
Lim JK, Tan DX, Lanni F, Tilton RD and Majetich SA. Optical imaging and magnetophoresis of nanorods. J. Magnetism Mag. Mater. 321: 1557-1562, 2009.
Lim JK, Eggeman A, Lanni F, Tilton RD and Majetich SA. Synthesis and single-particle optical detection of low-polydispersity plasmonic-superparamagnetic nanoparticles. Adv. Mater. 20: 1721-1726, 2008.
Levitan ES, Lanni F and Shakiryanova D. In vivo imaging of vesicle motion and release at the Drosophila neuromuscular junction. Nature Protocols 2: 117-1125, 2007.
Nauman JV, Campbell PG, Lanni F and Anderson JL. Diffusion of insulin-like growth factor-I and ribonuclease through fibrin gels. Biophys. J. 92:4444-4450, 2007.
Lanni F, Pane DA, Weinstein SJ and Waggoner AS. Compact flashlamp-based fluorescence imager for use under ambient-light conditions. Rev. Sci. Instr. 78:033702, 2007.
Lanni F. Fluorescence grating imager systems for optical-sectioning microscopy. In: Imaging in Neuroscience and Development. R.M. Yuste and A. Konnerth, eds. Cold Spring Harbor Laboratory Press, 2005. pp805-813 (Chapter 101), 2005.
Vanni S, Lagerholm BC, Otey C, Taylor DL and Lanni F. Internet-based image analysis quantifies contractile behavior of individual fibroblasts inside model tissue. Biophysical Journal, 84:2715-2727, 2003.
Lagerholm, B.C., S. Vanni, D.L. Taylor and F. Lanni. Cytomechanics applications of optical sectioning microscopy. Meth. Enzymol. 361:175-197, 2003.
Full PubMed Listings