Biology Faculty: Melinda Larsen

Melinda Larsen

Associate Professor of Biological Sciences
Ph.D., Baylor College of Medicine

Office LS1086
Telephone (518) 591-8882
Fax (518) 442-4767

Areas of Interest

  • Cell and molecular basis for salivary gland branching morphogenesis
  • Cell-extracellular matrix signaling
  • Cell-cell signaling
  • Salivary gland tissue engineering
  • Salivary gland tissue regeneration


Get PDF My lab is interested in deciphering the molecular mechanisms controlling branching morphogenesis, which is a process required for the development of many mammalian organs, including the lung, kidney, prostate, mammary glands, and salivary glands. Branching requires coordination of many cellular processes such as proliferation, cytoskeletal contraction, and basement membrane remodeling. These cellular processes result in cleft formation and bud outgrowth, which together comprise the process of branching morphogenesis (Figure 1). Understanding the control and coordination of these cellular processes may lead to a better understanding of how adult tissues can be repaired or regenerated.

Figure 1. Branching morphogenesis in the salivary gland and other organs requires coordination of multiple signaling pathways initiated by transmembrane signaling proteins, including integrins and growth factor receptors (GFR), which lead to the cellular processes of proliferation, cytoskeletal contraction, and basement membrane remodeling. These cellular processes result in cleft formation and bud outgrowth that together comprise branching morphogenesis. From Larsen, et al. 2006. Current Opinion in Cell Biology. 2006. 18:463-471. 

We recently demonstrated that cell migration is involved in salivary gland branching morphogenesis. We use embryonic salivary glands as a model system for the study of branching morphogenesis. In embryonic salivary glands grown as organ cultures, we can monitor changes in temporal-spatial distribution of targets using time-lapse confocal microscopy. By tracking cells in embryonic day 13 (E13) salivary glands that were labeled with green fluorescent protein (GFP), we observed that early embryonic epithelial cells undergo substantial, rapid cell migration during the early stages of branching morphogenesis (Figure 2). This cell migration is independent of cell division and does not occur later in development when the epithelial cells have started to differentiate and become polarized. A current question under investigation is: how are cell movements controlled during branching morphogenesis? The Rho family of small GTPases regulates the actin cytoskeleton to induce changes in cell shape and in cell motility and are candidate molecules to serve this function. A current project is to investigate a role for Rho proteins in regulating actin rearrangements during branching morphogenesis.

  Figure 2. Still frames from time-lapse image analysis. A. E13 salivary glands were labeled with green fluorescent protein (GFP, green) and Alexa-Fluor-647-fibronectin (pseudocolored red), and images were captured at multiple time-points, shown are images captured at 0:00 and 4:06 hrs. B. Tracking of individual cell movements through all frames of the time-lapse showed that cells are migrating during branching morphogenesis. An example cell track is displayed on a single XY frame (bottom right), a XZ projection (top) and a YZ projection (left). Bars, 50 µm. Modified from Larsen, et. al. 2006. Journal of Cell Science, 119: 3376-3384. 

The extracellular matrix plays a critical function during branching morphogenesis. We previously found that the extracellular matrix protein, fibronectin, is required for branching morphogenesis (Figure 1). It is expressed in the cleft, a structure in the basement membrane where branching initiates. Knockdown of fibronectin mRNA with siRNAs or inhibition of protein function with inhibitory antibodies prevented morphogenesis. Pulse-chase labeling of exogenously-added, fluorescently labeled fibronectin (Alexa-Fluor-647-fibronectin), indicated that fibronectin is assembled inward into the gland, providing a driving force for formation of clefts and, thus, progression of branching morphogenesis. Current projects are focused on the upstream signal driving expression of fibronectin and on the downstream targets of fibronectin signaling through its integrin receptors.

We use cell, molecular, biochemical, and imaging techniques to address developmental questions. To profile gene expression during development in vivo and in 3D cell and organ culture models, we use the SAGE gene profiling technique as well as real-time PCR and in situ analysis. Protein expression is evaluated by Western analysis, and confocal imaging. We manipulate gene expression and protein function using small inhibitory RNAS (siRNAs), inhibitory antibodies, and pharmacological inhibitors. To study branching morphogenesis in real time, we image the 3D salivary gland organ culture system using both standard light microscopy and live time-lapse confocal microscopy.


  • Nimit Dhulekar, Shayoni Ray, Daniel Yuan, Abhirami Baskaran, Basak Oztan, Melinda Larsen, and Bülent Yener. 2016. Prediction of Growth Factor-Dependent Cleft Formation During Branching Morphogenesis Using a Dynamic Graph-Based Growth Model. IEEE IEEE/ACM Transactions on Computational Biology and Bioinformatics pp. 13, 350-364.
  • Get PDFElise M. Gervais, Kara A. DeSantis, Nicholas Pagendarm, Deirdre A. Nelson, Kathrine Skarstein, Janicke Liaaen Jenssen, and Melinda Larsen. 2015. Changes in the Submandibular Salivary Gland Epithelial Cell Subpopulations During Progression of Sjögren's Syndrome in the NOD/ShiLtJ Mouse Model. Anatomical Record (Hoboken) pp. 298, 1622-1634.
  • Get PDFHae Ryong Kwon and Melinda Larsen. 2015. Branching Morphogenesis of the Mammalian Salivary Gland. Current Opinion in Genetics and Development. pp. 32, 47-54.
  • Get PDFDeirdre A. Nelson and Melinda Larsen. 2015. Heterotypic Control of Basement Membrane Dynamics During Branching Morphogenesis. Developmental Biology. pii: S0012-1606(14)00637-X. doi: 10.1016/j.ydbio.2014.12.011. [Epub ahead of print] PMID: 25527075.
  • Sarah B. Peters, Deirdre A. Nelson, Hae Ryong Kwon, Mathew Koslow, Kara A. DeSantis, and Melinda Larsen. 2015. TGFb Signaling Promotes Matrix Assembly During Mechanosensitive Salivary Gland Restoration. Matrix Biology. pii: S0945-053X(15)00034-7, doi: 10.1016/j.matbio.2015.01.020. PMID: 25652203
  • Shayoni Ray, Joseph A. Fanti, Diego P. Macedo, and Melinda Larsen. 2014. LIM Kinase Regulation of Cytoskeletal Dynamics is Required for Salivary Gland Branching Morphogenesis. Molecular Biology of the Cell. 25(16):2393-407. doi: 10.1091/mbc.E14-02-0705. PMID: 24966172
  • Sarah B. Peters, Nyla Naim, Deirdre A. Nelson, Aaron Mosier, Nathaniel C. Cady, and Melinda Larsen. 2014. Biocompatible Tissue Scaffold Compliance Promotes Salivary Gland Morphogenesis and Differentiation. Tissue Engineering, Part A, 20, (11-12)1632-42. PMID: 24410370
  • Aaron P. Mosier, Sarah B. Peters, Melinda Larsen, and Nathaniel C. Cady. 2014 Microfluidic Platform for the Elastic Characterization of Mouse Submandibular glands by Atomic Force Microscopy. Biosensors, 4:18-27 manuscripts. doi:10.3390/bios4010018.
  • Shomita S. Matthew, Bethsaida Nieves, Sharon Sequeira, Savitha Sambadamoorthy, Kevin Pumiglia, Melinda Larsen, and Susan E. Laflamme. 2014. Integrins Promote Cytokinesis Through the RSK Signaling Axis. Journal of Cell Science 127, 534-45. PMID: 24284076 doi: 10.1242/jcs.133280
  • Interactive Visual Atlas of Protein Localization: Development of the Salivary Gland Web resource, 2013.
  • Shayoni Ray, Daniel Yuan, Nimit Dhulekar, Basak Otzan, Bulent Yener, and Melinda Larsen. 2013. Cell-Based Multi-Parametric Model of Cleft Progression During Submandibular Salivary Gland Branching Morphogenesis. 2013. PLOS Computational Biology 9(11): e1003319. DOI: 10.1371/journal.pcbi.1003319
  • Michael J. Gerdes, Christopher J. Sevinsky, Anup Sood, Sudeshna Adak, Musodiq Bello, Ali Can, Sean Dinn, Robert J. Filkins, Melinda Larsen, Qing Li, Michael C. Montalto, Jens Rittscher, James E. Rothman, Zhengyu Pang, Brion D. Sarachan, Maximilian L. Seel, Antti Seppo, Jingyu Zhang, and Fiona Ginty. 2013 High-Order Multiplexed Fluorescence Imaging for Quantitative, in Situ Subcellular Analysis of Cancer Tissue. PNAS. 110: 29, 11982–11987 doi: 10.1073/pnas.1300136110
  • David Soscia, Sharon J. Sequeira, Robert Schramm, Kavitha Jayarathanam, Shraddha I. Cantara, Melinda Larsen, and James Castracane. 2013. Salivary gland cell differentiation and organization on micropatterned PLGA nanofiber craters, Biomaterials. 34: 6773-6784. Article.
  • Deirdre A. Nelson, Charles Manhardt, Vidya Kamath, Yunxia Sui, Alberto Santamaria-Pang, Ali Can, Musodiq Bello, Alex Corwin, Sean Dinn, Michael Lazare, Musodiq Bello, Alex Corwin, Elise M. Gervais, Sarah B. Peters, Sharon J. Sequeira, Fiona Ginty, Michael J. Gerdes, and Melinda Larsen. 2013. Quantitative Single Cell Analysis of Cell Population Dynamics During Submandibular Salivary Gland Development and Differentiation. Biology Open. 2(5): 439-447. doi: 10.1242/bio.20134309
  • Shraddha Cantara, David Soscia, Sharon J. Sequeira, Riffard P. Jean-Gilles, James Castracane, and Melinda Larsen. 2012. Selective Functionalization of Nanofiber Scaffolds to Regulate Salivary Gland Epithelial Cell Proliferation and Polarity. Biomaterials. 33:8372-8382.
  • *Sharon J. Sequeira, *Elise M. Gervais, Shayoni Ray, and Melinda Larsen. Genetic Modification and Recombination of Salivary Gland Organ Cultures. 2012. Journal of Visualized Experiments(71), e50060, doi:10.3791/50060 (2013). *these authors contributed equally to the work
  • Cemal Cagatay Bilgin, Shayoni Ray, William P. Daley, Banu Baydil, Melinda Larsen, and Bulent Yener. 2012 Multiscale Feature Analysis of Salivary Gland Branching Morphogenesis. PLOS One7(3): e32906. doi:10.1371/journal.pone.0032906 [these authors contributed equally to the work]  PMC3293912.
  • Sharon J. Sequeira, David Soscia, Basak Oztan, Riffard Jean-Gilles, Anand Gadre, Bulent Yener, James Castracane and Melinda Larsen. 2012. Nanofiber Artificial Scaffolds Regulate Salivary Gland Epithelial Cell Morphology and Focal Adhesion Complex Formation. Biomaterials33(11): 3175-3186. PMC348071.
  • William P. Daley, Elise M. Gervais, Samuel W. Centanni, Kathryn M. Gulfo, Deirdre A. Nelson and Melinda Larsen. 2012. ROCK1-Directed Directed Basement Membrane Positioning Coordinates Epithelial Tissue Polarity. Development 139(2):411-222. doi:10.1242/dev.075366. Abstract
  • William P. Daley, Joshua M. Kohn and Melinda Larsen. 2011. A Focal Adhesion Protein-Based Mechanochemical Checkpoint Regulates Cleft Progression During Branching Morphogenesis. Developmental Dynamics 240:2069–2083. DOI 10.1002/dvdy.22714 featured in“Highlights of Developmental Dynamics” December 2011 issue PMC 312957 Abstract
  • Helga S. Larsen, Marit H. Aure, Sarah B. Peters, Melinda Larsen, Eward B. Messelt, Hilde Kanli Galtung. 2011. Localization of AQP5 during development of the mouse submandibular salivary gland. Journal of Molecular Histology 42(1), 71-81. doi: 10.1007/s10735-010-9308-0 abstract
  • Mary Ann Stepp, William P Daley, Audrey M Bernstein, Sonali Pal-Ghosh, Gauri Tadvalkar, Alexey Shashurin, Sarah Palsen, Rosalyn A Jurjus and M Larsen. 2010. Syndecan-1 regulates cell migration and fibronectin fibril assembly. Experimental Cell Research, 316: 2322-39. abstract
  • William P. Daley, Kathryn M. Gulfo, Sharon J. Sequeira, and Melinda Larsen. 2009. Identification of a mechanochemical checkpoint and negative feedback loop regulating branching morphogenesis. Developmental Biology 336:169-182
  • abstract
  • William P. Daley, Sarah B. Peters and Melinda Larsen. 2008. Extracellular Matrix Dynamics: Roles in Development and Implications for Regenerative Medicine. Journal of Cell Science. 121:255-264. abstract
  • Fiona Ginty, Sudeshna Adak, Ali Can, Michael J. Gerdes, Melinda Larsen, Harvey Cline, Robert Filkins, Zhengyu Pang, Qing Li, Michael C. Montalto. 2008. The Relative Distribution of Membranous and Cytoplasmic Met Is a Prognostic Indicator in Stage I and II Colon Cancer. Clinical Cancer Research 14(12): 3814:3822. abstract
  • Mary Ann Stepp, Yueyuan Liu, Sonali Pal-Ghosh, Rosalyn A. Jurjus, Gauri Tadvalkar, Adith Sekaran, Kristen LoSicco, Li Jiang, Melinda Larsen, Luowei Li, and Stuart H. Yuspa. 2007. Reduced Migration Rates and Enhanced TGF-β1 Signaling in Primary Mouse Keratinocytes Lacking Syndcan-1. Journal of Cell Science 120: 2851-2863. abstract
  • Cindy H. Wei, Melinda Larsen, Matthew P. Hoffman, and Kenneth M. Yamada. 2007. Self-Organization and Branching Morphogenesis of Primary Salivary Epithelial Cells. Tissue Engineering. 13(4):721-735. abstract
  • Melinda Larsen, Vira V. Artym, J. Angelo Green, and Kenneth M. Yamada. 2006. The Matrix Remodeled: Extractellular Matrix Remodeling and Integrin Signaling. Current Opinion in Cell Biology 18:463-471. abstract
  • Melinda Larsen, Cindy H. Wei, Susana S. Hahn, Kenneth M. Yamada. 2006. Cell and Fibronectin Dynamics During Branching Morphogenesis. J. Cell Science 119: 3376-3384 (with journal cover, featured in Journal of Cell Science “In this Issue”) abstract
  • Takayoshi Sakai, Melinda Larsen, and Kenneth M. Yamada. 2005. Morphogenesis and Branching of Salivary Glands: Characterization of New Matrix and Signaling Regulators. Oral Biosci. Med. 213: 105-113.
  • Zachary Steinberg, Christopher Myers, Benjamin L. Kidder, Vernon M. Heim, Ivan T. Rebustini, Julian S. Stewart, Melinda Larsen, and Matthew P. Hoffman. 2005. FGR2b Signaling Regulates ex vivo Submandibular Gland Epithelial Cell Proliferation and Branching Morphogenesis. Development 132:1223-1234. abstract
  • Takayoshi Sakai, Melinda Larsen, Mikihiko Kogo, and Kenneth M. Yamada. 2004. Molecular Analysis of Salivary Gland Branching Morphogenesis. Oral Science International 1: 16-21.
  • Melinda Larsen, Michel L. Tremblay, and Kenneth M. Yamada. 2003. Phosphatases in Cell-Matrix Adhesion and Migration. Nature Reviews Molecular Cell Biology 4: 700-711. abstract
  • Takayoshi Sakai, Melinda Larsen, and Kenneth M. Yamada. 2003. Fibronectin Requirement in Branching Morphogenesis. Nature 423: 876-881. (Featured in Journal of Cell Biology “Research Roundup” and Nature Reviews Molecular Cell Biology “Research Highlights”) abstract
  • Melinda Larsen, Matthew P. Hoffman, Takayoshi Sakai, Justin C. Neibaur, Jonathan Mitchell, and Kenneth M. Yamada. 2003. Role of PI 3-kinase and PIP3 in Submandibular Gland Branching Morphogenesis. Developmental Biology 255: 178-191. (with journal cover) abstract
  • Michael J. Gerdes, Melinda Larsen, Truong D. Dang, Steven J. Ressler, and David R. Rowley. 2003. Regulation of Prostate Stromal Cell Myodifferentiation by Androgen and TGF-β1. The Prostate 58 (3): 299-307. abstract
  • Stephanie J. McAlhany, Steven J. Ressler, Melinda Larsen, Truong D. Dang, and David R. Rowley. 2003. Promotion of Angiogenesis by ps20 in the Differential Reactive Stroma Prostate Cancer Xenograph Model. Cancer Research 63 (18): 5859-65 abstract
  • Takayoshi Sakai, Melinda Larsen, and Kenneth M. Yamada. 2002. Microanalysis of Gene Expression in tissues Using T7-SAGE: Serial Analysis of Gene Expression After High-Fidelity T7-Based RNA amplification. Current Protocols in Cell Biology 19.3.1-19.4.10 John Wiley & Sons, New York. abstract
  • Matthew P. Hoffman, Benjamin Kidder, Zachary Steinberg, Saba Lakhani, Susan Ho, Hynda K. Kleinman and Melinda Larsen. 2002. Gene Expression Profiles of Mouse Submandibular Gland Development: FGFR1 Regulates Branching Morphogenesis in Vitro Through BMP- and FGF-Dependent Mechanisms. Development 129: 5767-5778. abstract
  • Sun-Ho Kee, Shyh-Ing Jang, Bijan Ahvazi, Melinda Larsen, Kenneth M. Yamada, and Peter M. Steinert. 2002. Cell-Cell Adhesion and Rho A-Mediated Actin Polymerization are Independent Phenomena in Microtubule Disrupted Keratinocytes. The Journal of Investigative Dermatology 119 (3): 440-448. abstract
  • Melinda Larsen, Steven J. Ressler, Michael J. Gerdes, Bing Lu, Meg Bryan, Jeanne B. Lawrence, and David R. Rowley. 2000. The WFDC1 Gene Encoding ps20 Localizes to 16q24, a Region of LOH in Multiple Cancers. Mammalian Genome 11: 767-773. abstract
  • Melinda Larsen, Steven J. Ressler, Bing Lu, Michael J. Gerdes, Lauren McBride, Truong D. Dang, and David R. Rowley. 1998. Molecular Cloning and Expression of ps20 Growth Inhibitor: A Novel WAP-Type "Four-Disulfide Core" Domain Protein Expressed in Smooth Muscle. Journal of Biological Chemistry 273(8): 4574-4584. abstract
  • Michael J. Gerdes, Melinda Larsen, Lauren McBride, Truong D. Dang, Bing Lu, and David R. Rowley. 1998. Localization of Transforming Growth Factor-β1 and Type II Receptor in Developing Normal Prostate and Carcinoma Tissues. The Journal of Histochemistry and Cytochemistry 46(3): 379-388. abstract
  • Michael J. Gerdes, Truong D. Dang, Melinda Larsen, and David R. Rowley. 1998. Transforming Growth Factor-β1 Induces Nuclear to Cytoplasmic Distribution of Androgen Receptor and Inhibits Androgen Response in Prostate Smooth Muscle Cells. Endocrinology 129(8): 3569-3577. abstract
  • Michael J. Gerdes, Truong D. Dang, Bing Lu, Melinda Larsen, Lauren McBride, and David R. Rowley. 1996. Androgen-Regulated Proliferation and Gene Transcription in a Prostate Smooth Muscle Cell Line (PS-1). Endocrinology 137(3): 864-872. abstract
  • David R. Rowley, Truong D. Dang, Melinda Larsen, Michael J. Gerdes, Lauren McBride, and Bing Lu. 1995. Purification of a Novel Protein (ps20) from Urogenital Sinus Mesenchymal Cells with Growth Inhibitory Properties in vitro. Journal of Biological Chemistry 270(37): 22058-22065. abstract
  • David R. Rowley, Truong D. Dang, Lauren McBride, Michael J. Gerdes, Bing Lu, and Melinda Larsen. 1995. β-2 Microglobulin is Mitogenic to PC-3 Prostatic Carcinoma Cells and Antagonistic to Transforming Growth Factor-β1 Action. Cancer Research 55: 781-786. abstract