Daniel S. Greenspan, PhD

Portrait of Daniel S. Greenspan, PhD
Cell and Regenerative Biology
K4/430 CSC
600 Highland Avenue
Madison, WI 53792
(608) 262-4676
Focus Groups: 
Cancer Biology
Signal Transduction
PhD, New York University
Research Summary: 
Extracellular modulators of cellular behaviors in development, homeostasis, and disease
Research Detail: 

Our focus has been on genes and gene products important to vertebrate development and human disease. We have previously discovered a number of developmentally important genes, and determined their involvement in normal morphogenesis and in genetic abnormalities. For, example, we were involved in isolating and characterizing the locus for the disfiguring and ultimately fatal heritable skin disorder dystrophic epidermolysis bullosa. We've also found and helped characterize the locus for classic Ehlers-Danlos syndrome, which occurs in about 1 in 20,000 births and produces individuals with fragile connective tissues.

Much work in the lab currently focuses on extracellular regulatory proteins that control and orchestrate events as diverse as growth factor signaling and formation of the extracellular matrix (ECM). Such events are critical in adult vertebrates (e.g. for maintenance of the cardiovascular system, wound healing, turnover of the skeleton and synaptic plasticity) and are even more dynamic during development. One class of the regulatory molecules that we study comprises small families of proteases that activate and inactivate various growth factors, enzymes and extracellular structural macromolecules. An example is the BMP1/Tolloid-like family of proteinases (see the Figure, below). Another class comprises antagonists of signaling by members of the TGFb superfamily of growth factors. Three additional classes of regulatory molecules under study modify actions of the first two by as yet unclear mechanisms. Molecules we study play central roles in morphogenetic processes and defects in these proteins may underlie human disease. Our studies employ biochemical, genetic and developmental analyses, including characterizing standard and conditional "knockout" mice, and zebrafish and examining possible links between defects in genes of interest and human development and disease.

Current studies in the lab also include roles of extracellular proteins in adipocyte biology, diabetic symptoms, atherosclerosis, and organ transplant rejection. The latter two studies include translational studies of human patients. roteins for in vitro and cell culture assays of protein function; high throughput screens for protein:protein interactions; the production and characterization of standard and conditional "knockout" mice that have altered alleles for the genes of interest, and examination of possible links between defects in the genes we study and human developmental abnormalities.

Selected Publications: 
Procollagen C-proteinase enhancer 1 (PCPE-1) functions as an anti-angiogenic factor and enhances epithelial recovery in injured cornea. Massoudi D, Germer CJ, Glisch JM, Greenspan DS. Cell Tissue Res. 2017 Dec;370(3):461-476. doi: 10.1007/s00441-017-2689-6. Epub 2017 Sep 21. PMID: 28936615
WBSCR16 Is a Guanine Nucleotide Exchange Factor Important for Mitochondrial Fusion. Huang G, Massoudi D, Muir AM, Joshi DC, Zhang CL, Chiu SY, Greenspan DS. Cell Rep. 2017 Jul 25;20(4):923-934. doi: 10.1016/j.celrep.2017.06.090. PMID: 28746876
Deficits in Col5a2 Expression Result in Novel Skin and Adipose Abnormalities and Predisposition to Aortic Aneurysms and Dissections. Park AC, Phan N, Massoudi D, Liu Z, Kernien JF, Adams SM,Davidson JM, Birk DE, Liu B, Greenspan DS. Am J Pathol. 2017 Oct;187(10):2300-2311. doi: 10.1016/j.ajpath.2017.06.006. Epub 2017 Jul 19. PMID: 28734943
α3 Chains of type V collagen regulate breast tumour growth via glypican-1. Huang G, Ge G, Izzi V, Greenspan DS. Nat Commun. 2017 Jan 19;8:14351. doi: 10.1038/ncomms14351. PMID: 28102194
Essential Roles of Bone Morphogenetic Protein-1 and Mammalian Tolloid-like 1 in Postnatal Root Dentin Formation. Wang J, Muir AM, Ren Y, Massoudi D, Greenspan DS, Feng JQ. JEndod. 2017 Jan;43(1):109-115. doi: 10.1016/j.joen.2016.09.007. Epub 2016 Nov 12. PMID: 27847137
BMP1-like proteinases are essential to the structure and wound healing of skin. Muir AM, Massoudi D, Nguyen N, Keene DR, Lee SJ, Birk DE, Davidson JM, Marinkovich MP, Greenspan DS. Matrix Biol. 2016 Dec;56:114-131. doi: 10.1016/j.matbio.2016.06.004. Epub 2016 Jun 27. PMID: 27363389
Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance. Park AC, Huang G, Jankowska-Gan E, Massoudi D, Kernien JF, Vignali DA, Sullivan JA, Wilkes DS, Burlingham WJ, Greenspan DS. J Biol Chem. 2016 Feb 12;291(7):3359-70. doi: 10.1074/jbc.M115.681882. Epub 2015 Dec 31. PMID: 26721885
Homozygosity and Heterozygosity for Null Col5a2 Alleles Produce Embryonic Lethality and a Novel Classic Ehlers-Danlos Syndrome-Related Phenotype. Park AC, Phillips CL, Pfeiffer FM, Roenneburg DA, Kernien JF, Adams SM, Davidson JM, Birk DE, Greenspan DS. Am J Pathol. 2015 Jul;185(7):2000-11. doi: 10.1016/j.ajpath.2015.03.022. Epub 2015 May 16. PMID: 2598725
Induced ablation of Bmp1 and Tll1 produces osteogenesis imperfecta in mice. Muir AM, Ren Y, Butz DH, Davis NA, Blank RD, Birk DE, Lee SJ, Rowe D, Feng JQ, Greenspan DS. Hum Mol Genet. 2014 Jun 15;23(12):3085-101. doi: 10.1093/hmg/ddu013. Epub 2014 Jan 12. PMID: 24419319
IL-17 induces type V collagen overexpression and EMT via TGF-β-dependent pathways in obliterative bronchiolitis. Vittal R, Fan L, Greenspan DS, Mickler EA, Gopalakrishnan B, Gu H, Benson HL, Zhang C, Burlingham W, Cummings OW, Wilkes DS. Am J Physiol Lung Cell Mol Physiol. 2013 Mar 15;304(6):L401-14. doi: 10.1152/ajplung.00080.2012. Epub 2012 Dec 21. PMID: 23262228