Our research is currently focused on several classes of extracellular regulatory molecules that play key roles in vertebrate and invertebrate development and homeostasis.
One class of these regulatory molecules is composed of a small family of proteases that appear key to the biosynthetic processing of a number of structural proteins and enzymes from precursor molecules to their mature functional forms. Examples of this first class of molecules are Tolloid, in Drosophila, and the mammalian proteases, discovered and characterized in this lab, Bone Morphogenetic Protein-1 (BMP-1), mammalian Tolloid (mTLD) and mammalian Tolloid-like 1 and 2 (mTLL-1 and mTLL-2).
Another class of regulatory molecules under study in the lab comprises antagonists of signaling by the bone morphogenetic protein subset of transforming growth Factor-b (TGF-b)-like growth factors. An example of the latter class of regulatory molecules is the protein Chordin.
Two additional classes of regulatory molecules modify the actions of the first two by, as yet, unclear mechanisms. Examples of the latter class of molecules are twisted gastrulation (TSG) and procollagen C-proteinase enhancers 1 and 2 (PCPE 1 and PCPE 2).
Interactions between the various regulatory molecules listed above and other proteins appear to orchestrate the deposition of extracellular matrix with growth factor signaling in morphogenetic processes and in the remodeling of tissues in the adult (e.g. wound healing, bone remodeling and synaptic plasticity associated with learning).
Our studies employ biochemical, genetic and developmental analyses. Such studies include the production of recombinant versions of proteins of interest for in vitro and cell culture assays of protein function; the production, characterization and intercrossing of “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 diseases.
A final facet of what we are doing involves collaborative interactions with biotechnology companies seeking to develop inhibitors of some of the proteases that we study. Such inhibitors are of potential use in therapeutic interventions for treatment of fibrotic conditions and certain types of cancer.
Current Greenspan lab members include:
- Research Specialist: Guy Hoffman
- Postdoctoral Fellow: Guorui Huang PhD
Past pre-doctoral members of the Greenspan lab include:
- Amanda Branam, PhD – Post-doctoral in Dr. Richard Peterson’s Lab, School of Pharmacy, University of Wisconsin-Madison
- Delana Hopkins, PhD – Senior Scientist at Pharmaceutical Product Development (Madison, WI)
- LIsa Zhang, PhD – Unknown.
- Seung-Taek Lee, Professor and Chair, Dept. of Biochemistry, College of Science, Yonsei University, Seoul, S. Korea
- Seungbok Lee, Assistant Professor Developmental and Molecular Biology, Seoul, National University, S. Korea
- Barry Steiglitz, Stratatech Corporation
- William Pappano, Jane Coffin Childs Post doctoral fellow, HHMI, Dept of Molecular, Biology and Genetics, Johns Hopkins University
- Mandy Wang, Scientist I, R&D Systems
- Reema Jasuja, Postdoctoral Fellow, Beth Israel Deaconess Medical Center, Harvard Medical School
Former post-doctoral members of the Greenspan lab include:
- Kazuhiko Takahara, Associate Professor of Physiology, Kyoto University
- Timothy G. Clark, Associate Professor of Cellular and Molecular Biology, University of South Dakota Medical School
- Ian C. Scott, Senior Research Scientist/Pre-project manager, AstraZeneca
- Yasutada Imamura, Associate professor of Applied Chemistry, Kogakuin University
- Bagavathi Gopalakrishnan, Senior Scientist I/Team Leader, Mirus Biotech
- Gaoxiang Ge, Investigator/Professor 4th grade Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences
Honors & Awards
- 2005 – Editorial Board, Journal of Biological Chemistry
- 2004 – Kellett Mid-Career Award
- Muir AM, Ren Y, Hopkins Butz D, Davis NA, Blank RD, Birk DE, Lee S-J, Rowe D, Feng JQ, Greenspan DS. Induced ablation of Bmp1 and Tll1 produces osteogenesis imperfecta in mice. Hum Mol Genet 23, 3085-3101 (2014). PMCID: PMC4030766
- Park AC, Phillips CL, Pfeiffer FM, Roenneburg DS, Kernien JF, Adams SM, Davidson JM, Birk DE, Greenspan DS. Homozygosity and heterozygosity for null Col5a2 alleles produce embryonic lethality and a novel classic Ehlers-Danlos syndrome-related phenotype. Am J. Pathol. 185, 2000-2011 (2015).
- Vittal R, Fan L, Greenspan DS, Mickler EA, Gopalakrishnan B, Gu H, Benson HL, Zhang C, Burlingham W, Cummings OW, and Wilkes DS (2013). IL-17 Induces Type V Collagen Overexpression and EMT via TGF-β dependent Pathways in Obliterative Bronchiolitis. Am J Physiol Lung Cell Mol Physiol. 304:L401-414. [Epub ahead of print] PMID: 23262228
- Yang C, Park AC, Davis NA, Russell JD, Kim B, Brand DD, Lawrence MJ, Ge Y, Westphall MS, Coon JJ, and Greenspan DS (2012). Comprehensive mass spectrometric mapping of the hydroxylated amino acid residues of the α1(V) collagen chain. J Biol Chem. 287:40598-610. Epub 2012 Oct 11. PMID: 23060441
- Asharani PV, Keupp K, Semler O, Wang W, Li Y, Thiele H, Yigit G, Pohl E, Becker J, Frommolt P, Sonntag C, Altmüller J, Zimmermann K, Greenspan DS, Akarsu NA, Netzer C, Schönau E, Wirth R, Hammerschmidt M, Nürnberg P, Wollnik B, and Carney TJ (2012). Attenuated BMP1 function compromises osteogenesis, leading to bone fragility in humans and zebrafish. Am J Hum Genet. 90:661-74. PMID:22482805