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Matthew B. Greenblatt, MD, PhD, Principal Investigator
Approximately half of all women and a fifth of all men will experience a skeletal fracture due to low bone mass. These fractures kill as many women each year as breast cancer. Improving clinical outcomes in this area will ultimately require finding new therapeutic agents that promote the activity of osteoblasts, the cells that build bone, which in turn will require improving our understanding of the molecular pathways involved in this process. To this end, we are focused on using a combination of genetics, cellular biochemistry and genome-wide screening to discover new molecular pathways that regulate the activity of osteoblasts. In particular, we are interested in how tuning the activity of the genes involved in the ability of osteoblasts to perceive signals from their environment can control the formation of bone, focusing on an ancient and fundamentally important family of signaling molecules, the mitogen activated protein kinases (MAPKs). Currently, we are exploring how dysregulation of MAPK signaling contributes to skeletal disease and how MAPK pathways can be targeted to benefit bone health.
Active Projects:
Currently, an area of focus in the lab is understanding how alterations in the signaling of mitogen activated protein kinases contribute to the development of both osteoporosis and rare skeletal disorders, with a particular emphasis on discovering approaches to target these pathways for therapeutic benefit in humans.
Active Grants:
- Development of an Antibody Inhibitor of SLITRK5 for the Treatment of Osteoporosis
PI: Matthew Greenblatt, MD, PhD
Tri-Institutional Therapeutics Discovery Institute - Defining the role of a Novel Periosteal Mesenchymal Stem Cell in Skeletal Morphogenesis and Development
PI: Matthew Greenblatt, MD, PhD
March of Dimes Basil O’ Connor Starter Scholar Research Award - Novel Mechanisms of Bone Formation
PI: Matthew Greenblatt, MD, PhD
Burroughs Wellcome Fund Career Award for Medical Scientists - Modulation of Bone Formation by SHN3
PI: Matthew Greenblatt, MD, PhD
National Institutes of Health (NIH) Early Independence Award
Selected Publications
CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts
Matthew B. Greenblatt, MD, PhD
CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts
J Exp Med. 2015 Jul 27;212(8):1283-301.
Greenblatt MB, Park KH, Oh H, Kim JM, Shin DY, Lee JM, Lee JW, Singh A, Lee KY, Hu D, Xiao C, Charles JF, Penninger JM, Lotinun S, Baron R, Ghosh S, Shim JH.
PMID: 26195726; PMCID: PMC4516796
Read MoreImpact of a prospective review program for reference laboratory testing requests
Matthew B. Greenblatt, MD, PhD
Impact of a prospective review program for reference laboratory testing requests
Am J Clin Pathol. 2015 May;143(5):627-34.
Greenblatt MB, Nowak JA, Quade CC, Tanasijevic M, Lindeman N, Jarolim P.
PMID: 25873495
Read Morep38α MAPK is required for tooth morphogenesis and enamel secretion
Matthew B. Greenblatt, MD, PhD
p38α MAPK is required for tooth morphogenesis and enamel secretion
J Biol Chem. 2015 Jan 2;290(1):284-95
Greenblatt MB, Kim JM, Oh H, Park KH, Choo MK, Sano Y, Tye CE, Skobe Z, Davis RJ, Park JM, Bei M, Glimcher LH, Shim JH.
PMID: 25406311; PMCID: PMC4281732.
Read MoreUse of potassium concentrations as a quality-of-service metric for phlebotomists detects systematic preanalytical biases and facilitates their correction
Matthew B. Greenblatt, MD, PhD
Use of potassium concentrations as a quality-of-service metric for phlebotomists detects systematic preanalytical biases and facilitates their correction
Clin Chem. 2014 Nov;60(11):1453-5.
Greenblatt MB, Torre M, Means J, Tanasijevic M, Vitale Pedulla L, Bunnell CA, Conrad MJ, Jarolim P.
PMID: 25161146
Read MoreXBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway
Matthew B. Greenblatt, MD, PhD
XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway
Nature. 2014 Apr 3;508(7494):103-7.
Chen X, Iliopoulos D, Zhang Q, Tang Q, Greenblatt MB, Hatziapostolou M, Lim E, Tam WL, Ni M, Chen Y, Mai J, Shen H, Hu DZ, Adoro S, Hu B, Song M, Tan C, Landis MD, Ferrari M, Shin SJ, Brown M, Chang JC, Liu XS, Glimcher LH.
PMID: 24670641; PMCID: PMC4105133
Read MoreS6K1 negatively regulates TAK1 activity in the toll-like receptor signaling pathway
Matthew B. Greenblatt, MD, PhD
S6K1 negatively regulates TAK1 activity in the toll-like receptor signaling pathway
Mol Cell Biol. 2014 Feb;34(3):510-21.
Kim SY, Baik KH, Baek KH, Chah KH, Kim KA, Moon G, Jung E, Kim ST, Shim JH, Greenblatt MB, Chun E, Lee KY.
PMID: 24277938; PMCID: PMC3911500
Read MoreNFATc1 and NFATc2 repress spontaneous osteoarthritis
Matthew B. Greenblatt, MD, PhD
NFATc1 and NFATc2 repress spontaneous osteoarthritis
Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19914-9.
Greenblatt MB, Ritter SY, Wright J, Tsang K, Hu D, Glimcher LH, Aliprantis AO.
PMID: 24248346; PMCID: PMC3856808
Read MoreSchnurri-3 regulates ERK downstream of WNT signaling in osteoblasts
Matthew B. Greenblatt, MD, PhD
Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts
J Clin Invest. 2013 Sep;123(9):4010-22.
Shim JH, Greenblatt MB, Zou W, Huang Z, Wein MN, Brady N, Hu D, Charron J, Brodkin HR, Petsko GA, Zaller D, Zhai B, Gygi S, Glimcher LH, Jones DC.
PubMed PMID: 23945236; PMCID: PMC3754267
Read MoreThe microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2
Matthew B. Greenblatt, MD, PhD
The microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2
J Exp Med. 2013 Aug 26;210(9):1793-806.
Zou W, Greenblatt MB, Brady N, Lotinun S, Zhai B, de Rivera H, Singh A, Sun J, Gygi SP, Baron R, Glimcher LH, Jones DC.
PMID: 23918955; PMCID: PMC3754873
Read MoreOsteoimmunology: a brief introduction
Matthew B. Greenblatt, MD, PhD
Osteoimmunology: a brief introduction
Immune Netw. 2013 Aug;13(4):111-5.
Greenblatt MB, Shim JH.
PMID: 24009537; PMCID: PMC3759707
Read MoreMitogen-activated protein kinase pathways in osteoblasts
Matthew B. Greenblatt, MD, PhD
Mitogen-activated protein kinase pathways in osteoblasts
Annu Rev Cell Dev Biol. 2013;29:63-79.
Greenblatt MB, Shim JH, Glimcher LH.
PMID: 23725048
Read MoreThe immune pathogenesis of scleroderma: context is everything
Matthew B. Greenblatt, MD, PhD
The immune pathogenesis of scleroderma: context is everything
Curr Rheumatol Rep. 2013 Jan;15(1):297.
Greenblatt MB, Aliprantis AO.
PMID: 23288576; PMCID: PMC3539168
Read MoreA TAK1/p38 Signaling Axis Regulates RUNX2 Activity and Osteoblast Functions
Matthew B. Greenblatt, MD, PhD
A TAK1/p38 Signaling Axis Regulates RUNX2 Activity and Osteoblast Functions
Greenblatt MB, Shim JH, Zou WG, Glimcher LH.
In: Choi YW, editor. Osteoimmunology: Interactions of the Immune and Skeletal Systems.
New York: Springer New York; 2013. p.49-56.
Read MoreInterspecies comparison of human and murine scleroderma reveals IL-13 and CCL2 as disease subset-specific targets
Matthew B. Greenblatt, MD, PhD
Interspecies comparison of human and murine scleroderma reveals IL-13 and CCL2 as disease subset-specific targets
Am J Pathol. 2012 Mar;180(3):1080-94.
Greenblatt MB, Sargent JL, Farina G, Tsang K, Lafyatis R, Glimcher LH, Whitfield ML, Aliprantis AO.
PMID: 22245215; PMCID: PMC3349888
Read MoreAdministration of BMP2/7 in utero partially reverses Rubinstein-Taybi syndrome-like skeletal defects induced by Pdk1 or Cbp mutations in mice
Matthew B. Greenblatt, MD, PhD
Administration of BMP2/7 in utero partially reverses Rubinstein-Taybi syndrome-like skeletal defects induced by Pdk1 or Cbp mutations in mice
J Clin Invest. 2012 Jan;122(1):91-106.
Shim JH, Greenblatt MB, Singh A, Brady N, Hu D, Drapp R, Ogawa W, Kasuga M, Noda T, Yang SH, Lee SK, Rebel VI, Glimcher LH.
Erratum in: J Clin Invest. 2012 May 1;122(5):1948.
PMID: 22133875; PMCID: PMC3248303
Read MoreGraft versus host disease in the bone marrow, liver and thymus humanized mouse model
Matthew B. Greenblatt, MD, PhD
Graft versus host disease in the bone marrow, liver and thymus humanized mouse model
PLoS One. 2012;7(9):e44664.
Greenblatt MB, Vrbanac V, Tivey T, Tsang K, Tager AM, Aliprantis AO.
Erratum in: PLoS One. 2013;8(5). Vbranac, Vladimir [corrected to Vrbanac, Vladimir].
PMID: 22957096; PMCID: PMC3434179.
Read MoreMLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice
Matthew B. Greenblatt, MD, PhD
MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice
J Clin Invest. 2011 Nov;121(11):4383-92.
Zou W, Greenblatt MB, Shim JH, Kant S, Zhai B, Lotinun S, Brady N, Hu DZ, Gygi SP, Baron R, Davis RJ, Jones D, Glimcher LH.
PMID: 21965325; PMCID: PMC3204846
Read MoreDerlin-2-deficient mice reveal an essential role for protein dislocation in chondrocytes
Matthew B. Greenblatt, MD, PhD
Derlin-2-deficient mice reveal an essential role for protein dislocation in chondrocytes
Mol Cell Biol. 2011 Mar;31(6):1145-59.
Dougan SK, Hu CC, Paquet ME, Greenblatt MB, Kim J, Lilley BN, Watson N, Ploegh HL.
PMID: 21220515; PMCID: PMC3067910
Read MoreThe p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice
Matthew B. Greenblatt, MD, PhD
The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice
J Clin Invest. 2010 Jul;120(7):2457-73.
Greenblatt MB, Shim JH, Zou W, Sitara D, Schweitzer M, Hu D, Lotinun S, Sano Y, Baron R, Park JM, Arthur S, Xie M, Schneider MD, Zhai B, Gygi S, Davis R, Glimcher LH.
PMID: 20551513; PMCID: PMC2898605
Read MoreCalcineurin regulates innate antifungal immunity in neutrophils
Matthew B. Greenblatt, MD, PhD
Calcineurin regulates innate antifungal immunity in neutrophils
J Exp Med. 2010 May 10;207(5):923-31.
Greenblatt MB, Aliprantis A, Hu B, Glimcher LH.
PMID: 20421389; PMCID: PMC2867274
Read MoreTAK1 mediates BMP signaling in cartilage
Matthew B. Greenblatt, MD, PhD
TAK1 mediates BMP signaling in cartilage
Ann N Y Acad Sci. 2010 Mar;1192:385-90.
Greenblatt MB, Shim JH, Glimcher LH.
PMID: 20392264; PMCID: PMC3096020
Read MoreTAK1 is an essential regulator of BMP signalling in cartilage
Matthew B. Greenblatt, MD, PhD
TAK1 is an essential regulator of BMP signalling in cartilage
EMBO J. 2009 Jul 22;28(14):2028-41.
Shim JH, Greenblatt MB, Xie M, Schneider MD, Zou W, Zhai B, Gygi S, Glimcher LH.
PMID: 19536134; PMCID: PMC2699391
Read MoreA toll-like receptor that prevents infection by uropathogenic bacteria
Matthew B. Greenblatt, MD, PhD
A toll-like receptor that prevents infection by uropathogenic bacteria
Science. 2004 Mar 5;303(5663):1522-6.
Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, Ghosh S.
PMID: 15001781
Read More