Regulation of Bone Mass Laboratory

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Regulation of Bone Mass Laboratory

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:

  • 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
  • Promoting skeletal healing through the SHN3 pathway
    PI: Matthew Greenblatt, MD, PhD
    Musculoskeletal Transplant Foundation (MTF) Research Grant
  • Assessment of MEKK2 as a Novel Therapeutic Target in Neurofibromatosis
    PI: Matthew Greenblatt, MD, PhD
    Department of Defense (CDMRP) Research Grant
  • Development of an Antibody inhibitor of SLITRK5 for the Treatment of Osteoporosis
    PI: Matthew Greenblatt, MD, PhD
    Tri-Institutional Therapeutics Discovery institute (Tri-I TDI) Research Grant

Body

Regulation of Bone Mass Laboratory

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:

  • 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
  • Promoting skeletal healing through the SHN3 pathway
    PI: Matthew Greenblatt, MD, PhD
    Musculoskeletal Transplant Foundation (MTF) Research Grant
  • Assessment of MEKK2 as a Novel Therapeutic Target in Neurofibromatosis
    PI: Matthew Greenblatt, MD, PhD
    Department of Defense (CDMRP) Research Grant
  • Development of an Antibody inhibitor of SLITRK5 for the Treatment of Osteoporosis
    PI: Matthew Greenblatt, MD, PhD
    Tri-Institutional Therapeutics Discovery institute (Tri-I TDI) Research Grant

Selected Publications EXPAND ALL ON THIS PAGE

CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts

July 27, 2015
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.

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

Impact of a prospective review program for reference laboratory testing requests

May 1, 2015
Greenblatt MB, Nowak JA, Quade CC, Tanasijevic M, Lindeman N, Jarolim P.

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

p38α MAPK is required for tooth morphogenesis and enamel secretion

January 2, 2015
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.

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.

Use of potassium concentrations as a quality-of-service metric for phlebotomists detects systematic preanalytical biases and facilitates their correction

November 1, 2014
Greenblatt MB, Torre M, Means J, Tanasijevic M, Vitale Pedulla L, Bunnell CA, Conrad MJ, Jarolim P.

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

XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway

April 3, 2014
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.

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

S6K1 negatively regulates TAK1 activity in the toll-like receptor signaling pathway

February 1, 2014
Kim SY, Baik KH, Baek KH, Chah KH, Kim KA, Moon G, Jung E, Kim ST, Shim JH, Greenblatt MB, Chun E, Lee KY.

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

NFATc1 and NFATc2 repress spontaneous osteoarthritis

December 3, 2013
Greenblatt MB, Ritter SY, Wright J, Tsang K, Hu D, Glimcher LH, Aliprantis AO.

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

Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts

September 1, 2013
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.

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

The microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2

August 26, 2013
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.

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

Osteoimmunology: a brief introduction

August 1, 2013
Greenblatt MB, Shim JH.

Osteoimmunology: a brief introduction

Immune Netw. 2013 Aug;13(4):111-5. 

Greenblatt MB, Shim JH. 

PMID: 24009537; PMCID: PMC3759707

Mitogen-activated protein kinase pathways in osteoblasts

May 1, 2013
Greenblatt MB, Shim JH, Glimcher LH.

Mitogen-activated protein kinase pathways in osteoblasts

Annu Rev Cell Dev Biol. 2013;29:63-79.

Greenblatt MB, Shim JH, Glimcher LH.

PMID: 23725048

A TAK1/p38 Signaling Axis Regulates RUNX2 Activity and Osteoblast Functions

January 1, 2013
Greenblatt MB, Shim JH, Zou WG, Glimcher LH

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. 

The immune pathogenesis of scleroderma: context is everything

January 1, 2013
Greenblatt MB, Aliprantis AO.

The immune pathogenesis of scleroderma: context is everything

Curr Rheumatol Rep. 2013 Jan;15(1):297.

Greenblatt MB, Aliprantis AO.

PMID: 23288576; PMCID: PMC3539168

Interspecies comparison of human and murine scleroderma reveals IL-13 and CCL2 as disease subset-specific targets

March 1, 2012
Greenblatt MB, Sargent JL, Farina G, Tsang K, Lafyatis R, Glimcher LH, Whitfield ML, Aliprantis AO.

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

Administration of BMP2/7 in utero partially reverses Rubinstein-Taybi syndrome-like skeletal defects induced by Pdk1 or Cbp mutations in mice

January 1, 2012
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.

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

Graft versus host disease in the bone marrow, liver and thymus humanized mouse model

January 1, 2012
Greenblatt MB, Vrbanac V, Tivey T, Tsang K, Tager AM, Aliprantis AO.

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.

MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice

November 1, 2011
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.

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

Derlin-2-deficient mice reveal an essential role for protein dislocation in chondrocytes

March 1, 2011
Dougan SK, Hu CC, Paquet ME, Greenblatt MB, Kim J, Lilley BN, Watson N, Ploegh HL.

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

The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice

July 1, 2010
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.

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

Calcineurin regulates innate antifungal immunity in neutrophils

May 10, 2010
Greenblatt MB, Aliprantis A, Hu B, Glimcher LH.

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

TAK1 mediates BMP signaling in cartilage

March 1, 2010
Greenblatt MB, Shim JH, Glimcher LH.

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

TAK1 is an essential regulator of BMP signalling in cartilage

July 22, 2009
Shim JH, Greenblatt MB, Xie M, Schneider MD, Zou W, Zhai B, Gygi S, Glimcher LH.

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

A toll-like receptor that prevents infection by uropathogenic bacteria

March 5, 2004
Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, Ghosh S.

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

General Contact

Matthew B. Greenblatt, MD, Ph.D.
Assistant Professor of Pathology and Laboratory Medicine
Weill Cornell Medical College
1300 York Ave, LC-929a
New York, NY 10065
Office: 212-746-1602
Lab: 212-746-1095
mag3003@med.cornell.edu

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