Gabriel Mbalaviele, Ph.D.

Associate Professor
Internal Medicine
Bone & Mineral Diseases

Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program

Research Abstract:

My research focuses on the role of the NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome in skeletal development and remodeling, based on clinical findings indicating that gain-offunction mutations in the NLRP3 gene cause autoinflammatory disorders known as cryopyrinopathies, in which skeletal deformities are one of the major complications. Using mouse models of global or cellspecific conditional Nrlp3 activation, my research aims at elucidating the cellular and molecular mechanisms by which activated NLRP3 inflammasome causes skeletal manifestations. We are also interested in understanding the interactions of this inflammasome with other key pathways that affect skeletal homeostasis. By carrying out some of these studies with specimens harvested from affected patients, our ultimate goal is to translate our findings in animals to human pathophysiology. We anticipate that these studies will ascribe this inflammasome as a potential new target for therapeutic intervention in skeletal diseases.

Selected Publications:

1) Wang C, Hockerman S, Jacobsen EJ, Alippe Y, Selness SR, Hope HR, Hirsch JL, Mnich SJ, Saabye MJ, Hood WF, Bonar SL, Abu-Amer Y, Haimovich A, Hoffman HM, Monahan JB, Mbalaviele G. Selective inhibition of the p38α MAPK-MK2 axis inhibits inflammatory cues including inflammasome priming signals. J Exp Med. 2018 Mar 16. PMID: 29549113.

2) Mbalaviele G, Novack VD, Schett G, Teitelbaum S. Inflammatory osteolysis: a conspiracy against bone. J Clin Invest, 2017, 127:2030-2039. PMID: 28569732.

3)Wang C, Xu C-X, Alippe Y, Qu C, Schipani E, Civitelli R, Abu-Amer Y, Mbalaviele G. Mesenchymal Cell Non-autonomous Actions of NLRP3 Drive Growth Plate Dysplasia in NOMID Mice. Sci Rep, 2017; 7:12600, PMID: 28974699.

4)Alippe Y, Wang C, Ricci B, Xiao J, Qu C, Zou W, Novack DV, Abu-Amer Y, Civitelli R, Mbalaviele G. Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation. Sci Rep, 2017;7:6630, PMID: 28747793.

5)Wang C, Qu C, Alippe Y, Bonar SL, Civitelli R, Abu-Amer Y, Hottiger MO, Mbalaviele G. Poly-ADP-ribosylation-mediated degradation of ARTD1 by the NLRP3 inflammasome is a prerequisite for osteoclast maturation. Cell Death Dis, 2016; 7:e2153, PMID: 27010854.

6)Novack DV, Mbalaviele G. Osteoclasts, key players in skeletal health and disease. Microbiol Spectrum, 2016; 4(3), PMID: 27337470.

7)Swarnkar G, Shim K, Nasir AM, Seehra K, Chen TH, Mbalaviele G, Abu-Amer Y. Myeloid Deletion of NEMO Causes Osteopetrosis in Mice Owing to Up-regulation of Transcriptional Repressors. Sci Rep, 2016; PMID: 27435916.

8)Qu C, Bonar SL, Hickman-Brecks CL, Abu-Amer S, McGeough MD, Pea CA, Broderick L, Yang C, Grimston SK, Kading J, Abu-Amer Y, Novack DV, Hoffman HM, Civitelli R, Mbalaviele G. NLRP3 mediates osteolysis through inflammation-dependent and independent mechanisms. FASEB J, 2015; 29:1269-79. PMID: 25477279.

9)Swarnkar G, Karuppaiah K, Chen T, Mbalaviele G, Abu-Amer Y. Osteopetrosis in TAK1 Deficient Mice Owing to Defective NF-kB and NOTCH Signaling. PNAS, 2015; 112:154-9. PMID: 25535389.

10) Bonar SL, Brydges SD, James L. Mueller JL, McGeough MD, Pena C , Grimston SK, Novack DV, Civitelli R, Kastner D, Hoffman HM, Mbalaviele G. Constitutively activated NLRP3 inflammasome causes inflammation and abnormal skeletal development in mice. PLoS One 2012; e35979. PMID: 22558291.

Last Updated: 3/30/2018 9:50:22 AM

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