Gabriel Mbalaviele, Ph.D.

Professor
Internal Medicine
Bone & Mineral Diseases

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

Research Abstract:

We study the responses of normal mice and mice harboring loss-of- or gain-of-function mutations of various components of the inflammasome pathways to challenges such as injury, radiotherapy, and chemotherapy. We complement genetic strategies with pharmacological approaches. The expectations are that knowledge gained from these animal studies will help understand how dysregulated inflammasome functions in humans contribute to defective restoration of tissue homeostasis after injury and exacerbate off-target effects of anti-neoplastic therapies.
We also the differentiation of macrophages into osteoclasts, a process that is associated with downregulation of inflammasome activities. While macrophages are key players in innate immunity and the clearance of debris, the osteoclasts are specialized in the removal of organic and inorganic bone elements. Thus, the immune function of macrophages is lost during osteoclastogenesis. We are interested in deciphering the molecular mechanisms that downregulate the inflammasome pathways during this differentiation process.

Selected Publications:

Wang C, Yang T, Xiao J, Xu C, Alippe Y, Sun K, Kanneganti TD, Monahan JB, Abu-Amer Y, Lieberman J, Mbalaviele G. NLRP3 inflammasome activation triggers gasdermin D-independent inflammation. Sci Immunol, 2021 Oct 22;6(64):eabj3859. PMID: 34678046. Free-access link: https://www.science.org/stoken/author-tokens/ST-117/full

Alippe Y, Kress D, Ricci B, Sun K, Yang T, Wang C, Xiao J, Abu-Amer Y, Mbalaviele G. Actions of the NLRP3 and NLRC4 inflammasomes overlap in bone resorption. FASEB J, 2021 Sep;35(9):e21837. PMID: 34383985.

Xiao J, Wang C, Yao JC, Alippe Y, Yang T, Kress D, Sun K, Kostecki KL, Monahan JB, Veis DJ, Abu-Amer Y, Link DC, Mbalaviele G. Radiation causes tissue damage by dysregulating inflammasome-gasdermin D signaling in both host and transplanted cells. PLoS Biol, 2020 Aug 6;18(8):e3000807. PMID: 32760056

Alippe Y, Mbalaviele G. Omnipresence of inflammasome activities in inflammatory bone diseases. Seminars in Immunopathology, 2019, 41:607. PMID: 31520179

Xiao J, Wang C,Yao JC, Alippe Y, Xu C, Kress D, Civitelli R, Abu-Amer Y, Kanneganti TD, Link DC, Mbalaviele G. Gasdermin D mediates the pathogenesis of neonatal-onset multisystem inflammatory disease in mice. PLoS Biol, 2018, 16:e3000047. PMID: 30388107.

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, 215:1315-1325. PMID: 29549113.

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

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.

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.

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: 10/29/2021 2:56:47 PM

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