BBS Faculty Member - Bruce Spiegelman

Bruce Spiegelman

Department of Cell Biology

Dana Farber Cancer Institute
CLS Building, 11th Floor, Room 11146
3 Blackfan Circle
Boston, MA 02115
Tel: 617-632-3567
Fax: 617-582-7176
Email: bruce_spiegelman@dfci.harvard.edu
Lab Members: 10 postdoctoral fellows, 2 instructors, 1 senior scientist
Visit my lab page here.



The overall theme of our lab is the regulation of energy homeostasis in mammalian systems, with special reference to adipose and muscle tissues. While we have long been interested in diabetes and obesity, our current interests extend to muscle disorders, neurodegeneration and cancer cell metabolism. We are particularly interested in mitochondrial metabolism and dynamics in these disorders and in the development of novel therapeutic approaches. We work at both the biochemical and physiological levels, employing cultured cells and in vivo murine models. The lab welcomes applications from qualified Ph.D. students and those looking for post-doctoral positions.

The following are major current research areas:

PGC1a and the control of energy homeostasis

We discovered the transcriptional coactivator PGC1
a in 1998. Work from our lab and others have demonstrated that this molecule is the dominant regulator of mitochondrial biogenesis in most tissues and is conserved from humans to flies. We are currently focused on the new modes of regulation of this critical molecule, including regulation of mRNA translation and post-translational modifications of the protein itself.

We are also interested in how PGC1
a particularly in muscle, talks to other tissues beyond where its expressed. PGC1a in muscle is induced in exercise as part of the adaptation to endurance exercise. We are now trying to identify comprehensively all of the secreted proteins expressed by muscle cells under the influence of elevated PGC1a. We are testing these for their effects on tissues known to experience benefits of exercise in humans: muscle itself, adipose tissues, liver, kidney and brain.

Development and function of brown and beige adipose tissues

We have a long-standing interest in adipose cells and tissues. Most recently we have been focused on how thermogenic fat cells, brown and beige, form and function. We are especially focused on the bioenergetics pathways in mitochondria that lead to energy expenditure. How these same pathways can be used to combat obesity and diabetes has been under study. We are also interested in how thermogenic fat cells become much more highly innervated by the sympathetic nervous systems compared to other kinds of fat cells.

Protein factors secreted from muscle, fat and other tissues are being examined for their ability to stimulate “browning” of adipose tissues. These include Slit2-C, irisin and meteorin-like. Preclinical studies are preparing the way for what we hope will be clinical studies, as will identification of their cognate receptors.

PPARg and its role in cancer biology and cancer treatment

There is increasing interest in the metabolism of cancer cells and this has led to interest in whether treatments for metabolic diseases have a place in cancer therapy. We have shown, over many years, that drugs that activate PPAR
g can slow down the growth of tumor cells and be used on models of cancer in mice. More recently we have shown that PPARg ligands can synergize with DNA damaging agents to inhibit tumor cell growth. We are trying to understand whether these striking effects are through actions on DNA damage/repair processes and how this can be leveraged in the human cancer clinic.



Last Update: 12/6/2017



Publications

For a complete listing of publications click here.

 


 

Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scimè A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR and Spiegelman BM.  PRDM16 controls a brown fat/skeletal muscle switch.  Nature 2008; 454:961-967.

Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang A, Khandekar M, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerbäck S, Schrauwen P and Spiegelman BM.  Beige Adipocytes are a Distinct Type of Thermogenic Fat Cell in Mouse and Human. Cell 2012;  150(2):366-376.

Kazak L, Chouchani ET, Jedrychowski MP, Erickson BK, Shinoda K,  Cohen P, Vetrivelan R, Lu GZ, Laznik-Bogoslavski D, Hasenfuss SC, Kajimura S, Gygi SP, Spiegelman BM.  A  Creatine-Driven Substrate Cycle Enhances Energy Expenditure and Thermogenesis in Beige Fat.   Cell 2015;   163(3):643-655.

Long JZ, Svensson KJ, Bateman LA, Lin H, Kamenecka T, Lokurkar IA, Lou J, Rao RR, Chang MR, Jedrychowski MP, Paulo JA, Gygi SP, Griffin PR, Nomura DK, Spiegelman BM.  PM20D1 secretion by thermogenic adipocytes regulates lipidated amino acid uncouplers of mitochondrial respiration.  Cell 2016;  166(2):424-435.

Kazak L, Chouchani ET, Lu GZ, Jedrychowski MP, Bare CJ, Mina AI, Kumari M, Zhang S, Vuckovic I, Laznik-Bogoslavski D, Dzeja P, Banks AS, Rosen ED, Spiegelman BM.  Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity.  Cell Metab. 2017;  26(4):660-671.



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