Research Interests: Cell biology of fuel utilization in adipocytes and skeletal muscle.
The modern Western diet coupled with a sedentary lifestyle has led to an epidemic of obesity, a consequence of which is a dramatic rise in the incidence of type II diabetes mellitus, a malfunction in insulin-regulated metabolism. At the cellular level, type II diabetes is characterized by failure of insulin to act in liver, muscle and fat. We study aspects of insulin signaling and action in the latter two tissues. Insulin resistance in muscle (and fat) derives from the failure of insulin to activate the tissue-specific glucose transporter GLUT4. The activation mechanism for this process involves vesicle trafficking and protein targeting with regard to GLUT4 and the insulin receptor. We are characterizing the formation and protein content of GLUT4-containing vesicles; we are trying to identify the organelles through which they pass on their way to and from the cell surface and we are determining the communication mechanism(s) (signaling) from the insulin receptor to the GLUT4-containing vesicles. These studies involve both fat and muscle cells, and we are also studying the physiological role of cell surface (plasma membrane) micro-domains called caveolae that are particularly abundant in these tissues. We have evidence for the hypothesis that caveolae (for little caves that are small invaginations of the plasma membrane into the cytosol) are involved in lipid trafficking.
We continue to study other aspects of adipocyte and muscle cell biology to understand the interplay between glucose and fat metabolism as well as the interplay between adipocytes and muscle required for overall metabolic homeostasis. Indeed, we wish to uncover the mechanism(s) by exercise also regulates some of these same parameters independent of insulin. Understanding these pathways will help us to figure out how they are compromised in pathophysiological states such as diabetes.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- Professor, Molecular Medicine, Medicine, Boston University School of Medicine
- Research Professor, Physiology & Biophysics, Boston University School of Medicine
- Boston Medical Center
- Purdue University, PhD
- Temple University, BA
- Published on 1/12/2018
Williams JJL, Alotaiq N, Mullen W, Burchmore R, Liu L, Baillie GS, Schaper F, Pilch PF, Palmer TM. Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability. Nat Commun. 2018 01 12; 9(1):168. PMID: 29330478.
- Published on 3/9/2017
Ding SY, Liu L, Pilch PF. Muscular dystrophy in PTFR/cavin-1 null mice. JCI Insight. 2017 Mar 09; 2(5):e91023. PMID: 28289716.
- Published on 12/8/2016
Scheller EL, Doucette CR, Learman BS, Cawthorn WP, Khandaker S, Schell B, Wu B, Ding SY, Bredella MA, Fazeli PK, Khoury B, Jepsen KJ, Pilch PF, Klibanski A, Rosen CJ, MacDougald OA. Corrigendum: Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues. Nat Commun. 2016 Dec 08; 7:13775. PMID: 27929114.
- Published on 8/16/2016
Liu L, Pilch PF. PTRF/Cavin-1 promotes efficient ribosomal RNA transcription in response to metabolic challenges. Elife. 2016 Aug 16; 5. PMID: 27528195.
- Published on 9/18/2015
Jedrychowski MP, Liu L, Laflamme CJ, Karastergiou K, Meshulam T, Ding SY, Wu Y, Lee MJ, Gygi SP, Fried SK, Pilch PF. Adiporedoxin, an upstream regulator of ER oxidative folding and protein secretion in adipocytes. Mol Metab. 2015 Nov; 4(11):758-70. PMID: 26629401.
- Published on 8/31/2015
Lo HP, Nixon SJ, Hall TE, Cowling BS, Ferguson C, Morgan GP, Schieber NL, Fernandez-Rojo MA, Bastiani M, Floetenmeyer M, Martel N, Laporte J, Pilch PF, Parton RG. The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle. J Cell Biol. 2015 Aug 31; 210(5):833-49. PMID: 26323694.
- Published on 8/6/2015
Scheller EL, Doucette CR, Learman BS, Cawthorn WP, Khandaker S, Schell B, Wu B, Ding SY, Bredella MA, Fazeli PK, Khoury B, Jepsen KJ, Pilch PF, Klibanski A, Rosen CJ, MacDougald OA. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues. Nat Commun. 2015; 6:7808. PMID: 26245716.
- Published on 7/18/2014
Liu L, Hansen CG, Honeyman BJ, Nichols BJ, Pilch PF. Cavin-3 knockout mice show that cavin-3 is not essential for caveolae formation, for maintenance of body composition, or for glucose tolerance. PLoS One. 2014; 9(7):e102935. PMID: 25036884.
- Published on 2/7/2014
Ding SY, Lee MJ, Summer R, Liu L, Fried SK, Pilch PF. Pleiotropic effects of cavin-1 deficiency on lipid metabolism. J Biol Chem. 2014 Mar 21; 289(12):8473-83. PMID: 24509860.
- Published on 7/11/2013
Fernández-Rojo MA, Gongora M, Fitzsimmons RL, Martel N, Martin SD, Nixon SJ, Brooks AJ, Ikonomopoulou MP, Martin S, Lo HP, Myers SA, Restall C, Ferguson C, Pilch PF, McGee SL, Anderson RL, Waters MJ, Hancock JF, Grimmond SM, Muscat GE, Parton RG. Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling. Cell Rep. 2013 Jul 25; 4(2):238-47. PMID: 23850288.
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