Richard Thomas Premont, PhD

Associate Professor in Medicine
Faculty Network Member of the Duke Institute for Brain Sciences
Campus mail 905 S. Lasalle St, Snyderman GSRB1 Room 1073D, Durham, NC 27710
Phone (919) 684-5620
Email address richard.premont@duke.edu

Critical physiological events throughout the body are controlled by extracellular signals from neurotransmitters and hormones acting on cell surface receptors. Receptors transduce these signals to alter intracellular metabolism and cellular responsiveness through heterotrimeric G protein/second messenger pathways or through small GTP-binding protein/protein kinase cascades.

The mechanisms that control the responsiveness of target organ G protein-coupled receptors include receptor phosphorylation and desensitization by G protein-coupled receptor kinases (GRKs). We have created mice lacking each of the three members of the GRK4 subfamily of GRKs (GRK4, GRK5 and GRK6), and are examining the functional effects of this loss of function on the physiology of receptors controlling gastrointestinal, heart, lung, immune and brain functions.

An important open question in the study of cellular regulation is understanding how cells coordinate the activity of multiple receptor pathways into a coherent cellular response. Our recent discovery that large multidomain ARF GTPase-activating proteins (GAPs) of the GIT family can serve as oligomeric scaffolding proteins for numerous signaling molecules and help coordinate heterotrimeric G protein and multiple small GTP-binding protein pathways, suggests that other multidomain ARF GAPs may also function in analogous manner as coordination centers. We are examining the functional roles of GIT proteins and related ARF GAPs in crosstalk among cellular signaling pathways, with particular emphasis on gastrointestinal and behavioral roles using GIT1 and GIT2 knockout mice.

Education and Training

  • Ph.D., City University of New York, 1992

Publications

Du, K, Hyun, J, Premont, RT, Choi, SS, Michelotti, GA, Swiderska-Syn, M, Dalton, GD, Thelen, E, Rizi, BS, Jung, Y, and Diehl, AM. "Hedgehog-YAP Signaling Pathway Regulates Glutaminolysis to Control Activation of Hepatic Stellate Cells." April 2018.

PMID
29305935
Full Text

van Gastel, J, Boddaert, J, Jushaj, A, Premont, RT, Luttrell, LM, Janssens, J, Martin, B, and Maudsley, S. "GIT2-A keystone in ageing and age-related disease." Ageing research reviews 43 (February 13, 2018): 46-63. (Review)

PMID
29452267
Full Text

Chen, W, Mook, RA, Premont, RT, and Wang, J. "Niclosamide: Beyond an antihelminthic drug." Cellular signalling 41 (January 2018): 89-96. (Review)

PMID
28389414
Full Text

Martyn, AC, Toth, K, Schmalzigaug, R, Hedrick, NG, Rodriguiz, RM, Yasuda, R, Wetsel, WC, and Premont, RT. "GIT1 regulates synaptic structural plasticity underlying learning." Plos One 13, no. 3 (January 2018): e0194350-null.

PMID
29554125
Full Text

Rein, LA, Wisler, JW, Kim, J, Theriot, B, Huang, L, Price, T, Yang, H, Chen, M, Chen, W, Sipkins, D, Fedoriw, Y, Walker, JK, Premont, RT, and Lefkowitz, RJ. "β-Arrestin2 mediates progression of murine primary myelofibrosis." JCI insight 2, no. 24 (December 21, 2017).

PMID
29263312
Full Text

Jewell, M, de Castro, GC, Premont, RT, and Diehl, AM. "Fn14 and Wnt Signaling Pathway Crosstalk Controls Liver Progenitor Expansion in 3D Organoid Culture." October 2017.

Scholars@Duke

Oh, S-H, Swiderska-Syn, M, Jewell, M, Premont, RT, and Diehl, AM. "Yap1 Activation Induces TGF-beta Signaling and Epithelial-to-Mesenchymal Transition (EMT) in Regenerating Hepatocytes After Partial Hepatectomy." October 2017.

Scholars@Duke

Lu, D, Cai, H, Park, S-S, Siddiqui, S, Premont, RT, Schmalzigaug, R, Paramasivam, M, Seidman, M, Bodogai, I, Biragyn, A, Daimon, CM, Martin, B, and Maudsley, S. "Correction for Lu et al., "Nuclear GIT2 Is an ATM Substrate and Promotes DNA Repair"." Molecular and Cellular Biology 37, no. 17 (September 2017).

PMID
28801458
Full Text

Bhattacharyya, J, Ren, X-R, Mook, RA, Wang, J, Spasojevic, I, Premont, RT, Li, X, Chilkoti, A, and Chen, W. "Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth." Nanoscale 9, no. 34 (August 2017): 12709-12717.

PMID
28828438
Full Text

Xie, G, Swiderska-Syn, M, Jewell, ML, Machado, MV, Michelotti, GA, Premont, RT, and Diehl, AM. "Loss of pericyte smoothened activity in mice with genetic deficiency of leptin." Bmc Cell Biology 18, no. 1 (April 20, 2017): 20-null.

PMID
28427343
Full Text

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