CURRICULUM VITAE

Richard Thomas Premont, Ph.D. Institute for Transformative Molecular Medicine Case Western Reserve University and Harrington Discovery Institute University Hospitals Cleveland Medical Center Cleveland, Ohio 44106 [email protected] [email protected]

Education:

Mount Sinai School of Medicine, Graduate School of Biomedical Sciences City University of New York (CUNY), New York City, New York Department of Pharmacology 8/87-4/92 M.Ph. in Biomedical Sciences, October 1990 Ph.D. in Biomedical Sciences (Pharmacology), April 1992

Baylor College of Medicine, Graduate School Houston, Texas Department of Cell Biology 8/86-7/87 (transfer to CUNY)

California Institute of Technology Pasadena, California Majors: Biology, Chemistry 9/81-6/85 B.S., June 1985

Professional Experience:

Associate Professor, Department of Internal Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 9/19-present

Senior Researcher, Harrington Discovery Institute, University Hospitals Cleveland Medical Center, and Institute for Transformative Molecular Medicine, Case Western Reserve University, Cleveland, Ohio 6/18-present

Associate Research Professor, Department of Medicine (Division of Gastroenterology) Duke University Medical Center, Durham, North Carolina 3/06-6/18

Assistant Research Professor, Department of Medicine (Division of Gastroenterology) Duke University Medical Center, Durham, North Carolina 4/99-2/06

Assistant Research Professor, Department of Medicine (Division of Cardiology) Duke University Medical Center, Durham, North Carolina 9/96-3/99 Dr. Robert Lefkowitz, Howard Hughes Medical Institute and Department of Medicine

Research Associate/Helen Hay Whitney Foundation Postdoctoral Fellow Duke University Medical Center, Durham, North Carolina 7/92-8/96 Dr. Robert Lefkowitz, Howard Hughes Medical Institute and Department of Medicine

Research Associate Mount Sinai School of Medicine, New York, New York Dr. Ravi Iyengar, Department of Pharmacology 4/92-6/92

Graduate Student Mount Sinai School of Medicine, CUNY, New York, New York Dr. Ravi Iyengar, Department of Pharmacology 8/87-4/92 Thesis: "Multiple Mechanisms Underlying Desensitization of the Liver Adenylyl Cyclase System. Structure and cAMP Regulation of Liver Adenylyl Cyclases." Richard Premont, page 2

Graduate Student Baylor College of Medicine, Houston, Texas Dr. Ravi Iyengar, Department of Cell Biology 8/86-7/87 (transfer when advisor moved)

Research Technician I Baylor College of Medicine, Houston, Texas Dr. Ravi Iyengar, Department of Cell Biology 6/85-8/86

Honors and Awards:

Helen Hay Whitney Foundation Postdoctoral Fellowship, 1992-1995

Mount Sinai School of Medicine, Doctoral Dissertation Award, 1992

National Science Foundation Predoctoral Fellowship, 1987-90

Professional Organizations:

Sigma Xi, 1988-present

American Association for the Advancement of Science, 1994-present

American Society for Biochemistry and Molecular Biology, 1996-present

Society for Neuroscience, 1999-present

Professional Service:

Duke Office of Faculty Mentoring, member, Academy of Faculty Mentoring, 2014-2018

Duke University School of Medicine, Admissions Committee, screener member, 2014-2018

Duke University Medical Center, member, Department of Medicine Research Development Council (grant concept review and mentoring), 2012-2018

Duke Path To Independence grant mentoring, reviewer and review facilitator, 2012-2018

Duke University Medical Center, member, Shared Resources Task Force, 2004-2006

National Institutes of Health, MIST study section, ad-hoc reviewer, June 2009, Feb 2010, Feb 2012, Oct 2012, Oct 2013; ZHG1 HGR-M (01) special emphasis panel, July 2009

American Heart Association, Mid-Atlantic Consortium, MAT5 study section, 2006-2007; National, Molecular Signaling study section, 2008-2011, 2013-2016

FASEB Summer Research Conference “G Protein-Coupled Receptor : From Molecules to Diseases”, Steamboat Springs, CO, June 2014 Founding Organizer (with Eugenia Gurevich and Raul Gainetdinov)

Frontiers in Endocrinology, Molecular and Structural Endocrinology section, Editorial Review Board member, 2015-present

Alliance for Cell Signaling, editorial board member, AfCS/Nature Molecule pages, 2003-2010

Peer Reviewer for BMC Cell Biol., Current Biology, EMBO J., FASEB J., J. Biol. Chem., J. Clin. Richard Premont, page 3

Invest., J. Neurochem., Mol. Cancer, Mol. Endocrinology, Nature, Nature Medicine, PNAS and others

Teaching: Duke University, Graduate Program in Cell and Molecular Biology (CMB) CMB 797 Modern Molecular Methods, lectures on Recombinant Proteins, Protein Purification, Protein-Protein Interactions, Recombinant DNA Techniques, 2015-2018 CMB 760 Cellular Signaling, lectures on Hedgehog signaling pathway, 2017-2018

Research Impact Scores: h-index: 57 Research Gate RG score: 50.89 NIH iCite Cumulative Relative Citation Ratio (RCR): 295.63

Primary Peer-Reviewed Publications:

ORCID ID 0000-0002-8053-5026

1] D. R. Rowley, R. T. Premont, M. P. Johnson, C. Y. F. Young and D. J. Tindall, "Properties of an intermediate-sized androgen receptor: association with RNA." (1986) Biochemistry, 25: 6988- 6995.

2] E. Padrell, J. T. Herberg, B. Monsatirsky, G. Floyd, R. T. Premont and R. Iyengar, "The hepatic glucagon receptor: a comparative study of the regulatory and structural properties." (1987) Endocrinology, 120 (6): 2316-2325.

3] C. Marchetti, R. T. Premont and A. M. Brown, "A whole-cell and single channel study of a voltage-dependent outward potassium current in avian hepatocytes" (1988) Journal of General Physiology, 91: 255-274.

4] R. Iyengar, K. A. Rich, J. T. Herberg, R. T. Premont and J. Codina, "Glucagon receptor mediated activation of Gs is accompanied by subunit dissociation." (1988) Journal of Biological Chemistry, 263 (30): 15348-15353.

5] R. T. Premont and R. Iyengar, "Glucagon induced desensitization of adenylyl cyclase in primary cultures of chick hepatocytes: evidence for multiple pathways." (1988) Journal of Biological Chemistry, 263 (31): 16087-16095.

6] T. M. Moriarty, B. Gillo, D. J. Carty, R. T. Premont, E. M. Landau and R. Iyengar, "bg- Subunits of GTP-binding proteins inhibit muscarinic receptor stimulation of phospholipase C." (1988) Proceedings of the National Academy of Sciences, USA, 85: 8865-8869.

7] R. T. Premont and R. Iyengar, "Heterologous desensitization of liver adenylyl cyclase: analysis of the role of G proteins." (1989) Endocrinology, 125 (3): 1151-1160.

8] R. T. Premont, A. Buku and R. Iyengar, "The Gaz product in human erythrocytes: identification as a 41 kDalton protein." (1989) Journal of Biological Chemistry, 264 (25): 14960- 14964.

9] R. T. Premont, "A bovine brain cDNA purported to encode calmodulin-insensitive adenylyl cyclase has extensive identity with neural cell adhesion molecules (N-CAMs)." (1991) FEBS Letters, 295 (1,2,3): 230-231.

10] R. T. Premont, J. Chen, H.-W. Ma, M. Ponnapalli and R. Iyengar, "Two members of a widely- Richard Premont, page 4 expressed subfamily of hormone-stimulated adenylyl cyclases." (1992) Proceedings of the National Academy of Sciences, USA, 89: 9809-9813.

11] S. D. Kroll, J. Chen, M. De Vivo, D. J. Carty, A. Buku, R. T. Premont and R. Iyengar, "The

Q205L-Go-a subunit expressed in NIH-3T3 cells induces transformation." (1992) Journal of Biological Chemistry, 267 (32): 23183-23188.

12] R. T. Premont, O. Jacobowitz and R. Iyengar, "Lowered responsiveness of the catalyst of adenylyl cyclase to stimulation by Gs in heterologous desensitization." (1992) Endocrinology, 131 (6): 2774-2784.

13] O. Jacobowitz, J. Chen, R. T. Premont and R. Iyengar, "Stimulation of specific types of Gs- stimulated adenylyl cyclases by phorbol ester treatment." (1993) Journal of Biological Chemistry, 268 (6): 3829-3832.

14] R. D. Blitzer, G. Omri, M. De Vivo, D. J. Carty, R. T. Premont, J. Codina, L. Birnbaumer, S. Cotecchia, M. G. Caron, R. J. Lefkowitz, E. M. Landau and R. Iyengar, "Coupling of the expressed a1B-adrenergic receptor to the phospholipase C pathway in Xenopus oocytes: The role of Go." (1993) Journal of Biological Chemistry, 268 (10): 7532-7337.

15] J. P. Pieroni, D. Miller, R. T. Premont and R. Iyengar, "Type 5 adenylyl cyclase distribution." (1993) Nature, 363: 679.

16] H.-W. Ma, R. D. Blitzer, E. C. Healy, R. T. Premont, E. M. Landau and R. Iyengar, "Receptor evoked Cl- current in Xenopus oocytes is mediated through a b-type phospholipase C: cloning of a new form of the ." (1993) Journal of Biological Chemistry, 268 (27): 19915-19918.

17] R. T. Premont*, W. J. Koch*, J. Inglese and R. J. Lefkowitz, "Identification, purification and characterization of GRK5, a member of the family of G protein-coupled receptor kinases." (1994) Journal of Biological Chemistry, 269 (9): 6832-6841.

18] R. H. Stoffel, R. R. Randall, R. T. Premont, R. J. Lefkowitz and J. Inglese, "Palmitoylation of G protein-coupled receptor , GRK6: Lipid modification diversity in the GRK family." (1994) Journal of Biological Chemistry, 269 (45): 27791-27794.

19] E. M. Rohlfs, K. W. Daniel, R. T. Premont, L. P. Kozak and S. Collins, "Regulation of the uncoupling protein gene (Ucp) by b1-, b2-, and b3-adrenergic receptor subtypes in immortalized brown adipose cell lines." (1995) Journal of Biological Chemistry, 270 (18): 10723-10732.

20] K. Palczewski, H. Ohguro, R. T. Premont and J. Inglese, " autophosphorylation. Characterization of site-specific mutations." (1995) Journal of Biological Chemistry, 270 (25): 15294-15298.

21] N. Mons, A. Harry, P. Dubourg, R. T. Premont, R. Iyengar and D. M. F. Cooper, "Immunohistochemical localization of adenylyl cyclase in rat brain indicates a highly selective concentration at synapses." (1995) Proceedings of the National Academy of Sciences, USA, 92: 8473-8477.

22] R. T. Premont, A. D. Macrae, R. H. Stoffel, N. Chung, J. A. Pitcher, C. Ambrose, J. Inglese, M. E. MacDonald, and R. J. Lefkowitz, "Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants." (1996) Journal of Biological Chemistry, 271 (11): 6403-6410.

23] L. Menard, S. S. G. Ferguson, L. S. Barak, L. Bertrand, R. T. Premont, A.-M. Colapietro, R. Richard Premont, page 5

J. Lefkowitz, and M. G. Caron, “Members of the G protein-coupled receptor kinase family that phosphorylate the b2-adrenergic receptor facilitate sequestration.” (1996) Biochemistry, 35 (13): 4155-4160.

24] R. T. Premont, I. Matsuoka, M.-G. Mattei, Y. Pouille, N. Defer, and J. Hanoune, "Identification and characterization of a widely expressed form of adenylyl cyclase." (1996) Journal of Biological Chemistry, 271 (23): 13900-13907.

25] J. A. Pitcher, Z. L. Fredericks, W. C. Stone, R. T. Premont, R. H. Stoffel, W. J. Koch, and R.

J. Lefkowitz, “Phosphatidylinositol-4,5-bisphosphate (PIP2)-enhanced G protein-coupled receptor kinase (GRK) activity. Location, structure and regulation of the PIP2 distinguishes the GRK subfamilies.” (1996) Journal of Biological Chemistry, 271 (40): 24907-24913.

26] A. D. Macrae, R. T. Premont, M. Jaber, A. S. Peterson and R. J. Lefkowitz, "Cloning, characterization and chromosomal location of Rec1.3, a member of the G protein-coupled receptor family highly expressed in brain.” (1996) Molecular Brain Research, 42 (3): 245-254.

27] M. A. Shetzline, R. T. Premont, J. K. L. Walker, S. R. Vigna, and M. G. Caron, “A role for receptor kinases in the regulation of class II G protein-coupled receptors: phosphorylation and desensitization of the secretin receptor.” (1998) Journal of Biological Chemistry, 273 (12): 6756- 6762.

28] R. A. Hall, R. T. Premont, C.-W. Chow, J. T. Blitzer, J. A. Pitcher, A. Claing, R. H. Stoffel

III, L. S. Barak, S. Shenolikar, E. J. Weinman, S. Grinstein, and R. J. Lefkowitz, “The b2-adrenergic receptor interacts with the Na+/H+ exchanger regulatory factor to regulate Na+/H+ exchange.” (1998) Nature, 392(6676): 626-630.

29] R. A. Hall, L. S. Ostedgaard, R. T. Premont, J. T. Blitzer, N. Rahman, M. J. Welsh, and R. J.

Lefkowitz, “A carboxyl-terminal motif found in the b2-adrenergic receptor, P2Y1 receptor and CFTR determines binding to the NHERF family of PDZ proteins.” (1998) Proceedings of the National Academy of Sciences, USA, 95: 8496-8501.

30] R. H. Stoffel, J. Inglese, A. D. Macrae, R. J. Lefkowitz, and R. T. Premont, "Palmitoylation increases the kinase activity of the G protein-coupled receptor kinase, GRK6.” (1998) Biochemistry, 37 (46): 16053-16059.

31] R. T. Premont, A. Claing, N. Vitale, J. L. R. Freeman, J. A. Pitcher, W. A. Patton, J. Moss, M.

Vaughan, and R. J. Lefkowitz, “b2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP-ribosylation factor GTPase-activating protein.” (1998) Proceedings of the National Academy of Sciences, USA, 95 (24): 14082-14087.

32] P. H. McDonald, N. L. Cote, F.-T. Lin, R. T. Premont, J. A. Pitcher, and R. J. Lefkowitz,

"Identification of NSF as a b-arrestin1-binding protein. Implications for b2-adrenergic receptor regulation." (1999) Journal of Biological Chemistry, 274 (16): 10677-10680.

33] S. Bagrodia, D. Bailey, Z. Lenard, M. J. Hart, J. L. Guan, R. T. Premont, S. J. Taylor, and R. A. Cerione, “A tyrosine phosphorylated protein that binds to an important regulatory region on the Cool family of Pak-binding proteins.” (1999) Journal of Biological Chemistry, 274 (32): 22393-22400.

34] R. A. Hall, R. F. Spurney, R. T. Premont, N. Rahman, J. T. Blitzer, J. A. Pitcher, and R. J. Lefkowitz, “G protein-coupled receptor kinase 6A phosphorylates the Na+/H+ exchanger regulatory factor (NHERF) via a PDZ domain-mediated interaction.” (1999) Journal of Biological Chemistry, 274 (34): 24328-24334. Richard Premont, page 6

35] R. T. Premont, A. D. Macrae, S. A. J. R. Aparicio, H. E. Kendall, J. E. Welch, and R. J. Lefkowitz, “The GRK4 subfamily of G protein-coupled receptor kinases: , gene structure, and sequence conservation.” (1999) Journal of Biological Chemistry, 274 (41): 29381-29389.

36] J. K. L. Walker, R. T. Premont, L. S. Barak, M. G. Caron, and M. A. Shetzline, “Secretin receptor internalization involves a mechanism distinct from clathrin-coated pit-dependent endocytosis.” (1999) Journal of Biological Chemistry, 274 (44): 31515-31523.

37] R. R. Gainetdinov, L. Bohn, J. K. L. Walker, S. A. Laporte, A. D. Macrae, M. G. Caron, R. J. Lefkowitz, and R. T. Premont, "Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice." (1999) Neuron, 24 (4): 1029-1036.

38] A. Claing, S. J. Perry, M. Archilio, J. K. L. Walker, J. P. Albanesi, R. J. Lefkowitz, and R. T. Premont, "Sensitivity to GIT1 delineates distinct pathways of G protein-coupled receptor internalization." (2000) Proceedings of the National Academy of Sciences, USA, 97 (3): 1119- 1124.

39] N. Vitale, W. Patton, J. Moss, M. Vaughan, R. J. Lefkowitz, and R. T. Premont, "GIT proteins, a novel family of phosphatidylinositol 3,4,5-trisphosphate-stimulated GTPase-activating proteins for ARF6." (2000) Journal of Biological Chemistry, 275 (18): 13901-13906.

40] R. T. Premont, A. Claing, N. Vitale, S. J. Perry, and R. J. Lefkowitz, “The GIT family of ARF GTPase-activating proteins: Functional diversity of GIT2 through alternative splicing.” (2000) Journal of Biological Chemistry, 275 (29): 22373-22380.

41] A. Claing, W. Chen, W. E. Miller, N. Vitale, J. Moss, R. T. Premont, and R. J. Lefkowitz,

"barrestin-mediated ARF6 activation and b2-adrenergic receptor endocytosis" (2001) Journal of Biological Chemistry, 276 (45): 42509-42513.

42] L. A. Hu, W. Chen, R. T. Premont, M. Cong, and R. J. Lefkowitz, "G protein-coupled receptor kinase 5 regulates b1-adrenergic receptor association with PSD-95." (2001) Journal of Biological Chemistry, 277 (2): 1607-1613.

43] A. M. Fong, R. T. Premont, R. M. Richardson, Y.-R. A. Yu, R. J. Lefkowitz, and D. D. Patel "Defective lymphocyte in b-arrestin2- and GRK6-deficient mice." (2002) Proceedings of the National Academy of Sciences, USA, 99 (11): 7478-7483.

44] M. A. Shetzline, J. K. L. Walker, K. Valenzano, and R. T. Premont, "Vasoactive intestinal peptide type-1 receptor regulation. Desensitization, phosphorylation and sequestration." (2002) Journal of Biological Chemistry, 277 (28): 25519-25526.

45] J.-S. Yang, S. Y. Lee, M. Gao, S. Bourgoin, P. A. Randazzo, R. T. Premont, and V. W. Hsu, "ARFGAP1 promotes the formation of COPI vesicles, suggesting function as a component of the coat" (2002) Journal of Cell Biology, 159 (1): 69-78.

46] S. Kim, J. Ko, H. Shin, J.-R. Lee, C. Lim, J.-H. Han, W. D. Altrock, C. C. Garner, E. D. Gundelfinger, R. T. Premont, B.-K. Kaang and E. Kim, "The presynaptic cytomatrix protein Piccolo associates with the GIT family of ARF GAP proteins in an active zone precursor vesicle." (2003) Journal of Biological Chemistry, 278 (8): 6291-6300.

Richard Premont, page 7

47] J. Ko, S. Kim, J. G. Valtschanoff, H. Shin, J.-R. Lee, M. Sheng, R. T. Premont, R. J. Weinberg and E. Kim, "Interaction between Liprin-a and GIT1 is required for AMPA Receptor Targeting." (2003) Journal of Neuroscience, 23(5): 1667-1677.

48] R. R. Gainetdinov, L. M. Bohn, T. D. Sotnikova, M. Cyr, G. E. Torres, A. D. Macrae, K.-M. Kim, R. J. Lefkowitz, M. G. Caron, and R. T. Premont, "Cocaine supersensitivity in G protein- coupled receptor kinase 6-deficient mice." (2003) Neuron 38 (2): 291-303.

49] L. A. Hu, W. Chen, N. P. Martin, E. J. Whalen, R. T. Premont, and R. J. Lefkowitz, "GIPC interacts with the b1-adrenergic receptor and regulates b1-adrenergic receptor mediated ERK activation." (2003) Journal of Biological Chemistry, 278 (28): 26295-26301.

50] A. Kavelaars, A. Vroon, R. Raatgever, A. M. Fong, R. T. Premont, D. D. Patel, R. J. Lefkowitz and C. J. Heijnen, "Increased acute inflammation, leukotriene B4-induced chemotaxis and signaling in mice deficient for GRK6" (2003) Journal of Immunology, 171 (11): 6128- 6134.

51] S. Liu, R. T. Premont, C. D. Kontos, and D. C. Rockey, "Endothelin-1 activates endothelial cell nitric oxide synthase (eNOS) via heterotrimeric G-protein bg subunit signaling to B/Akt." (2003) Journal of Biological Chemistry, 278 (50): 49929-49935.

52] J. K. L. Walker, R. R. Gainetdinov, D. S. Feldman, P. K. McFawn, M. G. Caron, R. J. Lefkowitz, R. T. Premont, and J. T. Fisher, “G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation.” (2003) American Journal of Physiology: Lung Cellular and Molecular Physiology, 286 (2): L312-L319.

53] A. Vroon, C. J. Heijnen, R. Raatgever, I. P. Touw, R. E. Ploemacher, R. T. Premont and A. Kavelaars, "GRK6 deficiency is associated with enhanced CXCR4-mediated chemotaxis in vitro and impaired responsiveness to G-CSF in vivo." (2004) Journal of Leukocyte Biology, 75 (4): 698-704.

54] S. Audebert, C. Navarro, C. Nourry, S. Chasserot-Golaz, P. Lécine, Y. Bellaiche, J.-L. Dupont, R.T. Premont, C. Sempéré, Jean-M. Strub, A. Van Dorseelaer, N. Vitale and J.-P. Borg, "Mammalian Scribble forms a tight complex with the bPIX exchange factor." (2004) Current Biology 14 (11): 987-995.

55] R. T. Premont, S. J. Perry, R. Schmalzigaug, J. T. Roseman, Y. Xing and A. Claing, "The GIT/PIX complex: An oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors." (2004) Cellular Signaling 16 (9): 1001-1011.

56] H.-Y. Yoon, K. Jacques, B. Nealon, S. Stauffer, R. T. Premont and P. A. Randazzo "Differences between ASAP1, AGAP1 and Arf GAP1 in substrate recognition: Interaction with the N-terminus of Arf1." (2004) Cellular Signaling, 16 (9): 1033-1044.

57] J. Dai, J. Li, E. Bos, M. Porcionatto, R. T. Premont, S. Bourgoin, P. J. Peters and V. W. Hsu, "ACAP1 promotes endocytic recycling by recognizing recycling sorting signals" (2004) Developmental Cell, 7 (5): 771-776.

Richard Premont, page 8

58] S. Y. Lee, J.-S. Yang, W. Hong, R. T. Premont and V. W. Hsu, "ArfGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation." (2005) Journal of Cell Biology,.168 (2): 281-290.

59] P. Seeman, D. Weinshenker, R. Quirion, L. K. Srivastava, S. K. Bhardwaj, D. K. Grandy, R. T. Premont, T. D. Sotnikova, P. Boksa, M. El-Ghundi, B. F. O’Dowd, S. R. George, M. L. Perreault, P. T. Mannisto, S. Robinson, R. D. Palmiter., and T. Tallerico, "Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis." (2005) Proceedings of the National Academy of Sciences, USA 102 (9): 3513-3518.

60] Z. Nie, J. Fei, R. T. Premont and P. A. Randazzo, "The Arf GAPs AGAP1 and AGAP2 distinguish between the adaptor protein complexes AP-1 and AP-3." (2005) Journal of Cell Science 118(15): 3555-3566.

61] S. Liu, R. T. Premont, C. D. Kontos, S. Zhu and D. C. Rockey, "A critical role for GRK2 in regulation of endothelial cell nitric oxide synthase function in injured endothelial cells in portal hypertension." (2005) Nature Medicine 11(9): 952-958.

62] R. Luo, K. Jacques, B. Ahvazi, S. Stauffer, R. T. Premont and P. A. Randazzo, "Mutational analysis of Arf1•GTP/Arf GAP interface reveals an Arf1 mutant that selectively affects the Arf GAP ASAP1." (2005) Current Biology, 15(23): 5164-69.

63] S. K. Shenoy, M. T. Drake, C. D. Nelson, D. A. Houtz, K. Xiao, S. Madabushi, E. Reiter, R. T. Premont, O. Lichtarge, and R. J. Lefkowitz, "b--dependent, G protein-independent ERK1/2 activation by the b2 adrenergic receptor" (2005) Journal of Biological Chemistry, 281(2): 1261-1273.

64] M. Z. Meyer, N. Déliot, S. Chasserot-Golaz, R. T. Premont, M.-F. Bader and N. Vitale, "Regulation of Neuroendocrine Exocytosis by the Arf6 GTPase-Activating Protein GIT1." (2006) Journal of Biological Chemistry, 281(12): 7919-7926.

65] K. Rajagopal, E. J. Whalen, J. D.Violin, J. A. Stiber, P. B. Rosenberg, R. T. Premont, T. M. Coffman, H. A. Rockman and R. J. Lefkowitz, "b-Arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes." (2006) Proceedings of the National Academy of Sciences USA, 103(44): 16284-16289.

66] J.-H. Wu, R. Goswami, X Cai, S. T. Exum, X. Huang, L. Zhang, L. Brian, K. Peppel, R. T. Premont and N. J. Freedman, "Regulation of the platelet-derived growth factor receptor-b by G protein-coupled receptor kinase 5 in vascular smooth muscle cells involves the phosphatase Shp2" (2007) Journal of Biological Chemistry , 281(49): 37758-37772 .

67] N. Eijkelkamp, C. J. Heijnen, A. Lucas, R. T. Premont, S. Elsenbruch, M. Schedlowski and A. Kavelaars, "G protein-coupled receptor kinase 6 contols chronicity and severity of DSS- induced colitis in mice." (2007) Gut, 56(6): 847-854. PMID: 17229795 PMC1954868

Richard Premont, page 9

68] R. Schmalzigaug, M.-L. Garron, J. T. Roseman, Y. Xing, C. E. Davidson, S. T. Arold and R. T. Premont, "GIT1 Utilizes a Focal Adhesion Targeting-Homology Domain to Bind Paxillin." (2007) Cellular Signaling 19(8): 1733-1744. PMID: 17467235 PMC2025689

69] R. Schmalzigaug, H. Phee, C. E. Davidson, A. Weiss and R. T. Premont, "Differential Expression of the Arf GAP GIT1 and GIT2 in Mouse Tissues." (2007) The Journal of Histochemistry and Cytochemistry 55(10): 1039-1048. PMID: 17565117

70] Z. Suo, A. A. Cox, N. Bartelli, I. Rasul, B. W. Festoff, R. T. Premont and G. W. Arendash, "GRK5 Deficiency Leads to Early Alzheimer-like Pathology and Working Memory Impairment." (2007) Neurobiology of Aging 28(12): 1873-1888. PMID: 17011668

71] T. K. Tarrant, R. R. Rampersad, D. Esserman, L. R. Rothlein, P. Liu, R. T. Premont, R. J. Lefkowitz, D. M. Lee, and D. D. Patel, "Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN)." (2008) Clinical Immunology 129: 115-122. PMID: 18662895 PMC2637521

72] R. A. Kahn, E. Bruford, H. Inoue, J. M. Logsdon, Jr., Z. Nie, R. T. Premont, P. A. Randazzo, M. Satake, A. B. Theibert, M. L. Zapp, and D. Cassel, "Consensus nomenclature for the human ArfGAP domain-containing proteins." (2008) Journal of Cell Biology 182(6): 1039-44. PMID: 18809720 PMC2542466

73] L. Li, I. Rasul, J. Liu, B. Zhao, R. Tang, R. T. Premont, and W. Z. Suo, "Augmented axonal defects and synaptic degenerative changes in female GRK5 deficient mice." (2009) Brain Research Bulletin 78(4-5): 145-151. PMID: 18955119

74] X. Cai, J.-H. Wu, S. T. Exum, M. Oppermann, R. T. Premont, S. K. Shenoy, and N. J. Freedman, "Reciprocal Regulation of the Platelet-derived Growth Factor Receptor-β and G Protein-coupled Receptor Kinase 5 by Cross-Phosphorylation: Effects on Catalysis" (2009) Molecular Pharmacology 75(3): 626-636. PMID: 19092051 PMC2684914

75] R. Schmalzigaug, R. M. Rodriguiz, L. E. Phillips, C. E. Davidson, W. C. Wetsel, and R. T. Premont, "Anxiety-like behaviors in mice lacking GIT2." (2009) Neuroscience Letters 451: 156-161. PMID: 19114090 PMC2648396

76] R. Schmalzigaug, R. M. Rodriguiz, P. E. Bonner, C. E. Davidson, W. C. Wetsel, and R. T. Premont, "Impaired fear responses in mice lacking GIT1." (2009) Neuroscience Letters 458: 79-83. PMID: 19383529 PMC2685762

77] J. Liu, I. Rasul, G. Wu, L. Li, R. T. Premont, and W. Z. Suo, "GRK5 deficiency leads to reduced hippocampal acetylcholine level via impaired presynaptic M2 autoreceptor desensitization" (2009) Journal of Biological Chemistry 284 (29): 19564-71. PMID: 19478075 PMC2740582

78] K. M. Raehal, C. L. Schmid, I. O. Medvedev, R. R. Gainetdinov, R. T. Premont, and L. M. Bohn, "Morphine-Induced Physiological and Behavioral Responses in Mice Lacking G Protein- Richard Premont, page 10

Coupled Receptor Kinase 6." (2009) Drug and Alcohol Dependence 104(3): 187-196 PMID: 19497686 PMC2771341

79] M. Chen, M. Philippe, J. Wang, R. T. Premont, T. R. Garrison, M. G. Caron, R. J. Lefkowitz, and W. Chen, "Activation of Wnt Receptor LRP6 via phosphorylation by G Protein-Coupled Receptor Kinases 5 and 6." (2009) Journal of Biological Chemistry 284(50): 35040-35048 PMID: 19801552 PMC2787365

80] Y. Jung, R. P. Witek, W. K. Syn, S. S. Choi, A. Omenetti, R. T. Premont, C. D. Guy, and A. M. Diehl, “Signals from dying hepatocytes trigger growth of liver progenitors.” (2010) Gut 59(5): 655-665 PMID: 20427400

81] S. Cheng, L. Li, S. He, J. Liu, Y. Sun, M. He, K. Grasing, R. T. Premont, W. Z. Suo, “GRK5 deficiency accelerates Aβ accumulation in Tg2576 mice via impaired cholinergic activity.” (2010) Journal of Biological Chemistry 285(53):41541-41548 PMID: 21041302 PMC3009881

82] S. Liu, R. T. Premont, and D. C. Rockey, " G-protein-coupled receptor kinase interactor-1 (GIT-1) is a new endothelial nitric oxide synthase (eNOS) interactor with functional effects on vascular homeostasis." (2012) Journal of Biological Chemistry 287(15): 12309-12320 PMID: 22294688 PMC3320980

83] F. Managò, S. Espinoza, A. Salahpour, T. D. Sotnikova, M. G. Caron, R. T. Premont, R. R. Gainetdinov, “The role of GRK6 in animal models of Parkinson’s disease and L-DOPA treatment.” (2012) Scientific Reports 2: 301 (1-10) PMID: 22393477 PMC3293148

84] X. Wang, S. Liao, E. R. Nelson, R. Schmalzigaug, R. F. Spurney, F. Guilak, R. T. Premont, and D. Gesty-Palmer, “The Cytoskeletal Regulatory Scaffold Protein GIT2 Modulates Mesenchymal Stem Cell Differentiation and Osteoblastogenesis.” (2012) Biochemical and Biophysical Research Communications 425(2): 407-412. PMID: 22846567 PMC3432571

85] J. I. Gold, E. Gao, X. Shang, R. T. Premont, and W. J. Koch, “Determining the absolute requirement of G protein-coupled receptor kinase 5 in pathological cardiac hypertrophy” (2012) Circulation Research 111(8):1048-1053. PMID: 22859683 PMC3752304

86] Y. Chen, S. S. Choi, G. A. Michelotti, I. S. Chan, M. Swiderska, G. F. Karaca, G. Xie, C. A. Moylan, F. Garibaldi, R. T. Premont, H. B. Suliman, C. A. Piantodosi and A. M. Diehl, “Hedgehog Controls Hepatic Stellate Cell Fate by Regulating Metabolism” (2012) Gastroenterology 143(5): 1319-1329. PMID: 22885334 PMC3480563

87] G. A. Michelotti, G. Xie, M. Swiderska, S. S. Choi, G. Karaca, L. Krüger, R. T. Premont, L. Yang, W.-K. Syn, D. Metzger and A. M. Diehl, “Smoothened is a master regulator of adult liver repair.” (2013) Journal of Clinical Investigation 123(6): 2380-2394. PMID: 23563311 PMC3668809

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88] G. Xie, G. Karaca, M. Swiderska-Syn, G. A. Michelotti, L. Krüger, Y. Chen, R. T. Premont, S. S. Choi, and A. M. Diehl, “Cross-talk between notch and hedgehog regulates hepatic stellate cell fate.” (2013) Hepatology 58(5):1801-1813 PMID: 23703657 PMC3758784

89] M. D. Burkhalter, G. B. Fralish, R. T. Premont, M. G. Caron, and M Philipp, “Grk5l Controls Heart Development by Limiting mTOR Signaling during Symmetry Breaking” (2013) Cell Reports 4(4): 625-632. PMID: 23972986 PMC3792657

90] M. Swiderska-Syn, W. K. Syn, G. Xie, L. Krüger, M. V. Machado, G. Karaca, G. A. Michelotti, S. S. Choi, R. T. Premont, and A. M. Diehl, “Myofibroblastic Cells Function as Progenitors to Regenerate Murine Livers after Partial Hepatectomy” (2014) Gut 63(8): 1333- 44. PMID: 24173292 PMC4006344

91] M. Korthals, K. Schilling, P. Reichardt, D. Mamula, T. Schlüter, M. Steiner, K. Langnäse, U. Thomas, E. Gundelfinger, R. T. Premont, K. Tedford and K.-D. Fischer, “αPIX RhoGEF Supports Positive Selection by Restraining Migration and Promoting Arrest of Thymocytes.” (2014) Journal of Immunology 192(7): 3228-3238. PMID: 24591366

92] S. Liu, R. T. Premont, and D. C. Rockey, “Endothelial Nitric-oxide Synthase (eNOS) Is Activated Through G-protein-coupled Receptor Kinase-interacting Protein 1 (GIT1) Tyrosine Phosphorylation and Src Protein” (2014) Journal of Biological Chemistry 289(26): 18163- 18174. PMID: 24764294

93] M. Chen, A. Hegde, Y. H. Choi, B. S. Theriot, R. T. Premont, W. Chen, and J. K. L. Walker, “Genetic Deletion of β-arrestin-2 Mitigates Established Airway Hyperresponsiveness in a Murine Asthma Model” (2015) American Journal of Respiratory Cell and Molecular Biology 53(3): 346-354. PMID: 25569510

94] G. Michelotti, A. Tucker, M. Machado, M. Swiderska-Syn, L. Kruger, S. S. Choi, E. Soderblom, J. W Thompson, M. Mayer-Salman, H. Himburg, C. Moylan, C. D. Guy, J. P. Chute, K. Garman, R. T. Premont, and A. M. Diehl, “Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches” (2015) Gut 65(4):683-692. doi: 10.1136/gutjnl-2014-308176) PMID: 25596181

95] D. Lu, H. Cai, S.-S. Park, S. Siddiqui, R. T. Premont, R Schmalzigaug, M. Paramasivam, M. Seidman, I. Bodogai, A. Biragyn, C. Daimon, B. Martin, and S. Maudsley, "Nuclear GIT2 is an ATM substrate and promotes DNA repair" (2015) Molecular Cellular Biology 35(7): 1081- 1096. PMID: 25605334

96] M. V. Machado, G. A. Michelotti, T. Pereira de Almeida, G. Xie, R. T. Premont, H. Cortez- Pinto, and A. M. Diehl, “Accumulation of duct cells with activated YAP parallels fibrosis progression in Non-Alcoholic Fatty Liver Disease” (2015) Journal of Hepatology 63(4): 962- 970. PMID: 26070409 PMCID: PMC4575842

97] M. Singh, H. Gao, W. Sun, Z. Song, R. Schmalzigaug, R. T. Premont and Q. Zhang, “Structure-activity Relationship Studies of QS11, a Small Molecule Regulator of Wnt/β-catenin Richard Premont, page 12

Signaling Pathway and ADP-ribosylation Factor GTPase-Activating Protein 1” (2015) Bioorganic and Medicinal Chemistry Letters 25(21): 4838-4842. PMID: 26152429

98] M. S. Montesinos, K. Goff, B. Das, D. Guerro-Givens, W. Dong, R. Schmalzigaug, R. T. Premont, N. Kamasawa, and S. M. Young, Jr. “Presynaptic deletion of GIT proteins increases release probability at a mammalian central synapse.” (2015) Neuron 88(5): 918-925. PMID: 26637799

99] B. Martin, W. Chadwick, J. Janssens, R. T. Premont, R. Schmalzigaug, K. G. Becker, E. Lehrmann, W. H. Wood III, Y. Zhang, S. Siddiqui, S.-S. Park, W.-N. Cong, C. M. Daimon, and S. Maudsley, “GIT2 acts as a systems-level coordinator of neurometabolic activity and pathophysiological aging” (2016) Frontiers in Endocrinology (Lausanne) 6: 191 doi: 10.3389/fendo.2015.00191. PMID: 26834700

100] M. V. Machado, G. A. Michelotti, Guanhua Xie, T. de Almeida Pereira, M. Jewell, R. T. Premont, and A. M. Diehl, “Ancestral starvation-activated caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease." (2016) Cell Death and Disease 7: e2096. doi: 10.1038/cddis.2016.19 PMID: 26890135

101] M. Swiderska-Syn, G. Xie, G. M. Michelotti, M. L. Jewell, R. T. Premont, W. K. Syn and A. M Diehl, “Hedgehog regulates Yes-associated protein 1 in regenerating mouse liver.” (2016) Hepatology 64(1): 232-244. doi: 10.1002/hep.28542. PMID: 26970079

102] M. He, P. Singh, S. Cheng, Q. Zhang, W. Peng, X. Ding, L. Li, J. Liu, R. T. Premont, D. Morgan, J. Burns, R. H. Swerdlow, and W. Z. Suo, “GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability.” (2016) Scientific Reports 6: 26116. doi: 10.1038/srep26116. PMID: 27193825

103] M. J. Kim, J. Biag, D. M. Fass, M. C. Lewis, Q. Zhang, M. Fleishman, S. P. Gangwar, M. Machius, M. Fromer, S. M. Purcell, S. A. McCarroll, G. Rudenko, R. T. Premont, E. M. Scolnick, and S. J. Haggarty, “Functional Analysis of Rare Variants Found in Schizophrenia Implicates a Critical Role for GIT1-PAK3 Signaling in Neuroplasticity.” (2017) Molecular Psychiatry 22(3): 417-429. doi: 10.1038/mp.2016.98. PMID: 27457813

104] S. Liu, R. T. Premont, S. Singh and D. C. Rockey, “Caveolin-1 and GRK2 co-regulate eNOS activity in sinusoidal endothelial cells.” (2017) American Journal of Pathology 187(4): 896-907. doi: 10.1016/j.ajpath.2016.11.017 PMID: 28162981

105] S. Siddiqui, A. Lustig, A. D. Carter, M. Sankar, C. M. Daimon, R. T. Premont, H. Etienne, J. van Gastel, A. Azmi, J. Janssens, K.G. Becker, Y. Zhang, W. Wood, E. Lehrman, J. G. Martin, B. Martin, D. D. Taub, and S. Maudsley, “Genomic deletion of GIT2 induces a premature age- related thymic dysfunction and systemic immune system disruption.” (2017) Aging (Albany, NY) 9(3): 706-740. doi: 10.18632/aging.101185 PMID: 28260693

106] G. Xie, M. Swiderska-Syn, M. L. Jewell, M. V. Machado, G. A. Michelotti, R. T. Premont, and A. M. Diehl, “Loss of Pericyte Smoothened Activity in Mice with Genetic Deficiency of Richard Premont, page 13

Leptin” (2017) BMC Cell Biology 18(1): 20. doi: 10.1186/s12860-017-0135-y. PMID: 28427343 PMCID: PMC5399438

107] J. Bhattacharyya, X.-R. Ren, R. A. Mook Jr., J. Wang, I. Spasojevic, R. T. Premont, X. Li, A. Chilkoti and W. Chen, “Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth.” (2017) Nanoscale 9(34): 12709-12717. doi: 10.1039/c7nr01973d. PMID: 28828438

108] L. A. M. Rein, J. W. Wisler, J. Kim, B. Theriot, LY. Huang, T. Price, H. Yang, M. Chen, W. Chen, D. Sipkins, Y. Fedoriw, J. K. L. Walker, R. T. Premont, and R. J. Lefkowitz, “barrestin2 mediates progression of murine primary myelofibrosis.” (2017) JCI Insight. 2(23): e98094. doi: 10.1172/jci.insight.98094. PMID: 29263312

109] K. Du, S. Choi, G. A. Michelotti, M. Swiderska-Syn, G. D. Dalton, R. T. Premont, E. Thelen, B. S. Rizi, and A. M. Diehl, “Hedgehog-YAP Signaling Pathway Regulates Glutaminolysis to Control Activation of Hepatic Stellate Cells.” (2018) Gastroenterology 154(5): 1465-1479.e13. doi: 10.1053/j.gastro.2017.12.022. PMID: 29305935 See Editorial Commentary: L.D. Harvey and S.Y. Chan, “YAPping About Glutaminolysis in Hepatic Fibrosis.” (2018) Gastroenterology 154(5): 1231-1233. doi: 10.1053/j.gastro.2018.03.007. PMID: 29510133

110] A. C. Martyn*, K. Toth*, R. Schmalzigaug, N. Hedrick, R. M. Rodriguiz, R. Yasuda, W. C. Wetsel, and R. T. Premont, “GIT1 Regulates Synaptic Plasticity Underlying Learning” (2018) PLOS One 13(3): e0194350. doi: 10.1371/journal.pone.0194350. PMID: 29554125

111] S.-H. Oh, M. Swiderska-Syn, M. L. Jewell, R. T. Premont, and A. M. Diehl, “Liver regeneration requires Yap1-TGF-b-dependent epithelial-mesenchymal transition in hepatocytes.” (2018) Journal of Hepatology 69(2):359-367 doi: 10.1016/j.jhep.2018.05.008. PMID: 29758331

112] S. Wang, Y. Jung, J. Hyun, M. Friedersdorf, J. Kim, R T. Premont, J. Keene, A. M. Diehl, “RNA Binding Proteins Control Trans-differentiation of Hepatic Stellate Cells into Myofibroblasts” (2018) Cellular Physiology and Biochemistry 48(3): 1215-1229. doi: 10.1159/000491987. PMID: 30045014

113] A. T. Reese, F. C. Pereira, A. Schintlmeister, D. Berry, M. Wagner, L. P. Hale, H. K. Durand, X. Zhou, R. T. Premont, A. M. Diehl, T. M. O’Connell, S. C. Alberts, T. R. Kartzinel, R. M. Pringle, R. R. Dunn, J. P. Wright, and L. A. David, “Microbial nitrogen limitation in the mammalian large intestine.” (2018) Nature Microbiology 3(12): 1441-1450. doi: 10.1038/s41564-018-0267-7 PMID: 30374168

114] J. Wang, X.-R. Ren, H. Piao, S. Zhao , T. Osada, R. T. Premont, R. A. Mook, M. A. Morse, H. K. Lyerly, and W. Chen, “Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy.” (2019) Biochemical Journal 476(3):535-546. doi: 10.1042/BCJ20180385. PMID: 30635359 See Editorial Commentary: P. T. Newton ,“New insights into niclosamide action: autophagy activation in colorectal cancer.” Biochemical Journal (2019) 476:779–781. https://doi.org/10.1042/BCJ20190020

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115] J. Hyun, S.-H. Oh, R. T. Premont, C. D. Guy, C. L. Berg, A. M. Diehl. “Dysregulated Activation of Fetal Liver Program in Acute Liver Failure.” (2019) Gut 68(6):1076-1087. doi: 10.1136/gutjnl-2018-317603. PMID: 30670575

116] J. D. Reynolds, R. T. Premont, and J. S. Stamler, “Letter by Reynolds et al Regarding “Hemoglobin β93 Cysteine is Not Required for Export of Nitric Oxide Bioactivity From the Red Blood Cell” (2019) Circulation 140:e758–e759. doi: 10.1161/CIRCULATIONAHA.119.041389. PMID: 31682530.

117] C. T. Stomberski*, P. Anand*, N. M. Venetos, A. Hausladen, H.-L. Zhou, R. T. Premont, and J. S. Stamler, “AKR1A1 is a novel mammalian S-nitroso-glutathione reductase.” (2019) The Journal of Biological Chemistry 294(48):18285-18293. doi 10.1074/jbc.RA119.011067 PMID: 31649033

118] M. L. Jewell*, J. Gibson*, C. D. Guy, J. Hyun, K. Du, S.-H. Oh, R. T. Premont, D. S. Hsu, T. Ribar, S. G. Gregory, and A. M. Diehl, “Single cell RNA sequencing identifies YAP1- dependent hepatic mesothelial progenitors in fibrolamellar carcinoma.” (2020) American Journal of Pathology 90(1):93-107. doi 10.1016/j.ajpath.2019.09.018 PMID: 31669305

119] K. Du, S. Chitneni, A. Suzuki, Y. Wang, R. Hanao, J. Hyun, R. T. Premont, S. Naggie, C. Moylan, M. R. Bashir, M. F. Abdelmalek, A. M. Diehl, “Increased Glutaminolysis Marks Active Scarring in Nonalcoholic Steatohepatitis Progression.” (2020) Cellular and Molecular Gastroenterology and Hepatology 10 (1):1-21. doi: 10.1016/j.jcmgh.2019.12.006. PMID: 31881361. See Editorial Commentary: A. E. Garcia Whitlock and P. M. Titchenell, “Glutamine Breakdown as a Potential Metabolic Biomarker for Nonalcoholic Steatohepatitis.” (2020) Cellular and Molecular Gastroenterology and Hepatology 10(1):195-196. doi: 10.1016/j.jcmgh.2020.03.001. PMID: 32220558

120] S. Liu, L. M. Luttrell, R. T. Premont, and D C. Rockey, “β-arrestin-2 is a critical component of the GPCR-eNOS signalosome” Proceedings of the National Academy of Sciences USA 117(21):11483-11492. doi: 10.1073/pnas.1922608117 PMID: 32404425. See Editorial Commentary: L. B. Ray, “Controlling blood flow in the liver” (2020) Science 368(6496):1202 doi: 10.1126/science.368.6496.1202-b

121] S. Liu, L. M. Luttrell, R. T. Premont, and D. C. Rockey, “Response to Schierwagen et al.” Proceedings of the National Academy of Sciences USA 117(44): In Press 9/10/20. See Companion Letter: R. Schierwagen, P. Dietrich, S. Klein, F. E. Uschner, C. Ortiz, O. Tyc, S. Torres, C. Hellerbrand, T. Sauerbruch, and J. Trebicka, “Beta-arrestin-2 is increased in liver fibrosis in humans and rodents.” Proceedings of the National Academy of Sciences USA 117(44): In Press

122] A. Badea *, R. Schmalzigaug *, W. Kim, P. Bonner, U. Ahmed, G. A. Johnson, G. Cofer, M. Foster, R. J. Anderson, C. Badea, and R. T. Premont, “Microcephaly with Altered Cortical Layering in GIT1 Deficiency Revealed by Quantitative Neuroimaging” Magnetic Resonance Imaging Sep 30:S0730-725X(20)30453-7. In Press doi: 10.1016/j.mri.2020.09.023 PMID: 33010377.

Preprints

Richard Premont, page 15

D. M. Fass*, M. C. Lewis*, R. Ahmad*, M. Szucs, Q. Zhang, M. Fleishman, D. Wang, M. J. Kim, J. Biag, S. A. Carr, E. M. Scolnick, R. T. Premont and S. J. Haggarty, “Brain-Specific Deletion of GIT1 Impairs Cognition and Alters Phosphorylation of Synaptic Protein Networks Implicated in Schizophrenia Susceptibility.” Molecular Psychiatry In Revision 12/1/18 Preprint available at BioRxiv.org #290312 doi: 10.1101/290312

K. Toth *, A. C. Martyn *, N. Bastrokova, W. Kim, R. M. Rodriguiz, U. Ahmed, R. Schmalzigaug, S. M. Dudek, W. C. Wetsel, and R. T. Premont, “GIT2 is dispensable for normal learning and memory function due to a predominant brain GIT2 splice variant that evades GIT/PIX complexes.” Preprint available at BioRxiv.org #538223 doi: 10.1101/538223

Reviews and Book Chapters:

1] R. T. Premont and R. Iyengar, "Glucagon receptor: structure and function" (1987) In: Peptide Hormone Receptors. (M. Y. Kalimi and J. R. Hubbard, eds.) Walter de Gruyter & Co., Berlin New York pp. 129-177.

2] R. T. Premont and R. Iyengar, "Adenylyl cyclase and its regulation by Gs." (1990) In: G Proteins. (R. Iyengar and L. Birnbaumer, eds.) Academic Press, San Diego pp. 147-178.

3] R. T. Premont and R. Iyengar, "Multiple pathways for glucagon-induced heterologous desensitization of liver adenylyl cyclase." (1990) In: Activation and Desensitization of Transducing Pathways. (T. M. Konijn, M. D. Houslay, P. J. M. Van Haastert, eds.) NATO ASI series, vol. H44 Springer-Verlag, Berlin pp. 85-97.

4] D. J. Carty, R. T. Premont and R. Iyengar, "Quantitative immunoblotting of G-protein subunits." (1991) In: Adenylyl Cyclase, G Proteins, and Guanylyl Cyclase. Methods in Enzymology, vol. 195 (R. A. Johnson and J. D. Corbin, eds.) Academic Press, San Diego pp. 302-315.

5] R. T. Premont and R. Iyengar, "Liver adenylyl cyclases: structure and regulation by cAMP- dependent phosphorylation." (1992) In: Adenine Nucleotides in Cellular Energy Transfer and . (S. Papa, A. Azzi, and J. M. Trager, eds.) Birkhäuser Verlag, Basel pp. 325-334.

6] R. T. Premont, J. Chen, O. Jacobowitz and R. Iyengar, "Molecular diversity of mammalian adenylyl cyclases: functional consequences." (1993) In: GTPases in Biology II. Handbook of Experimental Pharmacology, vol. 108/II (B. Dickey and L. Birnbaumer, eds.) Springer-Verlag, Berlin Chapter 55, pp. 189-212.

7] R. J. Lefkowitz and R. T. Premont, "Diseased G protein-coupled receptors." (1993) Journal of Clinical Investigation 92: 2089-2089.

8] R. T. Premont, "Identification of adenylyl cyclases by amplification using degenerate primers." (1994) In: Heterotrimeric G-Protein Effectors. Methods in Enzymology, vol. 238 (R. Iyengar, ed.) Academic Press, San Diego, pp. 116-127.

9] H.-W. Ma, R. Iyengar and R. T. Premont, "Amplification of phosphatidylinositol-specific phospholipase C-ß isoforms using degenerate primers." (1994) In: Heterotrimeric G-Protein Effectors. Methods in Enzymology, vol. 238 (R. Iyengar, ed.) Academic Press, San Diego, pp. 244-252.

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10] R. T. Premont, J. Inglese and R. J. Lefkowitz, "Kinases that phosphorylate activated G protein- coupled receptors." (1995) FASEB Journal 9 (2): 175-182.

11] J. Inglese, R. T. Premont, W. J. Koch, J. Pitcher and R. J. Lefkowitz, "b-Adrenergic receptor kinase." (1995) In: The Protein Kinase FactsBook. (D. G. Hardie and S. K. Hanks, eds.) Academic Press London, San Diego volume I, pp. 98-101.

12] J. Inglese, R. T. Premont, W. J. Koch, J. Pitcher and R. J. Lefkowitz, "Rhodopsin kinase." (1995) In: The Protein Kinase FactsBook. (D. G. Hardie and S. K. Hanks, eds.) Academic Press London, San Diego volume I, pp. 102-104.

13] J. Inglese and R. T. Premont, “Lipid modifications of G protein-coupled receptor kinases.” (1996) Biochemical Society Transactions 24: 714-717.

14] R. A. Hall, R. T. Premont, and R. J. Lefkowitz, “Heptahelical receptor signaling: beyond the G protein paradigm.” (1999) Journal of Cell Biology 145 (5): 927-932.

15] R. R. Gainetdinov, R. T. Premont, M. G. Caron, and R. J. Lefkowitz, "Reply: Receptor specificity of G protein-coupled receptor kinases." (2000) Trends in Pharmacological Sciences 21: 366-367.

16] R. T. Premont and N. Vitale, "Purification and Characterization of GIT Family of ADP- Ribosylation Factor (ARF) GTPase-Activating Proteins." (2001) In: Regulators and Effectors of Small GTPases, Part E: GTPases Involved in Vesicular Traffic. Methods in Enzymology, vol. 329 (W. E. Balch, C. J. Der and A. Hall, eds.) Academic Press, San Diego, pp. 335-343.

17] R. T. Premont, R. R. Gainetdinov, and M. G. Caron, "Commentary: Following the Trace of Elusive Amines." (2001) Proceedings of the National Academy of Sciences, USA, 98 (17): 9474- 9475

18] R. T. Premont, and R. A. Hall, "Identification of novel GPCR-interacting proteins." (2002) In: G Protein Pathways, Part A: Receptors. Methods in Enzymology, vol. 343 (R. Iyengar and J. D. Hildebrandt, eds.) Academic Press, San Diego, pp. 611-621.

19] K. L. Pierce, R. T. Premont and R. J. Lefkowitz, “Seven-Transmembrane Receptors.” (2002) Nature Reviews Molecular Cell Biology, 3: 639-650.

20] R. Schmalzigaug and R. T. Premont, "The GIT family of ARF GTPase-activating proteins." (2004) In: ARF Family GTPases. (R. A. Kahn, ed.). Proteins and Cell Regulation, volume 1 (A. Ridley and J. Frampton, series eds.). Kluwer Academic Publishers, Dordrecht, The Netherlands, pp 159-184.

21] R. R. Gainetdinov, R. T. Premont, L. M. Bohn, R. J. Lefkowitz and M. G. Caron, "Desensitization of G protein-coupled receptors and neuronal functions." (2004) Annual Review of Neuroscience, 27: 107-144.

22] R. T. Premont, "Once and Future Signaling: G protein-coupled receptor kinase control of neuronal sensitivity." (2005) NeuroMolecular Medicine, 7(1): 129-148.

23] R. T. Premont and R. R. Gainetdinov, "Physiological Roles of G protein-coupled Receptor Kinases and ." (2007) Annual Review of Physiology 69: 511-534.

24] R. T. Premont and R. Schmalzigaug, "Metastasis: Wherefore Arf Thou?" (2009) Current Biology 19(22): R1036-1038. Richard Premont, page 17

25] E. V. Gurevich, R. T. Premont, and R. Gainetdinov, “G protein-coupled receptor kinases: From molecules to diseases” (2015) FASEB Journal 29(2): 361-364. PMID: 25649814

26] J. B. Black, R. T. Premont, and Y. Daaka, “Feedback regulation of G protein-coupled receptor signaling by GRKs and arrestins.” (2016) Seminars in Cell and Developmental Biology 50: 95- 104. PMID: 26773211

27] W. Zhou, X. Li, and R. T. Premont, “Expanding functions of GIT family Arf GTPase- activating proteins, PIX Rho guanine nucleotide exchange factors, and GIT-PIX complexes.” (2016) Journal of Cell Science 129(10): 1963-1974. PMID: 27182061

28] W. Chen, R. T. Premont, R. A. Mook, Jr, and Jiangbo Wang, “Niclosamide: beyond an antihelminthic drug.” (2018) Cellular Signaling 41: 89-96. doi: 10.1016/j.cellsig.2017.04.001 PMID: 28389414

29] J. van Gastel, J. Boddaert, A. Jushaj, R. T. Premont, L. M. Luttrell, J. Janssens, B. Martin, and S. Maudsley, “GIT2 – a keystone in ageing and age-related disease.” (2018) Ageing Research Reviews 43: 46-63. doi: 10.1016/j.arr.2018.02.002 PMID: 29452267

30] J. Hendrickx, J. Van Gastel, H. Leysen, P. Santos-Otte, R. T. Premont, B. Martin, and S. Maudsley, “GRK5 - a functional bridge between cardiovascular and neurodegenerative disorders.” (2018) Frontiers in Pharmacology 9(1484): 1-23 doi: 10.3389/fphar.2018.01484 PMID: 30618771

31] R. T. Premont, J. D. Reynolds, R. Zhang and J. S. Stamler, “Role of Nitric Oxide Carried by Hemoglobin in Cardiovascular Physiology: Developments on a Three-Gas Respiratory Cycle.” (2020) Circulation Research 126(1): 129-158. doi: 10.1161/CIRCRESAHA.119.315626 PMID: 31590598

32] R T. Premont, and J. S. Stamler, “Essential role for hemoglobin bCys93 in cardiovascular physiology” (2020) Physiology (Bethesda) 35(4):234-243. doi: 10.1152/physiol.00040.2019. PMID: 32490751

33] R T. Premont, R. Zhang, J. R. Reynolds and J. S. Stamler, “Red blood cell-mediated S- nitrosohemoglobin-dependent vasodilation: lessons learned from a Cys93 knock-in mouse” (2020) Antioxidants and Redox Signaling (Forum Review Article) In Press Jun 27. doi: 10.1089/ars.2020.8153. Online ahead of print. PMID: 32597195

34] R. T. Premont, “Keys to the Kingdom: GPCR phosphorylation patterns direct β-arrestin” (2020) EMBO Reports 21(9):e51249 doi: 10.15252/embr.202051249 PMID: 32840039

Abstracts (recent):

U. Ahmed*, R. T. Premont, “GIT/PIX as a Rac Effector” (2016) Triangle Society for Neuroscience Annual Spring Conference, Research Triangle Park, NC (poster) * Duke undergraduate

Richard Premont, page 18

M. Jewell, M. Swiderska-Syn, G. Xie, G. Karaca, R. T. Premont, A. M. Diehl, “MMP9 is a potential mediator of TWEAK-Fn14 signaling in a rodent model of acute alcoholic steatohepatitis” (2016) Hepatology 64(1), Supp: 836A (poster)

R. T. Premont, M. Swiderska-Syn, M. Jewell, A. M. Diehl, “Hepatic stellate cell Yes-associated protein 1 (Yap1) is necessary for liver regeneration” (2016) Hepatology 64(1), Supp: 837A (poster)

R. Brudney*, R. T. Premont, “Analyzing novel interactions between Rho family GTPases and oligomeric GIT/PIX complexes. (2017) Triangle Society for Neuroscience Annual Spring Conference, Research Triangle Park, NC (poster) * Duke undergraduate

Y. Jung, S. Wang, M. Friedersdorf, R. T. Premont, S. H. Oh, J. Keene, and A. M. Diehl, “RNA- Binding Protein IGF2BP3 Regulates Cell Fate Decisions that Drive Cirrhosis Pathogenesis” (2017) Gastroenterology 152(5):S1073 (poster)

M. Jewell, G. C. de Castro., R. T. Premont, A. M. Diehl, “Fn14 and Wnt Signaling Pathway Crosstalk Controls Liver Progenitor Expansion in 3D Organoid Culture” (2017) Hepatology 66(1), Supp: 706A (poster)

S.-H. Oh, M. Swiderska-Syn, M. Jewell, R. T. Premont, Anna Mae Diehl, “Yap1 Activation Induces TGF-β Signaling and Epithelial-to-Mesenchymal Transition (EMT) in Regenerating Hepatocytes After Partial Hepatectomy” (2017) Hepatology 66(1), Supp: 1329A (poster)

G. D. Dalton, H. Navarro-Imaz, K. Du, S. Choi, Y. Rueda, O. Fresnedo, R. T. Premont, A. M. Diehl, “HDL Inhibits Hedgehog Signaling And Promotes Browning Of 3T3-L1 Adipocytes” (2018) Endocrine Society 2018 (poster)

J. Hyun, S.-H. Oh, R. T. Premont, C. Berg, A. M. Diehl, “YAP1-dependent Induction of IGF2BP3 Reprograms Hepatocytes Into Stem-like Cells During Liver Regeneration” (2018) Gastroenterology 154(6):S7 (short talk)

K. Du, R. T. Premont, J. Hyun, M. V. Machado, C. A. Moylan, M. Abdelmalek, C. D. Guy, A. M. Diehl, “Pathophysiological Role of Glutaminolysis in Human NAFLD Progression” (2018) Gastroenterology 154(6):S950-S951 (poster)

G. Dalton, S.-H. Oh, R. T. Premont, M. Matz, B. Loeffler, R. Gebhardt, A. M. Diehl, “Hedgehog Signaling Directly Regulates Metabolism and Proliferation in Hepatocytes and Is Critical For Normal Liver Regeneration Following Partial Hepatectomy in Mice” (2018) Gastroenterology 154(6):S166 (short talk)

R. T. Premont, M. L. Jewell, D. Hsu, C. D. Guy, A. M. Diehl, “Epithelial-Stromal Signaling in Fibrolamellar Hepatocellular Carcinoma” (2018) Gastroenterology 154(6):S172 (short talk)

K. Du, S. K. Chitneni, A. Suzuki, Y. Wang, R. Henao, J. Hyun, R. T. Premont, S. Naggie, C. A. Moylan, M.R. Bashir, M. F. Abdelmalek, and A. M. Diehl, “Increased Glutaminolysis Marks Active Scarring in Nonalcoholic Steatohepatitis Progression” (2019) Submitted to AASLD

S.-H. Oh, M. L. Jewell, R. T. Premont, J. Gibson, W. Glover, E. L. Wauthier, L. M. Reid, S. G. Gregory, D. S. Hsu, C. Guy, and A. M. Diehl, “Yap1 as a Therapeutic Target in Fibrolamellar Carcinoma” (2019) Submitted to AASLD

Richard Premont, page 19

Research Funding:

Currently Active:

1R01DK113159 D.C. Rockey (MUSC); Premont subcontract 09/20/17-08/31/21 NIH/NIDDK A Molecular Approach to the Pathogenesis of Portal Hypertension The goal of this project is to understand how GIT1 regulation of eNOS in liver sinusoidal endothelial cells contributes liver blood flow, and how dysfunctional of this system following liver injury contributes to portal hypertension. Role: co-PI

5 P01 HL075443 H.A. Rockman(Duke); Case (Stamler) subcontract 08/01/15 – 05/31/20 NIH / NHLBI Novel Mechanisms and Therapies in Heart Failure Project 3 (PI: Stamler): Regulation of Beta-Adrenergic Receptor Signaling by S-Nitrosylation Goal: To elucidate the role of post-translational modification by S-nitrosylation of b-arrestin, in signal transduction through G protein-coupled receptors and in particular through the b2-adrenergic receptor, which is a central player in cardiovascular function. Role: Co-Investigator

1 R01 DK119506 (PI: Stamler) 09/25/18 – 08/31/2023 NIH / NIDDK Novel Regulation of Renal Function by S-Nitrosylation Goal: To explore the role of PKM2 S-nitrosylation in renoprotection and develop a new class of drugs that targets S-nitroso-co-enzyme A reductase. Role: Co-Investigator

Completed Funding:

5R37-AA010154-20 (Anna Mae Diehl) 08/01/94 – 07/31/19 NIH/NIAAA TNF-Alpha and Recovery from Alcoholic Liver Disease Goal: To determine mechanisms to regulate liver regeneration in normal and alcohol-fed mice. Role: Research Scientist

5R01-DK077794-08 (Anna Mae Diehl) 04/01/07 - 03/31/17 NIH/NIDDK Hedgehog Signaling and Adult Liver Regeneration Goal: To determine how stellate cell-derived Hh ligands regulate viability and growth of ductular cells. Role: Research Scientist

1R56-DK106633-01 (Anna Mae DiehlI) 09/15/15 – 08/31/16 NIH/NIDDK Pathogenesis of NASH Cirrhosis Goal: To determine how pleiotrophin inhibits Hedgehog activity in myofibroblasts and to determine how pleiotrophin-mediated inhibition of Hedgehog in myofibroblasts reduces NASH cirrhosis. Role: Research Scientist

1R01-HL089263-01A2 (Julia Walker/Raymond Penn) 07/01/10 – 06/30/15 Richard Premont, page 20

NIH/NHLBI (subcontract from University of Maryland) Arrestin Selectivity for GPCR’s in Airway Smooth Muscle This study will provide a high mechanistic analysis of arrestin selectivity in ASM and identify approaches for differentially regulating receptors that mediate both contraction and relaxation of ASM.

DM102564 (Premont) 2/15/11 - 11/14/14 Department of Defense, CDMRP, Basic Research Award GIT2 gene: a key regulator of PTSD susceptibility versus resilience The objective of these proposed studies is to identify specific brain alterations that occur in a genetically-modified strain of mice lacking the signal integrator, GIT2, and to correlate these with human PTSD symptoms in order to assess the extent to which these mice are a useful animal model for this disorder.

1R21-MH090556-01A1 (Premont) 9/29/10 – 6/30/12 NIH/NIMH PTSD-like phenotype of mice lacking GIT2 The major aims of this project are to define the effect of SSRI treatment on fear behavior in GIT2- KO mice, to define the hormonal/neurochemical responses to stress in GIT2-KO mice, and to identify cellular signaling mechanisms through which GIT2 affects fear responses in mice.

3R01-DK077794-02S1 (Anna Mae Diehl) 09/20/09 - 02/28/11 NIH/NIDDK Hedgehog Signaling and Adult Liver Regeneration We wish to determine the role of Hedgehog signaling in vivo, and had proposed to use the Smoothened antagonist cyclopamine to treat mice systemically. We propose an alternative approach using conditional gene ablation to knock out the Smoothened gene only in response to treatment with the drug tamoxifen and in only those cells actively expressing smooth actin.

5R01-HL077185-06 (Neil Freedman) 08/01/05 - 07/31/11 NIH/NHLBI Desensitization of Vascular Receptor Tyrosine Kinases The major goals of this project are to determine the molecular mechanisms by which G protein- coupled receptor kinase-5 (GRK5) desensitizes the platelet-derived growth factor receptor- , and to determine the extent to which other cardiovascular receptor protein tyrosine kinases are regulated by the ubiquitously expressed GRKs.

0655454U (Premont) 7/1/2006 - 6/30/09 American Heart Association, Mid-Atlantic Affiliate Cardiac Receptor Regulation by GIT Proteins. The goals of this project are to determine the role of GIT proteins in regulating -adrenergic receptor trafficking and signaling in the hearts of GIT1 and GIT2 knockout and transgenic mice.

5R01 DA016347-05 (Premont) 4/1/04 - 3/31/09 NIH/NIDA Regulation by GRKs in Drug Abuse. The goals of this project are to identify the dopamine receptor subtypes that GRK6 regulates in striatum, to determine whether cocaine sensitization alters GRK6 levels or activity, and to identify the cellular locus of GRK6 regulation of dopamine receptors critical for behavioral sensitivity observed in GRK6 knockout mice.

5R01 GM59989-05 (Premont) 5/01/01 -4/30/07 NIH/NIGMS Signaling Pathways of ARF GTPases and ARF GAPs. Richard Premont, page 21

The goals of this project are to determine the role of GIT proteins and other ARF regulatory proteins in regulating -coupled receptor trafficking and receptor signaling, and to determine whether GIT proteins themselves respond to G protein-coupled receptor activation.

11/2020