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Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR.

Wingler LM, Skiba MA, McMahon C, Staus DP, Kleinhenz ALW, Suomivuori CM, Latorraca NR, Dror RO, Lefkowitz RJ, Kruse AC.

Science. 2020 Feb 21;367(6480):888-892. doi: 10.1126/science.aay9813.


Molecular mechanism of biased signaling in a prototypical G protein-coupled receptor.

Suomivuori CM, Latorraca NR, Wingler LM, Eismann S, King MC, Kleinhenz ALW, Skiba MA, Staus DP, Kruse AC, Lefkowitz RJ, Dror RO.

Science. 2020 Feb 21;367(6480):881-887. doi: 10.1126/science.aaz0326.


Structure of the M2 muscarinic receptor-β-arrestin complex in a lipid nanodisc.

Staus DP, Hu H, Robertson MJ, Kleinhenz ALW, Wingler LM, Capel WD, Latorraca NR, Lefkowitz RJ, Skiniotis G.

Nature. 2020 Jan 16. doi: 10.1038/s41586-020-1954-0. [Epub ahead of print]


Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex.

Nguyen AH, Thomsen ARB, Cahill TJ 3rd, Huang R, Huang LY, Marcink T, Clarke OB, Heissel S, Masoudi A, Ben-Hail D, Samaan F, Dandey VP, Tan YZ, Hong C, Mahoney JP, Triest S, Little J 4th, Chen X, Sunahara R, Steyaert J, Molina H, Yu Z, des Georges A, Lefkowitz RJ.

Nat Struct Mol Biol. 2019 Dec;26(12):1123-1131. doi: 10.1038/s41594-019-0330-y. Epub 2019 Nov 18.


Saving the Endangered Physician-Scientist - A Plan for Accelerating Medical Breakthroughs.

Jain MK, Cheung VG, Utz PJ, Kobilka BK, Yamada T, Lefkowitz R.

N Engl J Med. 2019 Aug 1;381(5):399-402. doi: 10.1056/NEJMp1904482. No abstract available.


Detergent- and phospholipid-based reconstitution systems have differential effects on constitutive activity of G-protein-coupled receptors.

Staus DP, Wingler LM, Pichugin D, Prosser RS, Lefkowitz RJ.

J Biol Chem. 2019 Sep 6;294(36):13218-13223. doi: 10.1074/jbc.AC119.009848. Epub 2019 Jul 30.


Mechanism of β2AR regulation by an intracellular positive allosteric modulator.

Liu X, Masoudi A, Kahsai AW, Huang LY, Pani B, Staus DP, Shim PJ, Hirata K, Simhal RK, Schwalb AM, Rambarat PK, Ahn S, Lefkowitz RJ, Kobilka B.

Science. 2019 Jun 28;364(6447):1283-1287. doi: 10.1126/science.aaw8981. Epub 2019 Jun 27.


V211D Mutation in MEK1 Causes Resistance to MEK Inhibitors in Colon Cancer.

Gao Y, Maria A, Na N, da Cruz Paula A, Gorelick AN, Hechtman JF, Carson J, Lefkowitz RA, Weigelt B, Taylor BS, Zhao H, Reis-Filho JS, de Stanchina E, Rosen N, Yao Z, Yaeger R.

Cancer Discov. 2019 Sep;9(9):1182-1191. doi: 10.1158/2159-8290.CD-19-0356. Epub 2019 Jun 21.


Rates and occupational characteristics of international seafarers with mental illness.

Lefkowitz RY, Slade MD, Redlich CA.

Occup Med (Lond). 2019 Jun 24;69(4):279-282. doi: 10.1093/occmed/kqz069.


Distinctive Activation Mechanism for Angiotensin Receptor Revealed by a Synthetic Nanobody.

Wingler LM, McMahon C, Staus DP, Lefkowitz RJ, Kruse AC.

Cell. 2019 Jan 24;176(3):479-490.e12. doi: 10.1016/j.cell.2018.12.006. Epub 2019 Jan 10.


Angiotensin Analogs with Divergent Bias Stabilize Distinct Receptor Conformations.

Wingler LM, Elgeti M, Hilger D, Latorraca NR, Lerch MT, Staus DP, Dror RO, Kobilka BK, Hubbell WL, Lefkowitz RJ.

Cell. 2019 Jan 24;176(3):468-478.e11. doi: 10.1016/j.cell.2018.12.005. Epub 2019 Jan 10.


β-arrestin 1 regulates β2-adrenergic receptor-mediated skeletal muscle hypertrophy and contractility.

Kim J, Grotegut CA, Wisler JW, Li T, Mao L, Chen M, Chen W, Rosenberg PB, Rockman HA, Lefkowitz RJ.

Skelet Muscle. 2018 Dec 27;8(1):39. doi: 10.1186/s13395-018-0184-8.


Sorafenib for Advanced and Refractory Desmoid Tumors.

Gounder MM, Mahoney MR, Van Tine BA, Ravi V, Attia S, Deshpande HA, Gupta AA, Milhem MM, Conry RM, Movva S, Pishvaian MJ, Riedel RF, Sabagh T, Tap WD, Horvat N, Basch E, Schwartz LH, Maki RG, Agaram NP, Lefkowitz RA, Mazaheri Y, Yamashita R, Wright JJ, Dueck AC, Schwartz GK.

N Engl J Med. 2018 Dec 20;379(25):2417-2428. doi: 10.1056/NEJMoa1805052.


EGFR and MET Amplifications Determine Response to HER2 Inhibition in ERBB2-Amplified Esophagogastric Cancer.

Sanchez-Vega F, Hechtman JF, Castel P, Ku GY, Tuvy Y, Won H, Fong CJ, Bouvier N, Nanjangud GJ, Soong J, Vakiani E, Schattner M, Kelsen DP, Lefkowitz RA, Brown K, Lacouture ME, Capanu M, Mattar M, Qeriqi B, Cecchi F, Tian Y, Hembrough T, Nagy RJ, Lanman RB, Larson SM, Pandit-Taskar N, Schöder H, Iacobuzio-Donahue CA, Ilson DH, Weber WA, Berger MF, de Stanchina E, Taylor BS, Lewis JS, Solit DB, Carrasquillo JA, Scaltriti M, Schultz N, Janjigian YY.

Cancer Discov. 2019 Feb;9(2):199-209. doi: 10.1158/2159-8290.CD-18-0598. Epub 2018 Nov 21.


Association of MRI T2 Signal Intensity With Desmoid Tumor Progression During Active Observation: A Retrospective Cohort Study.

Cassidy MR, Lefkowitz RA, Long N, Qin LX, Kirane A, Sbaity E, Hameed M, Coit DG, Brennan MF, Singer S, Crago AM.

Ann Surg. 2018 Nov 9. doi: 10.1097/SLA.0000000000003073. [Epub ahead of print]


Manifold roles of β-arrestins in GPCR signaling elucidated with siRNA and CRISPR/Cas9.

Luttrell LM, Wang J, Plouffe B, Smith JS, Yamani L, Kaur S, Jean-Charles PY, Gauthier C, Lee MH, Pani B, Kim J, Ahn S, Rajagopal S, Reiter E, Bouvier M, Shenoy SK, Laporte SA, Rockman HA, Lefkowitz RJ.

Sci Signal. 2018 Sep 25;11(549). pii: eaat7650. doi: 10.1126/scisignal.aat7650.


Bronchial hyper-responsiveness: a technical update.

Borak J, Lefkowitz RY, Linde B.

Occup Med (Lond). 2018 Nov 16;68(8):519-522. doi: 10.1093/occmed/kqy122.


G protein-coupled receptor kinases (GRKs) orchestrate biased agonism at the β2-adrenergic receptor.

Choi M, Staus DP, Wingler LM, Ahn S, Pani B, Capel WD, Lefkowitz RJ.

Sci Signal. 2018 Aug 21;11(544). pii: eaar7084. doi: 10.1126/scisignal.aar7084.


A Phase II Trial of Sorafenib and Dacarbazine for Leiomyosarcoma, Synovial Sarcoma, and Malignant Peripheral Nerve Sheath Tumors.

D'Adamo DR, Dickson MA, Keohan ML, Carvajal RD, Hensley ML, Hirst CM, Ezeoke MO, Ahn L, Qin LX, Antonescu CR, Lefkowitz RA, Maki RG, Schwartz GK, Tap WD.

Oncologist. 2019 Jun;24(6):857-863. doi: 10.1634/theoncologist.2018-0160. Epub 2018 Aug 20.


GPCR signaling: conformational activation of arrestins.

Kahsai AW, Pani B, Lefkowitz RJ.

Cell Res. 2018 Aug;28(8):783-784. doi: 10.1038/s41422-018-0067-x. No abstract available.


Biased G Protein-Coupled Receptor Signaling: Changing the Paradigm of Drug Discovery.

Wisler JW, Rockman HA, Lefkowitz RJ.

Circulation. 2018 May 29;137(22):2315-2317. doi: 10.1161/CIRCULATIONAHA.117.028194. Review. No abstract available.


Small-Molecule Positive Allosteric Modulators of the β2-Adrenoceptor Isolated from DNA-Encoded Libraries.

Ahn S, Pani B, Kahsai AW, Olsen EK, Husemoen G, Vestergaard M, Jin L, Zhao S, Wingler LM, Rambarat PK, Simhal RK, Xu TT, Sun LD, Shim PJ, Staus DP, Huang LY, Franch T, Chen X, Lefkowitz RJ.

Mol Pharmacol. 2018 Aug;94(2):850-861. doi: 10.1124/mol.118.111948. Epub 2018 May 16.


Sortase ligation enables homogeneous GPCR phosphorylation to reveal diversity in β-arrestin coupling.

Staus DP, Wingler LM, Choi M, Pani B, Manglik A, Kruse AC, Lefkowitz RJ.

Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):3834-3839. doi: 10.1073/pnas.1722336115. Epub 2018 Mar 26.


Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade.

Ariyan CE, Brady MS, Siegelbaum RH, Hu J, Bello DM, Rand J, Fisher C, Lefkowitz RA, Panageas KS, Pulitzer M, Vignali M, Emerson R, Tipton C, Robins H, Merghoub T, Yuan J, Jungbluth A, Blando J, Sharma P, Rudensky AY, Wolchok JD, Allison JP.

Cancer Immunol Res. 2018 Feb;6(2):189-200. doi: 10.1158/2326-6066.CIR-17-0356. Epub 2018 Jan 16.


Biased signalling: from simple switches to allosteric microprocessors.

Smith JS, Lefkowitz RJ, Rajagopal S.

Nat Rev Drug Discov. 2018 Apr;17(4):243-260. doi: 10.1038/nrd.2017.229. Epub 2018 Jan 5. Review.


β-Arrestin2 mediates progression of murine primary myelofibrosis.

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, Lefkowitz RJ.

JCI Insight. 2017 Dec 21;2(24). pii: 98094. doi: 10.1172/jci.insight.98094.


Injury, illness, and disability risk in American seafarers.

Lefkowitz RY, Slade MD, Redlich CA.

Am J Ind Med. 2018 Feb;61(2):120-129. doi: 10.1002/ajim.22802. Epub 2017 Dec 17.


The Limits of Pattern Recognition: Nodular Lung Disease in a Syrian Refugee.

Lefkowitz RY, Mitma AA, Altassan K, Redlich CA.

Ann Am Thorac Soc. 2017 Oct;14(10):1591-1594. doi: 10.1513/AnnalsATS.201702-163CC. No abstract available.


Mechanism of intracellular allosteric β2AR antagonist revealed by X-ray crystal structure.

Liu X, Ahn S, Kahsai AW, Meng KC, Latorraca NR, Pani B, Venkatakrishnan AJ, Masoudi A, Weis WI, Dror RO, Chen X, Lefkowitz RJ, Kobilka BK.

Nature. 2017 Aug 24;548(7668):480-484. doi: 10.1038/nature23652. Epub 2017 Aug 16.


A Serendipitous Scientist.

Lefkowitz RJ.

Annu Rev Pharmacol Toxicol. 2018 Jan 6;58:17-32. doi: 10.1146/annurev-pharmtox-010617-053149. Epub 2017 Jul 17.


β-Arrestin2 Couples Metabotropic Glutamate Receptor 5 to Neuronal Protein Synthesis and Is a Potential Target to Treat Fragile X.

Stoppel LJ, Auerbach BD, Senter RK, Preza AR, Lefkowitz RJ, Bear MF.

Cell Rep. 2017 Mar 21;18(12):2807-2814. doi: 10.1016/j.celrep.2017.02.075.


Distinct conformations of GPCR-β-arrestin complexes mediate desensitization, signaling, and endocytosis.

Cahill TJ 3rd, Thomsen AR, Tarrasch JT, Plouffe B, Nguyen AH, Yang F, Huang LY, Kahsai AW, Bassoni DL, Gavino BJ, Lamerdin JE, Triest S, Shukla AK, Berger B, Little J 4th, Antar A, Blanc A, Qu CX, Chen X, Kawakami K, Inoue A, Aoki J, Steyaert J, Sun JP, Bouvier M, Skiniotis G, Lefkowitz RJ.

Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):2562-2567. doi: 10.1073/pnas.1701529114. Epub 2017 Feb 21.


Allosteric "beta-blocker" isolated from a DNA-encoded small molecule library.

Ahn S, Kahsai AW, Pani B, Wang QT, Zhao S, Wall AL, Strachan RT, Staus DP, Wingler LM, Sun LD, Sinnaeve J, Choi M, Cho T, Xu TT, Hansen GM, Burnett MB, Lamerdin JE, Bassoni DL, Gavino BJ, Husemoen G, Olsen EK, Franch T, Costanzi S, Chen X, Lefkowitz RJ.

Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1708-1713. doi: 10.1073/pnas.1620645114. Epub 2017 Jan 27.


Clinical features and response to systemic therapy in a historical cohort of advanced or unresectable mucosal melanoma.

Shoushtari AN, Bluth MJ, Goldman DA, Bitas C, Lefkowitz RA, Postow MA, Munhoz RR, Buchar G, Hester RH, Romero JA, Fitzpatrick LJ, Weiser MR, Panageas KS, Wolchok JD, Chapman PB, Carvajal RD.

Melanoma Res. 2017 Feb;27(1):57-64. doi: 10.1097/CMR.0000000000000306.


Myxoinflammatory Fibroblastic Sarcoma: Clinical, Imaging, Management and Outcome in 29 Patients.

Kumar R, Lefkowitz RA, Neto AD.

J Comput Assist Tomogr. 2017 Jan;41(1):104-115. doi: 10.1097/RCT.0000000000000490.


GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling.

Thomsen ARB, Plouffe B, Cahill TJ 3rd, Shukla AK, Tarrasch JT, Dosey AM, Kahsai AW, Strachan RT, Pani B, Mahoney JP, Huang L, Breton B, Heydenreich FM, Sunahara RK, Skiniotis G, Bouvier M, Lefkowitz RJ.

Cell. 2016 Aug 11;166(4):907-919. doi: 10.1016/j.cell.2016.07.004. Epub 2016 Aug 4.


Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation.

Staus DP, Strachan RT, Manglik A, Pani B, Kahsai AW, Kim TH, Wingler LM, Ahn S, Chatterjee A, Masoudi A, Kruse AC, Pardon E, Steyaert J, Weis WI, Prosser RS, Kobilka BK, Costa T, Lefkowitz RJ.

Nature. 2016 Jul 21;535(7612):448-52. Epub 2016 Jul 13.


Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor.

Kahsai AW, Wisler JW, Lee J, Ahn S, Cahill Iii TJ, Dennison SM, Staus DP, Thomsen AR, Anasti KM, Pani B, Wingler LM, Desai H, Bompiani KM, Strachan RT, Qin X, Alam SM, Sullenger BA, Lefkowitz RJ.

Nat Chem Biol. 2016 Sep;12(9):709-16. doi: 10.1038/nchembio.2126. Epub 2016 Jul 11.


Thrombin generation assay in untreated whole human blood.

Modestino A, Tyndall M, Yu J, Lefkowitz RB, Schmid-Schönbein GW, Heller MJ.

Electrophoresis. 2016 Aug;37(15-16):2248-56. doi: 10.1002/elps.201600061.


Patterns of Energy Drink Use and Associated Symptoms Among a Population of Connecticut Factory Workers.

Pensa MA, Galusha DH, Stowe MH, Lefkowitz RY, Redlich CA.

J Occup Environ Med. 2016 May;58(5):e188-90. doi: 10.1097/JOM.0000000000000728. No abstract available.


Infiltrative pattern of carcinomatosis in extremity muscles on MRI.

Soliman F, Hwang S, Landa J, Lefkowitz RA, Panicek DM.

Clin Imaging. 2016 May-Jun;40(3):451-5. doi: 10.1016/j.clinimag.2015.12.012. Epub 2016 Jan 15.


Acute myonecrosis on MRI: etiologies in an oncological cohort and assessment of interobserver variability.

Cunningham J, Sharma R, Kirzner A, Hwang S, Lefkowitz R, Greenspan D, Shapoval A, Panicek DM.

Skeletal Radiol. 2016 Aug;45(8):1069-78. doi: 10.1007/s00256-016-2389-4. Epub 2016 Apr 22.


Paederus dermatitis in a seafarer diagnosed via telemedicine collaboration.

Lefkowitz RY, Ridge GE.

J Travel Med. 2016 Mar 28;23(3). pii: taw017. doi: 10.1093/jtm/taw017. Print 2016 Mar.


Clinical validation of a noninvasive prenatal test for genomewide detection of fetal copy number variants.

Lefkowitz RB, Tynan JA, Liu T, Wu Y, Mazloom AR, Almasri E, Hogg G, Angkachatchai V, Zhao C, Grosu DS, McLennan G, Ehrich M.

Am J Obstet Gynecol. 2016 Aug;215(2):227.e1-227.e16. doi: 10.1016/j.ajog.2016.02.030. Epub 2016 Feb 17.


Alfred Goodman Gilman (1941-2015).

Lefkowitz RJ.

Nature. 2016 Jan 21;529(7586):284. doi: 10.1038/529284a. No abstract available.


Bronchial hyperresponsiveness.

Borak J, Lefkowitz RY.

Occup Med (Lond). 2016 Mar;66(2):95-105. doi: 10.1093/occmed/kqv158. Epub 2015 Nov 20. Review.


The role of β-arrestin2-dependent signaling in thoracic aortic aneurysm formation in a murine model of Marfan syndrome.

Wisler JW, Harris EM, Raisch M, Mao L, Kim J, Rockman HA, Lefkowitz RJ.

Am J Physiol Heart Circ Physiol. 2015 Nov;309(9):H1516-27. doi: 10.1152/ajpheart.00291.2015. Epub 2015 Sep 14.


Inspiring the next generation of physician-scientists.

Lefkowitz RJ.

J Clin Invest. 2015 Aug 3;125(8):2905-7. doi: 10.1172/JCI83222. Epub 2015 Aug 3.


A Phase I/II Study for Analytic Validation of 89Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer.

Pandit-Taskar N, O'Donoghue JA, Durack JC, Lyashchenko SK, Cheal SM, Beylergil V, Lefkowitz RA, Carrasquillo JA, Martinez DF, Fung AM, Solomon SB, Gönen M, Heller G, Loda M, Nanus DM, Tagawa ST, Feldman JL, Osborne JR, Lewis JS, Reuter VE, Weber WA, Bander NH, Scher HI, Larson SM, Morris MJ.

Clin Cancer Res. 2015 Dec 1;21(23):5277-85. doi: 10.1158/1078-0432.CCR-15-0552. Epub 2015 Jul 14.


Risk factors for merchant seafarer repatriation due to injury or illness at sea.

Lefkowitz RY, Slade MD, Redlich CA.

Int Marit Health. 2015;66(2):61-6. doi: 10.5603/IMH.2015.0016.

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