Selected Publications


The GPCR-Gαs-PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure.
Wu VH, Yung BS, Faraji F, Saddawi-Konefka R, Wang Z, Wenzel AT, Song MJ, Pagadala MS, Clubb LM, Chiou J, Sinha S, Matic M, Raimondi F, Hoang TS, Berdeaux R, Vignali DAA, Iglesias-Bartolome R, Carter H, Ruppin E, Mesirov JP, Gutkind JS.
Nat Immunol. 24(8):1318-1330, 2023.

High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma.
Arang N, Lubrano S, Ceribelli M, Rigiracciolo DC, Saddawi-Konefka R, Faraji F, Ramirez SI, Kim D, Tosto FA, Stevenson E, Zhou Y, Wang Z, Bogomolovas J, Molinolo AA, Swaney DL, Krogan NJ, Yang J, Coma S, Pachter JA, Aplin AE, Alessi DR, Thomas CJ, Gutkind JS.
Cell Rep Med. 4(11):101244, 2023.

Lymphatic-Preserving Treatment Sequencing with Immune Checkpoint Inhibition Unleashes cDC1-Dependent Antitumor Immunity in HNSCC.
Saddawi-Konefka R, O’Farrell A, Faraji F, Clubb L, Allevato MM, Jensen SM, Yung BS, Wang Z, Wu VH, Anang N-A, Al Msari R, Schokrpur S, Pietryga IF, Molinolo AA, Mesirov JP, Simo B, Fox B, Bui JD, Sharabi A, Cohen EEW, Califano JA, Gutkind JS.
Nature Commun. 13(1):4298, 2022.

Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions.
Gutkind JS, Molinolo A, Wu X, Wang Z, Nachmanson D, Harismendy O, Alexandrov LB, Wuertz BR, Ondrey FG, Laronde DM, Rock LD, Rosin MP, Coffey CS, Butler VD, Bengtson L, Hsu CH, Bauman JE, Hewitt SM, Cohen EE, Chow HHS, Lippman SM, Szabo E.
JCI Insight. 6(17):e147096, 2021.

Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer.
Wang Z, Goto Y, Allevato M, Wu V, Saddawi-Konefka R, Gilardi M, Alvarado D, Yung B, O’Farrell A, Molinolo A, Duvvuri U, Grandis J, Califano J, Cohen E, Gutkind JS.
Nature Commun. 177 (7), 12(1):2383,2021.

Synthetic Lethal Screens Reveal Co-Targeting FAK and MEK as a Multimodal Precision Therapy for GNAQ-Driven Uveal Melanoma.
Paradis JS, Acosta M, Saddawi-Konefka R, Kishore A, Lubrano S, Gomes FG, Arang N, Tiago M, Coma S, Wu X, Ford K, Day CP, Merlino G, Mali P, Pachter JA, Sato T, Aplin AE, Gutkind JS.
Clin Cancer Res., 27(11):3190-3200, 2021.

A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.
Swaney DL, Ramms DJ, Wang Z, Park J, Goto Y, Soucheray M, Bhola N, Kim K, Zheng F, Foussard H, Zeng Y, O’Keefe R, Jin N, VanLandingham NK, Von Dollen J, Herrington KA, Bouhaddou M, McGregor M, Jimenez-Morales D, Obernier K, Kreisberg JF, Kim M, Johnson DE, Jura N, Grandis JR, Gutkind JS, Ideker T, and Krogan N.
Science.74(6563):eabf2911, 2021.

Illuminating the Onco-GPCRome: Novel G protein-coupled receptor-driven oncocrine networks and targets for cancer immunotherapy.
Wu V, Yeerna H, Nohata N, Chiou J, Harismendy O, Raimondi F, Inoue A, Russell RB, Tamayo P, Gutkind JS.
J Biol Chem. 294(29):11062-11086, 2019.

A Platform of Synthetic Lethal Gene Interaction Networks Reveals That the GNAQ Uveal Melanoma Oncogene Controls the Hippo Pathway Through FAK.
Feng X, Arang N, Rigiracciolo DC, Lee JS, Yeerna H, Wang Z, Lubrano S, Kishore A, Pachter JA, König GM, Maggiolini M, Kostenis E, Schlaepfer DD, Tamayo P, Chen Q, Ruppin E, Gutkind JS.
Cancer Cell. 35 (3), 457-472.e5, 2019.



Ras-dependent activation of MAP kinase pathway mediated by G-proteinβγ subunits.
Crespo P, Xu N, Simonds WF, Gutkind JS.
Nature, 369:418-420, 1994.

The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK (SAPK) signaling pathway.
Coso O, Chiariello M, Yu J-C, Crespo P, Teramoto H, Xu N, Miki T, Gutkind JS.
Cell, 81:1137-1148, 1995.

Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase g.
Lopez-Ilasaca M, Crespo P, Pellici PG, Gutkind JS., and Wetzker R.
Science, 275:394-397, 1997.

Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product.
Crespo P, Schuebel KE, Ostrom AA, Gutkind JS, Bustelo XR.
Nature, 385:169-172, 1997.

Regulation of c-myc expression by PDGF through Rho GTPases.
Chiariello M, Marinissen MJ, Gutkind JS.
Nature Cell Biol., 3:580-586, 2001.

Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi’s sarcomagenesis and can promote the tumorigenic potential of viral latent genes.
Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, Li Y, Ray PE, Gutkind JS.
Cancer Cell, 3:23-36, 2003.

Akt plays a central role in sarcomagenesis induced by Kaposi’s sarcoma herpesvirus-encoded G protein-coupled receptor.
Sodhi A, Montaner S, Patel V, Román JG, Li Y, Sausville EA, Sawai ET, Gutkind JS.
Proc. Natl. Acad. Sci. U.S.A., 101:4821-4826, 2004.

Prostaglandin E2 promotes colon cancer cell growth through a novel Gs-axin-β-catenin signaling axis.
Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS.
Science, 310:1504-1510, 2005.

mTOR, a molecular target in squamous cell carcinomas of the head and neck.
Amornphimoltham P, Patel V, Sodhi A, Nikitakis NG, Sauk JJ, Sausville EA, Molinolo AA, Gutkind JS.
Cancer Research, 65:9953-9961, 2005.

The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi’s Sarcoma Associated Herpesvirus G Protein-Coupled Receptor.
Sodhi A, Chaisuparat R, Hu J, Ramsdell AK, Manning BD, Sausville EA, Sawai ET, Molinolo A, Gutkind JS, Montaner S.
Cancer Cell, 10:133-143, 2006.

Semaphorin4D provides a link between anon guidance processes and tumor-induced angiogenesiS,
Basile JR, Castilho RM, Williams VP, and Gutkind JS.
PNAS, 103:9017-9022, 2006.

Dissecting the Akt/mTOR signaling network: Emerging results from the Head and Neck Cancer Tissue Array Initiative.
Molinolo AA, Hewitt S, Amornphimoltham P, Keelawat S, Rangdaeng S, Meneses García A, Raimondi AR, Jufe R, Itoiz M, Gao Y, Saranath D, Kaleebi GS, Yoo GH, Leak L, Myers EM, Shintani S, Wong D, Massey HD, Yeudall WA, Lonardo F, Ensley J, Gutkind JS.
Clinical Cancer Research, 13:4964-4973, 2007.

mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging.
Castilho R.M, Squarize C.H, Chodosh L.A, Williams B.O., and Gutkind JS.
Cell Stem Cell, 5:279-289, 2009.

Targeting mTOR by rapamycin prevents tumor progression in an oral-specific chemical carcinogenesis model.
Czerninski R, Amornphimoltham P, Patel V, Molinolo AA, and Gutkind JS.
Cancer Prevention Research, 2:27-36, 2009.

PI3Kγ mediates Kaposi’s sarcoma-associated herpesvirus vGPCR-induced sarcomagenesis.
Martin D, Galisteo R, Molinolo AA, Wetzker R, Hirsch E, Gutkind JS.
Cancer Cell, 19: 805-813, 2011.

Decreased lymphangiogenesis and lymph node metastasis by mTOR inhibition in head and neck cancer.
Patel V, Marsh CA, Dorsam RT, Masedunskas A, Amornphimoltham P, Nathan CO, Singh B, Weigert R, Molinolo AA, and Gutkind JS.
Cancer Research, 71:7103-7112, 2011.

A synthetic biology approach reveals a CXCR4-G13-Rho signaling axis driving transendothelial migration of metastatic breast cancer cells.
Yagi H, Tan W, Dillenburg-Pilla P, Armando S, Amornphimoltham P, Simaan M, Weigert R, Molinolo AA, Bouvier M, and Gutkind JS.
Science Signaling, 4:ra60, 2011.

Metformin prevents the development of oral squamous cell carcinomas from carcinogen-induced premalignant lesions.
Vitale-Cross L, Molinolo AA, Martin D, Younis RH, Maruyama T, Patel P, Chen W, Schneider A, and Gutkind JS.
Cancer Prevention Research, 5:562-573, 2012.

mTOR inhibition protects from epithelial stem cell senescence and radiation-induced mucositis.
Iglesias-Bartolome R, Patel V, Cotrim A, Leelahavanichkul K, Molinolo AA, Mitchell JB, Gutkind JS.
Cell Stem Cell, 11:401-414, 2012.

A genome-wide RNAi screen reveals a Trio-regulated Rho GTPase circuitry transducing GPCR-initiated mitogenic signals.
Vaqué JP, Dorsam RT, Feng X, Iglesias-Bartolome R, Forsthoefel DJ, Chen Q, Debant A, Seeger MA, Ksander BR, Teramoto H, Gutkind JS.
Molecular Cell, 49:94-108, 2013.

The emerging mutational landscape of G-proteins and G-protein-coupled receptors in cancer. (Analysis)
O’Hayre M, Vázquez-Prado J, Kufareva I, Stawiski EW, Handel T, Seshagiri S, Gutkind JS.
Nature Reviews Cancer 13(6):412-424, 2013.

Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a Trio-regulated Rho GTPase signaling circuitry.
Feng X, Degese MS, Iglesias-Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, Zaidi MR, Ksander BR, Merlino M, Sodhi A, Chen Q, Gutkind JS.
Cancer Cell, 25:831-845, 2014.

mTOR inhibition overcomes cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations.
Wang Z, Martin D, Molinolo AA, Patel V, Iglesias-Bartolome R, Degese MS, Vitale-Cross L, Chen Q, Gutkind JS.
J Natl. Cancer Inst., 106(9), 2014.

RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock.
Mikelis CM, Simaan M, Ando K, Fukuhara S, Sakurai A, Amornphimoltham P, Masedunskas A, Weigert R, Chavakis T, Adams R, Offermanns S, Mochizuki N, Zheng Y, Gutkind JS.
Nature Commun, 6:6725, 2015.

Inactivation of a Gαs-PKA tumor suppressor pathway in skin stem cells initiates basal-cell carcinogenesis.
Iglesias-Bartolome R, Torres D, Marone R, Feng X, Martin D, Simaan M, Chen M, Weinstein LS, Taylor SS, Molinolo AA, Gutkind JS.
Nature Cell Biol., 17:793-803, 2015.

Prevention of tumor growth driven by PIK3CA and HPV oncogenes by targeting mTOR signaling with metformin in oral squamous carcinomas expressing OCT3.
Madera D, Vitale-Cross L, Martin D, Schneider A, Molinolo AA, Gangane N, Carey TE, McHugh JB, Komarck CM, Walline HM, William WN Jr, Seethala RR, Ferris RL, Gutkind JS.
Cancer Prevention Res., PMID25681087. 8:197-207, 2015.

Genetic identification of SEMA3F as an anti-lymphangiogenic metastasis suppressor gene in head and neck squamous carcinoma.
Doçi CL, Mikelis C.M, Lionakis MS, Molinolo AA, and Gutkind JS.
Cancer Research, 75: 2937-2948, 2015.

Expression of an active Gαs mutant in skeletal stem cells is sufficient and necessary for fibrous dysplasia initiation and maintenance.
Zhao X, Deng P, Iglesias-Bartolome R, Amornphimoltham P, Steffen DJ, Jin Y, Molinolo AA, de Castro LF, Ovejero D, Yuan Q, Chen Q., Han X, Bai D, Taylor SS, Yang Y, Collins MT, and Gutkind JS.
Proc Natl Acad Sci U.S.A. 115:E428-E437, 2017.

Genetic evidence that β-arrestins are dispensable for the initiation of β2-adrenergic receptor signaling to ERK.
O’Hayre M, Eichel K, Avino S., Zhao X, Steffen DJ, Feng X, Kawakami K, Aoki J, Messer K, Sunahara R, Inoue A, von Zastrow M, and Gutkind JS.
Science Signaling. 10(484) pii: eaal3395, 2017.

Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer.
Carter H, Marty R, Hofree M, Gross A, Jensen J, Fisch KM, Wu X, DeBoever C, Van Nostrand EL, Song Y, Wheeler E, Kreisberg JF, Lippman SM, Yeo G, Gutkind JS, Ideker T
Cancer Discovery. 7:410-423, 2017.

Assembly and Activation of the Hippo Signalome by the FAT1 Tumor Suppressor.
Martin D, Degese MS, Vitale-Cross L, Iglesias-Bartolome R, Callejas Valera JL, Wang Z. Feng X, Yeerna H, Vadmal V, Moroishi C, Thorne R, Zaida M, Siegele B., Cheong S.C, Molinolo AA, Samuels Y, Tamayo P, Guan KL, Lippman SM, Lyons JG, Gutkind JS.
Nature Comm., 9:2372, 2018.

Arrestins as rheostats of GPCR signaling.
Gutkind JS., Kostenis E.
Nat. ReV Mol. Cell Biol., 10.1038/s41580-018-0041-y, 2018 Jul 19.

Transcriptional signature primes human oral mucosa for rapid wound healing.
Iglesias-Bartolome R, Uchiyama A, Molinolo AA, Abusleme L, Brooks SR, Callejas-Valera JL, Edwards D, Doci C, Asselin-Labat ML, Onaitis MW, Moutsopoulos NM, Gutkind* JS., Morraso* MI (*Co-corresponding authors).
Sci. Transl. Med., eaap8798, 2018 10.

4E-BP1 Is a Tumor Suppressor Protein Reactivated by mTOR Inhibition in Head and Neck Cancer.
Wang Z, Feng X, Molinolo AA, Martin D, Vitale-Cross L, Nohata N, Ando M, Wahba A, Amornphimoltham P, Wu X, Gilardi M, Allevato M, Wu V, Steffen DJ, Tofilon P, Sonenberg N, Califano J, Chen Q, Lippman SM, Gutkind JS.
Cancer Res. 2019.

Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial.
Day TA, Shirai K, O’Brien PE, Matheus MG, Godwin K, Sood AJ, Kompelli A, Vick JA, Martin D, Vitale-Cross L, Callejas-Varela JL, Wang Z, Wu X, Harismendy O, Molinolo AA, Lippman SM, Van Waes C, Szabo E, Gutkind JS.
Clin Cancer Res. 25(4):1156-1164, 2019

Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.
Wang Z, Wu VH, Allevato MM, Gilardi M, He Y, Callejas-Valera JL, Vitale-Cross L, Martin D, Amornphimoltham P, Mcdermott J, Yung BS, Goto Y, Molinolo AA, Sharabi AB, Cohen EEW, Chen Q, Lyons JG, Alexandrov LB, Gutkind JS.
Nature Comm., 10(1):5546, 2019.

Gαs-Protein Kinase A (PKA) Pathway Signalopathies: The Emerging Genetic Landscape and Therapeutic Potential of Human Diseases Driven by Aberrant Gαs-PKA Signaling.
Ramms DJ, Raimondi F, Arang N, Herberg FW, Taylor SS, Gutkind JS.
Pharmacol Rev., 73(4):155-197, 2021.

Interpretation of cancer mutations using a multi-scale map of protein systems.
Zheng F, Kelly MR, Ramms DJ, Heintschel M, Tao K, Tutuncuoglu B, Lee J, Ono K, Foussard H, Chen M, Herrington KA, Silva E, Liu S, Chen J, Churas C, Wilson N, Kratz A, Park J, Kuenzi B, Yu MK, Licon K, Pratt D, Kreisberg JF, Kim M, Swaney DL, Nan X, Fraley SI, Gutkind JS, Krogan NJ, and Ideker T.
Science., 374(6563):eabf3067, 2021.

Challenges and Emerging Opportunities for Targeting mTOR in Cancer.
Wood KC, Gutkind JS.
Cancer Res., 82(21):3884-3887. 2022.

Gαs is dispensable for β-arrestin coupling but dictates GRK selectivity and is predominant for gene expression regulation by β2-adrenergic receptor.
Burghi V, Paradis JS, Officer A, Adame-Garcia SR, Wu X, Matthees ESF, Barsi-Rhyne B, Ramms DJ, Clubb L, Acosta M, Tamayo P, Bouvier M, Inoue A, von Zastrow M, Hoffmann C, Gutkind JS.
J Biol Chem., 299(11):105293, 2023.