Selected Publications


Tipifarnib as a Precision Therapy for HRAS-Mutant Head and Neck Squamous Cell Carcinomas.
Gilardi M, Wang Z, Proietto M, Chillà A, Calleja-Valera JL, Goto Y, Vanoni M, Janes M, Mikulski Z, Gualberto A, Molinolo AA, Ferrara N, Gutkind JS*, Burrows F.
Mol Cancer Ther. 19(9):1784-1796, 2020.

Muscarinic receptors promote castration-resistant growth of prostate cancer through a FAK-YAP signaling axis.
Goto Y, Ando T, Izumi H, Feng X, Arang N, Gilardi M, Wang Z, Ando K, Gutkind JS.
Oncogene. 39(20):4014-4027, 2020.

Pathway-specific genome editing of PI3K/mTOR tumor suppressor genes reveals that PTEN loss contributes to cetuximab resistance in head and neck cancer.
Izumi H, Wang Z, Goto Y, Ando T, Wu X, Zhang X, Li H, Johnson DE, Grandis JR, Gutkind JS.
Mol Cancer Ther. 19(7):1562-1571, 2020.

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., doi: 10.1158/1078-0432.CCR-20-3363. [Epub ahead of print], 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.

Illuminating G-Protein-Coupling Selectivity of GPCRs.
Inoue A, Raimondi F, Ngako Kadji FM, Singh G, Kishi T, Uwamizu A, Ono Y, Shinjo Y, Ishida S, Arang N, Kawakami K, Gutkind JS, Aoki J, Russell RB.
Cell. 177 (7), 1933-1947.e25, 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.

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.