Gerard P. Zambetti, PhD
Gerard P. Zambetti, PhD

Gerard P. Zambetti, PhD

Member, St. Jude Faculty

  • Vice President and Director of Academic Programs in Biomedical Sciences
  • Associate Director, Education and Training, Comprehensive Cancer Center

Departments

Education

MS – Emory University, Atlanta, Georgia
PhD – University of Florida, Gainesville

Research Interests

  • Function of wild-type and mutant p53 in tumor suppression and oncogenesis
  • Regulation of cell cycle, cell survival and differentiation
  • The biology of pediatric adrenocortical carcinoma

Selected Publications

Qian M, Cao X, Devidas M, Yang W, Cheng C, Carroll A, Heerema N, Zhang H, Moriyama T, Gastier-Foster JM, Xu H, Raetz EA, Larsen E, Winick N, Bowman WP, Martin PL, Mardis E, Fulton R, Zambetti GP, Borowitz M, Wood BL, Nichols KE, Carroll WL, Pui CH, Mullighan CG, Evans WE, Hunger SP, Relling MV, Loh ML, Yang JJ. TP53 germline variations influence the predisposition and prognosis of B-cell acute lymphoblastic leukemia in children. J Clin Oncol 2017 (in press).

Pinto EM, Rodriguez-Galindo C, Pounds S, Wang L, Garfinkle E,  Jenkins J, Neale G, Lam C, Levy CF, Grimberg A, Pappo A, Zambetti GP*,  Ribeiro RC*. Clinical, Biological and Outcome Features of Children with Adrenocortical Tumors without Germline TP53 Mutations. J Clin Oncol Oct 2017.

Jung S, Nagy Z, Fassnacht M, Zambetti G, Weiss M, Reincke M, Igaz P, Beuschlein F, Hantel C. Preclinical progress and first translational research steps for a novel liposomal chemotherapy against adrenocortical carcinoma. Endocrine-Related Cancer 23:825-837, 2016.

Pinto EM, Rodriguez-Galindo C, Choi JK, Pounds S, Liu Z, Neale G, Finkelstein D, Pappo AS, Figueiredo B, Ribeiro RC*, Zambetti GP*. Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children’s Oncology Group Study. Clin Cancer Res 22:6247-6255, 2016.

Beuschlein F, Jakoby J, Mentz S, Zambetti G, Jung S, Reincke M, Süss R, Hantel C. IGF1-R inhibition and liposomal doxorubicin: progress in preclinical evaluation for the treatment of adrenocortical carcinoma. Mol Cell Endocrinol 428:82-88, 2016.

Pinto EM, Chen X, Easton J, Liu Z, Pounds S, Finkelstein D, Rodriguez-Galindo C, Yunes A, Lund T, Dyer MA, Pappo A, Zhang J*, Downing JR, Ribeiro RC*, Zambetti GP*. The Mutational Landscape of Pediatric Adrenocortical Tumors. Nature Commun 6:6302, 2015.

Wasserman JD, Novokmet A, Eichler-Jonsson C, Ribeiro RC, Rodriguez-Galindo C, Zambetti GP, Malkin D. TP53 mutations associated with pediatric adrenocortical carcinoma: descriptive analysis and functional characterization of a large international cohort. J Clin Oncol 33:602-9, 2015.

Zambetti GP. Expanding the reach of the p53 signaling pathway. Cell Death & Diff 21:505-506, 2014.

Huether R, Dong L, Chen X, Wu G, Parker M, Wei L, Ma J, Edmonson M, Hedlund E, Rusch M, Shurtleff  S, Mulder H, Boggs K, Vadodaria B, Cheng  J, Yergeau D, Song G, Becksfort J, Cai Z, Lemmon G, Dang J, Weber C, Walsh M, Gedman SL, Faber Z, Easton J, Gruber T, Kriwacki R, Partridge J, Ding L, Wilson R, Mardis E, Mullighan C, Gilbertson R, Baker S, Zambetti GP, Ellison D, Downing J, Zhang J. The landscape of somatic mutations in epigenetic regulators across 1000 pediatric cancer genomes. Nature Commun 5:3630, 2014.

Burikhanov R,  Shrestha-Bhattara T, Hebbar  N, Qiu S, Zhao Y, Zambetti GP, Rangnekar VM. Paracrine Apoptotic Effect of p53 Mediated by Tumor Suppressor Par-4 Secretion. Cell Reports 6:271-277, 2014.

Cam M, Bid HK, Linlin X, Zambetti GP, Houghton PJ, Cam H. p53/TAp63 and AKT regulate mTORC1 signaling through two independent parallel pathways in the presence of DNA damage.  J Biol Chem 289:4083-94, 2014.

Lieu KG, Shim EH, Tao T, Zambetti GP, Jans DA. An Importin β-binding-like Domain within the Etoposide-Induced Tumor Suppressor Ei24 Confers a Novel Ability to Inhibit Nuclear Import. J Cell Biol 205:301-312, 2014.

van der Deen M, Taipaleenmäki H, Zhang Y, Teplyuk NM, Cinghu S, Gupta A, Nathan SS, Leong DT, Cool SM, Ito Y, Salto-Tellez M, Zielenska M, Squire JA, Bae SC, Hesse E, Lian JB, Stein JL, Zambetti GP,  Jones SN,  Galindo M, Stein GS,van Wijnen AJ. MicroRNA-34c inversely couples the biological functions of the bone-specific transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma. J Biol Chem 288:21307-21319, 2013.

Custódio G, Parise GA, Kiesel Filho N, Komechen H, Sabbaga CC, Rosati R, Grisa L, Parise I, Pianovski MA, Fiori C, Ledesma JA, Barbosa RS, Figueiredo F, Sade ER, Ibañez HC, Arram S, Stinghen ST, Mengarelli LR, Figueiredo M, Carvalho D, Avilla S, Woiski TD, Poncio LC, Lima G, Pontarolo R, Lalli E, Zambetti GP, Ribeiro RC, Figueiredo BC. Impact of Neonatal Screening and Surveillance for the TP53 R337H Mutation on Early Detection of Childhood Adrenocortical Tumors. J Clin Oncol 31:2619-2626, 2013.

Pinto EM, Morton CL, Rodriguez-Galindo C, McGregor L, Davidoff AM, Mercer KS, Debelenko L, Billups CA, Ribeiro RC, Zambetti GP. Establishment and Characterization of the First Pediatric Adrenocortical Carcinoma Xenograft Model Identifies Topotecan as a Potential Chemotherapeutic Agent. Clin Cancer Res 19:1740-1747, 2013 (Featured article).

Bean GR, Ganesan YT, Dong Y, Takeda S, Liu H, Chan PM, Huang Y, Chodosh LA, Zambetti GP, Hsieh JJ, Chang E. Puma and Bim are required for oncogene inactivation-induced apoptosis. Science Signaling 6:ra20, 2013.

Parker M, Chen X, Bahrami A, Dalton J, Rusch M, Wu G, Easton J, Cheung NK, Dyer M, Marids E, Wilson R,  Mullighan C, Gilbertson R, Baker S, Zambetti GP, Ellison D, Downing JR, Zhang J. Assessing telomere content in pediatric cancers using whole-genome sequencing data. Genome Biology 13:R113, 2012.

Garrison SP, Phillips DC, Jeffers JR, Chipuk JE, Parsons MJ, Opferman JT, Green DR, Zambetti GP. Genetically defining the mechanism of Puma- and Bim- induced apoptosis. Cell Death Diff 19:642-649, 2012.

Pinto EM, Ribeiro RC, Li J, Taja-Chayeb L, Carrasco LF, de Lourdes Peña-Torres M, Vidal-Millán S, Maldonado-Mtz H, Dueñas-González A, McGregor L, Zambetti GP. An identical, complex TP53 mutation arising independently in two unrelated families with diverse cancer profiles: The complexity of interpreting cancer risk in carriers. Oncogenesis 1:e1, 2012.

Show More

Wasserman JD, Zambetti GP, Malkin D. Towards an understanding of the role of p53 in adrenocortical carcinogenesis. Mol Cell Endocrinol 351(1):101-10, 2012.

Ribeiro RC, Pinto EM, Zambetti GP, Rodriguez-Galindo C. The International Pediatric Adrenocortical Tumor Registry initiative: contributions to clinical, biological, and treatment advances in pediatric adrenocortical tumors. Mol Cell Endocrinol October 23, 2011.

Kuribayashi K, Finnberg N, Jeffers JR, Zambetti GP, El-Deiry WS. The relative contribution of pro-apoptotic p53-target genes in the triggering of apoptosis following DNA damage in vitro and in vivo. Cell Cycle 10(14):2380-9, 2011.

Zambetti GP. Diving into in vivo p53 tumor suppressor studies using a new platform mouse model. Cell Cycle10(16), 2011.

Pinto EM, Ribeiro RC, Figueiredo BC, Zambetti GP. TP53-associated pediatric malignancies. Genes Cancer2(4):485-90, 2011.

Stadanlick JE, Zhang Z, Lee SY, Hemann M, Biery M, Carleton MO, Zambetti GP, Anderson SJ, Oravecz T, Wiest DL. Developmental arrest of T cells in Rpl22-deficient mice is dependent upon multiple p53 effectors. J Immunol 127(2):664-75, 2011.

Mandl A, Pham LH, Toth K, Zambetti G, Erhardt P. Puma deletion delays cardiac dysfunction in murine heart failure models through attenuation of apoptosis. Circulation 124(1):31-104, 2011.

Link DC, Schuettpelz LG, Shen D, Wang J, Walter MJ, Kulkarni S, Payton JE, Ivanovich J, Goodfellow PJ, Le Beau M, Koboldt DC, Dooling DJ, Fulton RS, Bender RHF, Fulton LL, Delehaunty KD, Fronick CC, Appelbaum EL, Schmidt H, Abbott R, O'Laughlin M, Chen K, McLellan MD, Varghese N, Nagarajan R, Heath S, Graubert TA, Ding L, Ley TJ, Zambetti GP, Wilson RK,Mardis ER. Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. JAMA 305(15):1568-1576, 2011.

Boechat GAP, Stinghen ST, Custodio G, Pianovski MAD, Figueiredo FRdO, Jenkins J, Zambetti GP, Ribeiro RC, Figueiredo BC. Placental alkaline phosphatase in pediatric adrenocortical cancer. J Pediatr Hematol Oncol33(4):149-53, 2011.

El Wakil A, Doghman M, De Late PL, Zambetti GP, Figueiredo BC, Lalli E. Genetics and genomics of childhood adrenocortical tumors. Mol Cell Endocrinol336(1-2):169-173, 2011.

Coloff JL, Mason EF, Altman BJ, Gerriets VA, Liu T, Nichols AN, Zhao Y, Wofford JA, Jacobs SR, Ilkayeva O, Garrison SP, Zambetti GP, Rathmell JC. Akt requires glucose metabolism to suppress puma expression and prevent apoptosis of leukemic T cells. J Biol Chem286(7):5921-33, 2011.

Bernstein AI, Garrison SP, Zambetti GP, O'Malley KL. 6-OHDA generated ROS induces DNA damage and p53-and PUMA-dependent cell death. Mol Neurodegener 6(2):1-13 2011.

Kasper LH, Thomas MC, Zambetti GP, Brindle PK. Double null cells reveal that CBP and p300 are dispensable for p53 targets p21 and Mdm2 but variably required for target genes of other signaling pathways. Cell Cycle 10(2), 2011.

Garrison SP, Thornton JA, Hacker H, Webby R, Rehg JE, Parganas E, Zambetti GP, Tuomanen EI. The p53-target gene puma drives neutrophil-mediated protection against lethal bacterial sepsis. PLoS Pathog 6(12):e1001240, 2010.

Pinto EM, Ribeiro RC, Kletter GB, Lawrence JP, Jenkins JJ, Wang J, Shurtleff S, McGregor L, Kriwacki RW, Zambetti GP. Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor. Fam Cancer October 22, 2010.

Liu D, Ou L, Clemenson GD, Chao C, Lutske ME, Zambetti GP, Gage FH, Xu Y. Puma is required for p53-induced depletion of adult stem cells. Nat Cell Biol12(10):993-U226, 2010.

Ribeiro RC, Pinto EM, Zambetti GP. Familial predisposition to adrenocortical tumors: clinical and biological features and management strategies. Best Pract Res Clin Endocrinol Metab 24(3):477-90, 2010.

Steimer DA, Boyd K, Takeuchi O, Fisher JK, ZambettiGP, Opferman JT. Selective roles for anti-apoptotic MCL-1 during granulocyte development and macrophage effector function. Blood 2009 (in press).

Russell-Swetek A, West AN, Mintern JE, Jenkins J, Rodriguez-Galindo C, Ribeiro R, Zambetti GP. Identification of a novel TP53 germline mutation E285V in a rare case of paediatric adrenocortical carcinoma and choroid plexus carcinoma. J Med Genet 45:603-606, 2008.

Assumpção JG, Seidinger AL, Mastellaro MJ, Ribeiro RC, Zambetti GP, Ganti R, Srivastava K, Shurtleff S, Pei D, Zeferino LC, Dufloth RM, Brandalise SR, Yunes JA. Association of the germline TP53 R337H mutation with breast cancer in southern Brazil. BMC Cancer 8:357, 2008.

Garrison SP, Jeffers JR, Yang C, Nilsson JA, Rehg J, Yue W, Yu J, Zhang L, Sample JT, Cleveland JL, Zambetti GP. Selection against PUMA gene expression in Myc-driven B cell lymphomagenesis. Mol Cell Biol 28:5391-5402, 2008. *Featured in Nature Reviews of Cancer 8:568-69, 2008.

Qui W, Carson-Walter EB, Liu H, Epperly M, Greenberger JS, Zambetti GP, Zhang L, Yu J. The BH3-only Protein PUMA regulates intestinal stem cell radiosensitivity. Cell Stem Cell 2:576-583, 2008. *See Preview Cell Stem Cell 2: 517-18, 2008.

Rosati R, Cerrato F, Doghman M, Pianovski M, Parise GA, Custódio G, Zambetti GP, Riccio A, Ribeiro RC, Figueiredo BC, Lalli E. High frequency of loss of heterozygosity at 11p15 and IGF2 overexpression is not associated with clinical outcome in childhood adrenocortical tumors positive for the R337H TP53mutation. Cancer Genet Cytogenet 186: 19-24, 2008.

Zambetti GP. The p53 mutation “Gradient Effect” and its clinical implications. J Cell Phys 213:370-73, 2007.

Doghman M, Karpova T, Rodrigues G, Arhatte M, De Moura J, Cavalli LR, Virolle V, Barbry P, Zambetti GP, Figueiredo BC, Heckert LL, Lalli E. Increased Steroidogenic Factor-1 dosage triggers adrenocortical cell proliferation and cancer. Mol Endo 21:2968-87, 2007.

Doghman M, Arhatte M, Thibout H, Rodrigues G, De Moura J, Grosso S, Laurent M, Mas JC, Bongain A, Zambetti GP, Figueiredo BC, Auberger P, Martinerie C, Lalli E. NOV/CCN3 is a selective pro-apoptotic factor for adrenocortical cells downregulated in childhood adrenocortical tumors. J Clin Endo Metab 92:3253-60, 2007.

Ribeiro R, Figueiredo BC, Rodriguez-Galindo C, Mastellaro MJ, West AN, Kriwacki R, Zambetti GP. Germline TP53 R337H mutation is not sufficient to determine Li-Fraumeni or Li-Fraumeni-like syndrome. Can Lett247:353-55, 2007.

West AN, Neale GA, Pounds S, Figueredo BC, Rodriguez Galindo C, Pianovski MA, Oliveira Filho AG, Malkin D, Lalli E, Ribeiro R, Zambetti GP. Gene Expression Profiling of Childhood Adrenocortical Tumors. Cancer Res 67:600-608, 2007.

Wu B, Qiu W, Wang P, Yue W, Yu H, Cheng T, Zambetti GP, Zhang L, Yu J. PUMA is a mediator of p53-independent intestinal apoptosis induced by ischemia reperfusion. Gut 56:645-54, 2007.

Broniscer A, Baker SJ, West AN, Fraser MM, Kocak M, Dalton J, Zambetti GP, Gajjar A, Gilbertson RJ, Fuller CE Clinical and molecular characteristics of malignant transformation of low-grade glioma in children: the St. Jude Children’s Research Hospital experience. J Clin Oncol 25:682-89, 2007.

Pianovski MA, Cavalli LR, Figueiredo BC, Santos SC, Doghman M,Ribeiro RC, Michalkiewicz E, Zambetti GP, Haddad BR, Lalli E. SF-1 Overexpression in Childhood Adrenocortical Tumors. Int J Cancer 42:1040-43, 2006.

Zambetti GP, Horwitz EM, Schipani E. Skeletons in the p53 tumor suppressor closet: Genetic evidence that p53 blocks bone differentiation and development. J Cell Biol 172:795-97, 2006.

Kim H, Tu HC, Rafiuddin-Shah M, Jeffers JR, Zambetti GP, Hsieh J, Cheng EHY. Hierarchical Regulation of Mitochondrion-Dependent Apoptosis by BCL-2 Subfamilies. Nat Cell Biol 8:1348-58, 2006. *See News & Views, Nat Cell Biol 8:1317-19.

Opferman JT, Zambetti GP. Translational Research? Ribosome integrity and a new p53 tumor suppressor checkpoint. Cell Death Diff 13:898-901, 2006.

West AN, Ribeiro RC, Jenkins J, Rodriguez-Galindo C, Figueiredo BC, Kriwacki R, Zambetti GP. Identification of a Novel Germline Variant Hotspot Mutant p53-R175L in Pediatric Adrenal Cortical Carcinoma. Can Res 66:5056-62, 2006.

Toth A, Jeffers JR, Nickson P, Min JY, Morgan JP, Zambetti GP, Erhardt P. Targeted Deletion of Puma Attenuates Cardiomyocyte Death and Improves Cardiac Function during Ischemia/reperfusion. Am J Physiol Heart Circ Physiol 291:52-60, 2006. *See Editorial Focus.

Figueiredo BC, Sandrini R, Zambetti GP, Pereira RM, Cheng C, Lacerda L, Pianovski MA, Michalkiewicz E, Jenkins J, Rodriguez-Galindo C, Mastellaro MJ, Vianna S, Sandrini F, Arram SIB, Ribeiro RC. Penetrance of Adrenocortical Tumors Associated with the Germline TP53 R337H Mutation. J Med Genet 43:91-96, 2006.

Wu WS, Heinrichs S, Xu D, Garrison SP, Zambetti GP, Adams JM, Look AT. Slug Antagonizes p53-Mediated Apoptosis of Hematopoietic Progenitors by Repressing Puma. Cell 123:641-53, 2005. *Cover, see Previews.

Lozano G, Zambetti GP. Gankyrin: An intriguing name for a novel regulator of p53 and RB. Cancer Cell 8:3-4, 2005.

Myers MC, Wang J, Zambetti GP, Appella DH. Targeting mutant p53 using a new family of small molecules derived from serine. J Am Chem Soc 127:6152-53, 2005.

Lozano G, Zambetti GP. What have animal models taught us about the p53 pathway? J Path 205:206-20, 2005.

Figueiredo BC, Cavalli LR, Pianovski MA, Lalli E, Sandrini R, Ribeiro RC, Zambetti GP, DeLacerda L, Rodrigues GA, Haddad BR. Amplification of the steroidogenic factor 1 (SF-1) gene in childhood adrenocortical tumors. J Clin Endo Metab 90:615-19, 2005.

Rodriguez-Galindo C, de Figueiredo BC, Zambetti GP, Ribeiro RC. Biology, clinical characteristics and management of adrenocortical tumors in children. Pediatric Blood & Cancer 44:1-9, 2005.

Jeffers JR, Parganas E, Lee Y, Yang C, Wang J, Brennan J, MacLean KH, Han J, Chittenden T, Ihle JN, McKinnon PJ, Cleveland JL, Zambetti GP. Puma is an essential mediator of p53-dependent and -independent apoptotic pathways. Cancer Cell 4:321-328, 2003. *See Previews, Cancer Cell 4:248-49.

Lee AS, Galea C, DiGiammarino EL, Jun B, Murti G, Ribeiro RC, Zambetti GP, Schultz CP, Kriwacki RW. Structural polymorphism of the p53 tetramerization domain. J Mol Biol 327:699-709, 2003.

Weber JD, Zambetti GP. Renewing the Debate Over the p53 Apoptotic Response. Cell Death Diff 10:409-12, 2003.

Zambetti GP, Kastan MB. Overcoming p53 Parking Problems. Cell 112:1-2, 2003.

DiGiammarino EL, Lee AS, Cadwell C, Zhang W, Bothner B, Ribeiro RC, Zambetti GP, Kriwacki RW. Evidence for a novel molecular mechanism of tumorigenesis: pH-dependent destabilization of the p53 tetramer. Nat Struct Biol 9:12-16, 2002. *News & Views, Nat Med 8: 21-23, 2002.

DiGiammarino EL, Lee AS, Cadwell C, Zhang W, Bothner B, Ribeiro RC, Zambetti G, Kriwacki RW. A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer. Nat Struct Biol 9(1):12-16, 2002.

Last update: November 2017