Andrew Davidoff, MD

Andrew M. Davidoff, MD

Member, St. Jude Faculty
Chair, Surgery
St. Jude Endowed Chair in Surgical Research
Division Chief, General Pediatric Surgery
Director, Surgical Research

Departments

Surgery

Contact Information

Andrew Davidoff, MD
Surgery
MS133, Room B3019
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
Email: andrew.davidoff@stjude.org
Phone: (901) 595-4060
FAX: (901) 595-2207

Education

MD - University of Pennsylvania, Philadelphia, Pennsylvania


Research Interests

I am a board certified pediatric surgeon, having completed my residency training in general surgery at Duke University Medical Center and general and thoracic pediatric surgery at the Children's Hospital of Philadelphia. My academic interests at St Jude are focused on clinical and translational investigation and treatment of pediatric solid tumors, neuroblastoma, in particular. My research is focused on the development of new strategies for the treatment of neuroblastoma (and other tumor types). These include angiogenesis inhibition and gene therapy for cancer treatment. In addition, I have a significant effort in the area of gene therapy for monogenetic disorders, hemophilia, in particular.

Angiogenesis appears to be required for the neoplastic growth of tumor cells, making it a potential target for anti-cancer strategies. Long-term expression of an angiogenesis inhibitor is likely to be required for the successful treatment of cancer. Therefore, gene therapy-mediated delivery of these agents is an alternative way to provide long-term expression of these therapeutic proteins. Vectors expressing a number of different angiogenesis inhibitors are currently being designed and tested in vitro and in vivo in murine models of pediatric tumors.

Gene transfer for monogenetic disorders is an attractive approach in which long-term correction of the disease phenotype may be achieved after a single intervention or vector administration. Extensive pre-clinical and clinical studies are ongoing evaluating the safety and efficacy of adeno-associated virus (AAV) vectors.


Selected Publications

Davidoff AM, Fernandez-Pineda I, Santana VM, Shochat SJ. The role of neoadjuvant chemotherapy in children with malignant solid tumors. Semin Pediatr Surg 21(1):88-99, 2012.

Davidoff AM. Neuroblastoma. Semin Pediatr Surg 21(1):2-14, 2012.

Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C, O'Beirne J, Smith K, Pasi J, Glader B, Rustagi P, Ng CY, Kay MA, Zhou J, Spence Y, Morton CL, Allay J, Coleman J, Sleep S, Cunningham JM, Srivastava D, Basner-Tschakarjan E, Mingozzi F, High KA, Gray JT, Reiss UM, Nienhuis AW, Davidoff AM. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 365(25):2357-65, 2011.

Denbo JW, Williams RF, Orr WS, Sims TL, Ng CY, Zhou J, Spence Y, Morton CL, Nathwani AC, Duntsch C, Pfeffer LM, Davidoff AM. Continuous local delivery of interferon-ß stabilizes tumor vasculature in an orthotopic glioblastoma xenograft resection model. Surgery 150(3):497-504, 2011.

Mueller S, Yang X, Sottero TL, Gragg A, Prasad G, Polley MY, Weiss WA, Matthay KK, Davidoff AM, DuBois SG, Haas-Kogan DA. Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma: efficacy and underlying mechanisms. Cancer Lett 306(2):223-229, 2011.

Nathwani AC, Rosales C, McIntosh J, Rastegarlari G, Nathwani D, Raj D, Nawathe S, Waddington SN, Bronson R, Jackson S, Donahue RE, High KA, Mingozzi F, Ng CYC, Zhou J, Spence Y, McCarville MB, Valentine M, Allay J, Coleman J, Sleep S, Gray JT, Nienhuis AW, Davidoff AM. Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol Ther 19(5):876-85, 2011.

Allay JA, Sleep S, Long S, Tillman DM, Clark R, Carney G, Fagone P, McIntosh JH, Nienhuis AW, Davidoff AM, Nathwani AC, Gray JT. Good manufacturing practice production of self-complementary serotype 8 adeno-associated viral vector for a hemophilia B clinical trial. Hum Gene Ther 22(5):595-604, 2011.

Bray I, Tivnan A, Bryan K, Foley NH, Watters KM, Tracey L, Davidoff AM, Stallings RL. MicroRNA-542-5p as a novel tumor suppressor in neuroblastoma. Cancer Let 303(1):56-64, 2011.

Tivnan A, Tracey L, Buckley PG, Alcock LC, Davidoff AM, Stallings RL. MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma. BMC Cancer 11:33, 2011.

Tivnan A, Foley NH, Tracey L, Davidoff AM, Stallings RL. MicroRNA-184-mediated inhibition of tumour growth in an orthotopic murine model of neuroblastoma. Anticancer Res 30(11):4391-4395, 2010.

Myers AL, Williams RF, Ng CY, Hartwich JE, Davidoff AM. Bevacizumab-induced tumor vessel remodeling in rhabdomyosarcoma xenografts increases the effectiveness of adjuvant ionizing radiation. J Pediatr Surg 45(6):1080-1085, 2010.

McGee MC, Hamner JB, Williams RF, Rosati SF, Sims TL, Ng CY, Gaber MW, Calabrese C, Wu J, Nathwani AC, Duntsch C, Merchant TE, Davidoff AM. Improved intratumoral oxygenation through vascular normalization increases glioma sensitivity to ionizing radiation. Int J Radiat Oncol Biol Phys 76(5):1537-1545, 2010.

Sims TL, McGee M, Williams RF, Myers AL, Tracey L, Hamner JB, Ng C, Wu J, Gaber MW, McCarville B, Nathwani AC, Davidoff AM. IFN-{beta} restricts tumor growth and sensitizes alveolar rhabdomyosarcoma to ionizing radiation. Mol Cancer Ther March 2, 2010.

Nathwani AC, Cochrane M, McIntosh J, Gray JT, Ng CYC, Zhou J, Davidoff AM. Enhancing adeno-associated viral vector mediated gene transfer. Gene Therapy 16:60-69, 2009.

Sims TL, Hamner JB, Bush RA, Fischer PE, Kim SU, Aboody KS, McCarville MB, Danks MK, Davidoff AM. Neural progenitor cell-mediated delivery of osteoprotegerin limits disease progression in a pre-clinical model of neuroblastoma bone metastasis. J Pediatr Surg 44:204-210, 2009.

Hamner JB, Sims TL, Cutshaw A, Dickson PV, Rosati S, McGee M, Ng CY, Davidoff AM. The efficacy of combination therapy using adeno-associated virus--interferon beta and trichostatin A in vitro and in a murine model of neuroblastoma. J Pediatr Surg 43:177-82, 2008.

Davidoff AM, Giel DW, Jones DP, Jenkins JJ, Krasin MJ, Hoffer FA, Williams MA, Dome JS. The feasibility and outcome of nephron-sparing surgery for children with bilateral Wilms tumor: the St. Jude Children's Research Hospital experience: 1999-2006. Cancer 112:2060-2070, 2008.

Sims TL, Williams RF, Ng CYC, Rosati, SF, Spence Y, Davidoff AM. Bevacizumab suppresses neuroblastoma progression in the setting of minimal disease. Surgery 144:269-275. 2008.

Sims TL, Hamner JB, Bush RA, Williams RF, Zhou J, Kim SU, Aboody KS, Danks MK, Davidoff AM. Neural progenitor cell-mediated delivery of interferon-beta improves neuroblastoma response to cyclophosphamide. Ann Surg Oncol 15:3258-3267. 2008.

Rosati SF, Williams RF, Nunnally LC, McGee MC, Sims TL, Zhou J, Fan M, Ng CYC, Nathwani AC, Stewart CF, Pfeffer LM, Davidoff AM. Interferon-β sensitizes neuroblastoma to the anti-tumor activity of temozolomide through the modulation of O6-methylguanine-DNA methyltransferase expression. Mol Cancer Ther 7:3852-3858, 2008.

Hamner JB, Dickson PV, Sims TL, Zhou J, Spence Y, Ng CY, Davidoff AM. Bortezomib inhibits angiogenesis and reduces tumor burden in a murine model of neuroblastoma. Surgery 142:185-91, 2007.

Dickson PV, Hamner JB, Sims TL, Fraga CH, Ng CYC, Rajasekeran S, Hagedorn NL, McCarville MB, Stewart CF, Davidoff AM. Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy. Clin Cancer Res 13:3942-3950, 2007.

Dickson PV, Hamner JB, Streck CJ, Ng CYC, McCarville MB, Calabrese C, Gilbertson RJ, Stewart CF, Wilson CM, Gaber MW, Pfeffer LM, Skapek SX, Nathwani AC, Davidoff AM. Continuous delivery of interferon-β promotes sustained maturation of intratumoral vasculature. Mol Cancer Res 5:531-542, 2007.

Nathwani AC, McIntosh J, Gray JT, Ng CYC, Zhou J, Spence Y, Gray E, Cochrane M, Davidoff AM. Efficient transduction of the liver after a single peripheral vein infusion of self complementary AAV vector mediates stable therapeutic levels of human FIX in nonhuman primates. Blood 109:1414-1421, 2007.

Benjamin R, Khwaja A, Singh N, McIntosh J, Meager A, Wadhwa M, Streck CJ, Ng C, Davidoff AM, Nathwani AC. Continuous delivery of human type I interferons (α/β) has significant activity against acute myeloid leukemia cells in vitro and in a xenograft model. Blood 109:1244-1247, 2007.

Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, Oh EY, Gaber MW, Finklestein D, Allen M, Frank A, Bayazitov IT, Zakharenko SS, Gajjar A, Davidoff A, Gilbertson RJ. A perivascular niche for brain tumor stem cells. Cancer Cell 11:69-82, 2007.

Dickson PV, Hamner JB, Burger RA, Garcia E, Ouma AA, Kim SU, Ng CYC, Gray JT, Aboody KS, Danks MK, Davidoff AM. Intravascular administration of tumor tropic neural progenitor cells permits targeted delivery of interferon-β and restricts tumor growth in a murine model of disseminated neuroblastoma. J Pediatr Surg 42:48-53, 2007.

Dickson PV, Hagedorn NL, Hamner JB, Fraga CH, Ng CYC, Stewart CF, Davidoff AM. Interferon-β mediated vessel stabilization improves delivery and efficacy of systemically administered topotecan in a murine neuroblastoma model. J Pediatr Surg 42:160-165, 2007.

Nathwani AC, Gray JT, Ng CYC, Zhou J, Spence Y, Waddington S, Tuddenham EGD, Kemball-Cook G, McIntosh J, Boon-Spijker M, Mertens K, Davidoff AM. Self complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. Blood 107:2653-2661, 2006.

McCarville ME, Streck CJ, Dickson PV, Li CS, Nathwani AC, Davidoff AM. Quantitative, non-invasive measurement of intratumoral blood flow using contrast enhanced ultrasonography to assess the efficacy of angiogenesis inhibitors in vivo. Radiology 240:73-81, 2006.

Streck CJ, Ng CYC, Dickson P, McCarville ME, Zhou J, Gray JT, Nathwani AC, Davidoff AM. Anti-tumor efficacy of interferon-B is mediated through angiogenesis inhibition in murine neuroblastoma models. Clin Cancer Res 11:6020-6029, 2005.

Streck CJ, Dickson PV, Ng CYC, Zhou JF, Hall MT, Gray JT, Nathwani AC, Davidoff AM. Anti-tumor efficacy of AAV-mediated systemic delivery of interferon-B. Cancer Gene Ther 13:99-106, 2006.

Streck CJ, Ng CYC, Zhang Y, Zhou J, Nathwani AC, Davidoff AM. Interferon-mediated anti-angiogenic therapy for neuroblastoma. Cancer Lett 228:163-170, 2005.

Davidoff AM, Gray J, Ng CYC, Zhang Y, Zhou J, Spence Y, Bakar Y, Nathwani AC. Adeno-associated viral vectors pseudotyped with serotype 8 capsid transduce murine and nonhuman primate liver more efficiently and through a different mechanism than vectors based on serotypes 2 and 5. Mol Ther 6:875-888, 2005.

Davidoff AM, Ng CYC, Zhang Y, Streck C, Mabry S, Barton S, Baudino T, Zhou J, Kerbel RS, Vanin EF, Nathwani AC. Decoy receptor titering is required to inhibit tumor angiogenesis while avoiding adversely altering VEGF bioavailability. Mol Ther 11:300-310, 2005.

Streck CJ, Zhang Y, Miyamoto R, Zhou J, Ng CYC, Nathwani AC, Davidoff AM. Restriction of neuroblastoma angiogenesis and growth by interferon-a/b. Surgery 136:183-189, 2004.

Streck CJ, Zhou J, Ng CY, Zhang Y, Nathwani AC, Davidoff AM. Long-term recombinant adeno-associated virus-mediated liver-generated expression of an angiogenesis inhibitor improves survival in mice with disseminated neuroblastoma. J Am Coll Surg 199:78-86, 2004.

Davidoff AM, Ng CYC, Zhou J, Spence Y, Nathwani AC. Sex significantly influences transduction of murine liver by recombinant adeno-associated viral vectors through an androgen dependent pathway. Blood 102:480-488, 2003.

Spurbeck WW, Ng CYC, Strom T, Vanin EF, Davidoff AM. Enforced expression of tissue inhibitor of matrix metalloproteinase-3 affects functional capillary morphogenesis and inhibits tumor growth in a murine tumor model. Blood 100:3361-3368, 2002.

Nathwani AC, Davidoff AM, Hanawa H, Hu Y, Hoffer FA, Nikanorov A, Slaughter C, Ng CYC, Zhou J, Lozier JN, Mandrell TD, Vanin EF, Nienhuis AW. Sustained high level expression of human FIX following liver targeted delivery of recombinant adeno-associated virus encoding the human FIX gene in rhesus macaques. Blood 100:1662-1669, 2002.

Davidoff AM, Nathwani AC, Spurbeck WW, Ng CYC, Zhou J, Vanin EF. rAAV-mediated long-term liver-generated expression of an angiogenesis inhibitor can restrict renal tumor growth in mice. Cancer Res 62:3077-3083, 2002.

Davidoff AM, Ng CYC, Brown P, Leary MA, Spurbeck WW, Zhou J, Horwitz E, Vanin EF, Nienhuis AW. Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice. Clin Cancer Res 7:2870-2879, 2001.

Nathwani AC, Davidoff AM, Hanawa H, Zhou JF, Vanin EF, Nienhuis AW. Factors influencing in-vivo transduction by recombinant adeno-associated viral vectors expressing the human factor IX cDNA. Blood 97:1258-1265, 2001.


Last update: January 2012