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Faculty Detail    
Name JAMES MACDOWELL MARKERT
Chairman, Department of Neurosurgery
 
Campus Address FOT 1060 Zip 3410
Phone 205-975-6985
E-mail markert@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary    Professor
Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Secondary  Pediatrics   Pediatrics Chair Office Associate Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Professor
Center  Ctr for Glial Bio in Med  Ctr for Glial Bio in Med Professor
Center  General Clinical Research Center  Minority Health & Research Center Professor
Center  Neurology   Neuro-Oncology Center Professor

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Immunology 
Integrative Biomedical Sciences 
Medical Scientist Training Program 
Neuroscience 

Biographical Sketch 
James MacDowell Markert, Jr. received an AB degree from Harvard University then his MD and MPH from Columbia University College of Physicians and Surgeons. He subsequently completed a Neurosurgical residency at University of Michigan Medical Center in Ann Arbor, Michigan. During his residency, he returned to Harvard University where he completed a postdoctoral fellowship at Massachusetts General Hospital in Neuro-Oncology. Upon completion of his neurosurgical residency, he traveled to the University of Chicago as a Research Associate in Molecular Virology. Subsequently, he came to UAB where he currently serves as Associate Professor of Neurosurgery. In 2000, he received a secondary appointment in the Department of Physiology and Biophysics; in 2002, in the Department of Pediatrics; and in 2007, Cell Biology. He also holds appointments in the UAB Comprehensive Cancer Center and Gene Therapy Center and the MHRC.

Society Memberships
Organization Name Position Held Org Link
AANS     
American Academy of Neurological Surgery     
CNS     
Joint Section on Tumors--AANS/CNS     
Society of Neuro-Oncology     

Research/Clinical Interest
Title
Engineering Herpes Simplex Viruses for the Therapy of Cancer
Description
The main research objectives of our laboratory are to study and develop novel therapies for the treatment of brain tumors as well as studying the molecular and cellular characteristics of these tumors. Specifically, we are studying treatments for a group of tumors known as malignant gliomas. Much of our laboratory work is focused on the development of herpes simplex virus type I based vectors for treatment of gliomas. These vectors are conditionally replicating and destroy the tumors through oncolysis. Additionally, they can be used as gene therapy vehicles to add an additional tumoricidal affect. We have constructed genetically-engineered herpes simplex viruses that express a wide variety of cytokines and chemokines as well as cell surface antigens, suicide genes, and anti-angiogenic compounds as well as other proteins with antitumor effects. After construction, these viruses are tested in a variety of in vitro and in vivo models. Ultimately, we plan to take these anti-tumor viruses into clinical trials for the treatment of malignant tumors. One such virus, G207, has been studied at UAB in previous trials; a new trial in conjunction with radiation will begin soon. A second virus, M032, was created in our lab and expresses IL-12. M032 has received approval for clinical testing and has entered clinical trials. We are also developing other methods of increasing the efficacies of these viruses to increase their oncolytic efficacy, spread and persistence in tumor tissue. With the success of these agents in glioma, our area of interest has expanded to include other neoplasms, such as breast, pancreatic, colon, and melanoma.

Selected Publications 
Publication PUBMEDID
Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM. Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science. 1991 May 10;252(5007):854-6.   1851332 
Markert JM, Medlock MD, Rabkin SD, Gillespie GY, Todo T, Hunter WD, Palmer CA, Feigenbaum F, Tornatore C, Tufaro F, Martuza RL. Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther. 2000 May;7(10):867-74.   1084572 
Markert JM, Fuller CM, Gillespie GY, Bubien JK, McLean LA, Hong RL, Lee K, Gullans SR, Mapstone TB, Benos DJ. Differential gene expression profiling in human brain tumors. Physiol Genomics. 2001 Feb 7;5(1):21-33.   11161003 
Radbill AE, Fiveash JF, Falkenberg ET, Guthrie BL, Young PE, Meleth S, Markert JM. Initial treatment of melanoma brain metastases using gamma knife radiosurgery: an evaluation of efficacy and toxicity.Cancer. 2004 Aug 15;101(4):825-33.   15305416 
Markert JM, Liechty PG, Wang W, Gaston S, Braz E, Karrasch M, Nabors LB, Markiewicz M, Lakeman AD, Palmer CA, Parker JN, Whitley RJ, Gillespie GY. Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. Mol Ther. 2009 Jan;17(1):199-207. doi: 10.1038/mt.2008.228. Epub 2008 Oct 28.
 
18957964 
Advani SJ, Markert JM, Sood RF, Samuel S, Gillespie GY, Shao MY, Roizman B, Weichselbaum RR. Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1. Gene Ther. 2011 Nov;18(11):1098-102. doi: 10.1038/gt.2011.61. Epub 2011 May 5.   21544094 
Whitley RJ, Markert JM. Viral therapy of glioblastoma multiforme. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11672-3. doi: 10.1073/pnas.1310253110. Epub 2013 Jul 8.   23836634 
Nabors LB, Fiveash JB, Markert JM, Kekan MS, Gillespie GY, Huang Z, Johnson MJ, Meleth S, Kuo H, Gladson CL, Fathallah-Shaykh HM. A phase 1 trial of ABT-510 concurrent with standard chemoradiation for patients with newly diagnosed glioblastoma. Arch Neurol. 2010 Mar;67(3):313-9. doi:10.1001/archneurol.2010.16.   20212229 
Oliva CR, Nozell SE, Diers A, McClugage SG 3rd, Sarkaria JN, Markert JM,Darley-Usmar VM, Bailey SM,Gillespie GY, Landar A, Griguer CE. Acquisition of temozolomide chemoresistance in gliomas leads to remodeling of mitochondrial electron transport chain. J Biol Chem. 2010 Dec 17;285(51):39759-67. doi: 10.1074/jbc.M110.147504. Epub 2010 Sep 24.   20870728 
Dobelbower MC, Burnett Iii OL, Nordal RA, Nabors LB, Markert JM, Hyatt MD, Fiveash JB. Patterns of failure for glioblastoma multiforme following concurrent radiation and temozolomide. J Med Imaging Radiat Oncol. 2011 Feb;55(1):77-81.doi: 10.1111/j.1754-9485.2010.02232.x.   21382192 
Markert JM. The role of early resection vs biopsy in the management of low-grade gliomas. JAMA. 2012 Nov 14;308(18):1918-9.   23099540 
Griguer CE, Cantor AB, Fathallah-Shaykh HM, Gillespie GY, Gordon AS, Markert JM, Radovanovic I,Clement-Schatlo V, Shannon CN, Oliva CR. Prognostic relevance of cytochrome C oxidase in primary glioblastoma multiforme. PLoS One. 2013 Apr 10;8(4):e61035. doi: 10.1371/journal.pone.0061035.   23593382 
Kicielinski KP, Chiocca EA, Yu JS, Gill GM, Coffey M, Markert JM. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther. 2014 May;22(5):1056-62. doi: 10.1038/mt.2014.21. Epub 2014 Feb 20.   24553100 
Markert JM, Razdan SN, Kuo HC, Cantor A, Knoll A, Karrasch M, Nabors LB, Markiewicz M, Agee BS,Coleman JM, Lakeman AD, Palmer CA, Parker JN, Whitley RJ, Weichselbaum RR, Fiveash JB, Gillespie GY. A phase 1 trial of oncolytic HSV-1,G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Mol Ther. 2014 May;22(5):1048-55. doi:10.1038/mt.2014.22. Epub 2014 Feb 27.   24572 
Gebhardt BJ, Dobelbower MC, Ennis WH, Bag AK, Markert JM, Fiveash JB. Patterns of failure for glioblastoma multiforme following limited-margin radiation and concurrent temozolomide. Radiat Oncol. 2014 Jun 6;9:130. doi:10.1186/1748-717X-9-130. PubMed   24906388 

Keywords
glioma, gene therapy, brain tumors, herpes simplex, cancer therapy, immunotherapy, anti-angiogenic therapy