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Graeme F. Woodworth, MD, FACS

Academic Title:

Associate Professor

Primary Appointment:

Neurosurgery

Secondary Appointment(s):

Diagnostic Radiology Nuclear Medicine, Anatomy Neurobiology

Administrative Title:

Director Of The Brain Tumor Treatment & Research Center

Location:

UMMC S12D

Phone (Primary):

410-328-6148

Education and Training

Education

1997                            B.S., Chemistry, Tufts University

2005                            M.D., Johns Hopkins University School of Medicine

 

Post Graduate Education and Training

2005-2006                   Intern, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland

2006-2011                   Resident, Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland

2009-2011                   Fellow, Neuro-Oncology-NCI/Nanotechnology for Cancer Medicine Program, Johns Hopkins University School of      Medicine, Baltimore, Maryland

2011                            Fellow, Cranial Neuro-Endoscopy, Weill Cornell Department of Neurological Surgery, New York, New York

2011-2012                   Assistant Chief of Service, Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland

 

Biosketch

As the Director of the Brain Tumor Treatment and Research Center at the University of Maryland (UMd), I provide leadership and surgical care within a multidisciplinary team of radiologists, medical oncologists, radiation oncologists, neurosurgeons, and pathologists, treating brain cancer patients. This clinical role enables me to facilitate the cross-disciplinary group of engineers, cancer biologists, and clinician-scientists within the Translational Therapeutics Research Group (TTRG) to address key challenges in counteracting the patho-biology and improving the treatment of brain cancer. Much of this work is centered on the concept of using the operating room as a portal for discovery and opportunity to improve our understanding of and therapeutic delivery for brain cancer. I study and utilize advanced brain tumor models, including genetically-engineered and patient-derived versions directly from the operating room where the tumor tissue is rapidly passaged in vivo to avoid ischemia and biological transformation during extended manipulations or culturing conditions. We have developed a nestin-TV-A transgenic rat model to enhance investigations into the molecular and cellular mechanisms of the glioblastoma margin (GBm) and enable surgery-, local delivery-, focused ultrasound-, and targeted radiation-based studies.

A long-standing goal in treating patients with glioblastoma (GB), the most common and deadly primary brain cancer, is linking tumor specific features with effective anti-tumor therapies to generate long-term treatment responses. Ibelieve that following the principles of (1) maximal, safe tumor removal, (2) use of intra-operative access to better understand the disease and deliver therapies, and (3) targeting therapeutics to residual/unresectable invading cancer elements, we will turn GB from a uniformly fatal cancer into a chronic disease with the potential for cure. 

Research/Clinical Keywords

Brain tumor, Glioma, Transcranial focused ultrasound, Magnetic resonance imaging guided treatments, Nanomedicine

Highlighted Publications

Nance EA*, Woodworth GF*, Sailor K, Tamargo RJ, Eberhart CE, Hanes J. A dense poly(ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Science Translational Medicine, 2012, 4(149):149ra119. [* co-first authors]  (PMCID: 3718558)

Woodworth GF, Garzon-Muvdi T, Blakeley JO, Yu X, Weingart J & Burger PC, Histo-pathological correlates with survival in re-operated glioblastoma. J Neurooncol. 2013, 113: 485-93. (PMCID: 3994532)

Woodworth GF, Dunn GP, Nance EA, Hanes J, Brem H. Emerging insights into barriers to effective brain tumor therapeutics. Front. Oncology, 2014, 4: Article 126. (PMCID: 4104487)

Schneider CS, Perez-Bermudez J, Cheng E, Smith P, Winkles JA, Woodworth GF*, Kim AJ*. Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells. Biomaterials, 2015, 42: 42-51. (*Co-corresponding authors). (PMCID: 4279109)

Hersh DS, Wadajkar AS, Roberts NB, Perez JG, Connolly NP, Frenkel V, Winkles JA, Woodworth GF, Kim AJ. Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier. Curr Pharm Des. 2015 Dec 21. PMID: 26685681

Hersh DS, Houbova P, Castellani RJ, Rodriguez FJ, Mehta MP, Woodworth GF. Pathologic deposition of non-amyloid immunoglobulin in the brain leading to mass effect and neurological deficits. J Clin Neurosci. 2016 Mar 4. PMID: 26954763

Hersh DS, Nguyen BA, Dancy JG, Adapa AR, Winkles JA, Woodworth GF, Kim AJ, Frenkel V. Pulsed ultrasound expands the extracellular and perivascular spaces of the brain. Brain Res. 2016 Jun 28. pii: S0006-8993(16)30464-4. PMID: 27369449

Dancy JG, Wadajkar AS, Schneider CS, Mauban JR, Goloubeva OG, Woodworth GF, Winkles JA, Kim AJ. Non-specific binding and steric hindrance thresholds for penetration of particulate drug carriers within tumor tissue. J Control Release. 2016 Jul 25;238:139-148. PMID: 27460683

Hersh DS, Kim AJ, Winkles JA, Eisenberg HM, Woodworth GF, Frenkel V. Emerging Applications of Therapeutic Ultrasound in Neuro-oncology: Moving Beyond Tumor Ablation. Neurosurgery. 2016 Aug 22.  PMID: 27552589

Additional Publication Citations

McGirt MJ, Woodworth GF, Coon AC, Thomas G, Williams M, Rigamonti D. Diagnosis, treatment, and analysis of long-term outcomes in idiopathic normal pressure hydrocephalus. Neurosurgery, 2005, 57: 699-705.

Woodworth GF, Chaichana K, McGirt MJ, Sciubba D, Gokaslan ZPredictors of ambulatory status following resection of intramedullary spinal cords tumors. Neurosurgery, 2007 61: 99-105

Woodworth GF, McGirt  MJ, Huang J, Perler B, Clatterbuck RC, Tamargo RJ. Selective versus Routine Intraoperative Shunting during Carotid Endarterectomy: A Multivariate outcome analysis. Neurosurgery, 2007, 61: 1170-6.

Link T, Woodworth GF, Chaichana KL, Mayer SA, Grossman RS, Quinones-Hinojosa A.  Hyperglycemia is independently associated with post-operative function loss in primary glioblastoma. J Clin Neurosci., 2012, 19: 996-1000. (PMCID: 4859215)

McGirt MJ, Woodworth GF, Frazier JM, Coon AL, Olivi A, Weingart JD. Independent predictors of morbidity after image-guided stereotactic brain biopsy: A risk assessment of 270 cases. J Neurosurgery, 2005, 102: 897-901.

Woodworth GF, McGirt MJ, Samdani A, Garonzik I, Olivi A, Weingart JD. Accuracy of frameless and frame-based MRI-guided stereotactic brain biopsy in the diagnosis of glioma: Comparison of biopsy and open resection specimen.  Neurological Research, 2005 27: 358-62.

Woodworth GF, McGirt MJ, Samdani A, Garonzik I, Olivi A, Weingart JD. Frameless image-guided stereotactic brain biopsy: Diagnostic yield, operative morbidity, and comparison with the frame-based technique. J Neurosurgery, 2006, 104: 233-7

Woodworth GF, Garzon-Muvdi T, Blakeley JO, Yu X, Weingart J & Burger PC, Histo-pathological correlates with survival in re-operated glioblastoma. J Neurooncol. 2013, 113: 485-93.

Nance EA, Timble K, Miller, W, Song J, Louttit C, Klibanov A, Shih T, Swaminathan G, Tamargo RJ, Woodworth GF, Hanes J, Price RJ. Noninvasive delivery of stealth, brain-penetrating nanoparticles across the blood-brain barrier using MRI-guided focused ultrasound. J. Cont. Release, 2014, 189: 123-32. Received the Jorge Heller Outstanding Paper Award, Controlled Release Society 2015 (PMCID: 4125545)

Kim AJ, Woodworth GF*, Boylan NJ, Suk JS, Hanes J*. Highly compacted pH-responsive DNA nanoparticles mediate transgene silencing in experimental glioma. J. Mat. Chem. B 2014, 2: 8165-8173. (* corresponding author) (PMCID: 4254827)

Mastorakos P, Zhang C, Berry S, Oh Y, Lee S, Eberhart CG, Woodworth GF, Suk JS, Hanes J. Highly PEGylated DNA nanoparticles provide uniform and widespread gene transfer in the brain. Adv Healthcare Mater. 2015, 4: 1023-1033. (PMCID: 4433405)

Perez J, Tran N, Rosenblum M, Schneider C, Connolly N, Kim AJ, Woodworth GF, Winkles JA. The TWEAK receptor Fn14 is a potential cell surface portal for targeted gelivery of glioblastoma therapeutics. Oncogene 2016, 35: 2145-2155. (PMCID: 4850525)

Clinical Specialty Details

Diplomate, American Board of Neurological Surgeons

Fellow, American Association of Neurological Surgeons

Fellow, American College of Surgeons

Awards and Affiliations

2004          Clinical Research Award, Southern Society of Neurological Surgery Annual Meeting

2004          Medical Student Research Award, Alpha Omega Alpha Honors Society

2004          B. Wood Research Award, Johns Hopkins School of Medicine

2007          Patient Safety Research Award, Johns Hopkins Department of Neurosurgery

2009          T32 Award, Nanotechnology in Cancer Medicine, Johns Hopkins University

2009          Top Ten Abstract, CNS Annual Meeting, New Orleans, Louisiana

2010          Chairman’s Award for Patient Safety Research, Johns Hopkins Department of Neurosurgery

2011          Harvey Cushing Research Award, Johns Hopkins Department of Neurosurgery

2012          Neurosurgeon Research Career Development Program Award, Massachusetts General Hospital/NINDS

2013          Clinician-Scientist Award, The Passano Foundation

2014          Dean’s Challenge Award, University of Maryland School of Medicine

2014          Pilot Research Award, Greenebaum NCI Cancer Center, University of Maryland

2015          Innovation in Biotechnology Award, (co-awardee) American Association of Pharmaceutical Scientists and Genentech

2015          Jorge Heller Outstanding Paper Award, (co-awardee) Controlled Release Society

2016          Research Scholar Award, American Cancer Society

Grants and Contracts

NIH K08 NS090430                                                                                                                                                                09/15/2014-09/15/2019

“Brain-Penetrating Nanoparticle Therapeutics for Invasive Brain Cancer”

This Mentored Training Award project was designed to facilitate career development in translational neuro-oncology research and (1) formulate drug loaded nanoparticles for improved therapeutic delivery to brain cancer cells, and (2) assess the efficacy and safety of this delivery system in experimental invasive brain tumor models.


 American Cancer Society - 128970-RSG-16-012-01-CDD                                                                       07/01/2016-07/01/2020  

“Fn14-targeted Biodegradable BCNU-loaded Nanoparticles for Invasive Brain Cancer”

The goal of this proposal is to study and engineer nanoparticle technologies to specifically target brain-invading tumor cells. We will use FDA-approved materials to develop nanoparticle-drug formulations that minimize undesired effects while targeting the distant tumor cells via the invasive tumor marker, Fn14. 


NSF EAGER CBET - 1557922                                                                                                               07/01/2016-06/31/2017            

“Effect of Pulsed Focused Ultrasound on Microstructures in the Brain”   

The main goal of this project is to investigate the effect of pulsed focused ultrasound on tissue microstructures to enhance distribution of nanoparticles in the brain


 Focused Ultrasound Foundation                                                                                                             09/01/2016-07/012017        

“Focused Ultrasound Immunomodulation in a Mouse GL261 Intracranial Glioma Model”

The project’s goal is to investigate he ability of pulsed focused ultrasound to enhance the immunogenicity of brain tumors in order to increase the infiltration and/or activity of anti-tumor immune cells. The study will be carried out in an invasive glioma model in mice and the treated tumors and other tissues will be assayed for the expression of potentially beneficial factors for an immunotherapy response.