John Sampson

Overview:

Current research activities involve the immunotherapeutic targeting of a tumor-specific mutation in the epidermal growth factor receptor. Approaches used to target this tumor-specific epitope include unarmed and radiolabeled antibody therapy and cell mediated approaches using peptide vaccines and dendritic cells. Another area of interest involves drug delivery to brain tumors. Translational and clinical work is carried out in this area to formulate the relationship between various direct intratumoral infusion parameters and drug distribution within brain tumors and normal brain.

The Duke Brain Tumor Immunotherapy Program (BTIP) has an emphasis on translational research in Neuro-Oncology. There are two main areas of study. The first is novel mechanisms of delivery of large molecular weight molecules, such as monoclonal antibodies, throughout brain intersitial space using novel intracerebral infusion techniques developed by this laboratory. Studies exploring this technology are undertaken in both small and large laboratory animals and patients with brain tumors.

The other focus of the BTIP is translational immunotherapy. In this line of work, dendritic cell vaccination strategies and adoptive T-cell strategies have been developed to target novel and well-characterized tumor-specific antigens in patients with brain tumors. The BTIP integrates well with and works closely with the Preston Robert Tisch Brain Tumor Center at Duke. The BTIP is well funded and currently holds seven NIH grants, including a SPORE in Brain Cancer grant. There are a large number of investigators at various levels so that students will get exposure to various levels of research and mentorship.

Positions:

Robert H., M.D. and Gloria Wilkins Professor of Neurosurgery, in the School of Medicine

Neurosurgery
School of Medicine

Professor of Neurosurgery

Neurosurgery
School of Medicine

Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Professor of Immunology

Immunology
School of Medicine

Professor of Radiation Oncology

Radiation Oncology
School of Medicine

Professor of Pathology

Pathology
School of Medicine

Professor in Orthopaedic Surgery

Orthopaedic Surgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1990

University of Manitoba (Canada)

Ph.D. 1996

Duke University

M.H.S. 2007

Duke University School of Medicine

M.B.A. 2011

Duke University

Investigator in Cerebral Hydrodynamics Lab, Neurosurgery

University of Manitoba (Canada)

Intern, Surgery

Duke University

Resident in Neurosurgery, Surgery

Duke University

Grants:

Enhancing dendritic cell migration to drive potent anti-tumor immune responses

Administered By
School of Medicine
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Clinical Brain Tumor Development of a Cytomegalovirus-targeted Therapeutic with Vaccine pre-conditioning to Validate Novel Predictors of Vaccine Efficacy

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Quantitative Staging and Therapeutic Response in IDH-1 Mutated Glioblastomas

Administered By
Radiology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Targeting Translation Control in Malignant Glioma

Administered By
Neurosurgery, Neuro-Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Regional AGT Depletion of CNS and Leptomeningeal Tumors

Administered By
Neurosurgery, Neuro-Oncology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Publications:

Early Vasopressor Utilization Strategies and Outcomes in Critically Ill Patients With Severe Traumatic Brain Injury.

BACKGROUND: Early hypotension after severe traumatic brain injury (sTBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors, commonly norepinephrine and phenylephrine, to support blood pressure after TBI. However, guidelines do not specify vasopressor type, resulting in variation in clinical practice. We describe early vasopressor utilization patterns in critically ill patients with TBI and examine the association between utilization of norepinephrine, compared to phenylephrine, with hospital mortality after sTBI. METHODS: We conducted a retrospective cohort study of US hospitals participating in the Premier Healthcare Database between 2009 and 2018. We examined adult patients (>17 years of age) with a primary diagnosis of sTBI who were treated in an intensive care unit (ICU) after injury. The primary exposure was vasopressor choice (phenylephrine versus norepinephrine) within the first 2 days of hospital admission. The primary outcome was in-hospital mortality. Secondary outcomes examined included hospital length of stay (LOS) and ICU LOS. We conducted a post hoc subgroup analysis in all patients with intracranial pressure (ICP) monitor placement. Regression analysis was used to assess differences in outcomes between patients exposed to phenylephrine versus norepinephrine, with propensity matching to address selection bias due to the nonrandom allocation of treatment groups. RESULTS: From 2009 to 2018, 24,718 (37.1%) of 66,610 sTBI patients received vasopressors within the first 2 days of hospitalization. Among these patients, 60.6% (n = 14,991) received only phenylephrine, 10.8% (n = 2668) received only norepinephrine, 3.5% (n = 877) received other vasopressors, and 25.0% (n = 6182) received multiple vasopressors. In that time period, the use of all vasopressors after sTBI increased. A moderate degree of variation in vasopressor choice was explained at the individual hospital level (23.1%). In propensity-matched analysis, the use of norepinephrine compared to phenylephrine was associated with an increased risk of in-hospital mortality (OR, 1.65; CI, 1.46-1.86; P < .0001). CONCLUSIONS: Early vasopressor utilization among critically ill patients with sTBI is common, increasing over the last decade, and varies across hospitals caring for TBI patients. Compared to phenylephrine, norepinephrine was associated with increased risk of in-hospital mortality in propensity-matched analysis. Given the wide variation in vasopressor utilization and possible differences in efficacy, our analysis suggests the need for randomized controlled trials to better inform vasopressor choice for patients with sTBI.
Authors
Toro, C; Ohnuma, T; Komisarow, J; Vavilala, MS; Laskowitz, DT; James, ML; Mathew, JP; Hernandez, AF; Goldstein, BA; Sampson, JH; Krishnamoorthy, V
MLA Citation
Toro, Camilo, et al. “Early Vasopressor Utilization Strategies and Outcomes in Critically Ill Patients With Severe Traumatic Brain Injury.” Anesth Analg, vol. 135, no. 6, Dec. 2022, pp. 1245–52. Pubmed, doi:10.1213/ANE.0000000000005949.
URI
https://scholars.duke.edu/individual/pub1511913
PMID
35203085
Source
pubmed
Published In
Anesth Analg
Volume
135
Published Date
Start Page
1245
End Page
1252
DOI
10.1213/ANE.0000000000005949

Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma.

Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and is refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 is highly expressed in pro-tumor cells and is associated with worsened survival in patients with GBM. Host CaMKK2, specifically, reduces survival and promotes ICB resistance. Multimodal profiling of the TME reveals that CaMKK2 is associated with several ICB resistance-associated immune phenotypes. CaMKK2 promotes exhaustion in CD8+ T cells and reduces the expansion of effector CD4+ T cells, additionally limiting their tumor penetrance. CaMKK2 also maintains myeloid cells in a disease-associated microglia-like phenotype. Lastly, neuronal CaMKK2 is required for maintaining the ICB resistance-associated myeloid phenotype, is deleterious to survival, and promotes ICB resistance. Our findings reveal CaMKK2 as a contributor to ICB resistance and identify neurons as a driver of immunotherapeutic resistance in GBM.
Authors
Tomaszewski, WH; Waibl-Polania, J; Chakraborty, M; Perera, J; Ratiu, J; Miggelbrink, A; McDonnell, DP; Khasraw, M; Ashley, DM; Fecci, PE; Racioppi, L; Sanchez-Perez, L; Gunn, MD; Sampson, JH
MLA Citation
Tomaszewski, William H., et al. “Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma.” Nat Commun, vol. 13, no. 1, Oct. 2022, p. 6483. Pubmed, doi:10.1038/s41467-022-34175-y.
URI
https://scholars.duke.edu/individual/pub1555261
PMID
36309495
Source
pubmed
Published In
Nature Communications
Volume
13
Published Date
Start Page
6483
DOI
10.1038/s41467-022-34175-y

Immunobiology and Immune Therapy

Authors
MLA Citation
Choi, Bryan D., et al. “Immunobiology and Immune Therapy.” NEURO-ONCOLOGY: THE ESSENTIALS, 3RD EDITION, 2015, pp. 254–63.
URI
https://scholars.duke.edu/individual/pub1548467
Source
wos-lite
Published Date
Start Page
254
End Page
263

Malignant Glioma Immunotherapy: A Peptide Vaccine from Bench to Bedside

Authors
MLA Citation
Choi, Bryan D., et al. “Malignant Glioma Immunotherapy: A Peptide Vaccine from Bench to Bedside.” Tumors of the Central Nervous System, Volume 1, Springer Netherlands, 2011, pp. 349–56. Crossref, doi:10.1007/978-94-007-0344-5_36.
URI
https://scholars.duke.edu/individual/pub1548468
Source
crossref
Published Date
Start Page
349
End Page
356
DOI
10.1007/978-94-007-0344-5_36

Editorial: the impact of PhD training.

Authors
Oyesiku, NM
MLA Citation
Oyesiku, Nelson M. “Editorial: the impact of PhD training.” J Neurosurg, vol. 120, no. 3, Mar. 2014, pp. 727–28. Pubmed, doi:10.3171/2013.8.JNS131489.
URI
https://scholars.duke.edu/individual/pub1418962
PMID
24359006
Source
pubmed
Published In
J Neurosurg
Volume
120
Published Date
Start Page
727
End Page
728
DOI
10.3171/2013.8.JNS131489

Research Areas:

3T3 Cells
Abortion
Academic Medical Centers
Adipates
Administration, Oral
Adult
Aged
Aged, 80 and over
Alcohol Oxidoreductases
Amino Acid Sequence
Angiogenesis Inhibitors
Antibiotics, Antineoplastic
Antibodies
Antibodies, Bispecific
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antibodies, Neoplasm
Antibody Affinity
Antibody Formation
Antibody Specificity
Anticonvulsants
Antigen Presentation
Antigen-Antibody Complex
Antigen-Presenting Cells
Antigens
Antigens, CD3
Antigens, CD4
Antigens, Differentiation
Antigens, Neoplasm
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antineoplastic Combined Chemotherapy Protocols
Antitubercular Agents
Astrocytoma
Ataxia
Benzamides
Benzenesulfonates
Biological Assay
Biopsy
Bispecific antibodies
Blood-Brain Barrier
Blotting, Western
Body Burden
Body Mass Index
Bone Marrow Cells
Brain
Brain Diseases
Brain Neoplasms
Breast Neoplasms
CD4 Antigens
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
CHO Cells
Camptothecin
Cancer Vaccines
Carboplatin
Carcinogenicity Tests
Carmustine
Catalytic Domain
Catheterization
Catheters, Indwelling
Cell Culture Techniques
Cell Division
Cell Line
Cell Line, Tumor
Cell Membrane
Cell Movement
Cell Proliferation
Cell Survival
Cells, Cultured
Central Nervous System
Central Nervous System Neoplasms
Cerebral Cortex
Cerebrospinal Fluid Shunts
Cerebrovascular Disorders
Cervical Vertebrae
Chemokines
Chemoradiotherapy
Chemotherapy
Chemotherapy, Adjuvant
Chi-Square Distribution
Child
Child, Preschool
Chimera
Cholesterol
Chromatography
Cisplatin
Clinical Trials as Topic
Clinical Trials, Phase III as Topic
Cluster Analysis
Coculture Techniques
Cognition
Cohort Studies
Combined Modality Therapy
Complementarity Determining Regions
Cone-Beam Computed Tomography
Confidence Intervals
Contrast Media
Convection
Cranial Irradiation
Cranial Nerve Diseases
Cranial Nerve Neoplasms
Craniocerebral Trauma
Craniotomy
Culture Media, Conditioned
Cytochrome P-450 CYP3A
Cytokines
Cytotoxicity Tests, Immunologic
Cytotoxicity, Immunologic
DNA Methylation
DNA Modification Methylases
DNA Mutational Analysis
DNA Repair Enzymes
DNA Topoisomerases, Type I
Dacarbazine
Dactinomycin
Data Collection
Decanoic Acids
Decompression, Surgical
Dendritic Cells
Diagnosis, Differential
Diagnostic Imaging
Disease Models, Animal
Disease Progression
Disease-Free Survival
Dose Fractionation
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Drug Administration Routes
Drug Administration Schedule
Drug Delivery Systems
Drug Evaluation, Preclinical
Drug Implants
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Drug Synergism
Drug Therapy, Combination
Drugs, Chinese Herbal
Ear Neoplasms
Education, Graduate
Electrocoagulation
Electrophoresis, Gel, Two-Dimensional
Electrophoresis, Polyacrylamide Gel
Electroporation
Encephalomyelitis, Autoimmune, Experimental
Enzyme Inhibitors
Enzyme-Linked Immunosorbent Assay
Eosinophilic Granuloma
Epidermal Growth Factor
Epitopes
Equipment Design
Escherichia coli
Etoposide
Exophthalmos
Exosomes
Exotoxins
Facial Nerve
Female
Flow Cytometry
Follow-Up Studies
Forkhead Transcription Factors
Gadolinium DTPA
Gene Expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Transfer Techniques
Genetic Engineering
Genetic Techniques
Genetic Testing
Genetic Therapy
Genetic Vectors
Genotype
Glasgow Coma Scale
Glioblastoma
Glioma
Glossopharyngeal Nerve Diseases
Goals
Guanine
HIV Infections
Head
Head and Neck Neoplasms
Health Care Costs
Health Services Accessibility
Hemocyanin
Hemocyanins
Histocompatibility Antigens Class I
History, 20th Century
History, 21st Century
Homeless Persons
Homosexuality
Humans
Hydroxyurea
Hypersensitivity, Delayed
Image Processing, Computer-Assisted
Imaging
Immune System
Immunity
Immunity, Innate
Immunization
Immunocompetence
Immunocompromised Host
Immunoenzyme Techniques
Immunoglobulin G
Immunoglobulin Idiotypes
Immunohistochemistry
Immunologic Surveillance
Immunomodulation
Immunosuppression
Immunosuppressive Agents
Immunotherapy
Immunotherapy, Adoptive
Immunotoxins
Indicators and Reagents
Individualized Medicine
Indoleamine-Pyrrole 2,3,-Dioxygenase
Infant
Infratentorial Neoplasms
Infusion Pumps
Infusion Pumps, Implantable
Infusions, Intra-Arterial
Infusions, Intravenous
Injections, Intradermal
Injections, Intralesional
Injections, Intravenous
Injections, Intraventricular
Injury Severity Score
Interferon-gamma
Interleukin-13
Interleukin-2
Interleukin-2 Receptor alpha Subunit
Intraocular Pressure
Intraoperative Complications
Iodine Radioisotopes
Isocitrate Dehydrogenase
Isotope Labeling
Kaplan-Meier Estimate
Keratinocytes
Language
Linear Models
Liposomes
Lung Neoplasms
Lymph Nodes
Lymphocyte Activation
Lymphocyte Depletion
Lymphocytes
Lymphopenia
Macrophages
Magnetic Resonance Imaging
Male
Maximum Tolerated Dose
Melanoma
Melanoma, Experimental
Membrane Proteins
Meningeal Neoplasms
Meningioma
Meningitis
Methods
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Nude
Mice, Transgenic
Microcirculation
Microinjections
Microsurgery
Middle Aged
Models, Animal
Models, Molecular
Molecular Sequence Data
Molecular Targeted Therapy
Monitoring, Intraoperative
Monocytes
Movement
Multivariate Analysis
Mutagenesis, Site-Directed
Mutant Proteins
Mutation
Naphthoquinones
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Recurrence, Local
Neoplasm Staging
Neoplasm Transplantation
Neoplasm, Residual
Neoplasms
Neoplasms, Experimental
Neoplastic Stem Cells
Neovascularization, Pathologic
Nerve Compression Syndromes
Nervous System Autoimmune Disease, Experimental
Neural Stem Cells
Neuroma, Acoustic
Neurosurgical Procedures
Niacinamide
Nitrosourea Compounds
North Carolina
O(6)-Methylguanine-DNA Methyltransferase
Observer Variation
Oligodendroglioma
Oligonucleotide Array Sequence Analysis
Oncology
Oncolytic Virotherapy
Oncolytic Viruses
Opportunistic Infections
Pain Management
Pain Measurement
Palliative Care
Paraganglioma
Paranasal Sinus Diseases
Paresis
Patient Selection
Peptide Fragments
Peptides
Phenylurea Compounds
Phosphoproteins
Phosphorylation
Phytotherapy
Pilot Projects
Piperazines
Plant Extracts
Plants, Medicinal
Poliomyelitis
Polyesters
Positron-Emission Tomography
Postoperative Complications
Posture
Poverty
Precision Medicine
Predictive Value of Tests
Preoperative Care
Prevalence
Principal Component Analysis
Prognosis
Proportional Hazards Models
Prospective Studies
Protein Engineering
Protein Kinase Inhibitors
Protein Precursors
Protein-Serine-Threonine Kinases
Protein-Tyrosine Kinases
Proteome
Proteomics
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Publishing
Pyridines
Pyrimidines
Quality of Life
Quinazolines
RNA Viruses
Radiation Injuries
Radiation Tolerance
Radioimmunotherapy
Radioligand Assay
Radiometry
Radiopharmaceuticals
Radiosurgery
Radiotherapy
Radiotherapy Dosage
Radiotherapy Planning, Computer-Assisted
Radiotherapy, Adjuvant
Radiotherapy, High-Energy
Radiotherapy, Image-Guided
Radiotherapy, Intensity-Modulated
Randomized Controlled Trials as Topic
Receptor, Epidermal Growth Factor
Receptor, erbB-2
Receptors, Antigen, T-Cell
Receptors, Vascular Endothelial Growth Factor
Recombinant Fusion Proteins
Recombinant Proteins
Recombination, Genetic
Recurrence
Registries
Relative Biological Effectiveness
Remission Induction
Reoperation
Reproducibility of Results
Retinal Diseases
Retrospective Studies
Retroviridae
Retroviridae Infections
Risk Assessment
Risk Factors
Saccharomyces cerevisiae
Safety
Salvage Therapy
Sample Size
Saponins
Sensitivity and Specificity
Sequence Alignment
Serum Albumin, Radio-Iodinated
Signal Transduction
Single-Chain Antibodies
Sirolimus
Skin Neoplasms
Social Class
Socioeconomic Factors
Software
Solubility
Spinal Cord
Spinal Cord Injuries
Spinal Fusion
Spinal Neoplasms
Spleen
Standard of Care
Stereotaxic Techniques
Steroids
Subcutaneous Fat
Substrate Specificity
Supratentorial Neoplasms
Surface Plasmon Resonance
Surgical Wound Infection
Survival
Survival Analysis
Survival Rate
Swiss 3T3 Cells
T-Lymphocyte Subsets
T-Lymphocytes
T-Lymphocytes, Cytotoxic
T-Lymphocytes, Regulatory
Tenascin
Th2 Cells
Thiazoles
Thrombocytopenia
Time Factors
Tissue Distribution
Titrimetry
Tomography, Emission-Computed
Tomography, Emission-Computed, Single-Photon
Tomography, X-Ray Computed
Transfection
Transforming Growth Factor alpha
Transforming Growth Factor beta
Transplantation, Heterologous
Treatment
Treatment Failure
Treatment Outcome
Trigeminal Nerve
Tuberculosis, Multidrug-Resistant
Tuberculosis, Pulmonary
Tumor Burden
Tumor Cells, Cultured
Tumor Escape
Tumor Markers, Biological
Tumor Microenvironment
Tumor Suppressor Proteins
Tyrosine
Tyrphostins
United States
Urban Population
Vaccination
Vaccines, Subunit
Vascular Endothelial Growth Factor A
Viremia
Virulence Factors
Work Schedule Tolerance
Xenograft Model Antitumor Assays
Young Adult
Robert H., M.D. and Gloria Wilkins Professor of Neurosurgery, in the School of Medicine

Contact:

Profile

https://scholars.duke.edu/person/john.sampson

Email

john.sampson@duke.edu
1293 Orange Zone, Duke South, 200 Trent Dr, Durham, NC 27710
Box 3810 Med Ctr, Durham, NC 27710