Jeffrey K Harrison

Jeffrey K Harrison, Ph.D.

Professor

Department: MD-PHARMACOLOGY / THERAPEUTICS
Business Phone: (352) 627-9208
Business Email: jharriso@ufl.edu

Teaching Profile

Courses Taught
2019-2021
GMS6520 Medical Pharmacology and Therapeutics I: The Nervous System
2019-2025
GMS6530 Medical Pharmacology and Therapeutics II: Cardiovascular, Renal and Respiratory Systems
2014,2016-2018,2018-2023
GMS6001 Fundamentals of Biomedical Sciences I
2018-2025
GMS6560 Molecules to Man: Past, Present and Future Therapeutic Strategies for Disease
2020-2023
PAS5026 Pharmacotherapeu 2
2019-2021
GMS6551 Fundamentals of Medical Pharmacology and Therapeutics
2016-2023
GMS6847 Translational Research and Therapeutics: Bench, Bedside, Community, & Policy
2007-2016,2019-2022
GMS6590 Seminar in Pharmacology
2011,2013-2016,2016-2025
GMS5905 Special Topics in Biomedical Sciences
2011-2025
DEN6262 Prin of Pharmacology
2015-2016,2018-2021,2020-2025
GMS6009 Principles of Drug Action and Therapeutics
2018
GMS7980 Research for Doctoral Dissertation
2015,2018-2024,2024
BMS6638C Kidney & Urinary Tract
2015-2017
GMS6895 CTS Journal Club
2006-2008,2010-2014,2012-2017,2016-2017
GMS6051 Signal Transduction
2014,2016-2022,2022
MDU4002 Introduction to Medical Science Seminar 2
2013-2014,2023
BMS6031 Foundations of Med
2014
GMS6140 Principles of Immunology
2010
IDH4917 Undergrad Research
2023
BMS6635 Derm and Msk
2024-2025
BMS6633 The Cv System

Research Profile

Glioblastomas are a highly malignant type of brain tumor with very few treatment options. Efforts in Dr. Harrison’s laboratory are aimed toward understanding mechanisms by which immune cells contribute to tumor progression and resistance to immunotherapies. We focus on myeloid cell populations that gain access to the glioma microenvironment, studying the mechanisms by which they traffic to the tumor and exert their immune-suppressive functions. The development and application of chemokine receptor antagonists to treat these human high-grade gliomas is also a primary goal of the laboratory.

My laboratory has a long history of characterizing roles of chemokines in various physiological and pathological states of the central nervous and cardiovascular systems. Of particular emphasis has been the study of the chemokine fractalkine (CX3CL1) and its receptor, CX3CR1, as well as more recent efforts to target the CCL2/CCL7/CCR2 axis. Historically, the scope of the research program has included in vitro and in vivo approaches that include 1) structure-function analysis of chemokines and chemokine receptors, 2) studies on the regulation of expression of chemokines and chemokine receptors, 3) understanding signaling mechanisms associated with chemokine receptor activation, 4) use of chemokine receptor-deficient mice, to address the role of various chemokine systems in disease, with recent focus on using these mice to understand the roles of chemokine in malignant glioma, and 5) use of chemokine receptor antagonists in animal models of glioblastoma.

Areas of Interest
  • Cancer
  • Chemokines
  • Receptors
Open Researcher and Contributor ID (ORCID)

0000-0002-1080-5721

Publications

2024
DR5 disulfide bonding as a sensor and effector of protein folding stress.
bioRxiv : the preprint server for biology. [DOI] 10.1101/2024.03.04.583390. [PMID] 38496520.
2024
Glioma-derived M-CSF and IL-34 license M-MDSCs to suppress CD8+ T cells in a NOS-dependent manner.
bioRxiv : the preprint server for biology. [DOI] 10.1101/2024.06.05.597474. [PMID] 38895268.
2024
KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system.
bioRxiv : the preprint server for biology. [DOI] 10.1101/2024.01.26.577279. [PMID] 38501121.
2024
KR158 Spheres Harboring Slow-Cycling Cells Recapitulate High-Grade Glioma Features in an Immunocompetent System.
Cells. 13(11) [DOI] 10.3390/cells13110938. [PMID] 38891070.
2023
Global stability and parameter analysis reinforce therapeutic targets of PD-L1-PD-1 and MDSCs for glioblastoma.
Journal of mathematical biology. 88(1) [DOI] 10.1007/s00285-023-02027-y. [PMID] 38099947.
2022
Glioma-derived CCL2 and CCL7 mediate migration of immune suppressive CCR2+/CX3CR1+ M-MDSCs into the tumor microenvironment in a redundant manner.
Frontiers in immunology. 13 [DOI] 10.3389/fimmu.2022.993444. [PMID] 36685592.
2022
The Dynamics of Tumor-Infiltrating Myeloid Cell Activation and the Cytokine Expression Profile in a Glioma Resection Site during the Post-Surgical Period in Mice.
Brain sciences. 12(7) [DOI] 10.3390/brainsci12070893. [PMID] 35884700.
2021
Modulation of the chemokine/chemokine receptor axis as a novel approach for glioma therapy.
Pharmacology & therapeutics. 222 [DOI] 10.1016/j.pharmthera.2020.107790. [PMID] 33316289.
2020
Adult immuno-oncology: using past failures to inform the future.
Neuro-oncology. 22(9):1249-1261 [DOI] 10.1093/neuonc/noaa116. [PMID] 32391559.
2020
CCR2 inhibition reduces tumor myeloid cells and unmasks a checkpoint inhibitor effect to slow progression of resistant murine gliomas.
Proceedings of the National Academy of Sciences of the United States of America. 117(2):1129-1138 [DOI] 10.1073/pnas.1910856117. [PMID] 31879345.
2018
Involvement of Microglial Cells in Hypoxia-induced Pulmonary Hypertension.
American journal of respiratory cell and molecular biology. 59(2):271-273 [DOI] 10.1165/rcmb.2018-0042LE. [PMID] 30067089.
2017
Erratum to: CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes.
Journal of molecular medicine (Berlin, Germany). 95(5):565-566 [DOI] 10.1007/s00109-017-1530-8. [PMID] 28421250.
2016
Angiotensin II Regulation of Proliferation, Differentiation, and Engraftment of Hematopoietic Stem Cells.
Hypertension (Dallas, Tex. : 1979). 67(3):574-84 [DOI] 10.1161/HYPERTENSIONAHA.115.06474. [PMID] 26781279.
2016
CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes.
Journal of molecular medicine (Berlin, Germany). 94(11):1255-1265 [DOI] 10.1007/s00109-016-1433-0. [PMID] 27344677.
2015
Microglia Activate Migration of Glioma Cells through a Pyk2 Intracellular Pathway.
PloS one. 10(6) [DOI] 10.1371/journal.pone.0131059. [PMID] 26098895.
2015
VEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFβR signaling-dependent manner.
Cancer letters. 360(1):60-7 [DOI] 10.1016/j.canlet.2015.02.005. [PMID] 25676691.
2014
CXCL12 modulation of CXCR4 and CXCR7 activity in human glioblastoma stem-like cells and regulation of the tumor microenvironment.
Frontiers in cellular neuroscience. 8 [DOI] 10.3389/fncel.2014.00144. [PMID] 24904289.
2014
Detection of primary cilia in human glioblastoma.
Journal of neuro-oncology. 117(1):15-24 [DOI] 10.1007/s11060-013-1340-y. [PMID] 24510433.
2014
Signaling mechanisms that suppress the cytostatic actions of rapamycin.
PloS one. 9(6) [DOI] 10.1371/journal.pone.0099927. [PMID] 24927123.
2013
Expression and functional heterogeneity of chemokine receptors CXCR4 and CXCR7 in primary patient-derived glioblastoma cells.
PloS one. 8(3) [DOI] 10.1371/journal.pone.0059750. [PMID] 23555768.
2012
A model of GAG/MIP-2/CXCR2 interfaces and its functional effects.
Biochemistry. 51(28):5642-54 [PMID] 22686371.
2012
CCL5, CCR1 and CCR5 in murine glioblastoma: immune cell infiltration and survival rates are not dependent on individual expression of either CCR1 or CCR5.
Journal of neuroimmunology. 246(1-2):10-7 [DOI] 10.1016/j.jneuroim.2012.02.009. [PMID] 22425022.
2012
CXCR3 antagonism of SDF-1(5-67) restores trabecular function and prevents retinal neurodegeneration in a rat model of ocular hypertension.
PloS one. 7(6) [DOI] 10.1371/journal.pone.0037873. [PMID] 22675496.
2012
Hypoxia-induced endothelial CX3CL1 triggers lung smooth muscle cell phenotypic switching and proliferative expansion.
American journal of physiology. Lung cellular and molecular physiology. 303(10):L912-22 [DOI] 10.1152/ajplung.00014.2012. [PMID] 23002075.
2011
Chemokine receptor CXCR3 promotes growth of glioma.
Carcinogenesis. 32(2):129-37 [DOI] 10.1093/carcin/bgq224. [PMID] 21051441.
2011
Fractalkine and CX 3 CR1 regulate hippocampal neurogenesis in adult and aged rats.
Neurobiology of aging. 32(11):2030-44 [DOI] 10.1016/j.neurobiolaging.2009.11.022. [PMID] 20018408.
2010
Cx3Cr1 Microglial Receptor Modulates Hippocampal Synaptic Plasticity
Cell Transplantation. 19
2009
Hematopoietic- and neurologic-expressed sequence 1 (Hn1) depletion in B16.F10 melanoma cells promotes a differentiated phenotype that includes increased melanogenesis and cell cycle arrest.
Differentiation; research in biological diversity. 78(1):35-44 [DOI] 10.1016/j.diff.2009.04.001. [PMID] 19427096.
2009
Hematopoietic- and neurologic-expressed sequence 1 expression in the murine GL261 and high-grade human gliomas.
Pathology oncology research : POR. 15(3):437-44 [DOI] 10.1007/s12253-008-9147-4. [PMID] 19145478.
2008
CX3CL1 and CX3CR1 in the GL261 murine model of glioma: CX3CR1 deficiency does not impact tumor growth or infiltration of microglia and lymphocytes.
Journal of neuroimmunology. 198(1-2):98-105 [DOI] 10.1016/j.jneuroim.2008.04.016. [PMID] 18508133.
2008
Hn 1 Is a Novel Actin Complex-Binding Protein That Regulates B16.F10 Melanoma Cell Growth and Secretion of Melanin
Pigment Cell and Melanoma Research. 21:333-334
2008
Structure-Based Jaz Ligand-Ji and Its Analogues Show Strong Cytotoxic Effects On Glioma Cells in Vitro – a New Class of Glioma Therapy Drugs?
Journal of Neuropathology and Experimental Neurology. 67
2006
Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes.
Diabetes. 55(1):102-9 [PMID] 16380482.
2006
Proline 326 in the C terminus of murine CX3CR1 prevents G-protein and phosphatidylinositol 3-kinase-dependent stimulation of Akt and extracellular signal-regulated kinase in Chinese hamster ovary cells.
The Journal of pharmacology and experimental therapeutics. 316(1):356-63 [PMID] 16166268.
2005
Role of fractalkine (CX3CL1) in regulating neuron-microglia interactions: development of viral-based CX3CR1 antagonists.
Current Alzheimer research. 2(2):187-9 [PMID] 15974917.
2005
The facial motor nucleus transcriptional program in response to peripheral nerve injury identifies Hn1 as a regeneration-associated gene.
Journal of neuroscience research. 82(5):581-91 [PMID] 16267826.
2005
Transforming growth factor-beta1 increases CXCR4 expression, stromal-derived factor-1alpha-stimulated signalling and human immunodeficiency virus-1 entry in human monocyte-derived macrophages.
Immunology. 114(4):565-74 [PMID] 15804293.
2004
Adeno-associated virus type 2 VP2 capsid protein is nonessential and can tolerate large peptide insertions at its N terminus.
Journal of virology. 78(12):6595-609 [PMID] 15163751.
2004
Viral macrophage inflammatory protein-II and fractalkine (CX3CL1) chimeras identify molecular determinants of affinity, efficacy, and selectivity at CX3CR1.
Molecular pharmacology. 66(6):1431-9 [PMID] 15361546.
2004
Vitreous levels of vascular endothelial growth factor and stromal-derived factor 1 in patients with diabetic retinopathy and cystoid macular edema before and after intraocular injection of triamcinolone.
Archives of ophthalmology (Chicago, Ill. : 1960). 122(12):1801-7 [PMID] 15596583.
2003
Chemokine receptor binding and signal transduction in native cells of the central nervous system.
Methods (San Diego, Calif.). 29(4):326-34 [PMID] 12725799.
2003
Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3.
Gene expression patterns : GEP. 3(4):459-62 [PMID] 12915312.
2003
In situ hybridization analysis of chemokines and chemokine receptors in the central nervous system.
Methods (San Diego, Calif.). 29(4):312-8 [PMID] 12725797.
2002
TGF-beta1 upregulates CX3CR1 expression and inhibits fractalkine-stimulated signaling in rat microglia.
Journal of neuroimmunology. 133(1-2):46-55 [PMID] 12446007.
2000
Histologic, neurologic, and immunologic effects of methylmercury in captive great egrets.
Journal of wildlife diseases. 36(3):423-35 [PMID] 10941726.
1999
Inflammatory agents regulate in vivo expression of fractalkine in endothelial cells of the rat heart.
Journal of leukocyte biology. 66(6):937-44 [PMID] 10614775.
1998
Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia
Proceedings of the National Academy of Sciences. 95(18):10896-10901 [DOI] 10.1073/pnas.95.18.10896. [PMID] 9724801.
1996
Identification of two rat genes orthologous to the human interleukin-8 receptors.
Journal of Biological Chemistry. 271(51):32770-6 [DOI] 10.1074/jbc.271.51.32770. [PMID] 8955112.

Grants

Jun 2024 ACTIVE
Unleashing the power of mRNA for treatment of malignant brain tumors using novel vaccine construct
Role: Co-Investigator
Funding: FL DEPT OF HLTH
Jun 2024 ACTIVE
Evaluation of Chorionic Gonadotropin as a Treatment for Sepsis-induced Neuroinflammation and Cognitive Dysfunction in the Aged Brain
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Jun 2023 ACTIVE
Regulation of the Tumor Immune Cell Landscape by Ciliated Glioblastoma Cells
Role: Co-Investigator
Funding: NATL INST OF HLTH NINDS
Oct 2022 – Mar 2024
Selectively targeting macrophage subsets with dendrimer-based STING Agonist Prodrug
Role: Other
Funding: AMER BRAIN TUMOR ASSOCIATION
Aug 2022 ACTIVE
Mathematical Investigation of Cell Dynamics in Development and Cancer
Role: Faculty
Funding: NATL SCIENCE FOU
Aug 2022 ACTIVE
Metabolic interactions between tumor cells and the immunce system in GBM A potential Achilles heel of GBM for novel therapeutics
Role: Co-Investigator
Funding: NATL INST OF HLTH NINDS
Sep 2018 ACTIVE
Targeting CCR2-expressing myeloid cells to overcome immune checkpoint inhibitor resistance in glioma
Role: Principal Investigator
Funding: NATL INST OF HLTH NINDS
Jul 2018 – Jun 2024
Florida Center for Brain Tumor Research
Role: Project Manager
Funding: FL DEPT OF HLTH
Sep 2017 – Aug 2018
Optimizing systemic stem/progenitor cell therapy for AMD
Role: Principal Investigator
Funding: UNIV OF ALABAMA BIRMINGHAM via NATL INST OF HLTH NEI
Sep 2016 – Dec 2016
Bone Marrow Neuropathy Drive Diabetic Retinopathy
Role: Principal Investigator
Funding: INDIANA UNIV
Jul 2016 – Dec 2016
TO #1 – Evaluation of CXCR4 Antagonists in Pre-clinical Models of Glioblastoma
Role: Principal Investigator
Funding: X4 PHARMACEUTICALS
Jul 2016 – Jun 2018
Florida Center for Brain Tumor Research (FCBTR) Grant for 2016
Role: Co-Investigator
Funding: ACCELERATE BRAIN CANCER CURE
Sep 2015 – Aug 2016
Bone marrow neuropathy drives diabetic retinopathy
Role: Principal Investigator
Funding: INDIANA UNIV via NATL INST OF HLTH NEI
Feb 2015 – Oct 2023
UF Health Cancer Center Pilot Project Grants funded through the Florida Consortium of National Cancer Institute Centers Program
Role: Project Manager
Funding: UF HEALTH SHANDS HOSPITAL
Dec 2014 – Mar 2017
irradiAnti-CXCR4 antibody combined with Avastin alone or Avastin and irradiation for GBM
Role: Principal Investigator
Funding: BRISTOL MYERS SQUIBB CO
Jul 2014 – Jun 2016
Combining CXCR4, VEGFR, AND TGFBR inhibitors to synergistically inhibit GBM progression
Role: Principal Investigator
Funding: OCALA ROYAL DAMES FOR CANCER RESEARCH
Jul 2013 – Aug 2017
Role of CX3CR1 and CCR2 in controlling microglia and mononuclear cells in AMD
Role: Principal Investigator
Funding: INDIANA UNIV via NATL INST OF HLTH
Jul 2013 – Jun 2016
Indiana non-federal expenditures for Bone Marrow Neuropathy Drives Diabetic Retinopathy
Role: Principal Investigator
Funding: INDIANA UNIV

Education

PhD
1988 · University of Michigan
BS
1983 · University of Michigan

Contact Details

Phones:
Business:
(352) 627-9208
Emails:
Business:
jharriso@ufl.edu
Addresses:
Business Mailing:
PO Box 100267
GAINESVILLE FL 32610
Business Street:
1200 NEWELL DRIVE
GAINESVILLE FL 32610