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Joshua Hinkle, Ph.D.

Joshua Hinkle, Ph.D.

Position

IRTA Postdoctoral Fellow, Cellular Stress and Inflammation Section

Contact

Biomedical Research Center
251 Bayview Boulevard
Suite 200
Baltimore, MD 21224

Email: josh.hinkle@nih.gov

Education

Ph.D. – Neuroscience, University of Rochester School of Medicine & Dentistry (Advisor: Prof Kerry O’Banion)

M.S. - Neuroscience, University of Rochester School of Medicine & Dentistry

Research Interests

Josh Hinkle received his Ph.D. in Neuroscience at the University of Rochester under the guidance of Prof. Kerry O’Banion. His research focused on the effects of radiation on healthy rodent brains; both clinically relevant doses in response to tumor burden as well as space radiation to mimic the exposure to astronauts during deep space flight. His dissertation focused specifically on how cranial irradiation induces microglial activation and elevated complement levels that correlate with dendritic spine loss and subsequent cognitive impairment in mice. Following his Ph.D., Josh joined Dr. Brandon Harvey at the National Institute of Drug Abuse as a PostDoctoral Fellow in October 2020 and is currently exploring how SARS-CoV proteins can modulate ER homeostasis.

Selected Publications

2019

Hinkle, Joshua J; Olschowka, John A; Love, Tanzy M; Williams, Jacqueline P; O'Banion, Kerry M

Cranial irradiation mediated spine loss is sex-specific and complement receptor-3 dependent in male mice Journal Article

In: Scientific Reports, vol. 9, no. 1, pp. 18899, 2019, ISBN: 2045-2322.

Abstract | Links

@article{Hinkle:2019aa,
title = {Cranial irradiation mediated spine loss is sex-specific and complement receptor-3 dependent in male mice},
author = {Joshua J Hinkle and John A Olschowka and Tanzy M Love and Jacqueline P Williams and Kerry M O'Banion},
url = {https://pubmed.ncbi.nlm.nih.gov/31827187/},
doi = {10.1038/s41598-019-55366-6},
isbn = {2045-2322},
year = {2019},
date = {2019-01-01},
journal = {Scientific Reports},
volume = {9},
number = {1},
pages = {18899},
abstract = {Cranial irradiation is the main therapeutic treatment for primary and metastatic malignancies in the brain. However, cranial radiation therapy produces long-term impairment in memory, information processing, and attention that contribute to a decline in quality of life. The hippocampal neural network is fundamental for proper storage and retrieval of episodic and spatial memories, suggesting that hippocampal signaling dysfunction could be responsible for the progressive memory deficits observed following irradiation. Previous rodent studies demonstrated that irradiation induces significant loss in dendritic spine number, alters spine morphology, and is associated with behavioral task deficits. Additionally, the literature suggests a common mechanism in which synaptic elimination via microglial-mediated phagocytosis is complement dependent and associated with cognitive impairment in aging as well as disease. We demonstrate sexual dimorphisms in irradiation-mediated alterations of microglia activation markers and dendritic spine density. Further, we find that the significant dendritic spine loss observed in male mice following irradiation is microglia complement receptor 3 (CR3)-dependent. By identifying sex-dependent cellular and molecular factors underlying irradiation-mediated spine loss, therapies can be developed to counteract irradiation-induced cognitive decline and improve patient quality of life.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Cranial irradiation is the main therapeutic treatment for primary and metastatic malignancies in the brain. However, cranial radiation therapy produces long-term impairment in memory, information processing, and attention that contribute to a decline in quality of life. The hippocampal neural network is fundamental for proper storage and retrieval of episodic and spatial memories, suggesting that hippocampal signaling dysfunction could be responsible for the progressive memory deficits observed following irradiation. Previous rodent studies demonstrated that irradiation induces significant loss in dendritic spine number, alters spine morphology, and is associated with behavioral task deficits. Additionally, the literature suggests a common mechanism in which synaptic elimination via microglial-mediated phagocytosis is complement dependent and associated with cognitive impairment in aging as well as disease. We demonstrate sexual dimorphisms in irradiation-mediated alterations of microglia activation markers and dendritic spine density. Further, we find that the significant dendritic spine loss observed in male mice following irradiation is microglia complement receptor 3 (CR3)-dependent. By identifying sex-dependent cellular and molecular factors underlying irradiation-mediated spine loss, therapies can be developed to counteract irradiation-induced cognitive decline and improve patient quality of life.

Close

  • https://pubmed.ncbi.nlm.nih.gov/31827187/
  • doi:10.1038/s41598-019-55366-6

Close

2017

Richie, Christopher T; Whitaker, Leslie R; Whitaker, Keith W; Necarsulmer, Julie; Baldwin, Heather A; Zhang, Yajun; Fortuno, Lowella; Hinkle, Josh J; Koivula, Pyry; Henderson, Mark J; Sun, Wenzhi; Wang, Kai; Smith, Jeffrey C; Pickel, Jim; Ji, Na; Hope, Bruce T; Harvey, Brandon K

Near-infrared fluorescent protein iRFP713 as a reporter protein for optogenetic vectors, a transgenic Cre-reporter rat, and other neuronal studies. Journal Article

In: J Neurosci Methods, vol. 284, pp. 1–14, 2017, ISSN: 1872-678X (Electronic); 0165-0270 (Linking), (*First paper describing LE-Tg (DIO-iRFP)3Ottc rat. *First paper describing LE-Tg (DIO-iRFP)9Ottc rat.).

Abstract | Links

@article{Richie:2017aa,
title = {Near-infrared fluorescent protein iRFP713 as a reporter protein for optogenetic vectors, a transgenic Cre-reporter rat, and other neuronal studies.},
author = {Christopher T Richie and Leslie R Whitaker and Keith W Whitaker and Julie Necarsulmer and Heather A Baldwin and Yajun Zhang and Lowella Fortuno and Josh J Hinkle and Pyry Koivula and Mark J Henderson and Wenzhi Sun and Kai Wang and Jeffrey C Smith and Jim Pickel and Na Ji and Bruce T Hope and Brandon K Harvey},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28380331},
doi = {10.1016/j.jneumeth.2017.03.020},
issn = {1872-678X (Electronic); 0165-0270 (Linking)},
year = {2017},
date = {2017-04-02},
urldate = {2017-04-02},
journal = {J Neurosci Methods},
volume = {284},
pages = {1--14},
address = {Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, United States.},
abstract = {BACKGROUND: The use of genetically-encoded fluorescent reporters is essential for the identification and observation of cells that express transgenic modulatory proteins. Near-infrared (NIR) fluorescent proteins have superior light penetration through biological tissue, but are not yet widely adopted. NEW METHOD: Using the near-infrared fluorescent protein, iRFP713, improves the imaging resolution in thick tissue sections or the intact brain due to the reduced light-scattering at the longer, NIR wavelengths used to image the protein. Additionally, iRFP713 can be used to identify transgenic cells without photobleaching other fluorescent reporters or affecting opsin function. We have generated a set of adeno-associated vectors in which iRFP713 has been fused to optogenetic channels, and can be expressed constitutively or Cre-dependently. RESULTS: iRFP713 is detectable when expressed in neurons both in vitro and in vivo without exogenously supplied chromophore biliverdin. Neuronally-expressed iRFP713 has similar properties to GFP-like fluorescent proteins, including the ability to be translationally fused to channelrhodopsin or halorhodopsin, however, it shows superior photostability compared to EYFP. Furthermore, electrophysiological recordings from iRFP713-labeled cells compared to cells labeled with mCherry suggest that iRFP713 cells are healthier and therefore more stable and reliable in an ex vivo preparation. Lastly, we have generated a transgenic rat that expresses iRFP713 in a Cre-dependent manner. CONCLUSIONS: Overall, we have demonstrated that iRFP713 can be used as a reporter in neurons without the use of exogenous biliverdin, with minimal impact on viability and function thereby making it feasible to extend the capabilities for imaging genetically-tagged neurons in slices and in vivo.},
note = {*First paper describing LE-Tg (DIO-iRFP)3Ottc rat.
*First paper describing LE-Tg (DIO-iRFP)9Ottc rat.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

BACKGROUND: The use of genetically-encoded fluorescent reporters is essential for the identification and observation of cells that express transgenic modulatory proteins. Near-infrared (NIR) fluorescent proteins have superior light penetration through biological tissue, but are not yet widely adopted. NEW METHOD: Using the near-infrared fluorescent protein, iRFP713, improves the imaging resolution in thick tissue sections or the intact brain due to the reduced light-scattering at the longer, NIR wavelengths used to image the protein. Additionally, iRFP713 can be used to identify transgenic cells without photobleaching other fluorescent reporters or affecting opsin function. We have generated a set of adeno-associated vectors in which iRFP713 has been fused to optogenetic channels, and can be expressed constitutively or Cre-dependently. RESULTS: iRFP713 is detectable when expressed in neurons both in vitro and in vivo without exogenously supplied chromophore biliverdin. Neuronally-expressed iRFP713 has similar properties to GFP-like fluorescent proteins, including the ability to be translationally fused to channelrhodopsin or halorhodopsin, however, it shows superior photostability compared to EYFP. Furthermore, electrophysiological recordings from iRFP713-labeled cells compared to cells labeled with mCherry suggest that iRFP713 cells are healthier and therefore more stable and reliable in an ex vivo preparation. Lastly, we have generated a transgenic rat that expresses iRFP713 in a Cre-dependent manner. CONCLUSIONS: Overall, we have demonstrated that iRFP713 can be used as a reporter in neurons without the use of exogenous biliverdin, with minimal impact on viability and function thereby making it feasible to extend the capabilities for imaging genetically-tagged neurons in slices and in vivo.

Close

  • https://www.ncbi.nlm.nih.gov/pubmed/28380331
  • doi:10.1016/j.jneumeth.2017.03.020

Close

Song, Kang-Ho; Fan, Alexander C; Hinkle, Joshua J; Newman, Joshua; Borden, Mark A; Harvey, Brandon K

Microbubble gas volume: A unifying dose parameter in blood-brain barrier opening by focused ultrasound Journal Article

In: Theranostics, vol. 7, pp. 144-152, 2017.

Links

@article{thno15987,
title = {Microbubble gas volume: A unifying dose parameter in blood-brain barrier opening by focused ultrasound},
author = {Kang-Ho Song and Alexander C Fan and Joshua J Hinkle and Joshua Newman and Mark A Borden and Brandon K Harvey},
url = {https://pubmed.ncbi.nlm.nih.gov/28042323/},
doi = {10.7150/thno.15987},
year = {2017},
date = {2017-01-01},
journal = {Theranostics},
volume = {7},
pages = {144-152},
publisher = {Ivyspring International Publisher},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

  • https://pubmed.ncbi.nlm.nih.gov/28042323/
  • doi:10.7150/thno.15987

Close

2016

Kuo, Chi-Chung; Shen, Hui; Harvey, Brandon K; Yu, Seong-Jin; Kopajtic, Theresa; Hinkle, Josh J; Kyrkanides, Stephanos; Katz, Jonathan L; Wang, Yun

Differential modulation of methamphetamine-mediated behavioral sensitization by overexpression of Mu opioid receptors in nucleus accumbens and ventral tegmental area. Journal Article

In: Psychopharmacology (Berl), vol. 233, no. 4, pp. 661–672, 2016, ISSN: 1432-2072 (Electronic); 0033-3158 (Linking).

Abstract | Links

@article{Kuo:2016aa,
title = {Differential modulation of methamphetamine-mediated behavioral sensitization by overexpression of Mu opioid receptors in nucleus accumbens and ventral tegmental area.},
author = {Chi-Chung Kuo and Hui Shen and Brandon K Harvey and Seong-Jin Yu and Theresa Kopajtic and Josh J Hinkle and Stephanos Kyrkanides and Jonathan L Katz and Yun Wang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26554386},
doi = {10.1007/s00213-015-4134-4},
issn = {1432-2072 (Electronic); 0033-3158 (Linking)},
year = {2016},
date = {2016-02-01},
journal = {Psychopharmacology (Berl)},
volume = {233},
number = {4},
pages = {661--672},
address = {Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD, 21224, USA.},
abstract = {RATIONALE: Repeated administration of methamphetamine (Meth) induces behavioral sensitization which is characterized by a progressive increase in locomotor response after each injection. Previous studies have shown that Mu opioid receptors (MORs) can regulate Meth-mediated behavioral sensitization. However, the reported interactions are controversial; systemic activation of MORs either enhanced or suppressed Meth sensitization. It is possible that alteration of Meth sensitization after systemic administration of MOR ligands reflects the sum of distinct MOR reactions in multiple brain regions. OBJECTIVES: The purpose of the present study was to examine the actions of MORs on Meth sensitization after regionally selective overexpression of human MOR through an AAV6-based gene delivery system. METHOD: We demonstrated that adeno-associated virus (AAV)-MOR increased MOR immunoreactivity and binding in vitro. AAV-MOR or AAV-green fluorescent protein (GFP) was injected into the nucleus accumbens (NAc) or ventral tegmental area (VTA) of adult mice. Two weeks after viral infection, animals received Meth or saline for five consecutive days. Locomotor behavior and striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) level were determined. RESULTS: Repeated administration of Meth progressively increased locomotor activity; this sensitization reaction was attenuated by intra-NAc AAV-MOR microinjections. Infusion of AAV-MOR to VTA enhanced Meth sensitization. AAV-MOR significantly enhanced DA levels in VTA after VTA infection but reduced DOPAC/DA turnover in the NAc after NAc injection. CONCLUSION: Our data suggest a differential modulation of Meth sensitization by overexpression of MOR in NAc and VTA. Regional manipulation of MOR expression through AAV may be a novel approach to control Meth abuse and psychomimetic activity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

RATIONALE: Repeated administration of methamphetamine (Meth) induces behavioral sensitization which is characterized by a progressive increase in locomotor response after each injection. Previous studies have shown that Mu opioid receptors (MORs) can regulate Meth-mediated behavioral sensitization. However, the reported interactions are controversial; systemic activation of MORs either enhanced or suppressed Meth sensitization. It is possible that alteration of Meth sensitization after systemic administration of MOR ligands reflects the sum of distinct MOR reactions in multiple brain regions. OBJECTIVES: The purpose of the present study was to examine the actions of MORs on Meth sensitization after regionally selective overexpression of human MOR through an AAV6-based gene delivery system. METHOD: We demonstrated that adeno-associated virus (AAV)-MOR increased MOR immunoreactivity and binding in vitro. AAV-MOR or AAV-green fluorescent protein (GFP) was injected into the nucleus accumbens (NAc) or ventral tegmental area (VTA) of adult mice. Two weeks after viral infection, animals received Meth or saline for five consecutive days. Locomotor behavior and striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) level were determined. RESULTS: Repeated administration of Meth progressively increased locomotor activity; this sensitization reaction was attenuated by intra-NAc AAV-MOR microinjections. Infusion of AAV-MOR to VTA enhanced Meth sensitization. AAV-MOR significantly enhanced DA levels in VTA after VTA infection but reduced DOPAC/DA turnover in the NAc after NAc injection. CONCLUSION: Our data suggest a differential modulation of Meth sensitization by overexpression of MOR in NAc and VTA. Regional manipulation of MOR expression through AAV may be a novel approach to control Meth abuse and psychomimetic activity.

Close

  • https://www.ncbi.nlm.nih.gov/pubmed/26554386
  • doi:10.1007/s00213-015-4134-4

Close

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