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==== '''Neuroepigenetics: visualizing histone deacetylase enzymes with PET''' ====
==== '''Neuroepigenetics: visualizing histone deacetylase enzymes with PET''' ====
Work from Dr. Hooker’s group published in August of 2016 '' - '' Wey & Gilbert ''et al'' 2016 ''Science Translational Medicine'' revealed the first visual maps of neuroepigenetic function in the living human brain using the Class-I histone deacetylase (HDAC) PET imaging probe [<sup>11</sup>C]Martinostat. <ref>{{Cite journal|last=Wey|first=Hsiao-Ying|last2=Gilbert|first2=Tonya M.|last3=Zürcher|first3=Nicole R.|last4=She|first4=Angela|last5=Bhanot|first5=Anisha|last6=Taillon|first6=Brendan D.|last7=Schroeder|first7=Fredrick A.|last8=Wang|first8=Changing|last9=Haggarty|first9=Stephen J.|date=2016-08-10|title=Insights into neuroepigenetics through human histone deacetylase PET imaging|url=https://www.ncbi.nlm.nih.gov/pubmed/27510902|journal=Science Translational Medicine|volume=8|issue=351|pages=351ra106|doi=10.1126/scitranslmed.aaf7551|issn=1946-6242|pmid=27510902}}</ref>  This work demonstrated a link between quantitative HDAC maps of the brain and the expression of plasticity and disease-related genes under HDAC control.  The human imaging report was built on a background of tool development in the Hooker lab spanning seven years, wherein small molecule histone deacetylase (HDAC) inhibitors were systematically screened and refined to resolve chemical leads with Class-I HDAC isoform selectivity, outstanding brain penetrance and appropriate binding kinetics.<ref>{{Cite journal|last=Hooker|first=Jacob M.|last2=Kim|first2=Sung Won|last3=Alexoff|first3=David|last4=Xu|first4=Youwen|last5=Shea|first5=Colleen|last6=Reid|first6=Alicia|last7=Volkow|first7=Nora|last8=Fowler|first8=Joanna S.|date=2010-01-01|title=Histone deacetylase inhibitor, MS-275, exhibits poor brain penetration: PK studies of [C]MS-275 using Positron Emission Tomography|url=https://www.ncbi.nlm.nih.gov/pubmed/20657706|journal=ACS chemical neuroscience|volume=1|issue=1|pages=65–73|doi=10.1021/cn9000268|issn=1948-7193|pmc=PMC2908422|pmid=20657706}}</ref><ref>{{Cite journal|last=Wang|first=Changning|last2=Eessalu|first2=Thomas E.|last3=Barth|first3=Vanessa N.|last4=Mitch|first4=Charles H.|last5=Wagner|first5=Florence F.|last6=Hong|first6=Yijia|last7=Neelamegam|first7=Ramesh|last8=Schroeder|first8=Frederick A.|last9=Holson|first9=Edward B.|date=2013-01-01|title=Design, synthesis, and evaluation of hydroxamic acid-based molecular probes for in vivo imaging of histone deacetylase (HDAC) in brain|url=https://www.ncbi.nlm.nih.gov/pubmed/24380043|journal=American Journal of Nuclear Medicine and Molecular Imaging|volume=4|issue=1|pages=29–38|pmc=PMC3867727|pmid=24380043}}</ref><ref>{{Cite journal|last=Seo|first=Young Jun|last2=Muench|first2=Lisa|last3=Reid|first3=Alicia|last4=Chen|first4=Jinzhu|last5=Kang|first5=Yeona|last6=Hooker|first6=Jacob M.|last7=Volkow|first7=Nora D.|last8=Fowler|first8=Joanna S.|last9=Kim|first9=Sung Won|date=2013-12-15|title=Radionuclide labeling and evaluation of candidate radioligands for PET imaging of histone deacetylase in the brain|url=https://www.ncbi.nlm.nih.gov/pubmed/24210501|journal=Bioorganic & Medicinal Chemistry Letters|volume=23|issue=24|pages=6700–6705|doi=10.1016/j.bmcl.2013.10.038|issn=1464-3405|pmc=PMC4007514|pmid=24210501}}</ref><ref>{{Cite journal|last=Kim|first=Sung Won|last2=Hooker|first2=Jacob M.|last3=Otto|first3=Nicola|last4=Win|first4=Khaing|last5=Muench|first5=Lisa|last6=Shea|first6=Colleen|last7=Carter|first7=Pauline|last8=King|first8=Payton|last9=Reid|first9=Alicia E.|date=2013-10-01|title=Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET|url=https://www.ncbi.nlm.nih.gov/pubmed/23906667|journal=Nuclear Medicine and Biology|volume=40|issue=7|pages=912–918|doi=10.1016/j.nucmedbio.2013.06.007|issn=1872-9614|pmc=PMC3769509|pmid=23906667}}</ref><ref>{{Cite journal|last=Schroeder|first=Frederick A.|last2=Chonde|first2=Daniel B.|last3=Riley|first3=Misha M.|last4=Moseley|first4=Christian K.|last5=Granda|first5=Michael L.|last6=Wilson|first6=Colin M.|last7=Wagner|first7=Florence F.|last8=Zhang|first8=Yan-Ling|last9=Gale|first9=Jennifer|date=2013-08-29|title=FDG-PET imaging reveals local brain glucose utilization is altered by class I histone deacetylase inhibitors|url=https://www.ncbi.nlm.nih.gov/pubmed/23810801|journal=Neuroscience Letters|volume=550|pages=119–124|doi=10.1016/j.neulet.2013.06.016|issn=1872-7972|pmc=PMC3750730|pmid=23810801}}</ref><ref>{{Cite journal|last=Wang|first=Yajie|last2=Zhang|first2=Yan-Ling|last3=Hennig|first3=Krista|last4=Gale|first4=Jennifer P.|last5=Hong|first5=Yijia|last6=Cha|first6=Anna|last7=Riley|first7=Misha|last8=Wagner|first8=Florence|last9=Haggarty|first9=Stephen J.|date=2013-07-01|title=Class I HDAC imaging using [ (3)H]CI-994 autoradiography|url=https://www.ncbi.nlm.nih.gov/pubmed/23803584|journal=Epigenetics|volume=8|issue=7|pages=756–764|doi=10.4161/epi.25202|issn=1559-2308|pmc=PMC3781195|pmid=23803584}}</ref><ref>{{Cite journal|last=Schroeder|first=Frederick A.|last2=Lewis|first2=Michael C.|last3=Fass|first3=Daniel M.|last4=Wagner|first4=Florence F.|last5=Zhang|first5=Yan-Ling|last6=Hennig|first6=Krista M.|last7=Gale|first7=Jennifer|last8=Zhao|first8=Wen-Ning|last9=Reis|first9=Surya|date=2013-01-01|title=A selective HDAC 1/2 inhibitor modulates chromatin and gene expression in brain and alters mouse behavior in two mood-related tests|url=https://www.ncbi.nlm.nih.gov/pubmed/23967191|journal=PloS One|volume=8|issue=8|pages=e71323|doi=10.1371/journal.pone.0071323|issn=1932-6203|pmc=PMC3743770|pmid=23967191}}</ref><ref>{{Cite journal|last=Seo|first=Young Jun|last2=Kang|first2=Yeona|last3=Muench|first3=Lisa|last4=Reid|first4=Alicia|last5=Caesar|first5=Shannon|last6=Jean|first6=Logan|last7=Wagner|first7=Florence|last8=Holson|first8=Edward|last9=Haggarty|first9=Stephen J.|date=2014-07-16|title=Image-guided synthesis reveals potent blood-brain barrier permeable histone deacetylase inhibitors|url=https://www.ncbi.nlm.nih.gov/pubmed/24780082|journal=ACS chemical neuroscience|volume=5|issue=7|pages=588–596|doi=10.1021/cn500021p|issn=1948-7193|pmc=PMC4102966|pmid=24780082}}</ref><ref>{{Cite journal|last=Wang|first=Changning|last2=Schroeder|first2=Frederick A.|last3=Wey|first3=Hsiao-Ying|last4=Borra|first4=Ronald|last5=Wagner|first5=Florence F.|last6=Reis|first6=Surya|last7=Kim|first7=Sung Won|last8=Holson|first8=Edward B.|last9=Haggarty|first9=Stephen J.|date=2014-10-09|title=In vivo imaging of histone deacetylases (HDACs) in the central nervous system and major peripheral organs|url=https://www.ncbi.nlm.nih.gov/pubmed/25203558|journal=Journal of Medicinal Chemistry|volume=57|issue=19|pages=7999–8009|doi=10.1021/jm500872p|issn=1520-4804|pmc=PMC4191584|pmid=25203558}}</ref><ref>{{Cite journal|last=Schroeder|first=F. A.|last2=Wang|first2=C.|last3=Van de Bittner|first3=G. C.|last4=Neelamegam|first4=R.|last5=Takakura|first5=W. R.|last6=Karunakaran|first6=A.|last7=Wey|first7=H. Y.|last8=Reis|first8=S. A.|last9=Gale|first9=J.|date=2014-10-15|title=PET imaging demonstrates histone deacetylase target engagement and clarifies brain penetrance of known and novel small molecule inhibitors in rat|url=https://www.ncbi.nlm.nih.gov/pubmed/25188794|journal=ACS chemical neuroscience|volume=5|issue=10|pages=1055–1062|doi=10.1021/cn500162j|issn=1948-7193|pmc=PMC4198064|pmid=25188794}}</ref><ref>{{Cite journal|last=Wey|first=Hsiao-Ying|last2=Wang|first2=Changning|last3=Schroeder|first3=Frederick A.|last4=Logan|first4=Jean|last5=Price|first5=Julie C.|last6=Hooker|first6=Jacob M.|date=2015-05-20|title=Kinetic Analysis and Quantification of [¹¹C]Martinostat for in Vivo HDAC Imaging of the Brain|url=https://www.ncbi.nlm.nih.gov/pubmed/25768025|journal=ACS chemical neuroscience|volume=6|issue=5|pages=708–715|doi=10.1021/acschemneuro.5b00066|issn=1948-7193|pmc=PMC4439341|pmid=25768025}}</ref><ref>{{Cite journal|last=Strebl|first=Martin G.|last2=Wang|first2=Changning|last3=Schroeder|first3=Frederick A.|last4=Placzek|first4=Michael S.|last5=Wey|first5=Hsiao-Ying|last6=Van de Bittner|first6=Genevieve C.|last7=Neelamegam|first7=Ramesh|last8=Hooker|first8=Jacob M.|date=2016-05-18|title=Development of a Fluorinated Class-I HDAC Radiotracer Reveals Key Chemical Determinants of Brain Penetrance|url=https://www.ncbi.nlm.nih.gov/pubmed/26675505|journal=ACS chemical neuroscience|volume=7|issue=5|pages=528–533|doi=10.1021/acschemneuro.5b00297|issn=1948-7193|pmid=26675505}}</ref> The first-in-human imaging paper set the stage for Dr. Hooker’s ongoing work to measure and map HDAC density, distribution and connectivity in diverse diseases, ''in vivo.''
Work from Dr. Hooker’s group published in August of 2016 '' - '' Wey & Gilbert ''et al'' 2016 ''Science Translational Medicine'' revealed the first visual maps of neuroepigenetic function in the living human brain using the Class-I histone deacetylase (HDAC) PET imaging probe [<sup>11</sup>C]Martinostat. [2]  This work demonstrated a link between quantitative HDAC maps of the brain and the expression of plasticity and disease-related genes under HDAC control.  The human imaging report was built on a background of tool development in the Hooker lab spanning seven years, wherein small molecule histone deacetylase (HDAC) inhibitors were systematically screened and refined to resolve chemical leads with Class-I HDAC isoform selectivity, outstanding brain penetrance and appropriate binding kinetics.[3-14]  The first-in-human imaging paper set the stage for Dr. Hooker’s ongoing work to measure and map HDAC density, distribution and connectivity in diverse diseases, ''in vivo.''


==References ==
==References ==

Revision as of 02:27, 1 March 2017

Jacob M. Hooker Ph.D.

is an American chemist and expert in molecular imaging, particularly in the development and application of simultaneous MRI and PET. He has contributed major advances on the entire spectrum of research from fundamental chemistry methodology with radioisotopes to human neuroimaging.

Life and Education

Jacob grew up just outside of Asheville, North Carolina and attended Enka High School. He graduated from North Carolina State University in 2002 as class Valedictorian and summa cum laude with bachelor of science degrees in Textile Chemistry and Chemistry.  He then earned his doctorate of philosophy in Chemistry at the University of California, Berkeley, mentored by Professor Matt Francis. After hearing a neuroimaging presentation in 2006 by National Medal of Science recipient Dr. Joanna Fowler, Dr. Hooker immersed himself in postdoctoral training under her mentorship at the Brookhaven National Laboratory. Fowler recalls having Jacob as a postdoc “getting him was like winning the lottery” “He’s going to ask questions we haven’t thought of before."[1] Dr. Hooker conducted his postdoctoral training with Dr. Fowler as a Goldhaber Distinguished Fellow, developing new neuroscience-oriented imaging methods and protocols.

Research and Achievements

Dr. Hooker relocated to Charlestown, MA in 2009 at the initiation of his independent research career at the Martinos Center. He co-designed and scratch-built a cyclotron and radiopharmacy facility housing a Siemens Eclipse HP Cyclotron, completed early 2011. The production and imaging facility – part of the Martinos Center Research Core – provides imaging tools for all stages of translational research.

The mission of his academic research lab is “to accelerate the study of the living, human brain and nervous system through development and application of molecular imaging agents.”  An organic chemist by training, Dr. Hooker and his research group are devoted to enhance understanding of the healthy brain and dysfunction in diseases including Alzheimer’s, Autism and Schizophrenia. 

His research focus centers on the themes of i) neuroepigenetics, ii) radiochemistry methods development and iii) neuroimaging methods development; highlights are provided in the following section.

Major Publication Themes

Dr. Hooker has published over 100 papers [Hooker JM bibliography ] most notably in the domains of:

Neuroepigenetics: visualizing histone deacetylase enzymes with PET

Work from Dr. Hooker’s group published in August of 2016  -  Wey & Gilbert et al 2016 Science Translational Medicine revealed the first visual maps of neuroepigenetic function in the living human brain using the Class-I histone deacetylase (HDAC) PET imaging probe [11C]Martinostat. [2]  This work demonstrated a link between quantitative HDAC maps of the brain and the expression of plasticity and disease-related genes under HDAC control.  The human imaging report was built on a background of tool development in the Hooker lab spanning seven years, wherein small molecule histone deacetylase (HDAC) inhibitors were systematically screened and refined to resolve chemical leads with Class-I HDAC isoform selectivity, outstanding brain penetrance and appropriate binding kinetics.[3][4][5][6][7][8][9][10][11][12][13][14] The first-in-human imaging paper set the stage for Dr. Hooker’s ongoing work to measure and map HDAC density, distribution and connectivity in diverse diseases, in vivo.

References

  1. ^ Grant, Bob. "Jacob Hooker: Weaver of Brain Science". The Scientist. The Scientist. Retrieved 25 April 2016.
  2. ^ Wey, Hsiao-Ying; Gilbert, Tonya M.; Zürcher, Nicole R.; She, Angela; Bhanot, Anisha; Taillon, Brendan D.; Schroeder, Fredrick A.; Wang, Changing; Haggarty, Stephen J. (2016-08-10). "Insights into neuroepigenetics through human histone deacetylase PET imaging". Science Translational Medicine. 8 (351): 351ra106. doi:10.1126/scitranslmed.aaf7551. ISSN 1946-6242. PMID 27510902.
  3. ^ Hooker, Jacob M.; Kim, Sung Won; Alexoff, David; Xu, Youwen; Shea, Colleen; Reid, Alicia; Volkow, Nora; Fowler, Joanna S. (2010-01-01). "Histone deacetylase inhibitor, MS-275, exhibits poor brain penetration: PK studies of [C]MS-275 using Positron Emission Tomography". ACS chemical neuroscience. 1 (1): 65–73. doi:10.1021/cn9000268. ISSN 1948-7193. PMC 2908422. PMID 20657706.{{cite journal}}: CS1 maint: PMC format (link)
  4. ^ Wang, Changning; Eessalu, Thomas E.; Barth, Vanessa N.; Mitch, Charles H.; Wagner, Florence F.; Hong, Yijia; Neelamegam, Ramesh; Schroeder, Frederick A.; Holson, Edward B. (2013-01-01). "Design, synthesis, and evaluation of hydroxamic acid-based molecular probes for in vivo imaging of histone deacetylase (HDAC) in brain". American Journal of Nuclear Medicine and Molecular Imaging. 4 (1): 29–38. PMC 3867727. PMID 24380043.{{cite journal}}: CS1 maint: PMC format (link)
  5. ^ Seo, Young Jun; Muench, Lisa; Reid, Alicia; Chen, Jinzhu; Kang, Yeona; Hooker, Jacob M.; Volkow, Nora D.; Fowler, Joanna S.; Kim, Sung Won (2013-12-15). "Radionuclide labeling and evaluation of candidate radioligands for PET imaging of histone deacetylase in the brain". Bioorganic & Medicinal Chemistry Letters. 23 (24): 6700–6705. doi:10.1016/j.bmcl.2013.10.038. ISSN 1464-3405. PMC 4007514. PMID 24210501.{{cite journal}}: CS1 maint: PMC format (link)
  6. ^ Kim, Sung Won; Hooker, Jacob M.; Otto, Nicola; Win, Khaing; Muench, Lisa; Shea, Colleen; Carter, Pauline; King, Payton; Reid, Alicia E. (2013-10-01). "Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET". Nuclear Medicine and Biology. 40 (7): 912–918. doi:10.1016/j.nucmedbio.2013.06.007. ISSN 1872-9614. PMC 3769509. PMID 23906667.{{cite journal}}: CS1 maint: PMC format (link)
  7. ^ Schroeder, Frederick A.; Chonde, Daniel B.; Riley, Misha M.; Moseley, Christian K.; Granda, Michael L.; Wilson, Colin M.; Wagner, Florence F.; Zhang, Yan-Ling; Gale, Jennifer (2013-08-29). "FDG-PET imaging reveals local brain glucose utilization is altered by class I histone deacetylase inhibitors". Neuroscience Letters. 550: 119–124. doi:10.1016/j.neulet.2013.06.016. ISSN 1872-7972. PMC 3750730. PMID 23810801.{{cite journal}}: CS1 maint: PMC format (link)
  8. ^ Wang, Yajie; Zhang, Yan-Ling; Hennig, Krista; Gale, Jennifer P.; Hong, Yijia; Cha, Anna; Riley, Misha; Wagner, Florence; Haggarty, Stephen J. (2013-07-01). "Class I HDAC imaging using [ (3)H]CI-994 autoradiography". Epigenetics. 8 (7): 756–764. doi:10.4161/epi.25202. ISSN 1559-2308. PMC 3781195. PMID 23803584.{{cite journal}}: CS1 maint: PMC format (link)
  9. ^ Schroeder, Frederick A.; Lewis, Michael C.; Fass, Daniel M.; Wagner, Florence F.; Zhang, Yan-Ling; Hennig, Krista M.; Gale, Jennifer; Zhao, Wen-Ning; Reis, Surya (2013-01-01). "A selective HDAC 1/2 inhibitor modulates chromatin and gene expression in brain and alters mouse behavior in two mood-related tests". PloS One. 8 (8): e71323. doi:10.1371/journal.pone.0071323. ISSN 1932-6203. PMC 3743770. PMID 23967191.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  10. ^ Seo, Young Jun; Kang, Yeona; Muench, Lisa; Reid, Alicia; Caesar, Shannon; Jean, Logan; Wagner, Florence; Holson, Edward; Haggarty, Stephen J. (2014-07-16). "Image-guided synthesis reveals potent blood-brain barrier permeable histone deacetylase inhibitors". ACS chemical neuroscience. 5 (7): 588–596. doi:10.1021/cn500021p. ISSN 1948-7193. PMC 4102966. PMID 24780082.{{cite journal}}: CS1 maint: PMC format (link)
  11. ^ Wang, Changning; Schroeder, Frederick A.; Wey, Hsiao-Ying; Borra, Ronald; Wagner, Florence F.; Reis, Surya; Kim, Sung Won; Holson, Edward B.; Haggarty, Stephen J. (2014-10-09). "In vivo imaging of histone deacetylases (HDACs) in the central nervous system and major peripheral organs". Journal of Medicinal Chemistry. 57 (19): 7999–8009. doi:10.1021/jm500872p. ISSN 1520-4804. PMC 4191584. PMID 25203558.{{cite journal}}: CS1 maint: PMC format (link)
  12. ^ Schroeder, F. A.; Wang, C.; Van de Bittner, G. C.; Neelamegam, R.; Takakura, W. R.; Karunakaran, A.; Wey, H. Y.; Reis, S. A.; Gale, J. (2014-10-15). "PET imaging demonstrates histone deacetylase target engagement and clarifies brain penetrance of known and novel small molecule inhibitors in rat". ACS chemical neuroscience. 5 (10): 1055–1062. doi:10.1021/cn500162j. ISSN 1948-7193. PMC 4198064. PMID 25188794.{{cite journal}}: CS1 maint: PMC format (link)
  13. ^ Wey, Hsiao-Ying; Wang, Changning; Schroeder, Frederick A.; Logan, Jean; Price, Julie C.; Hooker, Jacob M. (2015-05-20). "Kinetic Analysis and Quantification of [¹¹C]Martinostat for in Vivo HDAC Imaging of the Brain". ACS chemical neuroscience. 6 (5): 708–715. doi:10.1021/acschemneuro.5b00066. ISSN 1948-7193. PMC 4439341. PMID 25768025.{{cite journal}}: CS1 maint: PMC format (link)
  14. ^ Strebl, Martin G.; Wang, Changning; Schroeder, Frederick A.; Placzek, Michael S.; Wey, Hsiao-Ying; Van de Bittner, Genevieve C.; Neelamegam, Ramesh; Hooker, Jacob M. (2016-05-18). "Development of a Fluorinated Class-I HDAC Radiotracer Reveals Key Chemical Determinants of Brain Penetrance". ACS chemical neuroscience. 7 (5): 528–533. doi:10.1021/acschemneuro.5b00297. ISSN 1948-7193. PMID 26675505.


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