19
1
49
2
8
1b
1d
18
34
3e
1d
2 29
1d
25
Julie A. Blendy, Ph.D.
78
3e
Professor of Pharmacology
7
8a
Department: Systems Pharmacology and Translational Therapeutics
4
1
23
1f
Graduate Group Affiliations
8
b
-
6a
- Pharmacology 64
- Neuroscience e
1d
46
Contact information
48
4
3
3
1d
48
Department of Pharmacology
30 2211 Translational Research Laboratories
1d 125 South 31st Street
51 University of Pennsylvania Medical School
Philadelphia, PA 19104-3403
26
30 2211 Translational Research Laboratories
1d 125 South 31st Street
51 University of Pennsylvania Medical School
Philadelphia, PA 19104-3403
30
Office: (215) 898-0730
35 Fax: (215) 573-2236
24
93
35 Fax: (215) 573-2236
24
Email:
BLENDY@MAIL.MED.UPENN.EDU
12
BLENDY@MAIL.MED.UPENN.EDU
18
Publications
23 a
3
2
29
23 a
Links
98 Search PubMed for articles
42 Pharmacological Sciences graduate group faculty webpage.
3f Neuroscience graduate group faculty webpage.
c
4
b
1f
98 Search PubMed for articles
42 Pharmacological Sciences graduate group faculty webpage.
3f Neuroscience graduate group faculty webpage.
c
13
Education:
21 9 B.S. 14 (Zoology) c
3d University of Maryland, College Park, 1981.
21 9 M.S. 14 (Zoology) c
3d University of Maryland, College Park, 1985.
21 a Ph.D. 19 (Pharmacology) c
2e Georgetown University, 1990.
c
3
3
3
3
90
Permanent link21 9 B.S. 14 (Zoology) c
3d University of Maryland, College Park, 1981.
21 9 M.S. 14 (Zoology) c
3d University of Maryland, College Park, 1985.
21 a Ph.D. 19 (Pharmacology) c
2e Georgetown University, 1990.
c
2 29
21
1e
1d
24
5e
85 gene targeting, mouse models, behavioral genetics, CRE-transcription factors (CREB, CREM, ICER), substance abuse, depression
8
1a RESEARCH INTERESTS
34 Molecular Basis of Addiction and Depression
8
1b RESEARCH TECHNIQUES
1a4 Generation of mouse models using the approaches of gene targeting in embryonic stem cells. Characterization of these mouse models by1) behavioral analysis: locomotor activity, morphine withdrawal response, Conditioned Place Preference, forced swim test, tail suspension test. 2) pharmacological analysis 3) molecular analysis: RNAse protection assays, real time PCR, EMSA, Western blots and immunohistochemistry
8
18 RESEARCH SUMMARY
75b My research is aimed at understanding the molecular basis for the biochemical and behavioral changes associated with chronic drug use. How drugs exert effects that lead to long-term adaptations within the central nervous system is not well understood. However, alterations in gene expression are a likely mechanism. A group of transcription factors, CREB (cAMP response element binding protein) and CREM (cAMP response element modulatory protein), have been identified as key proteins mediating a transcriptional response to elevated levels of cAMP and/or Ca++. We have shown that mice deficient in CREB show paradoxical responses in behavioral conditioning paradigms to morphine and cocaine. Current projects are aimed at investigating the molecular basis for this differential response with techniques ranging from EMSA's (electromobility shift assays), Western analyses, real time PCR, RNAse protection assays and immunohistochemistry. In addition, recent studies in our lab have identified alterations in depression-like phenotypes in CREB deficient mice, The clinical co-morbidity between addiction and depression is striking. While little is known regarding the cause-effect relationship between these disease states, there are striking similarities at a molecular level, and, as in the case of drugs of abuse, cAMP mediated gene transcription has been implicated in the mechanism(s) of action of antidepressant drugs. Future studies involve the development and use of tissue specific gene-targeting (Cre/loxP system) to inactivate known and/or novel CREB targets to further characterize the molecules and neural circuitry involved in the mechanism of action of drugs of abuse as well as antidepressant drugs. The combined use of pharmacological, behavioral and molecular studies should lead to a better understanding of the biological basis of addiction and depression.
e 29
27
Description of Research Expertise
1b KEY WORDS:85 gene targeting, mouse models, behavioral genetics, CRE-transcription factors (CREB, CREM, ICER), substance abuse, depression
8
1a RESEARCH INTERESTS
34 Molecular Basis of Addiction and Depression
8
1b RESEARCH TECHNIQUES
1a4 Generation of mouse models using the approaches of gene targeting in embryonic stem cells. Characterization of these mouse models by1) behavioral analysis: locomotor activity, morphine withdrawal response, Conditioned Place Preference, forced swim test, tail suspension test. 2) pharmacological analysis 3) molecular analysis: RNAse protection assays, real time PCR, EMSA, Western blots and immunohistochemistry
8
18 RESEARCH SUMMARY
75b My research is aimed at understanding the molecular basis for the biochemical and behavioral changes associated with chronic drug use. How drugs exert effects that lead to long-term adaptations within the central nervous system is not well understood. However, alterations in gene expression are a likely mechanism. A group of transcription factors, CREB (cAMP response element binding protein) and CREM (cAMP response element modulatory protein), have been identified as key proteins mediating a transcriptional response to elevated levels of cAMP and/or Ca++. We have shown that mice deficient in CREB show paradoxical responses in behavioral conditioning paradigms to morphine and cocaine. Current projects are aimed at investigating the molecular basis for this differential response with techniques ranging from EMSA's (electromobility shift assays), Western analyses, real time PCR, RNAse protection assays and immunohistochemistry. In addition, recent studies in our lab have identified alterations in depression-like phenotypes in CREB deficient mice, The clinical co-morbidity between addiction and depression is striking. While little is known regarding the cause-effect relationship between these disease states, there are striking similarities at a molecular level, and, as in the case of drugs of abuse, cAMP mediated gene transcription has been implicated in the mechanism(s) of action of antidepressant drugs. Future studies involve the development and use of tissue specific gene-targeting (Cre/loxP system) to inactivate known and/or novel CREB targets to further characterize the molecules and neural circuitry involved in the mechanism of action of drugs of abuse as well as antidepressant drugs. The combined use of pharmacological, behavioral and molecular studies should lead to a better understanding of the biological basis of addiction and depression.
e 29
23
10d Yohn NL, Blendy JA.: Adolescent Chronic Unpredictable Stress Exposure Is a Sensitive Window for Long-Term Changes in Adult Behavior in Mice. Neuropsychopharmacology doi: 10.1038/npp.2017.11, 2017.
ce Sanchez V, Carpenter MD, Yohn NL, Blendy JA.: Long-lasting effects of adolescent oxycodone exposure on reward-related behavior and gene expression in mice. 57 Psychopharmacology (Berl). 23-24(233 ): 3991-4002, Dec 2016.
159 Wood KH, Johnson BS, Welsh SA, Lee JY, Cui Y, Krizman E, Brodkin ES, Blendy JA, Robinson MB, Bartolomei MS, Zhou Z.: Tagging methyl-CpG-binding domain proteins reveals different spatiotemporal expression and supports distinct functions. Epigenomics 8(4): 455-73, Apr 2016.
167 Forcelli Patrick A, Turner Jill R, Lee Bridgin G, Olson Thao T, Xie Teresa, Xiao Yingxian, Blendy Julie A, Kellar Kenneth J: Anxiolytic- and antidepressant-like effects of the methadone metabolite 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP). Neuropharmacology 101: 46-56, Feb 2016.
e5 Falcone Mary, Lee Bridgin, Lerman Caryn, Blendy Julie A: Translational Research on Nicotine Dependence. Current topics in behavioral neurosciences Feb 2016.
186 Lee Bridgin G, Anastasia Agustin, Hempstead Barbara L, Lee Francis S, Blendy Julie A: Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 17(12): 1428-35, Dec 2015.
14d Yohn Nicole L, Bartolomei Marisa S, Blendy Julie A: Multigenerational and transgenerational inheritance of drug exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine. Progress in biophysics and molecular biology 118(1-2): 21-33, Jul 2015.
19f Zhang Yong, Picetti Roberto, Butelman Eduardo R, Ho Ann, Blendy Julie A, Kreek Mary Jeanne: Mouse model of the OPRM1 (A118G) polymorphism: differential heroin self-administration behavior compared with wild-type mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 40(5): 1091-100, Apr 2015.
13f Briand Lisa A, Lee Bridgin G, Lelay John, Kaestner Klaus H, Blendy Julie A: Serine 133 phosphorylation is not required for hippocampal CREB-mediated transcription and behavior. Learning & memory (Cold Spring Harbor, N.Y.) 22(2): 109-15, Feb 2015.
2c
7
1d
1f
Selected Publications
71 Eacret D, Lemchi C, Caulfield JI, Cavigelli SA, Veasey SC, Blendy JA. 77 : Chronic Sleep Deprivation Blocks Voluntary Morphine Consumption but Not Conditioned Place Preference in Mice 15 Front Neurosci 23 February 2022.10d Yohn NL, Blendy JA.: Adolescent Chronic Unpredictable Stress Exposure Is a Sensitive Window for Long-Term Changes in Adult Behavior in Mice. Neuropsychopharmacology doi: 10.1038/npp.2017.11, 2017.
ce Sanchez V, Carpenter MD, Yohn NL, Blendy JA.: Long-lasting effects of adolescent oxycodone exposure on reward-related behavior and gene expression in mice. 57 Psychopharmacology (Berl). 23-24(233 ): 3991-4002, Dec 2016.
159 Wood KH, Johnson BS, Welsh SA, Lee JY, Cui Y, Krizman E, Brodkin ES, Blendy JA, Robinson MB, Bartolomei MS, Zhou Z.: Tagging methyl-CpG-binding domain proteins reveals different spatiotemporal expression and supports distinct functions. Epigenomics 8(4): 455-73, Apr 2016.
167 Forcelli Patrick A, Turner Jill R, Lee Bridgin G, Olson Thao T, Xie Teresa, Xiao Yingxian, Blendy Julie A, Kellar Kenneth J: Anxiolytic- and antidepressant-like effects of the methadone metabolite 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP). Neuropharmacology 101: 46-56, Feb 2016.
e5 Falcone Mary, Lee Bridgin, Lerman Caryn, Blendy Julie A: Translational Research on Nicotine Dependence. Current topics in behavioral neurosciences Feb 2016.
186 Lee Bridgin G, Anastasia Agustin, Hempstead Barbara L, Lee Francis S, Blendy Julie A: Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 17(12): 1428-35, Dec 2015.
14d Yohn Nicole L, Bartolomei Marisa S, Blendy Julie A: Multigenerational and transgenerational inheritance of drug exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine. Progress in biophysics and molecular biology 118(1-2): 21-33, Jul 2015.
19f Zhang Yong, Picetti Roberto, Butelman Eduardo R, Ho Ann, Blendy Julie A, Kreek Mary Jeanne: Mouse model of the OPRM1 (A118G) polymorphism: differential heroin self-administration behavior compared with wild-type mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 40(5): 1091-100, Apr 2015.
13f Briand Lisa A, Lee Bridgin G, Lelay John, Kaestner Klaus H, Blendy Julie A: Serine 133 phosphorylation is not required for hippocampal CREB-mediated transcription and behavior. Learning & memory (Cold Spring Harbor, N.Y.) 22(2): 109-15, Feb 2015.
2c