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Giulio Maria Pasinetti

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Giulio Maria Pasinetti
Dr. Pasinetti presents: "Innate Neuroimmune Priming: Mechanisms and Potential Imaging Biomarkers" at TMII's STRIVE Seminar Series at Mount Sinai, YC in September 2018
NationalityAmerican, Italian
Alma materUniversity of Milan
EmployerIcahn School of Medicine at Mount Sinai
Known forBiological psychiatry, Alzheimer's disease
Websitehttp://www.mountsinai.org/profiles/giulio-m-pasinetti

Giulio Maria Pasinetti is the Program Director of the Center on Molecular Integrative Neuroresilience[1] and is the Saunders Family Chair in Neurology at the Icahn School of Medicine at Mount Sinai (ISMMS) in New York City.[2] Pasinetti is a Professor of Neurology, Psychiatry, Neuroscience, and Geriatrics and Palliative Medicine at ISMMS.[2]

As the Program Director of the NIH / NCCIH funded P50 Center on Molecular Integrative Neuroresilience, Pasinetti's focus is on understanding the molecular mechanisms and pathophysiology that may be at the basis of stress-induced mood disorders, including anxiety, depression, and other neuropsychiatric disorders, and their influence on cognitive dysfunction.

At the Veterans Health Administration, Pasinetti is the Director of the Basic and Biomedical Research and Training Program, Geriatric Research, Education, and Clinical Center (GRECC), as well as the Director of the Translational Neuroscience Laboratories at the James J. Peters Veterans Affairs Medical Center (JJPVAMC).[3]

Pasinetti has an h-index of 81, with over 20,000 citations.[4] He has published over 250 papers indexed in PubMed, as well as 6 book chapters.[5]

Biography

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Education

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Pasinetti received an M.D. from the Milan University School of Medicine (1982) and a Ph.D. in Pharmacology from the University of Milan (1988). He was a Research Fellow (Neuropharmacology, 1983-1984) at the University of Milan. Upon moving to the United States, he worked as a Research Associate (Neurogerontology, 1984-1988) and, eventually, as a Senior Research Associate (Neurogerontology, 1989-1990) at the University of Southern California in Los Angeles.[6]

Career

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Pasinetti began his career as an assistant professor at the California School of Gerontology and Biological Sciences at the University of Southern California (1990–1995) in Los Angeles. Since 1996, he has been a faculty member of the Icahn School of Medicine at Mount Sinai where he served as the Aidekman Family Chair and Professor in Neurology until 2009. Pasinetti was also the chief of the Friedman Brain Institute Center of Excellence for Novel Approaches to Neurodiagnostics and Neurotherapeutics, as well as, from 2008 to 2014, the director and principal investigator of the NIH-funded Center of Excellence for Research on Complementary and Alternative Medicine (CERC) in Alzheimer's disease.[2]

Awards

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Dr. Pasinetti's awards and honors include the Mount Sinai School of Medicine Faculty Council Award for Academic Excellence, the Charles Dana Alliance for Brain Initiatives Award from the Dana Foundation,[7] the Foundation Queen Sofia of Spain Research Center award on Alzheimer's Disease,[8] the Research Career Scientist Developmental Award from the Veterans Health Administration,[9] the Zenith Award from the Alzheimer's Association,[10] the Temple Foundation Discovery Award from the Alzheimer's Association,[10] the Nathan W. & Margaret T. Shock Aging Research Foundation Award from the Gerontological Society of America, the Turken Family fellowship from the Alzheimer's Association (Los Angeles Chapter) and the Nathan Shock New Investigator Award of the Gerontological Society of America.[11] Dr. Pasinetti was also awarded the 2017 Mary Swartz Rose Senior Investigator Award by The American Society for Nutrition and the American Society for Nutrition Foundation. Most recently, Dr. Pasinetti was named an Honorary Fellow of The University of Bergamo (Università degli Studi di Bergamo).

Grants and Research

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Pasinetti investigates the biological processes that occur when, during aging, subjects with normal cognitive function convert into the very earliest stages of Alzheimer's disease (AD) and then to frank dementia. He identified type 2 diabetes (T2D) as one of the major risk factors that might affect AD neuropathology and synaptic plasticity in part through epigenetic mechanisms.[12] By conducting genome wide association studies to clarify the molecular mechanisms in subjects with T2D who might be predisposed to the onset of Alzheimer's disease,[13] Pasinetti found that a subpopulation of individuals with T2D have a genetic predisposition to AD based on the evidence of shared common T2D/AD single nucleotide polymorphisms in gene pathways involved in chromatin modification enzymes, among others. Through this research, Pasinetti and his colleagues provided the basis for novel therapeutic targets towards the preservation of cognitive health in a subset of T2D subjects at risk for developing AD.[12][14][15][16]

With his group, Pasinetti has led research investigations on the neuromolecular mechanisms underlying age-related cognitive decline, dementia, and stress-induced psychological and cognitive impairment with the goal of utilizing repurposed natural products, specifically polyphenols, to promote resilience to such conditions.[17][18][19][20] With this in mind, Pasinetti initiated a drug repurposing study for AD, screening FDA-approved drugs and natural compounds for amyloid-lowering and anti-Aβ aggregation activities, and identified candidates for in vivo testing in AD animal models.[21][22][23][24] As a result of this study, Pasinetti's laboratory identified antihypertensive drugs lacking cardiovascular side effects but with enhanced anti-Aβ oligomerization activity.[25][26] Pasinetti's research has also validated that repurposing drugs that have already been well-characterized in terms of tolerability and safety profile may have several advantages over novel drugs. These studies provide new information about the potentially detrimental role of commonly prescribed drugs that can be used as a reference for physicians to consider, particularly when treating chronic degenerative disorders such as AD.[27][28][29]

Following these findings, as Chief of the Friedman Brain Institute Center of Excellence for Novel Approaches to Neurodiagnostics and Neurotherapeutics, Pasinetti developed drug discovery programs for Alzheimer's disease.[17][26][30] Here, he led a primary translational Center to determine whether interventions which appear to work in the preclinical animal model of the disease also show promise in treating patients who have the disease.[27][29][31]

Pasinetti is the Director of the NIH funded Botanical Center in Neuroresilience.[1] This Center supports three major projects which are being conducted through interdisciplinary collaborative efforts from Mount Sinai Hospital's Department of Neuroscience, Department of Neurology, Department of Genetics and Genomic Sciences, and the Friedman Brain Institute.[32][33] One project is the efficacy of using polyphenols specifically as dietary supplements to promote resilience against stressful events and clarifying the role of the microbiome at the genomic level in the promotion of cognitive and psychological health.[31] [33] This research is leading to safe and efficacious treatments of dietary botanical supplements to promote resilience in response to psychological and cognitive impairment.[32]

In a study released on February 2, 2018, scientists from the Icahn School of Medicine at Mount Sinai, led by Dr. Giulio Maria Pasinetti, described an extensive analysis of two novel grape-derived phytochemicals, or natural essential nutrients, dihydrocaffeic acid (DHCA) and malvidin-3’-O-glucoside (Mal-gluc), which might be developed as therapeutic agents for the treatment of depression. The study demonstrated that DHCA reversed improper epigenetic modifications that have been shown to promote the DNA transcription of numerous pro-inflammatory genes, such as interleukin 6 (IL-6). Mal-gluc was found to increase the transcription of the Rac1 gene, which influences the expression of genes responsible for synaptic plasticity in the brain. It was demonstrated that treatment with both DHCA and Mal-gluc is effective in attenuating depression-like phenotypes in a mouse model of increased systemic inflammation induced by transplantation of cells from the bone marrow of stress-susceptible mice. This Mount Sinai study provides novel preclinical evidence supporting the targeting of multiple key disease mechanisms through DNA epigenetic modification for the treatment of depression and strongly supports the need to test and identify novel compounds that target alternative pathologic mechanisms, such as inflammation and synaptic maladaptation, for individuals who are resistant to currently available treatments.[34]

With his involvement at the Veterans Administration, Pasinetti and his lab identified biomarkers to help diagnose the two signature injuries of the recent wars in Iraq and Afghanistan: mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). The focus was on four specific non-coding miRNA which were all found at significantly lower levels in those Veterans who had comorbid TBI plus PTSD, when compared to subjects who had only PTSD.[35][36] The availability of such biomarkers could provide more precise benchmarks and outcome measures in clinical trials of different TBI or PTSD therapies.

Pasinetti's lab is now working on tracing "downstream" molecular pathways in preclinical rodent models of mTBI, to eventually tie them back to TBI or PTSD symptoms and allow for identification of potential new drug targets to be further developed in the clinical setting.[37]

Taken together, the focus of Dr. Pasinetti's research determining the molecular basis of neurodegenerative disorders and TBI to provide targets for novel therapies has the ultimate goal of identifying unique treatment strategies that can be translated to improve pharmacological treatment in clinical care.

Publications (Partial List)

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References

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  1. ^ a b "Center for Molecular Integrative Neuroresilience". Icahn School of Medicine at Mount Sinai. Retrieved 13 October 2016.
  2. ^ a b c "Giulio Pasinetti". Mount Sinai Hospital Doctor Profile. Retrieved 27 September 2016.
  3. ^ "James J. Peters VA Medical Center". www.bronx.va.gov. Retrieved 17 October 2016.
  4. ^ "Giulio Maria Pasinetti - Google Scholar Citations". scholar.google.com. Retrieved 25 October 2021.
  5. ^ "Giulio M Pasinetti[au] - PubMed - NCBI". www.ncbi.nlm.nih.gov.
  6. ^ "USC Davis School of Gerontology: Faculty & Staff". www.usc.edu. Retrieved 1 October 2016.
  7. ^ "Search". www.dana.org. Retrieved 13 October 2016.
  8. ^ "Casa de Su Majestad el Rey de España - S.M. la Reina Doña Sofía - Queen Sofia Foundation". www.casareal.es. Retrieved 13 October 2016.
  9. ^ Pasinetti, Giulio Maria; Wang, Jun; Ho, Lap; Zhao, Wei; Dubner, Lauren (1 June 2015). "Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment". Biochim. Biophys. Acta. 1852 (6): 1202–1208. doi:10.1016/j.bbadis.2014.10.006. PMC 4380832. PMID 25315300.
  10. ^ a b Ho, Lap; Purohit, Dushyant; Haroutunian, Vahram; Luterman, James D.; Willis, Fitzroy; Naslund, Jan; Buxbaum, Joseph D.; Mohs, Richard C.; Aisen, Paul S.; Pasinetti, Giulio Maria (1 March 2001). "NEuronal cyclooxygenase 2 expression in the hippocampal formation as a function of the clinical progression of alzheimer disease". Archives of Neurology. 58 (3): 487–492. doi:10.1001/archneur.58.3.487. PMID 11255454.
  11. ^ "Awardees". The Gerontological Society of America. Retrieved 4 October 2016.
  12. ^ a b Wang, Jun; Gong, Bing; Zhao, Wei; Tang, Cheuk; Varghese, Merina; Nguyen, Tuyen; Bi, Weina; Bilski, Amanda; Begum, Shimul; Vempati, Prashant; Knable, Lindsay; Ho, Lap; Pasinetti, Giulio M. (1 February 2014). "Epigenetic Mechanisms Linking Diabetes and Synaptic Impairments". Diabetes. 63 (2): 645–654. doi:10.2337/db13-1063. ISSN 0012-1797. PMID 24154559.
  13. ^ Giulio, Pasinetti. "Mechanisms of BACE1 Degradation in Experimental Alzheimer's Disease Therapeutic". Retrieved 29 September 2016.
  14. ^ Hao, Ke; Di Narzo, Antonio Fabio; Ho, Lap; Luo, Wei; Li, Shuyu; Chen, Rong; Li, Tongbin; Dubner, Lauren; Pasinetti, Giulio Maria (June 2015). "Shared genetic etiology underlying Alzheimer's disease and type 2 diabetes". Molecular Aspects of Medicine. 43–44: 66–76. doi:10.1016/j.mam.2015.06.006. PMC 6021176. PMID 26116273.
  15. ^ "Potential Explanation for Link between Diabetes and Alzheimer's | Psych Central News". 20 July 2015. Retrieved 28 September 2016.
  16. ^ "Genetic markers linking risk for type 2 diabetes and Alzheimer's identified". Retrieved 28 September 2016.
  17. ^ a b Giulio, Pasinetti. "Protective roles of grape-derived polyphenols in Alzheimer's disease".
  18. ^ Gaffney, Jacob (2012-05-15). "Study Finds Hope in Treating Alzheimer's With Wine Polyphenol". Wine Spectator. Retrieved 2024-08-06.
  19. ^ "Calorie Restriction May Prevent Alzheimer's Through Promotion Of Longevity Program In The Brain". www.sciencedaily.com. Retrieved 28 September 2016.
  20. ^ Conick, Hal (2015-10-14). "Smart chocolate may eventually be used to treat Alzheimer's, says neurologist". confectionerynews.com. Retrieved 2024-08-06.
  21. ^ Jun, Wang; Merina, Varghese; Kenjiro, Ono; Masahito, Yamada; Samara, Levine; Nikos, Tzavaras; Bing, Gong; J., Hurst, William; D., Blitzer, Robert; Maria, Pasinetti, Giulio (1 January 2014). "Cocoa Extracts Reduce Oligomerization of Amyloid-β: Implications for Cognitive Improvement in Alzheimer's Disease". Journal of Alzheimer's Disease. 41 (2): 643–50. doi:10.3233/JAD-132231. ISSN 1387-2877. PMID 24957018. Retrieved 28 September 2016.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Wang, Jun; Bi, Weina; Cheng, Alice; Freire, Daniel; Vempati, Prashant; Zhao, Wei; Gong, Bing; Janle, Elsa M.; Chen, Tzu-Ying; Ferruzzi, Mario G.; Schmeidler, James; Ho, Lap; Pasinetti, Giulio M. (14 March 2014). "Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer's disease-experimental approach and therapeutic implications". Frontiers in Aging Neuroscience. 6: 42. doi:10.3389/fnagi.2014.00042. PMC 3954102. PMID 24672477.
  23. ^ Pasinetti, Giulio Maria; Wang, Jun; Ho, Lap; Zhao, Wei; Dubner, Lauren (June 2015). "Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1852 (6): 1202–1208. doi:10.1016/j.bbadis.2014.10.006. PMC 4380832. PMID 25315300.
  24. ^ Pasinetti, Giulio (11 March 2015). "Novel role of red wine-derived polyphenols in the prevention of Alzheimerʼs disease dementia and brain pathology: experimental approaches and clinical implications". Planta Medica. 78 (15): E24. doi:10.1055/s-0035-1545846. PMID 25760447.
  25. ^ Wang, Jun; Zhao, Zhong; Lin, Emi; Zhao, Wei; Qian, Xianjuan; Freire, Daniel; Bilski, Amanda E.; Cheng, Alice; Vempati, Prashant; Ho, Lap; Ono, Kenjiro; Yamada, Masahito; Pasinetti, Giulio M. (6 June 2013). "Unintended Effects of Cardiovascular Drugs on the Pathogenesis of Alzheimer's Disease". PLOS ONE. 8 (6): e65232. Bibcode:2013PLoSO...865232W. doi:10.1371/journal.pone.0065232. ISSN 1932-6203. PMC 3675203. PMID 23762322.
  26. ^ a b Giulio, Pasinetti; Paul, Rosenberg. "Pilot Trial of Carvedilol in Alzheimer's Disease".
  27. ^ a b Ward, Libby; Pasinetti, Giulio Maria (24 June 2016). "Recommendations for Development of Botanical Polyphenols as "Natural Drugs" for Promotion of Resilience Against Stress-Induced Depression and Cognitive Impairment". NeuroMolecular Medicine. 18 (3): 487–495. doi:10.1007/s12017-016-8418-6. PMC 4985489. PMID 27342633.
  28. ^ Wang, Jun; Tang, Cheuk; Ferruzzi, Mario G.; Gong, Bing; Song, Brian J.; Janle, Elsa M.; Chen, Tzu-Ying; Cooper, Bruce; Varghese, Merina; Cheng, Alice; Freire, Daniel; Bilski, Amanda; Roman, Jessica; Nguyen, Tuyen; Ho, Lap; Talcott, Stephen T.; Simon, James E.; Wu, Qingli; Pasinetti, Giulio M. (December 2013). "Role of standardized grape polyphenol preparation as a novel treatment to improve synaptic plasticity through attenuation of features of metabolic syndrome in a mouse model". Molecular Nutrition & Food Research. 57 (12): 2091–2102. doi:10.1002/mnfr.201300230. PMC 3855562. PMID 23963661.
  29. ^ a b Dubner, Lauren; Wang, Jun; Ho, Lap; Ward, Libby; Pasinetti, Giulio M. (27 October 2015). "Recommendations for Development of New Standardized Forms of Cocoa Breeds and Cocoa Extract Processing for the Prevention of Alzheimer's Disease: Role of Cocoa in Promotion of Cognitive Resilience and Healthy Brain Aging". Journal of Alzheimer's Disease. 48 (4): 879–889. doi:10.3233/JAD-150536. PMID 26402120.
  30. ^ Wang, Jun; Land, David; Ono, Kenjiro; Galvez, Jorge; Zhao, Wei; Vempati, Prashant; Steele, John W.; Cheng, Alice; Yamada, Masahito; Levine, Samara; Mazzola, Paolo; Pasinetti, Giulio M. (26 March 2014). "Molecular Topology as Novel Strategy for Discovery of Drugs with Aβ Lowering and Anti-Aggregation Dual Activities for Alzheimer's Disease". PLOS ONE. 9 (3): e92750. Bibcode:2014PLoSO...992750W. doi:10.1371/journal.pone.0092750. ISSN 1932-6203. PMC 3966818. PMID 24671215.
  31. ^ a b Wang, Dongjie; Ho, Lap; Faith, Jeremiah; Ono, Kenjiro; Janle, Elsa M.; Lachcik, Pamela J.; Cooper, Bruce R.; Jannasch, Amber H.; D'Arcy, Bruce R.; Williams, Barbara A.; Ferruzzi, Mario G.; Levine, Samara; Zhao, Wei; Dubner, Lauren; Pasinetti, Giulio M. (June 2015). "Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer's disease β-amyloid oligomerization". Molecular Nutrition & Food Research. 59 (6): 1025–1040. doi:10.1002/mnfr.201400544. PMC 4498582. PMID 25689033.
  32. ^ a b "Molecular Neuroresilience Research". Icahn School of Medicine at Mount Sinai. Retrieved 30 September 2016.
  33. ^ a b Giulio, Pasinetti; Richard, Dixon. "Pasinetti: Overall; Dietary Botanicals in the Preservation of Cognitive and Psychological Resilience (Pasinetti)". Retrieved 29 September 2016.
  34. ^ Wang, Jun; Hodes, Georgoa E.; Hongxing, Zhang; Pasinetti, Giulio Maria (2018). "Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice". Nature Communications. 9 (1): 477. Bibcode:2018NatCo...9..477W. doi:10.1038/s41467-017-02794-5. PMC 5797143. PMID 29396460.
  35. ^ Ho, Lap; Lange, Gudrun; Zhao, Wei; Wang, Jun; Rooney, Robert; Patel, Divyen H.; Fobler, Malusha M.; Helmer, Drew A.; Elder, Gregory; Shaughness, Michael C.; Ahlers, Stephen T.; Russo, Scott J.; Pasinetti, Giulio Maria (1 January 2014). "Select small nucleolar RNAs in blood components as novel biomarkers for improved identification of comorbid traumatic brain injury and post-traumatic stress disorder in veterans of the conflicts in Afghanistan and Iraq". American Journal of Neurodegenerative Disease. 3 (3): 170–181. ISSN 2165-591X. PMC 4299721. PMID 25628968.
  36. ^ Pasinetti, Giulio M.; Ho, Lap; Dooley, Christopher; Abbi, Bhavna; Lange, Gudrun (1 January 2012). "Select non-coding RNA in blood components provide novel clinically accessible biological surrogates for improved identification of traumatic brain injury in OEF/OIF Veterans". American Journal of Neurodegenerative Disease. 1 (1): 88–98. ISSN 2165-591X. PMC 3560446. PMID 22737634.
  37. ^ Zhao, Wei; Ho, Lap; Varghese, Merina; Yemul, Shrishailam; Dams-O'Connor, Kristen; Gordon, Wayne; Knable, Lindsay; Freire, Daniel; Haroutunian, Vahram; Pasinetti, Giulio Maria (1 January 2013). "Decreased level of olfactory receptors in blood cells following traumatic brain injury and potential association with tauopathy". Journal of Alzheimer's Disease. 34 (2): 417–429. doi:10.3233/JAD-121894. ISSN 1875-8908. PMC 3968322. PMID 23241557.
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