Source: Interfolio F180
Stuart A. Lipton, M.D., Ph.D.
Scripps Research Joint Appointments
Research Focus
Dr. Lipton is best known for first describing the mechanism of action and contributing to the clinical development of the FDA-approved Alzheimer's drug memantine (Namenda, NamendaXR, Namzaric) and for discovering the posttranslational redox modification known as protein S-nitrosylation. Recently, Lipton and colleagues combined memantine with S-nitrosylation chemistry to produce a new drug called NitroSynapsin, which displays disease-modifying activity in animal models of Alzheimer's disease, both protecting synapses and improving neurobehavioral deficits. Lipton's group also characterized HIV-related pathways to neuronal damage, discovered the NR3 (now known at GluN3) family of modulatory NMDA-type glutamate receptor subunits in the brain, characterized the molecular pathways for protecting neurons with Erythropoietin, and discovered the transcription factor MEF2C. His group showed that MEF2C activity is regulated by S-nitrosylation and serves as a master switch for neurogenesis from human neural stem cells. Dysregulated MEF2C is involved in the pathogenesis of Parkinson's disease, Alzheimer's disease, Autism-Spectrum Disorder, and Vascular dementia.
Ongoing research in the lab is focused on 2D human induced pluripotent stem cell (hiPSC)-derived cultures and 3D cerebral organoid models of neurodegenerative and neurodevelopmental disease and aberrant redox/S-nitrosylation pathways leading to synaptic damage. Using these approaches, the Lipton group is developing novel drugs to combat Alzheimer's disease (AD), Parkinson's disease (PD), Vascular dementia (VaD), and other neurodegenerative disorders, as well as Autism-Spectrum Disorder (ASD) and Intellectual and Developmental Disabilities (IDD). Tissue culture models complement whole-animal approaches. A plethora of techniques is employed, including chemical biology, molecular biology, patch-clamp electrophysiology, calcium imaging, and neurobehavioral paradigms.
Education
M.D. (Medicine), University of Pennsylvania, 1977Ph.D. (Biochemistry & Biophysics), University of Pennsylvania, 1977
B.A. (Immunology and Neurobiology), Cornell University, 1971
Professional Experience
Neurologist/neuroscientist Stuart Lipton, MD, PhD is a renowned expert in dementia. He was trained at Cornell University, the University of Pennsylvania, and Harvard University. In addition to running a basic-science laboratory at The Scripps Research Institute, he has an active clinical neurology practice at UC San Diego focusing on dementia and general neurology. Lipton completed his PhD thesis research with John Dowling at Harvard, followed by clinical residency and a postdoctoral fellowship at Harvard with Torsten Wiesel during the time that Wiesel won the Nobel prize. He was then on the Harvard faculty for over 20 years before moving to La Jolla as founding director of a new neuroscience center in 2000.
External Joint Appointments
Department of Neurosciences/Neurology, University of California, San Diego, School of Medicine (https://providers.ucsd.edu/details/22261/neurology)
Department of Neurology, Yale School of Medicine
(https://medicine.yale.edu/profile/stuart-lipton/)
Link to All Publications (h-index 150): https://pubmed.ncbi.nlm.nih.gov/?term=lipton+s&sort=date
Awards & Professional Activities
1968/1969 National Merit Finalist/Ford Foundation Scholarship (Six-year PhDProgram Cornell University)
1971 Phi Beta Kappa
1973 Mary Ellis Bell Prize for Research, University of Pennsylvania School of Medicine
1974 Alpha Omega Alpha (Medical Honor Society)
1976 Baluin-Lucke Memorial Prize for Research, University of Pennsylvania School of Medicine
1979 Von L. Meyer Research Award, Children's Hospital/Harvard Medical School, Boston, MA
1989 Pattison Award in Neuroscience Research
1994 Nobel Foundation Lecture, Karolinska Institute, Stockholm, Sweden
1995 Science Citation by The Scientist (based on data from Science Citation Index of the Institute for Scientific Information, Philadelphia) for publishing the hottest (most cited) paper of the preceding two-year period in the field of Biochemistry (Lipton et al., Nature 1993;364:626-632);
1995 Nobel Foundation Lecture, Nobel Symposium on HIV Infection in the Brain, Nobel Forum, Karolinska Institute, Stockholm, Sweden
1997 Science Citation by The Scientist (based on data from Science Citation Index of the Institute for Scientific Information, Philadelphia) for publishing the hottest (most cited) paper of the preceding two-year period in the field of Neuroscience (Ankarcrona et al., Neuron 1995;15:961-973)
2001 Invited Speaker, Nobel Symposium on Apoptosis, Stockholm, Sweden
2001 The Ellison Medical Foundation Senior Scholar Award
2002 San Diego Health Hero Award, American Parkinson’s Disease Association
2004 Ernst Jung Prize in Medicine (for drug development, characterization of mechanism of action, and therapeutic consequences of Memantine, the first potentially neuroprotective drug approved by the European Medicines Agency and FDA for moderate-to-severe Alzheimer’s disease)
2005 MRC Lectureship in Neurotoxicology
2005 NINDS/NIH Neurodegenerative Disease Annual Invited Lectureship
2010 Nobel Foundation Lecture, Nobel Symposium on the Cell Cycle and Cell Death, Nobel Forum, Stockholm, Sweden
2011 Elected AAAS Fellow, Neuroscience Section
2012 Honorary Citizen of New Orleans from New Orleans City Council for Service on Neurosciences Board of LSU Health Sciences Center
2012 Outstanding Student Research Mentorship Award, University of California San Diego Health Sciences Clinical and Translational Research Institute
2012 Seoul National University College of Medicine, Award Lecture on “Role of Transcription Factor MEF2C in Controlling Embryonic Stem Cell Neurogenesis and Autism Spectrum Disorder”
2012 John F. Anderson Memorial Lecture, University of Virginia, Charlottesville, VA
2013 Annual Distinguished Biomedical Scholar Lecture Series, Carver College of Medicine, University of Iowa, Iowa City, IA
2013 Courage and Hope Award for Scientific Research, Alzheimer’s Disease Association
2013 Redox Pioneer (one of ten awards made world-wide to that date) from the journal Antioxidants & Redox Signaling
2013 Featured Scientist studying Alzheimer's disease, The Economist http://www.economist.com/news/science-and-technology/21579792-search-treatment-dementia-continues-beta-testing
2014 Brain & Behavior Research Foundation Distinguished Investigator Award
2015 Featured Profile (Neurology), The Lancet http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S1474442215000113.pdf
2015 Dean's Distinguished Lecture Series, Weil Cornell Medical College, NYC
2016 NIH Director's Grant Award (Avant Garde) (DP1 DA041722)
2016 United States House of Representatives “Proclamation to Honor of Stuart A. Lipton” for developing the FDA-approved drug memantine for the treatment of Alzheimer’s disease, discovering protein S-nitrosylation and new medicines based on this discovery, and discovering the transcription factor MEF2C and its role in autism, Alzheimer’s and Parkinson’s disease.
2017- Step Family Foundation Endowed Chair, The Scripps Research Institute, La Jolla, CA
2023 DZNE (German Center for Translational Neuroscience Research) Lecture Award for aberrant protein S-nitrosylation in neurodegenerative disorders
2023 Society for Redox Biology & Medicine (SfRBM) Discovery Award for protein S-nitrosylation, nomination by Nobel laureate Lou Ignarro (UCLA)
Selected Publications
Uehara, T.; Nakamura, T.; Yao, D.; Shi, Z. Q.; Gu, Z.; Ma, Y.; Masliah, E.; Nomura, Y.; Lipton, S. A. S-Nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature 2006, 441, 513-517.
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Cho, D. H.; Nakamura, T.; Fang, J. G.; Cieplak, P.; Godzik, A.; Gu, Z.; Lipton, S. A. S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 2009, 324, 102-105.
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Ryan, S. D.; Dolatabadi, N.; Chan, S. F.; Zhang, X.; Akhtar, M. W.; Parker, J.; Soldner, F.; Sunico, C. R.; Nagar, S.; Talantova, M.; Lee, B.; Lopez, K.; Nutter, A.; Shan, B.; Molokanova, E.; Zhang, Y.; Han, X.; Nakamura, T.; Masliah, E.; Yates, J. R.; Nakanishi, N.; Andreyev, A. Y.; Okamoto, S.; Jaenisch, R.; Ambasudhan, R.; Lipton, S. A. Isogenic human iPSC Parkinson's model shows nitrosative stress-induced dysfunction in MEF2-PGC1 alpha transcription. Cell 2013, 155, 1351-1364.
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Nakamura, T.; Oh, C. K.; Liao, L.; Zhang, X.; Lopez, K. M.; Gibbs, D.; Deal, A. K.; Scott, H. R.; Spencer, B.; Masliah, E.; Rissman, R. A.; Yates, J. R.; Lipton, S. A. Noncanonical transnitrosylation network contributes to synapse loss in Alzheimer's disease. Science 2021, 371.
Yang, H.; Oh, C. K.; Amal, H.; Wishnok, J. S.; Lewis, S.; Schahrer, E.; Trudler, D.; Nakamura, T.; Tannenbaum, S. R.; Lipton, S. A. Mechanistic insight into female predominance in Alzheimer's disease based on aberrant protein S-nitrosylation of C3. Science Advances 2022, 8, eade0764.
Oh, C.; Nakamura, T.; Beutler, N.; Zhang, X.; Piña-Crespo, J.; Talantova, M.; Ghatak, S.; Trudler, D.; Carnevale, L. N.; McKercher, S. R.; Bakowski, M. A.; Diedrich, J. K.; Roberts, A. J.; Woods, A. K.; Chi, V.; Gupta, A. K.; Rosenfeld, M. A.; Kearns, F. L.; Casalino, L.; Shaabani, N.; Liu, H.; Wilson, I. A.; Amaro, R. E.; Burton, D. R.; Yates, J. R.; Becker, C.; Rogers, T. F.; Chatterjee, A. K.; Lipton, S. A. Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection. Nature Chemical Biology 2023, 19, 275-283.