Leslie Giselle Nucifora, PhD

• Director, Laboratory of Biochemical Neurobiology, Department of Psychiatry, Johns Hopkins School of Medicine
• Project Leader, Johns Hopkins Precision Medicine Center of Excellence for Schizoaffective Disorders

Assistant Professor of Psychiatry and Behavioral Sciences

• Johns Hopkins Precision Medicine Center of Excellence for Schizoaffective Disorders

• Johns Hopkins Press Release 05/08/2019. Broccoli Sprout Compound May Restore Brain Chemistry Imbalance Linked to Schizophrenia | Johns Hopkins Medicine (hopkinsmedicine.org).
• The New York Post 05/09/2019. Broccoli may help fight off schizophrenia: study.  By: Hannah Frishberg. Broccoli may fight schizophrenia: study | New York Post.
• BioTechniques. 05/16/2019. Broccoli balancing the brain. Sulforaphane a Potential for Schizophrenia Treatment? - BioTechniques.
• Brain and Behavior Research Fourndation Press Release, 06/13/2019. Evidence Links Abnormally Formed Proteins With Schizophrenia Pathology in Some Patients. Evidence Links Abnormally Formed Proteins With Schizophrenia Pathology in Some Patients | Brain & Behavior Research Foundation
• Johns Hopkins Press Release, 06/24/2019. Physical Evidence In The Brain for Types of Schizophrenia. Physical Evidence In The Brain for Types of Schizophrenia | Johns Hopkins Medicine (hopkinsmedicine.org).
• Psychiatry News, 06/25/2019. Abnormal Proteins May Contribute to Some Schizophrenia Cases. By: Nick Zagorski, Volume 54, Number 12. Abnormal Proteins May Contribute to Some Schizophrenia Cases | Psychiatric News
• Science Daily, 06/26/2019. Physical evidence in the brain for types of schizophrenia. Physical evidence in the brain for types of schizophrenia | ScienceDaily
• MedScape, 07/03/2019. Protein Buildup in the Brain a New Target for Schizophrenia? By Megan Brooks. Protein Buildup in the Brain a New Target for Schizophrenia?
• News in Proteomics Research. 07/09/2025. News in Proteomics Research: More evidence that schizophrenia is a protein aggregation disorder?

Department of Psychiatry and Behavioral Sciences

Division of Neurobiology
CMSC Building
Baltimore, MD 21287

Phone: (410) 614-0010
lfrank8@jhmi.edu

Neuropsychiatric diseases, Schizophrenia, Alzheimer's disease, Protein Aggregation, Proteostasis

My research focuses on understanding the underlying molecular basis of psychosis in neuropsychiatric disorders such as schizophrenia and Alzheimer’s disease. Through funding obtained by the Brain and Behavior Foundation, I made the novel discovery that protein aggregation occurs in a subset of patients with schizophrenia exhibiting severe cognitive impairment. Our lab is currently working on understanding the molecular mechanism of this subtype of schizophrenia, utilizing a multi-omics approach.  This work can provide insight into the pathways underlying the clinical phenotype in some patients with major mental illness and potentially provide an understanding of the psychiatric symptoms seen in Alzheimer’s disease. I am currently funded by the National Institute of Health/ National Institute of Aging, through a K01 mechanism, to study the molecular mechanisms that contribute to psychosis in Alzheimer’s disease. This research builds upon the discovery of aggregating proteins in schizophrenia brains, to further understand the molecular underpinnings of neuropsychiatric symptoms in Alzheimer’s disease. By elucidating cellular mechanisms of protein aggregation observed in schizophrenia, a disease characterized by psychosis and cognitive decline, and the wealth of proteomic and genomic data related to Alzheimer’s disease, the cellular abnormalities leading to psychosis associated with Alzheimer’s disease can be better understood. Understanding of etiology and pathogenesis may ultimately result in the identification of new therapeutic targets for the treatment of psychosis in Alzheimer’s disease.  

https://scholar.google.com/scholar?hl=en&as_sdt=0%2C21&authuser=1&q=Leslie+G+Nucifora&oq=

https://www.ncbi.nlm.nih.gov/myncbi/leslie.nucifora.1/bibliography/public/

• Nucifora LG, Ishizuka K, El Demerdash N, Lee BJ, Imai MT, Ayala-Grosso C, Yenokyan G, Cascella NG, Lin S, Schretlen DJ, Harvey PD, Margolis RL, Ross CA, Sawa A, Nucifora FC Jr. Protein aggregation identified in olfactory neuronal cells is associated with cognitive impairments in a subset of living schizophrenia patients. Mol Psychiatry. 2025;30(8):3673-3685.
• Tharakan R, Kreimer S, Ubaida-Mohien C, Lavoie J, Olexiouk V, Menschaert G, Ingolia NT, Cole RN, Ishizuka K, Sawa A, and Nucifora LG. (2020). A Methodology for Discovering Novel Brain-relevant Peptides: Combination of Ribosome Profiling and Peptidomics. Neuroscience Research, 151, 31-37. PMID: 30862443.
• Nucifora LG, MacDonald ML, Lee BJ, Peters ME, Norris AL, Orsburn BC, Yang K, Gleason K, Margolis RL, Pevsner J, Tamminga CA, Sweet RA, Ross CA, Sawa A, Nucifora FC Jr. Increased Protein Insolubility in Brains From a Subset of Patients With Schizophrenia. Am J Psychiatry. 2019;176(9):730-743.
• Nucifora FC Jr*, Nucifora LG*, Ng CH, Arbez N, Guo Y, Roby E, Shani V, Engelender S, Wei D, Wang XF, Li T, Moore DJ, Pletnikova O, Troncoso JC, Sawa A, Dawson TM, Smith W, Lim KL, Ross CA. Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1. Nat Commun. 2016;7:11792. *equal contribution.
• Nucifora LG, Burke KA, Feng X, Arbez N, Zhu S, Miller J, Yang G, Ratovitski T, Delannoy M, Muchowski PJ, Finkbeiner S, Legleiter J, Ross CA, Poirier MA. Identification of novel potentially toxic oligomers formed in vitro from mammalian-derived expanded huntingtin exon-1 protein. J Biol Chem. 2012;287(19):16017-28.

• Advanced Research Institute (ARI) in Mental Health and Aging Scholar, 2025
• ACNP Advocacy Ambassador for the 2021 SfN virtual Hill Day, 2021
• American College of Neuropsychopharmacology (ACNP) Travel Award, 2020
• NARSAD Young Investigator Award, Brain and Behavior Research Foundation, 2018-2020.
• Ruth L. Kirschstein National Research Service Award: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, 2011-2013
• Ruth L. Kirschstein National Research Service Award: Department of Biology, Johns Hopkins University, Baltimore, MD, 2002-2004

• American Society for Neuroscience
• Schizophrenia International Research Society