Luca Giliberto, MD, PhD

Dr. Giliberto’s approach to medicine and neurology has always been dual: basic research and clinical practice. Dr. Giliberto approached research on Alzheimer’s Disease (AD) during medical school where he was exposed to the genetics of AD, and to the intricacies of AD pathology. During his neurology residency, he worked on the properties of Amyloid beta peptides (Abeta) as signaling molecules, dissecting some of the pathways involved in it’s biology, including it’s role, and regulation by oxidative stress.

During this time, Dr. Giliberto also had the privilege to collaborate with eminent scientists such as Drs. George Perry, Mark Smith and Pierluigi Gambetti. During his PhD, Dr. Giliberto trained in the laboratory of Dr. Luciano D’Adamio at Albert Einstein College of medicine. There, they conducted extensive screening of interactors of the Amyloid Precursor Protein (APP) and identified numerous candidates which can bind and modulate the trafficking and processing of APP. Among them, they selected ITMB2 (BRI2) as an interesting modulator of APP physiology: they have created BRI2 transgenic mice and knock-out mice/knock-in mice for the 2 mutations that are known to produce human pathology, namely British and Danish Familial Dementias (FBD, FDD). This has allowed them to better dissect the pathways that lead to the modulation of APP processing and amyloid formation.

When Dr. Giliberto started to work at the Feinstein Institute for Medical Research Litwin-Zucker Center for Alzheimer’s Disease & Memory Disorders with Dr. Peter Davies, he continued to study the biology of amyloid peptides, searching for signaling effects of the different N-terminal truncated peptides on neurons. In parallel he started collaborating with Dr. Davies and Dr. Philippe Marambaud on existing projects, and started to deepen his understanding of the biology of Tau, and it’s interactions with Amyloid. He also started to consider AD pathogenic theories alternative to the mere accumulation of Amyloid and Tau.

The focus of Dr. Giliberto’s work is now the hypothesis that alterations of cell cycle can primarily create an imbalance of signals among brain cells, disrupting the network that exists between neurons, astrocytes and microglia, leading to death signals to neurons and accumulation of Tau and Amyloid, further exacerbating the network failure. He is taking advantage of novel murine and cellular models of cell cycle alteration, including the use of neuronal precursor cells and CRISPR technology. Together with Dr. Peter Davies and Dr. Cristina d’Abramo, they are also developing new strategies for passive immunization against Tau, where he is bringing the contribution of his molecular biology skills. Finally, Dr. Giliberto is digging into the biology and possible exploitation of mesenchymal stem cells in the field of AD, based on the vast modulatory effects of these cells on the inflammatory environment of the brain. This work is being done in collaboration with Dr. Antonio Uccelli at the University of Genova, Italy, one of the top researchers in the field of mesenchymal stem cells and Multiple Sclerosis.

Flanking Dr. Giliberto’s deep interest in the basic pathogenic mechanisms of AD is his love for clinical neurology. This has led him to become a neurology specialist in his country of origin, Italy, and to obtain the same degree in the USA. Dr. Giliberto has always pursued clinical trials in the field of AD, from the original Italian Ministry of Health and Industry trials on the Acetylcholine-Esterase inhibitors, to longitudinal and genetic correlate trials, and the current ones in which he is involved with at the Feinstein Institute, including Beta Secretase inhibitors and Anti-Tau immunotherapy. He currently has a specific interest in the prodromal and MCI stages of AD, and is recruiting patients. Since joining the Northwell Health neurology department, his interest has broadened to include the memory and behavioral alterations following TBI/CTE and concussion, with specific interest in providing comprehensive care, initiating clinical trials and investigating the pathogenesis of CTE, which shares a lot of features with AD and other neurodegenerative disorders. Having contact with patients, both as caregiver and in the setting of clinical trials, is a great way to provide immediate care and attention to patients affected by a disease that is so wide spread and still has currently so little hope of being cured. It is also a way to broaden my view of the disease itself, as the inspiration Dr. Giliberto receives from his patients at every encounter is invaluable.

Magdalena Kiprowska, PhD
Postdoctoral fellow
Email: mkiprowska@northwell.edu

Francesca Vitale, PharmD
Postdoctoral fellow
Email: fvitale@northwell.edu

Cristina d’Abramo, PhD
Assistant Professor
Email: Cdabramo@northwell.edu

Hofstra Northwell School of Medicine
Degree: Residency
2015
Field of Study: Neurology

NUMC, East Meadow, NY
Degree: Internship
2012

University of Genova, School of Medicine, Genova, Italy
Degree: PhD
2009
Field of Study: Neuroscience

University of Genova, School of Medicine, Genova, Italy
Degree: Residency
2004
Field of Study: Neurology

University of Milano, School of Medicine, Milano, Italy
Degree: MD
1991

1. Borghi R, Giliberto L, Assini A, Delacourte A, Perry G, Smith MA, Strocchi P, Zaccheo D, Tabaton M. “Increase of cdk5 is related to neurofibrillary pathology in progressive supranuclear palsy.” Neurology. 2002; 58(4):589-92. PubMed PMID: 11865137
2. Giliberto L, Zhou D, Weldon R, Tamagno E, De Luca P, Tabaton M, D’Adamio L. “Evidence that the Amyloid beta Precursor Protein-intracellular domain lowers the stress threshold of neurons and has a “regulated” transcriptional role.” Molecular neurodegeneration. 2008; 3:12. PubMed PMID: 18764939, PMCID: PMC2538519
3. Giliberto L, Borghi R, Piccini A, Mangerini R, Sorbi S, Cirmena G, Garuti A, Ghetti B, Tagliavini F, Mughal MR, Mattson MP, Zhu X, Wang X, Guglielmotto M, Tamagno E, Tabaton M. “Mutant presenilin 1 increases the expression and activity of BACE1.” The Journal of biological chemistry. 2009; 284(14):9027-38. PMID: 19196715, PMCID: PMC2666551
4. Guglielmotto M, Monteleone D, Giliberto L, Fornaro M, Borghi R, Tamagno E, Tabaton M. “Amyloid-β₄₂ activates the expression of BACE1 through the JNK pathway.” Journal of Alzheimer’s disease : JAD. 2011; 27(4):871-83. PubMed PMID: 21897006
5. Tamagno E, Guglielmotto M, Aragno M, Borghi R, Autelli R, Giliberto L, Muraca G, Danni O, Zhu X, Smith MA, Perry G, Jo DG, Mattson MP, Tabaton M. “Oxidative stress activates a positive feedback between the gamma- and beta-secretase cleavages of the beta-amyloid precursor protein.” Journal of neurochemistry. 2008;104(3):683-95. NIHMSID: NIHMS37980 PubMed PMID: 18005001, PMCID: PMC2220052
6. Guglielmotto M, Aragno M, Autelli R, Giliberto L, Novo E, Colombatto S, Danni O, Parola M, Smith MA, Perry G, Tamagno E, Tabaton M. “The up-regulation of BACE1 mediated by hypoxia and ischemic injury: role of oxidative stress and HIF1alpha.” Journal of neurochemistry. 2009; 108(4):1045-56. PubMed PMID: 19196431
7. Tamagno E, Guglielmotto M, Giliberto L, Vitali A, Borghi R, Autelli R, Danni O, Tabaton M. “JNK and ERK1/2 pathways have a dual opposite effect on the expression of BACE1.” Neurobiology of aging. 2009; 30(10):1563-73. PubMed PMID: 18255190
8. Guglielmotto M, Monteleone D, Boido M, Piras A, Giliberto L, Borghi R, Vercelli A, Fornaro M, Tabaton M, Tamagno E. “Aβ1-42-mediated down-regulation of Uch-L1 is dependent on NF-κB activation and impaired BACE1 lysosomal degradation.” Aging cell. 2012; 11(5):834-44. PubMed PMID: 22726800
9. Tamayev R, Matsuda S, Giliberto L, Arancio O, D’Adamio L. “APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant.” The EMBO journal. 2011; 30(12):2501-9. PubMed PMID: 21587206, PMCID:PMC3116289
10. Tamayev R, Giliberto L, Li W, d’Abramo C, Arancio O, Vidal R, D’Adamio L. “Memory deficits due to familial British dementia BRI2 mutation are caused by loss of BRI2 function rather than amyloidosis.” The Journal of neuroscience: the official journal of the Society for Neuroscience. 2010; 30(44):14915-24. NIHMSID: NIHMS250398 PubMed PMID: 21048150, PMCID: PMC3056548
11. Giliberto L, Matsuda S, Vidal R, D’Adamio L. “Generation and initial characterization of FDD knock in mice.” PloS one. 2009; 4(11):e7900. PubMed PMID: 19924302, PMCID: PMC2774945
12. Matsuda S, Giliberto L, Matsuda Y, McGowan EM, D’Adamio L. “BRI2 inhibits amyloid beta-peptide precursor protein processing by interfering with the docking of secretases to the substrate.” The Journal of neuroscience: the official journal of the Society for Neuroscience. 2008; 28(35):8668-76. PubMed PMID: 18753367, PMCID: PMC3844774.

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