Name: Roberto Frau

Position, Title: Research Assistant Professor, Ph.D.

Dept. of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari (Italy)

Scopus Author ID: 6602197467
ORCID ID: orcid.org/0000-­?0002-­?5922-­?2404

 

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

INSTITUTION AND LOCATION	DEGREE   (if applicable)	Completion Date   MM/YYYY	FIELD OF STUDY
Lyceum L.B. Alberti, Italy University of Cagliari, Italy Faculty of Medicine, University of Cagliari, Italy Faculty of Medicine, University of Cagliari, Italy	BS MS PhD Specialization Degree	06/1995 04/2002 02/2007 04/2010	General Sciences Biological Sciences Neuroscience Pharmacology

 

1. Personal Statement

My research is primarily focused on the characterization of the neurobiological underpinnings of neurodevelopmental disorders through the employment of behavioral tests with high translational value and predictive validity. In particular, my scientific interest is the identification of the interaction between lipid mediators (neuroactive steroids and endocannabinoids) and brain neurotransmitters, such as dopamine and serotonin. I am currently involved in two major translational research projects. The first aim of my research is the development of novel steroid- and cannabinoid-based tools for the therapy of impulse-control disorders, Tourette syndrome and schizophrenia. In particular, through a bench to bedside approach, our group has discovered the antipsychotic efficacy of neurosteroid-based therapies in patients affected by schizophrenia, Tourette syndrome and impulse-control disorders. The second target of my investigation is the characterization of the molecular substrates of gene x gender x environment interactions in impulsive aggression. Both projects involve multiple collaborations with basic and clinical scientists in US, Canada, Italy, Germany, Croatia and Malta, as I recently became a member of the European Cooperation in Science Technology (COST, action CM1103, “Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). I am currently a Research Assistant Professor at the University of Cagliari, Dept. of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, where I am pursuing behavioral and molecular studies to unravel the contribution of cannabinoid and neurosteroid signaling in schizophrenia, Tourette Syndrome and other neuropsychiatric disorders linked to alterations of the dopaminergic system.

 

1: Frau R, Savoia P, Fanni S, Fiorentini C, Fidalgo C, Tronci E, Stancampiano R, Meloni M, Cannas A, Marrosu F, Bortolato M, Devoto P, Missale C, Carta M. The 5-alpha reductase inhibitor finasteride reduces dyskinesia in a rat model of Parkinson’s disease. Exp Neurol. 2017 Jan 25. pii: S0014-4886(17)30021-3. doi: 10.1016/j.expneurol.2017.01.012. [Epub ahead of print] PubMed PMID: 28131725.

2: Frau R, Bini V, Soggiu A, Scheggi S, Pardu A, Fanni S, Roncada P, Puligheddu M, Marrosu F, Caruso D, Devoto P, Bortolato M. The Neurosteroidogenic Enzyme 5?-Reductase Mediates Psychotic-Like Complications of Sleep Deprivation. Neuropsychopharmacology. 2017 Jan 19. doi: 10.1038/npp.2017.13. [Epub ahead of print] PubMed PMID: 28102229.

3: Frau R, Mosher LJ, Bini V, Pillolla G, Pes R, Saba P, Fanni S, Devoto P, Bortolato M. The neurosteroidogenic enzyme 5?-reductase modulates the role of D1 dopamine receptors in rat sensorimotor gating. Psychoneuroendocrinology. 2016 Jan;63:59-67. doi: 10.1016/j.psyneuen.2015.09.014. PubMed PMID: 26415119; PubMed Central PMCID: PMC4695380.

4: Mosher LJ*, Frau R*, Pardu A, Pes R, Devoto P, Bortolato M. Selective activation of D1 dopamine receptors impairs sensorimotor gating in Long-Evans rats. Br J Pharmacol. 2016 Jul;173(13):2122-34. *, Equal authorship. doi: 10.1111/bph.13232. PubMed PMID: 26101934; PubMed Central PMCID: PMC4908197.

5: Frau R, Abbiati F, Bini V, Casti A, Caruso D, Devoto P, Bortolato M. Targeting neurosteroid synthesis as a therapy for schizophrenia-related alterations induced by early psychosocial stress. Schizophr Res. 2015 Nov;168(3):640-8. doi: 10.1016/j.schres.2015.04.044. PubMed PMID: 25999042; PubMed Central PMCID: PMC4628592.

6: Frau R, Bini V, Pes R, Pillolla G, Saba P, Devoto P, Bortolato M. Inhibition of 17?-hydroxylase/C17,20 lyase reduces gating deficits consequent to dopaminergic activation. Psychoneuroendocrinology. 2014 Jan;39:204-13. doi: 10.1016/j.psyneuen.2013.09.014. PubMed PMID: 24140269; PubMed Central PMCID: PMC3940882.

 

B. Positions and Honors

 

Positions and Employment

2007: Postdoctoral Fellow in Neuroscience, University of Cagliari, Dept. of Biomedical Sciences.

2008-2010: Visiting Scientist at the University of Southern California (USC), School of Pharmacy, Los Angeles (USA).

2010: Postdoctoral Fellow in Pharmacology, University of Cagliari, Dept. of Biomedical Sciences.

2010-2012: Research Fellow, University of Cagliari, Dept. Of Biomedical Sciences, “Tourette Syndrome and Sleep Disorder Center”, Cagliari (Italy).

2012-2014: Research Fellow, University of Cagliari, Dept. Of Biomedical Sciences, “Tourette Syndrome and Sleep Disorder Center”, Cagliari (Italy).

2015-present: Research Assistant Professor, University of Cagliari, Dept. Of Biomedical Sciences, “Tourette Syndrome and Sleep Disorder Center”, Cagliari (Italy).

 

Other Experience and Professional Memberships

2012-2015: Member, COST (European Cooperation in Science and Technology), Action CM1103, WG4 group.

 

Honors

2007: Young Scientists Award (EPHAR, The Federation of European Pharmacological Societies), Summer School of Neuroscience (Italy).

2008-2010: Research Fellowship, “Master and Back Program”, Region of Sardinia (Italy).

2010-2012: Research Fellowship, “Master and Back Program”, Region of Sardinia (Italy).

2015: Young Scientist Award, 1st World Congress on Tourette Syndrome & Tic Disorders, London, UK

2015: Local Organizer Support Award, COST (European Cooperation in Science and Technology), Action CM1103, WG4 group.

2016: Young Investigator Award, Dopamine meeting 2016, Vienna, Austria.

 

C. Contribution to Science

 

1. Targeting neurosteroidogenesis as a novel therapy for neuropsychiatric disorders

Neurosteroids are a subclass of steroids synthesized de novo in the brain that exert modulatory action on different types of neurotransmitters, including dopamine. In recent years, the involvement of neurosteroids in brain function and mental diseases has attracted much interest, with particular attention to their promising clinical and therapeutic aspects. Based on this framework, our group has investigated the role of 5-alpha reductase (5AR), the key enzyme in neurosteroidogenesis, in animal models of neuropsychiatric disorders linked to dysfunctions of the dopamine signaling. Our preclinical and clinical findings suggest that 5AR inhibitors, such as finasteride, elicit antidopaminergic effects in a number of disorders associated with dopaminergic hyperreactivity, including Tourette syndrome and schizophrenia. Of note, unlike the most used anti-dopaminergic drugs, these effects are strikingly dissociated from extrapyramidal symptoms and appear to be contributed by the negative modulation of D1 and D3 receptors in the nucleus accumbens. In addition, we recently identified that inhibitors of 17?-hydroxylase/17,20-lyase (CYP450-C17), the rate- limiting enzyme in androgens synthesis, exert behavioral effects akin to those produced by finasteride. The findings from our group indicate that targeting critical enzyme involved in neurosteroidogenesis may provide a novel pharmacological tool for the treatment of neuropsychiatric disorders associated to male predominance and dopamine dysfunctions, such as Tourette syndrome and schizophrenia.

 

1. Frau R, Mosher LJ, Bini V, Pillolla G, Pes R, Saba P, Fanni S, Devoto P, Bortolato M. The neurosteroidogenic enzyme 5?-reductase modulates the role of D1 dopamine receptors in rat sensorimotor gating. Psychoneuroendocrinology. 2016 Jan;63:59-67. PubMed PMID: 26415119; NIHMSID: NIHMS728511; PubMed Central PMCID: PMC4695380

1. Frau R, Abbiati F, Bini V, Casti A, Caruso D, Devoto P, Bortolato M. Targeting neurosteroid synthesis as a therapy for schizophrenia-related alterations induced by early psychosocial stress. Schizophr Res. 2015 Nov;168(3):640-8. PubMed PMID: 25999042; NIHMSID: NIHMS705183; PubMed Central PMCID: PMC4628592.

1. Frau R, Bini V, Pes R, Pillolla G, Saba P, Devoto P, Bortolato M. Inhibition of 17?-hydroxylase/C17,20 lyase reduces gating deficits consequent to dopaminergic activation. Psychoneuroendocrinology. 2014 Jan;39:204-13. PubMed PMID: 24140269; NIHMSID: NIHMS533202; PubMed Central PMCID: PMC3940882.

1. Frau R, Pillolla G, Bini V, Tambaro S, Devoto P, Bortolato M. Inhibition of 5?-reductase attenuates behavioral effects of D1-, but not D2-like receptor agonists in C57BL/6 mice. Psychoneuroendocrinology. 2013 Apr;38(4):542-51. PubMed PMID: 22877998; NIHMSID: NIHMS400903; PubMed Central PMCID: PMC3540184.

 

1. Role of cannabinoids in animal models of schizophrenia

Cannabis abuse in adolescence and during pregnancy is associated with a broad array of phenotypical consequences, including a higher risk for schizophrenia and other mental disturbances related to dopamine imbalances. However, great variability of the behavioral responses to cannabinoids has been highlighted and ascribed to genetic and vulnerability factors overlap. To address this issue, our group has studied the impact of acute and chronic treatment of synthetic cannabinoid agonists on animal models relevant to schizophrenia throughout the developmental phases in different strain of rats. We demonstrated that, while in Sprague-Dawley rats, no psychotic-like features have been exerted after prenatal and adolescent treatment, in Lewis rats, the juvenile cannabinoid exposure led to alterations in frontostriatal gliogenesis, as well as specific behavioral alterations time-locked to dopamine dysregulations.

 

1. Bortolato M, Bini V, Frau R, Devoto P, Pardu A, Fan Y, Solbrig MV. Juvenile cannabinoid treatment induces frontostriatal gliogenesis in Lewis rats. Eur Neuropsychopharmacol. 2014 Jun;24(6):974-85. PubMed PMID: 24630433.

1. Bortolato M, Aru GN, Frau R, Orrù M, Luckey GC, Boi G, Gessa GL. The CB receptor agonist WIN 55,212-2 fails to elicit disruption of prepulse inhibition of the startle in Sprague-Dawley rats. Psychopharmacology (Berl). 2005 Jan;177(3):264-71. PubMed PMID: 15290008.

1. Bortolato M, Frau R, Orrù M, Casti A, Aru GN, Fà M, Manunta M, Usai A, Mereu G, Gessa GL. Prenatal exposure to a cannabinoid receptor agonist does not affect sensorimotor gating in rats. Eur J Pharmacol. 2006 Feb 15;531(1-3):166-70. PubMed PMID: 16423346.

 

1. Positive allosteric modulation of GABAB receptors as a novel promising tool for antipsychotic treatment, with fewer side effects than GABABR agonists.

Converging evidence points to the involvement of ?-amino-butyric acid B receptors (GABABRs) in the regulation of information processing. We showed that GABABR agonists exhibit antipsychotic-like properties in rodent models of sensorimotor gating deficits, as measured by the prepulse inhibition of the acoustic startle reflex. The therapeutic potential of these agents, however, is limited by their neuromuscular side effects. Recently, we have found that rac-BHFF, a potent GABABR-positive allosteric modulator (PAM) countered spontaneous and pharmacologically induced PPI deficits across various rodent models.

1: Frau R, Bini V, Pillolla G, Malherbe P, Pardu A, Thomas AW, Devoto P, Bortolato M. Positive allosteric modulation of GABAB receptors ameliorates sensorimotor gating in rodent models. CNS Neurosci Ther. 2014 Jul;20(7):679-84. doi: 10.1111/cns.12261.

2: Bortolato M, Frau R, Orrù M, Piras AP, Fà M, Tuveri A, Puligheddu M, Gessa GL, Castelli MP, Mereu G, Marrosu F. Activation of GABA(B) receptors reverses spontaneous gating deficits in juvenile DBA/2J mice. Psychopharmacology (Berl). 2007 Oct;194(3):361-9. PubMed PMID: 17604981.

3: Bortolato M, Frau R, Aru GN, Orrù M, Gessa GL. Baclofen reverses the reduction in prepulse inhibition of the acoustic startle response induced by dizocilpine, but not by apomorphine. Psychopharmacology (Berl). 2004 Jan;171(3):322-30. PubMed PMID: 13680072.

 

Complete List of Published Work in my NCBI bibliography:

https://www.ncbi.nlm.nih.gov/sites/myncbi/167YifMG7yu5c/bibliography/50239258/public/?sort=date&direction= descending

 

D. Additional Information: Research Support and/or Scholastic Performance

 

Ongoing Research Support

Region of Sardinia grant, “Legge Regionale 7 agosto 2007, n.7 annualità 2015 – Capitale Umano ad Alta Qualificazione”

Title of the project: Therapeutic properties of finasteride in Tourette’s Syndrome: neurochemical and molecular approaches.

ID: CRP-29

Role: PI

 

The Italian Ministry of Health grant “Finalizzata”

Title of the project: Modulation of the startle response in REM sleep behavior disorder.

ID: PE-2011-02351898.

Role: Key personnel

 

Completed Research Support

Michael J Fox Foundation, Target Validation, 2014.

Title of the project: 5-alpha-reductase Inhibition for the Treatment of Levodopa-induced Dyskinesia.

ID: 9969

Role: Key Personnel

 

Tourette Syndrome Association.

Research grant and fellowship 2008/2009.

Title of the project: Therapeutic action of 5alpha-reductase inhibitors in Tourette Syndrome.

Role: Key Personnel

Research grant and fellowship 2010/2011 (2nd Year)

Title of the project: Therapeutic action of 5alpha-reductase inhibitors in Tourette Syndrome.

Role: Key Personnel

 

Region of Sardinia grant, Promotion of research, technology and innovation in Sardinia (2008)

Title of the project: A new therapeutic approach for the treatment of Tourette with finasteride: preclinical and clinical studies.

Role: Key Personnel

 

Region of Sardinia grant, Promotion of research, technology and innovation in Sardinia (2010)

Title of the project: Role of 5-alpha reductase substrates and products underlying the therapeutic effects of finasteride.

ID: CRP-25102, CUP-F71J11000920002

Role: Key Personnel