Our research is focused on molecular factors controlling human stem cell pluripotency, self-renewal, and differentiation potential as well as cellular maturation and function. The inaccessibility of human tissue coupled with the inadequacy of animal model systems is making the study of human development extremely challenging. Given the urgent need to develop new experimental systems using human cells, we have established advanced human stem cell-based models to better understand the molecular mechanisms underlying human development and disease, and ultimately to help design precision treatments. Our expertise includes human stem cell culture, viral vectors, gene editing, cellular reprogramming, cell transplantation, and single-cell omics.

0009 Fig 1

Developmental and regenerative biology

The ability to recreate differentiated and mature cells from human pluripotent stem cells (hPSCs) opens up exciting opportunities to study brain development and neural specification. It also provides access to a renewable source of cells potentially suitable for therapeutic applications, including drug screening and cell-based therapy.

We aim to investigate the molecular factors controlling human brain development by using brain organoids, tissue engineering, and cell transplantation.

Human brain disease modeling

The use of patient-derived hPSCs holds the promise of recreating key molecular and architectural disease features of human brain tissue. Patients’ somatic cells can be reprogrammed into induced PSCs (iPSCs), which can then be further differentiated into disease-relevant 3D brain tissue structures for modeling brain disorders in a dish.

The aim of our research is to investigate the patient-specific causal relationship between disease phenotype and molecular dysfunction by combining human stem cell-based models with single-cell analysis using iPSCs reprogrammed from both diseased and healthy individuals.

0009 Fig 2

 1) Single cell transcriptional and functional analysis of human dopamine neurons in 3D fetal ventral midbrain organoid like cultures. Birtele M, Sharma Y, Storm P, Kajtez J, Nelander Wahlestedt J, Sozzi E, Nilsson F, Stott S, Xiaoling LH, Mattsson B, Ottosson DR, Barker RA, Fiorenzano A and Parmar M. Development. 2022 Oct; 10.1242/dev.200504.

2) Silk scaffolding drives self-assembly of functional and mature human brain organoids. Sozzi E, Kajtez J, Bruzelius A, F.L. Wesseler M, Nilsson F, Giacomoni J,  Larsen NB,  Ottosson DR, Storm P, Parmar M and Fiorenzano A. Front. Cell Dev. Biol., 2022 Oct,   10.3389/fcell.2022.1023279

3) Generation of human ventral midbrain organoids derived from pluripotent stem cells. Sozzi E, Kajtez Storm P, Parmar M and Fiorenzano A. Current Prot, 2022 Sep; 10.1002/cpz1.555

4) Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids. Fiorenzano A, Sozzi E, Birtele M, Kajtez J, Giacomoni J, Nilsson F, Sharma Y, Zhang Y, Emnéus J, Ottosson DR, Storm P and Parmar M. Nat Commun., 2021 Dec; 10.1038/s41467-021-27464-5

5) A human-specific structural variation at the ZNF558 locus controls a gene regulatory network during forebrain development. Johansson P, Brattås PL, Douse CH, Hsieh P, Adami A, Pontis J, Grassi D, Garza R, Sozzi E, Cataldo R, Jönsson ME, Atacho D, Pircs K,  Eren F, Sharma Y, Johansson J, Fiorenzano A, Parmar M,  Fex M, Trono D,  Eichler E, Jakobsson J.. Cell Stem Cell. 2022 Jan; 10.1016/j.

6) Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing. Fiorenzano A, Sozzi E, Parmar M and Storm P. Cells, 202 Jun; 10.3390/cells10061366

7) Grafts derived from an α-Synuclein triplication patient mediate functional recovery but develop disease-associated pathology in the 6-OHDA model of Parkinson’s disease. Shrigley S, Fredrik N, Mattsson B, Fiorenzano A, Mudannayake J, Bruzelius A, Ottosson DR, Björklund A, Hoban D and Parmar M. J Parkinsons Dis., 2021 Dec, 10.3233/JPD-202366.

8) Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease. Tiklova K, Nolbrant S , Fiorenzano A, Björklund A, Sharma Y, Heuer A, Gillberg L, Hoban D, Cardoso T, Adler A, Birtele M, Lundén-Miguel H, Volakakis N, Kirkeby A, Perlmann T and Parmar M. Nat Commun. 2020 May; 10.1038/s41467-020-16225-5.

9) Single-cell RNA sequencing reveals midbrain dopamine neuron diversity emerging during mouse brain development.   Tiklova K, Bjorklund AK, Lahti L, Fiorenzano A, Nolbrant S, Gillberg L, Volakakis N, Yokota C, Holscher MM, Hauling T, Holmstrom F, Joodmardi E, Nilsson M, Parmar M and Perlmann T. Nat Commun. 2019 Feb, 10.1038/s41467-019-08453-1.

10) An Ultraconserved element containing lncRNA preserves transcriptional dynamics and maintains ESC Self-Renewal. Fiorenzano A, Pascale E, Gagliardi M, Terreri S, Papa M, Andolfi G, Galasso M, Tagliazucchi GM, Taccioli C, Patriarca EJ, Cimmino A, Matarazzo MR, Minchiotti G and, Fico A. Stem Cell Rep. 2018 Mar; 10.1016/j.stemcr.2018.01.014

11) Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency. Fiorenzano A, Pascale E, D'Aniello C, Acampora D, Bassalert C, Russo F, Angelini C, Zeuner A, Chazaud C, Patriarca E, Fico A and Minchiotti G.  Nat. Commun. Sep 2016, 10.1038/ncomms12589.

Alessandro has built his career in the stem cell field. He obtained his PhD in molecular and cellular biotechnology after training at the Italian National Research Council (CNR), where he consolidated his background in stem cell biology. During his PhD program, he studied the impact of the extracellular microenvironment on pluripotency and differentiation of human pluripotent stem cells (hPSCs), with particular emphasis on extrinsic and intrinsic pathways including PSC self-renewal regulation by noncoding RNAs. Alessandro spent 5 years as a postdoc at Lund University, Sweden, in the laboratory headed by Prof. Malin Parmar, a leading authority in cell-based therapy for neurodegenerative disorders. Here, Alessandro consolidated his background in stem cell biology and extended his knowledge of cutting-edge technologies in both in vivo and in vitro models to enhance cell replacement treatments for clinical translation.

His current focus is on investigating the molecular mechanisms underlying neuronal specification that efficiently drive controlled differentiation of human stem cells into specific neuronal subtypes for use in stem cell-based therapies for brain repair.

Current Position

2022 – present CNR Research Scientist, IGB-CNR, Naples, Italy. 

Research Training

2017–2022   Post-doc at Lund University, Sweden

2015-2017   Post-doc at IGB-ABT, CNR, Naples, Italy

2012-2015   PhD student at IGB-ABT, CNR, Naples, Italy

Education

Dec 2015          PhD in Molecular and Cellular Biotechnology.

                          University of Campania “Luigi Vanvitelli”, Italy of Naples, Italy

Dec 2012          Second Cycle Degree in Biology (equivalent to MSc), 110/110 summa cum laude 

                         University “Federico II” of  Naples, Italy.

Feb 2009           First Cycle Degree in General and Applied Biology (equivalent to BSc),

                          110/110  summa cum laude. University “Federico II” of Naples, Italy.