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iPS cell models of human brain development in health and disease

 

Anna Falk

Forskare

iPS cell models of human brain development in health and disease

 

Institution och organisatorisk tillhörighet:

Om mig

I started the Falk lab in 2012 and have since educated four PhD students to finalize their PhD degree with me as their main supervisor. The Falk lab has also had numerous amounts of post-docs and bachelor and master students through the years. 

I did my PhD at Karolinska Institutet with Professor Jonas Frisén and continued with a post-doc in the lab of Professor Austin Smith at the University of Cambridge, UK. A couple of years ago I did a sabbatical in the lab of Professor Rusty Gage at the Salk Institute in San Diego, US.

I really love my job and I do research since it is rewording to go from ideas, hypothesis, project plan, experimental design, experiments, analysis, validating, summarizing, writing a story about novel findings to understand disorders and with the potential to improve human health. 

Forskningsbeskrivning

The Falk lab is deriving cellular models of neural stem cells, neurons and glia from iPS cells to study proliferation, differentiation, migration, fate choosing mechanisms using assays of transcriptome of bulk or single cells. Our studies concentrate mostly on early neurogenesis and modeling of neurodevelopment and neuropsychiatric disorders. We have revealed neurite outgrowth phenotypes in iPS cell models of Lissencephaly and other neurodevelopment disorders. We have on the single cells level investigated how iPS cell derived neural stem cells are choosing fate between neurons and glia and how that mechanisms is skewed in iPS cells from individuals diagnosed with autism and schizophrenia.

The Falk lab is also driving translational projects investigating the regenerative potential of iPS cell derived neural cells in preclinical models with the aim to create ATMPs to take iPS derived cell to clinic. We have derived one of few clinical compliant GMP iPS cell lines that we have banked in a master bank and we are now investigating the route forward to clinic. 

The iPS Core facility at Karolinska Institutet is providing services in the area of fibroblast establishment, reprogramming, iPS cell culture, neural induction, neural stem cells, neurons, astrocytes, neural crest and soon also whole brain organoids. The services are custom-tailored spanning from providing vials of frozen cells, to hand-on training, to customers monthly subscribing for mature human neurons. The iPS Core is the Swedish "Cell vending machine" Get your cell model of interest arrayed in the format you need. https://ipscore.se

A few recent publications from the Falk lab (download full list below):

Čančer M, Hutter S, Holmberg KO, Rosén G, Sundström A, Tailor J, Bergström T, Garancher A, Essand M, Wechsler-Reya RJ, Falk A, Weishaupt H, Swartling FJ. Humanized Stem Cell Models of Pediatric Medulloblastoma Reveal an Oct4/mTOR Axis that Promotes Malignancy. Cell Stem Cell. 2019 Dec 5;25(6):855-870.e11

Lam M, Moslem M, Bryois J, Pronk RJ, Uhlin E, Ellström ID, Laan L, Olive J, Morse R, Rönnholm H, Louhivuori L, Korol SV, Dahl N, Uhlén P, Anderlid BM, Kele M, Sullivan PF, Falk A. Single cell analysis of autism patient with bi-allelic NRXN1-alpha deletion reveals skewed fate choice in neural progenitors and impaired neuronal functionality. Exp Cell Res. 2019 Jul 12:111469

Lundin A, Delsing L, Clausen M, Ricchiuto P, Sanchez J, Sabirsh A, Mei D, Synnergren J, Zetterberg H, Brolén G, Hicks R, Herland A, Falk A. Human iPS-derived astroglia from a stable neural precursor state; improved functionality compared to conventional astrocytic models. Stem Cell Reports. 2018 Mar 13;10(3):1030-1045

Shahsavani M, Pronk RJ, Falk R, Lam M, Moslem M, Linker SB, Salma J, Day K, Schuster J, Anderlid BM, Dahl N, Gage FH, Falk A. An in vitro Model of Lissencephaly: Expanding the Role of DCX During Neurogenesis. Mol Psychiatry. 2017 Jul;23(7):1674-1684.

Uhlin, E., Rönnholm, H., Day, K., Kele, M., Tammimies, K., Bölte, S., Falk, A. Derivation of human iPS cell lines from monozygotic twins in defined and xeno free conditions. Stem Cell Res. 2017 Jan;18:22-25

Pedagogiska meriter

I have been the organizer of a master and PhD courses about cellular reprogramming in addition to hand-on course and train for culturing stem cells. 

I am continuously lecturing at Karolinska Institutet and other Universities and supervising bachelor, master and PhD students.

Utbildning

I have a Master of Science in Molecular Biology from Umeå University

PhD in Molecular Biology from Karolinska Institutet about neural stem cells

Docent (Associate Professor) in Stem cell Biology 

Akademiska priser och utmärkelser

Selected to the career development program for young researcher as one of 10 young research leaders in Sweden across all sciences. This grant (6 MSEK from SSF) provides support for successful, young scientists to build up their own independent career. 

Research grant from SciLife Lab/ AZ to model human neurological disorders and to use the national core facilities at SciLife Lab (20 MSEK)

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