Hanna Lab

Jacob Hanna has made numerous seminal discoveries in the field of pluripotency and epigenetic-reprogramming including: (i) First proof-of-principle demonstration that iPSCs could be used to cure a genetic disease in mice. (ii) Development of drug-inducible “reprogrammable” mice that facilitate quantitative and mechanistic studies of iPSC generation, and demonstrated amenability to reprogram terminally differentiated cells. (iii) Identifying the role of several molecular regulators of pluripotency maintenance, induction and resolution like: Utx, C/EBPα, Gatad2a-Mbd3-NuRD complex and m6A mRNA methylation. His research on Utx highlighted the connection between iPSC reprogramming and in vivo primordial germ cell (PGC) development. His work on m6A methylation provided the first evidence for the importance of an mRNA epigenetic modification during in vivo development. (iv) Uncovered interconvertability of murine naive and primed pluripotent states and epigenetic repressors opposingly regulating them. (v) First derivation of transgene-dependent and -independent human naïve pluripotent cells, with distinct functional and regulatory properties. These findings are revolutionizing the human pluripotency field and bare dramatic influence on cross-species molecular analysis of pluripotency. (vi) The latter discovery also enabled the first in vitro generation of PGCs from human iPSCs. Not stopping there, Jacob uncovered species-specific transcriptional regulators of PGC induction (SOX17) differing between human and mice. This authentic PGC differentiation platform is also being used for biochemical dissection of human in vitro reprogramming and toward advancing novel infertility treatments. Collectively, Jacob’s contributions have facilitated deeper understanding of reprogramming mechanisms and established exacting platforms for enhanced utilization of pluripotent cells in basic and applied molecular research.