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Makiko Iwafuchi, PhD


  • Associate Professor, UC Department of Pediatrics

About

Biography

The long-term goal of my laboratory is to shed light on the gene regulatory and epigenetic principles that control cell fate and cell state during embryonic development, cellular reprogramming, tissue homeostasis and regeneration, and disease pathogenesis. Ultimately, we aim to translate these fundamental discoveries into practical tools for precise control of cell fate and state, with broad potential applications in personalized disease modeling and regenerative medicine.

My scientific journey has been shaped by a deep fascination with the remarkable capabilities of pioneer transcription factors (TFs), which play critical roles in gene regulation and epigenome organization across diverse biological and pathological processes. During my postdoctoral training, we elucidated molecular mechanisms underlying the chromatin-opening activity of pioneer TFs during embryonic development and liver homeostasis.

As a principal investigator, my research program seeks to define the molecular mechanisms that regulate lineage-specific epigenomes, with a current focus on (1) pioneer TF-mediated DNA demethylation and Polycomb regulation and (2) cell signaling-mediated heterochromatin organization. My lab leverages human pluripotent stem cell (hPSC) differentiation models together with cutting-edge approaches, including CRISPRi/d-based perturbations, genomic and proteomic profiling, and super-resolution expansion microscopy.

BS: Kitasato University, Japan

PhD: Osaka University, Japan

Fellowship: Postdoctoral, University of Pennsylvania, Philadelphia, PA

Interests

Chromatin regulation; pioneer transcription factors; cell programming and reprogramming

Publications

Selected

MAPK/ERK signaling regulates H3K9me3 heterochromatin reorganization to confer mesendoderm developmental competence. Matsui, S; Sampson, S; Mirizio, G; Granitto, M; Maeda, R; Tachibana, M; Ahn, C; Lim, H-W; Iwafuchi, M. Nucleic Acids Research (NAR). 2026; 54(12).

Selected

Interplay between pioneer transcription factors and epigenetic modifiers in cell reprogramming. Mirizio, G; Sampson, S; Iwafuchi, M. Regenerative Therapy. 2025; 28:246-252.

Selected

Protocol for establishing inducible CRISPRd system for blocking transcription factor-binding sites in human pluripotent stem cells. Matsui, S; Shiley, JR; Buckley, M; Lim, H-W; Hu, Y-C; Mayhew, CN; Iwafuchi, M. STAR Protocols. 2024; 5(3):103233.

Selected

Protocol for establishing inducible CRISPR interference system for multiple-gene silencing in human pluripotent stem cells. Matsui, S; Shiley, JR; Granitto, M; Ludwig, K; Buckley, M; Koigi, S; Mirizio, G; Hu, Y-C; Mayhew, CN; Iwafuchi, M. STAR Protocols. 2024; 5(3):103221.

Selected

Pioneer and PRDM transcription factors coordinate bivalent epigenetic states to safeguard cell fate. Matsui, S; Granitto, M; Buckley, M; Ludwig, K; Koigi, S; Shiley, J; Zacharias, WJ; Mayhew, CN; Lim, H-W; Iwafuchi, M. Molecular Cell. 2024; 84(3):476-489.e10.

Selected

Gene network transitions in embryos depend upon interactions between a pioneer transcription factor and core histones. Iwafuchi, M; Cuesta, I; Donahue, G; Takenaka, N; Osipovich, AB; Magnuson, MA; Roder, H; Seeholzer, SH; Santisteban, P; Zaret, KS. Nature Genetics. 2020; 52(4):418-427.

Selected

The mechanistic basis for chromatin regulation by pioneer transcription factors. Iwafuchi-Doi, M. Wiley Interdisciplinary Reviews: Systems Biology and Medicine. 2019; 11(1):e1427.

Selected

Molecular regulation of mammalian hepatic architecture. Huppert, SS; Iwafuchi-Doi, M. Current Topics in Developmental Biology. 2019; 132:91-136.

Selected

Chromatin Scanning by Dynamic Binding of Pioneer Factors. Zaret, KS; Lerner, J; Iwafuchi-Doi, M. Molecular Cell. 2016; 62(5):665-667.

Selected

Cell fate control by pioneer transcription factors. Iwafuchi-Doi, M; Zaret, KS. Development. 2016; 143(11):1833-1837.

From the Blog

How ‘Pioneers’ Blaze the One Trail that Determines Cell Fate
Research Annual Report 2024

How ‘Pioneers’ Blaze the One Trail that Determines Cell Fate

Makiko Iwafuchi, PhD, Hee Woong Lim, PhD1/10/2024