## Contact Information

Bethesda MD20892

naoko.mizuno@nih.gov

## Summary

Naoko Mizuno, Ph.D., graduated from the University of Tokyo in 1999 and received her doctoral degree in biophysics from the University of Tokyo/University of Texas Southwestern Medical Center (UTSW) in 2005. From 2007 to 2011, Dr. Mizuno was a research fellow at the NIAMS. She spent the next 8 years as an independent group leader at the Max Planck Institute of Biochemistry, Martinsried in Germany, before returning to the NIAMS (jointly appointed with NHLBI) in 2020.

Dr. Mizuno received several European awards and honors, including a Young Investigator Award from the European Molecular Biology Organization, a Boehringer Ingelheim Stiftung Plus3 program, and a consolidator grant from the European Research Council. She serves as an editor for the journal *FEBS Letters* and an evaluator for the Horizon 2020 program of the European Union.

## Research Statement

The Laboratory of Structural Cell Biology aims to understand the molecular mechanisms governing specialized cell shapes, such as neurons, platelets or activated immune cells, and specific cancer cells. We visualize the key factors determining cell morphologies using *in situ* cellular cryo-electron tomography combined with interdisciplinary techniques such as single-particle cryo-EM, X-ray crystallography, *in vitro* reconstitution, and light microscopy. 

Bottom-up reconstitution of the underlying molecular mechanisms and the signaling processes governing cell shape formation are challenging to elucidate within a cell due to their complexity and diverse crosstalk with other pathways. To precisely understand the molecular functions of critical components, we are taking a bottom-up approach to reconstitute and investigate the macromolecular machinery that can mimic cell shape formation processes using biophysical and structural biological methods. The functional relevance learned from the *in vitro* reconstitution analysis is validated inside cells using mutagenesis and *in situ* analysis.

### Neuronal cell formation

Neuronal cells are classic examples of specialized cell formation. To connect the distal end of the nervous system to the central brain, cells are shaped in a highly polarized fashion with a long stem part, the axon, shaped by microtubules. To create a neural network, individual cells form branching points from the axon, which serve as connection points. From these connections, membrane receptors respond to extracellular cues which start a directed signaling cascade and lead to the remodeling of the actin and microtubule cytoskeleton. Dynamic crosstalk of membrane, actin, and microtubules implicate axon branch formation. We aim to elucidate the molecular action that governs these cellular events.

### Wound healing and immunological cell formation

Platelets and immune cells undergo dynamic morphological changes during activation to adhere to each other or specific target antigens. Although the molecular bases of the actions are similar to those of neuronal cell formation, the morphological outcome can vary drastically. For example, activated platelets produce spikes on their surface, resembling the shape of a sunflower. We aim to understand the molecular re-organization during the activation process. We further study signaling defects that cause immunodeficiencies or problems with wound healing to identify molecular clues for cellular defects.

## Scientific Publications

###             In situ cryo-electron tomography reveals local cellular machineries for axon branch development.        

221(4).

###             Structural insights into integrin α(5)β(1) opening by fibronectin ligand.        

7(19).

###             Phosphoinositides regulate force-independent interactions between talin, vinculin, and actin.        

9().

###             The Architecture of Talin1 Reveals an Autoinhibition Mechanism.        

179(1).

###             Membrane association and remodeling by intraflagellar transport protein IFT172.        

9(1).

###             Direct induction of microtubule branching by microtubule nucleation factor SSNA1.        

20(10).

## Education

**University of Texas Southwestern Medical Center**Ph.D. Joint Program with University of Tokyo (2005)

**University of Tokyo**Ph.D. Multidisciplinary Science (Biophysics) (2005)

**University of Tokyo**M.S. (2001)

**University of Tokyo**B.A. (1999)

## Experience

**Independent Group Leader**Max Planck Institute of Biochemistry (2012-2020)

**Research Fellow**NIAMS, NIH (2007-2011)

**Postdoctoral Fellow** (wrap-up from Ph.D.)UTSW Medical Center (2005-2007)

June 2023

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