• Ruth L. Kirschstein National Research Service Award (F32), individual postdoctoral fellowship, National Institutes of Health (GM) (2003-2006)
• Individual Graduate Research Fellowship, National Science Foundation (1999-2002)
• Distinction in General Undergraduate Scholarship, UC Berkeley (1998)
• Undergraduate Honors in Molecular and Cellular Biology, UC Berkeley (1998)
• Chancellor's Undergraduate Scholar, UC Berkeley (1994-1998)

The Padrick Lab studies the mechanisms by which information flows through multiprotein complexes. In particular, we study how multiple signaling inputs are integrated by membrane-associated protein systems controlling the actin cytoskeleton, which has important roles across normal and pathological physiology.

Research in my lab is connected by an interest in how protein assemblies integrate diverse signals to produce a coherent output. In particular, we are interested in how large protein assemblies control dynamic changes in the actin cytoskeleton, which has important cellular roles in cell motility, cell division and lipid trafficking, in normal physiology, cancer invasion and metasis, and pathogenic infection.

Regulation of the actin nucleation

The actin related protein 2/actin related protein 3 (Arp2/3) complex is a ubiquitous actin nucleation machine, producing characteristic branches from the sides of preexisting actin filaments. This seven-membered protein complex is stimulated to nucleate new actin filaments by nucleation-promoting factors such as WASP family proteins, in a long-studied but still controversial mechanism. The goal of this project is to understand how the interaction between the Arp2/3 complex and the preexisting actin filament results in structural changes needed to initiate a new filament. This project will use a combination of computational modeling, reconstitution of actin filament nucleation with rationally designed Arp2/3 mutants, structural biology, and imaging based single filament experiments.

Control of actin filament growth by membrane-associated factors

The GAP43 protein plays an important role in guidance of neurons to their proper developmental targets in the brain. This small and intrinsically disordered protein is somehow able to integrate signals from membrane phosphoinositides, kinase signaling through PKC, and calcium signaling through binding to calmodulin, resulting in changes in cellular behavior. GAP43 binds actin in a fashion sensitive to phosphorylation, and it is thought that the upstream signals result in cytoskeletal reorganization that affect guidance directly. The mechanism of this action is very poorly understood, at least in part owing to the fact that GAP43 self-associates into clusters on the membrane, suggesting that conventional solution-phase biochemistry will be a poor tool to dissect its function. In this project we will dissect the structural basis of GAP43 association with actin, reconstitute the signaling system on artificial membranes and use cell biological tools to connect our observation at the molecular scale to large scale cellular behaviors.

“Awards Ceremony Celebrates Graduate School Class of 2024”
(May 14, 2024)

^ corresponding author
* equal author contributions
** peer reviewed
† articles cited more than 100 times via Google Scholar

**"Sequence Determinants of Intracellular Phase Separation by Complex Coacervation of a Disordered Protein"
Pak CW, Kosno M, Holehouse AS, Padrick SB, Mittal A, Ali R, Yunus AA, Liu DR, Pappu RV, Rosen MK
Molecular Cell. 63(1):72-85 (2016)

**"The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α"
Han T, Goralski M, Capota E, Padrick SB, Kim J, Xie Y, Nijhawan D
Nature Chemical Biology. 12(7):511-5 (2016)

**"On the acquisition and analysis of microscale thermophoresis data"
Scheuermann TH, Padrick SB, Gardner KH, Brautigam CA
Analytic Biochemistry. 496:79-93 (2016)

**"A novel role for WAVE1 in controlling actin network growth rate and architecture"
Sweeney MO, Collins A, Padrick SB, Goode BL
Molecular Biology of the Cell. 26(3):495-505 (2015)

**"Reconstitution of the WAVE Regulatory Complex"
Chen B, Padrick SB, Henry L, Rosen MK
Methods in Enzymology. 540:55-72 (2014)

**"The Bacterial Effector VopL Organizes Actin into Filament-Like Structures"
Zahm JA, Padrick SB, Chen Z, Yunus AA, Henry L, Tomchick DR, Chen Z, Rosen MK
Cell 155(2):423-34 (2013)

**"Three-color single molecule imaging shows WASP detachment from Arp2/3 complex triggers actin filament branch formation"
Smith BA*, Padrick SB*, Doolittle LK, Daugherty-Clarke K, Corrêa IR, Xu MQ, Goode BL, Rosen MK, Gelles J
eLife 2:e01008 (2013)

"Measurement and Analysis of in vitro Actin Polymerization"
Doolittle LK, Rosen MK, Padrick SB^
Methods in Molecular Biology 1046:273-93 (2013)

"Purification of Arp2/3 Complex from Saccharomyces cerevisiae"
Doolittle LK, Rosen MK, Padrick SB^
Methods in Molecular Biology 1046:251-71 (2013)

"Purification of Native Arp2/3 Complex from Bovine Thymus"
Doolittle LK, Rosen MK, Padrick SB^
Methods in Molecular Biology 1046:231-50 (2013)

**"GMF severs actin-Arp2/3 complex branch junctions by a cofilin-like mechanism"
Ydenberg CA*, Padrick SB*, Sweeney MO, Gandhi M, Sokolova O, Goode BL
Current Biology 23(12):1037-45 (2013)

**" Multi-Signal Sedimentation Velocity Analysis with Mass Conservation for Determining the Stoichiometry of Protein Complexes"
Brautigam CA, Padrick SB, Schuck P
PLoS One 8(5):e62694 (2013)

**"Arp2/3 complex is bound and activated by two WASP proteins"
Padrick SB, Doolittle LK, Brautigam CA, King DS, Rosen MK
Proceedings of the National Academy of Sciences, USA 108(33):E472-E479 (2011)

**"Evaluating the stoichiometry of macromolecular complexes using multisignal sedimentation velocity"
Padrick SB and Brautigam CA
Methods 54(1):39-55 (2011)

**†"Cooperative control mechanisms of actin polymerization by the WAVE complex"
Chen Z, Borek D*, Padrick SB*, Gomez TS, Metlagel Z, Ismail A, Umetani J, Billadeau DD, Otwinowski Z, Rosen MK
Nature 468(7323):533-8 (2010)
Extensively reviewed in Current Biology 2011 Jan 25;21(2):R66-8.

**"Determination of protein complex stoichiometry through multisignal sedimentation velocity experiments"
Padrick SB, Deka RK, Chuang JL, Wynn RM, Chuang DT, Norgard MV, Rosen MK, Brautigam CA.
Analytical Biochemistry 407(1):89-103 (2010)

**†"Physical Mechanisms of Signal Integration by WASP Family Proteins"
Padrick SB, Rosen MK
Annual Reviews in Biochemistry 79:707-35 (2010)

**"The WAVE regulatory complex is inhibited"
Ismail A, Padrick SB, Baoyu Chen, Umetani J, Rosen MK
Nature Structural and Molecular Biology 16(5):561-3 (2009)
Cover image, Nature Structural and Molecular Biology

**†"Hierarchical regulation of WASP/WAVE proteins"
Padrick SB*, Cheng HC*, Ismail AM*, Panchal SC, Doolittle LK, Kim S, Skehan BM, Umetani J, Brautigam CA, Leong JM, Rosen MK
Molecular Cell 32(3):426-38 (2008)
Extensively reviewed in Science Signal. 2009 Jan 27;2(55):pe5