About

Evan Miller is an Associate Professor of Chemistry and Molecular & Cell Biology, as well as an Associate Professor of Biochemistry, Biophysics & Structural Biology at the University of California, Berkeley. He holds a B.S. in Biology/Chemistry and a B.A. in Philosophy/Theology from Point Loma Nazarene University, obtained in 2004, and earned his Ph.D. in Chemistry from UC Berkeley in 2009 under the supervision of Christopher J. Chang. Following his doctoral studies, he completed post-doctoral training at the University of California, San Diego, from 2009 to 2013 with advisor Roger Y. Tsien, supported by an NIH NRSA Post-doctoral fellowship and a K99 Pathway to Independence Fellowship. His research operates at the interface of synthetic chemistry, biology, and neuroscience, focusing on chemical biology, organic chemistry, fluorescence microscopy, neuroscience, and imaging. Miller's lab develops molecular tools to study the nervous system, aiming to understand how the brain transmits information between cells. His work involves creating activity-dependent neuronal tracer dyes to follow signal transduction and developing synthetic and genetically encoded indicators for monitoring voltage changes in neurons. These tools are applied across various systems, from primary cell cultures to whole animals, to explore neuronal communication and information transfer, advancing our understanding of brain function.

Research topics

• Biology
• Chemistry
• Biochemistry
• Computer Science
• Neuroscience
• Cell biology
• Biophysics
• Genetics
• Psychology
• Data science
• Computational biology
• Photochemistry
• Organic chemistry

Selected publications

• Benzo[b]phosphole fluorophores for ratio-based live cell pH imaging

  ChemRxiv · 2026-05-05

  articleOpen accessSenior author

  Precise measurement of lysosomal pH is essential for understanding its role in health and disease, yet most existing chemical-genetic probes for acidic organelles are limited to intensity-based readouts. We introduce BPOEt-1HTL, a benzo[b]phosphole-derived, HaloTag-targetable pH indicator that delivers quantitative, ratiometric pH imaging. In human embryonic kidney cells, BPOEt-1HTL reports nuclear pH and detects drug-induced increases in lysosomal pH following treatment with Bafilomycin A1, an inhibitor of the vacuolar H+-ATPase. The probe supports both excitation and emission ratio-imaging under one- or two-photon excitation, making it compatible with a wide range of microscope systems. This versatile platform expands the toolkit for mapping pH in acidic organelles, offering new opportunities to investigate lysosomal function in disease-relevant contexts.

  PublisherOA PDFDOI

• National Estimates of Pediatric Sepsis in US Hospitals Using Clinical Data

  JAMA · 2026-03-22 · 2 citations

  articleOpen access

  Importance: Pediatric sepsis causes substantial morbidity and mortality, but population surveillance relies on administrative codes with limited and variable accuracy. Objective: To estimate US national incidence, mortality, and trends of sepsis in nonneonatal children using a Pediatric Sepsis Event (PSE) definition adapted from the 2024 Phoenix criteria for scalable electronic health record (EHR)-based surveillance using routinely captured clinical data. Design, Setting, and Participants: Retrospective cohort study of 3.9 million hospitalizations (age, >30 days to 17 years) in 2 EHR datasets: Epic Cosmos (245 health care systems, 2016-2023) and HCA Healthcare (146 hospitals, 2018-2023). Secondary datasets were analyzed to assess feasibility of implementation and face validity across heterogeneous settings. The PSE was validated through medical record reviews of 581 high-risk encounters at 3 geographically diverse hospitals. Exposures: A PSE required presumed infection with concurrent organ dysfunction using Phoenix-derived thresholds adapted for routine EHR data. Septic shock was defined as a PSE with cardiovascular dysfunction. Main Outcomes and Measures: Sepsis incidence, characteristics, and in-hospital mortality were calculated. Sensitivity and specificity of PSE for physician-adjudicated Phoenix sepsis were compared with administrative codes for severe sepsis/septic shock. National sepsis case counts and deaths in 2022 and temporal trends from 2016 to 2022 were estimated using regression models. Results: Among 3 925 809 pediatric hospitalizations from 2016 to 2023, 51 542 sepsis cases (mean age, 6.6 [SD, 6.0] years; 22 840 [44.3%] female) were identified (1.3% incidence); 37 405 (72.6%) were community onset and 31 744 (61.6%) had septic shock. In-hospital mortality was 10.1% and sepsis was present in 17.8% of hospitalizations that culminated in death. Incidence, characteristics, and mortality were broadly consistent across secondary datasets. On medical record review, the PSE definition had 69.9% sensitivity (95% CI, 58.1%-79.8%) and 93.1% specificity (95% CI, 89.6%-95.7%), with higher sensitivity than and comparable specificity with administrative codes. National estimates for 2022 were 18 231 sepsis cases (95% CI, 16 129-20 334) and 1877 deaths(95% CI, 1629-2126). Neither sepsis cases nor deaths changed significantly from 2016 to 2022 (annual change, 0.2% [95% CI, -2.2% to 2.7%] and 0.3% [95% CI, -3.1% to 3.8%], respectively). Conclusions and Relevance: An EHR-based definition for pediatric sepsis demonstrated strong validity compared with physician-adjudicated Phoenix sepsis and identified sepsis in 1.3% of pediatric hospitalizations with 10% mortality, corresponding to more than 18 000 cases and more than 1800 deaths annually in the US.

  PublisherOA PDFDOI

• Ultrafast Frame-Free Imaging of Neural Activity with Event Cameras

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-09

  articleOpen access

  Abstract Frame-based fluorescence imaging has long defined how neural activity is optically measured. This approach requires acquiring all pixels within an image, regardless of whether they carry meaningful neural dynamics, thereby intrinsically coupling spatial and temporal resolution while increasing data output. Here, we introduce an entirely different, frame-free approach that leverages the sparse nature of neural activity using event-based cameras, which asynchronously report fluorescence changes as spatiotemporal events. Compared with a frame-based camera, our method preserves signal fidelity while eliminating the fixed trade-off between spatial resolution, temporal resolution and data rate, thereby reducing data output by orders of magnitude. Applied to hippocampal preparations we demonstrate that the frame-free approach can resolve both single action potentials and fast network dynamics over large fields of view at kilohertz rates, enabling scalable, ultrafast optical recordings.

  PublisherOA PDFDOI

• On the interaction of strain and vorticity forsolutions of the Navier–Stokes equation

  Pure and Applied Analysis · 2026-03-15

  preprintOpen access1st authorCorresponding

  In this paper, we prove a new identity for divergence free vector fields, showing that \begin{equation*} \left<-ΔS,ω\otimesω\right>=0, \end{equation*} where $S_{ij}=\frac{1}{2}\left(\partial_iu_j+\partial_ju_i\right)$ is the symmetric part of the velocity gradient, and $ω=\nabla\times u$ is the vorticity. This identity will allow us to understand the interaction of different aspects of the nonlinearity in the Navier--Stokes equation from the strain and vorticity perspective, particularly as they relate to the depletion of the nonlinearity by advection. We will prove global regularity for the strain-vorticity interaction model equation, a model equation for studying the impact of the vorticity on the evolution of strain which has the same identity for enstrophy growth as the full Navier--Stokes equation. We will also use this identity to obtain several new regularity criteria for the Navier--Stokes equation, one of which will help to clarify the circumstances in which advection can work to deplete the nonlinearity, preventing finite-time blowup.

  PublisherOA PDFDOI

• A chemical-genetic approach to target voltage-sensitive fluorophores to mitochondria

  Mitochondrial Communications · 2025-01-01

  articleOpen accessSenior author

  Mitochondria play central roles in the physiology of eukaryotic cells. Mitochondrial membrane potential, in turn, is a key driver of mitochondrial physiology. We previously developed a system to localize voltage-sensitive fluorophores to mitochondria based on the hydrolysis of labile acetoxymethyl (AM) esters. One potential problem with this system is the premature hydrolysis of the labile AM ester prior to accumulation in the mitochondria. A possible solution is to replace the AM ester with a bulky cyclopropylmethylacetoxy (CPM) ester, which resists uncatalyzed hydrolysis but can be removed by certain esterases. When paired with exogenous expression of mitochondrially-targeted esterases like porcine liver esterase (PLE), this chemical-genetic hybrid approach can improve localization to mitochondria. In this manuscript, we use superresolution microscopy to show that a variety of proteins, including esterases from pig and bacteria can be effectively localized to mitochondria. Further, we establish that a CPM-modified rhodamine voltage reporter (RhoVR-CPM) shows improved localization to mitochondria in cells expressing mitochondrially-targeted esterases. Finally, RhoVR-CPM can be paired with fluorescence lifetime imaging microscopy (FLIM) to map changes in mitochondrial membrane potential.

  PublisherDOI

• A General Strategy for Enhancing the Brightness of Near-Infrared Fluorophores

  ChemRxiv · 2025-09-24

  preprintSenior author

  Near-infrared (NIR) fluorophores are foundational for fluorescence imaging in multicellular organisms. However, their fluorescence brightness, defined as the product of the molar extinction coefficient (ε) and fluorescence quantum yield (ΦF), often pales when compared to that of visible dyes. Although strategies exist to substantially enhance the brightness of visible dyes, when applied to NIR dyes, these approaches lead to only marginal gains. Here, we report a novel and generalizable strategy to improve NIR fluorophore brightness by leveraging the multiple resonance effect (MRE). Using a library of NIR xanthenes as a proof-of-principle, we demonstrate the ability to enhance fluorescence brightness up to ~240 fold by simultaneously improving ε and ΦF. Experimental and computational studies indicate that increased fluorescence brightness is achieved through a decrease in vibronic coupling of the dye, leading to reduced rates of non-radiative decay. Thorough photophysical studies provide a dataset that can be used to accurately predict the properties of new NIR dyes. Using insights from the MRE approach to rhodamine, we developed a new, MRE-inspired oxazine which shows substantial improvement in whole-mouse imaging. This MRE-inspired approach to organic NIR fluorophores improves existing NIR scaffolds and provides a conceptual framework for guiding the design of organic fluorophores in the NIR and visible windows.

  PublisherDOI

• Singular, finite-time $L^2$ attractors for odd, smooth solutions of Burgers equation on the torus

  ArXiv.org · 2025-11-12

  preprintOpen access1st authorCorresponding

  In this paper, we show that the positive multiples of a particular function $F$ -- which is singular with a jump discontinuity at the origin -- are finite-time global attractors in $L^2$ for generic odd, smooth solutions of the one dimensional inviscid Burgers equation. Furthermore, the identity that leads to this result provides to an alternative proof of finite-time blowup for the fractal Burgers equation in the supercritical range $0<α<\frac{1}{2}$. This proof is based on lower bounds on a Lyapunov functional given by the inner product of the solution with the global attractor $F$. We will also show that this property holds for a broader class of odd functions that are strictly increasing on $(0,π)$.

  PublisherOA PDFDOI

• Fluorogenic rhodamine B derivatives that become brighter at neutral pH

  ChemRxiv · 2025-07-09

  preprintOpen accessSenior author

  Rhodamines are useful fluorescent molecules for activity-based sensing. One powerful design strategy is to exploit chang-es in the open / closed equilibrium of rhodamine amides. In the context of amide derivatives of rhodamine B, a prototypi-cal member of the rhodamine family, this strategy has been especially useful in the development of activity-based indica-tors for protons and metal ions. This is because at neutral pH, the closed form of rhodamine B amides dominates, making this otherwise bright and fluorescent dye non-fluorescent. At acidic pH, the equilibrium favors the open form. Despite a wealth of methods to trigger Lewis acid-mediated fluorogenicity of rhodamine B amides, there are far fewer ways to shift the open-close equilibrium to favor the open form at neutral pH. Here, we demonstrate that a simple substitution substan-tially shifts the native rhodamine B amide equilibrium to favor the open, fluorescent form at neutral pH. Rhodamine B de-rivatives with an N-(2'-carboxy)-phenyl substitution (an ortho anthranilic acid, RhoB-AA) show strong absorbance and emission at pH 7.2, up to ~1500× greater than their unsubstituted N-phenyl derivatives (RhoB-Ph). The fluorescence of RhoB-AA at neutral pH is dependent on the free carboxylic acid. Esters of RhoB-AA are also ~1500× less fluorescent than RhoB-AA and have optical properties nearly identical to the unsubstituted RhoB-Ph. Esters of RhoB-AA can be converted by esterases to the fully fluorescent RhoB-AA, demonstrating that the simple ortho anthranilic acid substitution is a pow-erful strategy for activity-based sensing with rhodamine amides at neutral pH.

  PublisherOA PDFDOI

• Fluorogenic rhodamine B derivatives that become brighter at neutral pH

  Bioorganic & Medicinal Chemistry Letters · 2025-09-30 · 1 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Bis(trifluoromethyl)carborhodamines: Highly Fluorogenic, Far-Red to Near-Infrared Dyes for Live Cell Fluorescence Microscopy, Activity-Based Sensing, and Single-Molecule Microscopy

  Journal of the American Chemical Society · 2025-06-12 · 9 citations

  articleSenior authorCorresponding

  Synthetic fluorophores built on a classic rhodamine scaffold are essential for modern microscopy. An attractive feature of synthetic fluorophores is their potential to access long-wavelength excitation and emission profiles (>650 nm) that are difficult to achieve through genetically encoded methods like fluorescent proteins. Here, we present a new strategy to achieve excitation and emission above 650 nm: bis(trifluoromethyl)carborhodamine dyes, or BF dyes. In BF dyes, the geminal methyl groups of carborhodamines are replaced with trifluoromethyl (CF3) groups. This accomplishes two things. First, CF3 groups substantially red shift in the optical profile by over 90 nm compared to classic, oxygen-bridged rhodamine dyes, resulting in a dye framework with excitation and emission profiles >650 nm and high brightness (extinction coefficient >140,000 M–1 cm–1 and fluorescent quantum yield of 33%). Second, CF3 groups render BF dyes fluorogenic, by shifting the position of the open-closed equilibrium of the colorless lactone and colored zwitterion form, resulting in up to a 30-fold improvement in fluorogenicity compared to silicon-bridged rhodamines. In this paper, we present the design and computational analysis of BF dyes; synthetic studies to access over a dozen new BF dyes through a unique, late-stage functionalization strategy; spectra characterization; and applications in advanced fluorescence microscopy including no-wash intracellular labeling, functional imaging with chemigenetic indicators, and single molecule tracking in living cells. Together, this report shows that bis(trifluoromethyl)carborhodamine dyes provide a complementary approach to achieving long-wavelength, fluorogenic dyes for live cell microscopy that do not rely on dimethyl silicon rhodamines.

  PublisherDOI

Recent grants

• NeuroNex Innovation Award: Chemical and Genetic Methods to Measure and Manipulate Neurons with Light

  NSF · $800k · 2017–2020

• New Chemical Tools for Exploring Cellular Physiology

  NIH · $1.3M · 2016–2021

• NIH Grant K99NS078561

  NIH · $181k · 2014

• NIH Grant F32EB012423

  NIH · $67k · 2012

• Interrogating Neuronal Membrane Potential Dynamics with Optical Voltage Sensors

  NIH · $4.4M · 2017–2026

Frequent coauthors

• Christopher J. Chang

  Colorado State University

  39 shared

• Steven C. Boggess

  University of California, Berkeley

  26 shared

• Benjamin K. Raliski

  University of California, Berkeley

  21 shared

• Shimon Weiss

  University of California, Los Angeles

  20 shared

• Parker E. Deal

  University of California, San Francisco

  19 shared

• Julia R. Lazzari-Dean

  Enzo Life Sciences (United States)

  19 shared

• Kevin E. Healy

  18 shared

• Brittany Benlian

  University of California, Berkeley

  17 shared