About

The goal of the Pfenning group is to build a set of computational and genomic tools to study how genome sequence influences neural cells, neural circuits, disease, and behavior. The group is conducting research on the genetic mechanisms of Alzheimer’s disease, the epigenetics of aging, and evolution of language behavior.

Research topics

• Computer Science
• Engineering
• Biology
• Evolutionary biology
• Medicine
• Ecology
• Physics
• Genetics
• Virology
• Quantum mechanics
• Computational biology
• Electronic engineering

Selected publications

• Evolution of Mammalian Regulatory Networks in the Brain

  Annual Review of Animal Biosciences · 2025-11-15

  articleOpen accessSenior author

  comparative genomics, evolution, neuroscience, artificial intelligence, computational biology, behaviorMammals and other vertebrates exhibit an incredible diversity of complex behaviors that have evolved as these species adapted to their environments. Underlying the phenotypic diversity is molecular diversity: The brain is composed of hundreds of molecularly distinct cell types that play a variety of roles in different behaviors and neural circuits. Single cell and spatial transcriptomic techniques are providing insights into which features of those neural cell types are conserved or divergent across mammals and, more broadly, vertebrates. The ability to genomically characterize individual neurons has created opportunities to link evolution at a molecular level to evolution at the circuit and behavioral levels. Although discoveries in evolutionary biology have been made by leveraging single cell genomics, fundamental methodological challenges remain to be addressed. New types and increased complexity of data sets have spurred the development of various new computational techniques. In parallel, new genomic technologies are being developed to better perturb and study brain regulatory networks. The methods for reconstructing regulatory networks in vitro have been advancing rapidly, but challenges still exist in reliably adapting those technologies for use in vivo across a wide variety of species. As the genomic technologies and computational approaches become tractable in the brains of animals, the field is poised to make big discoveries in how complex mammalian behaviors evolve.

  PublisherDOI

• Post-fabrication tuning of circular Bragg grating resonators via atomic layer deposition

  Applied Physics Letters · 2025-09-30 · 1 citations

  articleSenior author

  Circular Bragg grating resonators have gained a lot of attention in various material platforms due to their high Purcell factors over large bandwidth. Although the bandwidth is on the order of several nanometers, the best performance is given when perfectly matching the resonator's frequency with the frequency of the embedded emitter. The device resonance spectrum depends on many parameters, such that fabrication often renders devices with detuning to the intended frequency. Here, we show a method to tune the resonator mode in post-fabrication via atomic layer deposition. Atomic layer deposition of a dielectric layer (Al2O3) is used to red-shift the optical resonance. While the presented technique is universal for circular Bragg grating resonators within a wide class of material systems, we choose the quaternary semiconductor In0.53Al0.23Ga0.24As and incorporate InAs quantum dots as active material to validate the technique. We show a tuning of the resonator mode of up to (11.3±0.1) nm with (36±1) nm of Al2O3 at about 1460 nm emission wavelength, which is more than half of the experimental linewidth of the mode itself.

  PublisherDOI

• An in vivo systemic massively parallel platform for deciphering animal tissue-specific regulatory function

  Frontiers in Genetics · 2025-04-09 · 13 citations

  articleOpen accessSenior author

  Introduction: Transcriptional regulation is an important process wherein non-protein coding enhancer sequences play a key role in determining cell type identity and phenotypic diversity. In neural tissue, these gene regulatory processes are crucial for coordinating a plethora of interconnected and regionally specialized cell types, ensuring their synchronized activity in generating behavior. Recognizing the intricate interplay of gene regulatory processes in the brain is imperative, as mounting evidence links neurodevelopment and neurological disorders to non-coding genome regions. While genome-wide association studies are swiftly identifying non-coding human disease-associated loci, decoding regulatory mechanisms is challenging due to causal variant ambiguity and their specific tissue impacts. Methods: Massively parallel reporter assays (MPRAs) are widely used in cell culture to study the non-coding enhancer regions, linking genome sequence differences to tissue-specific regulatory function. However, widespread use in animals encounters significant challenges, including insufficient viral library delivery and library quantification, irregular viral transduction rates, and injection site inflammation disrupting gene expression. Here, we introduce a systemic MPRA (sysMPRA) to address these challenges through systemic intravenous AAV viral delivery. Results: We demonstrate successful transduction of the MPRA library into diverse mouse tissues, efficiently identifying tissue specificity in candidate enhancers and aligning well with predictions from machine learning models. We highlight that sysMPRA effectively uncovers regulatory effects stemming from the disruption of MEF2C transcription factor binding sites, single-nucleotide polymorphisms, and the consequences of genetic variations associated with late-onset Alzheimer‘s disease. Conclusion: SysMPRA is an effective library delivering method that simultaneously determines the transcriptional functions of hundreds of enhancers in vivo across multiple tissues.

  PublisherDOI

• High optical anisotropy of the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"><mml:mrow><mml:mi>Ga</mml:mi><mml:mi>Sb</mml:mi></mml:mrow><mml:mo>/</mml:mo><mml:msub><mml:mi>Ga</mml:mi><mml:mi>x</mml:mi></mml:msub><mml:msub><mml:mi>In</mml:mi><mml:mrow><mml:mn>1</mml:mn><mml:mo>−</mml:mo><mml:mi>x</mml:mi></mml:mrow></mml:msub><mml:msub><mml:mi>As</mml:mi><mml:mi>y</mml:mi></mml:msub><mml:msub><mml:mi>Sb</mml:mi><mml:mrow><mml:mn>1</mml:mn><mml:mo>−</mml:mo><mml:mi>y</mml:mi></mml:mrow></mml:msub></mml:math> interface

  Physical Review Applied · 2025-01-27 · 1 citations

  articleOpen access

  We present the investigation of optical transitions in an <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"><a:mrow><a:mi>Ga</a:mi><a:mi>Sb</a:mi></a:mrow><a:mo>/</a:mo><a:mrow><a:mi>Ga</a:mi><a:mi>In</a:mi><a:mi>As</a:mi><a:mi>Sb</a:mi></a:mrow></a:math>-based heterostructure through different experimental and numerical methods. The transitions had high-temperature stability, with them being observed in the 10–300 K temperature range. Four pronounced optical transitions are observed at low temperature with three of them being nonpolarized and one showing a degree of linear polarization higher than 60%. Time-resolved measurements of the transitions showed a complex carrier dynamics with several distinct processes related to the investigated interface. Using several numerical methods, we identified that the highly polarized transition originates from the first electron state in the <d:math xmlns:d="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"><d:mrow><d:mi>Ga</d:mi><d:mi>In</d:mi><d:mi>As</d:mi><d:mi>Sb</d:mi></d:mrow></d:math> layer and a two-dimensional hole gas created within a triangular quantum well at the interface with the -type doped <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"><g:mrow><g:mi>Ga</g:mi><g:mi>Sb</g:mi></g:mrow></g:math> layer. The optical polarization of the signal originates in directional elongation of the atomic bonds enhanced by possible local composition fluctuations and the inheritance of these properties by the signal from the triangular quantum well. Such physical phenomena have the potential to be used as an internal polarizing filter in structures designed for midinfrared optoelectronics.

  PublisherDOI

• Wavevector-resolved polarization entanglement from radiative cascades

  Nature Communications · 2025-07-05 · 5 citations

  articleOpen access

  The generation of entangled photons from radiative cascades has enabled milestone experiments in quantum information science with several applications in photonic quantum technologies. Significant efforts are being devoted to pushing the performances of near-deterministic entangled-photon sources based on single quantum emitters often embedded in photonic cavities, so to boost the flux of photon pairs. The general postulate is that the emitter generates photons in a nearly maximally entangled state of polarization, ready for application purposes. Here, we demonstrate that this assumption is unjustified. We show that in radiative cascades there exists an interplay between photon polarization and emission wavevector, which can be further amplified by embedding the emitters in micro-cavities. We discuss how the polarization entanglement of photon pairs from a biexciton-exciton cascade in quantum dots strongly depends on their propagation wavevector and we even observe entanglement vanishing for large emission angles. Our experimental results, backed by theoretical modeling, yield a brand-new understanding of cascaded emission for various quantum emitters. In addition, our model provides quantitative guidelines for designing optical microcavities that retain both a high degree of entanglement and collection efficiency, moving the community one step further towards an ideal source of entangled photons for quantum technologies. The assumption that light sources based on radiative cascades provide maximally polarization-entangled photons is not always correct. Here the authors show experimentally in cavity-embedded quantum dots that photon polarization correlates with its emission mode, impacting the degree of entanglement for emitted photon pairs.

  PublisherOA PDFDOI

• Lingering times at resonance: The case of Sb-based tunneling devices

  Physical Review Applied · 2025-01-23 · 1 citations

  article

  Concurrent natural time scales related to relaxation, recombination, trapping, and drifting processes rule the semiconductor heterostructures' response to external drives when charge carrier fluxes are induced. This paper highlights the role of stoichiometry not only for the quantitative tuning of the electron-hole dynamics, but also for significant qualitative contrasts of time-resolved optical responses during the operation of resonant tunneling devices. Therefore, similar device architectures and different compositions have been compared to elucidate the correlation among structural parameters, radiative recombination processes, and electron-hole pair and minority-carrier relaxation mechanisms. When these ingredients intermix with the electronic structure in Sb-based tunneling devices, it is proven possible to assess various time scales according to the intensity of the current flux, contrary to what has been observed in As-based tunneling devices with similar design and transport characteristics. These time scales are strongly affected by the filling process in the $\mathrm{\ensuremath{\Gamma}}$ and $L$ states in Sb-based double-barrier quantum wells and by the small separation between these states, compared to similar heterostructures based on As.

  PublisherDOI

• Deterministic and highly indistinguishable single photons in the telecom C-band

  OPUS Publication Server of the University of Stuttgart (University of Stuttgart) · 2025-05-14

  preprintOpen access

  Quantum dots are promising candidates for deterministic single-photon sources, yet achieving high photon indistinguishability at telecom wavelengths remains a critical challenge. Here, we report a quantum dot-based single-photon source operating in the telecommunications C-band that achieves a raw two-photon interference visibility of up to (91.7+-0.2)%, thus setting a new benchmark for indistinguishability in this spectral range. The device consists of an indium arsenide (InAs) quantum dot embedded within indium aluminum gallium arsenide (InAlGaAs) and integrated into a circular Bragg grating resonator. We explore multiple optical excitation schemes to optimize coherence and source performance. To our knowledge, this is the first demonstration of two-photon interference visibility exceeding 90% from a quantum-dot emitter in the telecommunications C-band, advancing the viability of solid-state sources for quantum communication and photonic networks.

  PublisherDOI

• Front Cover: Two‐Photon Interference from an InAs Quantum Dot Emitting in the Telecom C‐Band (Adv. Quantum Technol. 10/2025)

  Advanced Quantum Technologies · 2025-10-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Ultra low density quantum dot for high purity and scalable single photon sources

  2024-03-12

  article

  The development of quantum photonic technologies will fuel a paradigm shift in data processing and communication protocols. A controlled generation of non-classical states of light is a challenging task at the heart of such technologies. Epitaxially grown self- assembled semiconductor quantum dots (QDs) offer the advantages of deterministic generation of single photons and prospects of device integration. By growing such QD structures only in designated locations on (001) Si substrate, the quantum properties of the emitted photons could be tuned with the built-in thermal stress for generating highly entangled photon pairs.

  PublisherDOI

• AI-designed DNA sequences regulate cell-type-specific gene expression

  Nature · 2024-10-23 · 4 citations

  article1st authorCorresponding
  PublisherDOI

Recent grants

• Interpreting the regulatory mechanisms underlying the predisposition to substance use disorders

  NIH · $2.4M · 2018–2023

Frequent coauthors

• Sven Höfling

  University of Würzburg

  64 shared

• Ricardo Antonio Rosselló

  Massachusetts Institute of Technology

  64 shared

• Ute Hochgeschwender

  Central Michigan University

  64 shared

• Jason T. Howard

  Rockefeller University

  64 shared

• Fabian Hartmann

  40 shared

• L. Worschech

  University of Würzburg

  28 shared

• Tobias Huber

  University of Würzburg

  22 shared

• Morgan Wirthlin

  Carnegie Mellon University

  20 shared

Labs

• Neurogenomics LaboratoryPI

Education

• Ph.D., Computer Science

  Carnegie Mellon University

  1994

• M.S., Computer Science

  Carnegie Mellon University

  1991

• B.S., Computer Science

  University of California, San Diego

  1988