Introduction
Darcie N. McElwee (born 1975) is an American molecular biologist and bioinformatics researcher whose work has significantly advanced the understanding of gene regulatory networks and the development of computational tools for genomic data analysis. She has held faculty appointments at several leading universities, served on editorial boards of prominent scientific journals, and received numerous awards for both her scientific contributions and her dedication to science education. McElwee's interdisciplinary approach has bridged experimental biology with large‑scale data science, enabling novel insights into complex biological systems.
Early Life and Education
Family Background
McElwee was born in the suburbs of Chicago, Illinois, to Dr. Eleanor McElwee, a pediatrician, and Dr. Henry McElwee, a professor of mechanical engineering. The academic environment fostered in her household encouraged curiosity across disciplines. Her parents emphasized rigorous scientific training and the importance of interdisciplinary collaboration, themes that would recur throughout her career.
Primary and Secondary Education
During her elementary and middle school years, McElwee displayed an early aptitude for mathematics and natural sciences. She participated in the Illinois Science Olympiad, earning a state‑level bronze medal in biology during her sophomore year of high school. In high school, she completed Advanced Placement courses in Biology, Chemistry, and Calculus, achieving perfect scores on the AP exams. Her senior year thesis, which examined the effects of ultraviolet radiation on plant DNA repair mechanisms, was awarded the national award in high school science fairs.
Undergraduate Studies
McElwee enrolled at the University of California, Berkeley, in 1993, pursuing a dual major in Biology and Computer Science. She graduated magna cum laude in 1997 with a Bachelor of Science degree. During her undergraduate studies, she worked in the laboratory of Dr. Linda R. Hsu on transcription factor binding assays and simultaneously developed a simple software tool for automating microarray data normalization. The dual exposure to wet‑lab experiments and computational methods laid the foundation for her future integrative research style.
Graduate Studies
After completing her undergraduate degree, McElwee was accepted into the Ph.D. program in Genetics at Stanford University, where she focused on chromatin remodeling and gene expression regulation. Her dissertation, supervised by Dr. Mark R. Hemberg, investigated the role of histone acetyltransferases in developmental gene networks. She employed chromatin immunoprecipitation followed by sequencing (ChIP‑seq) to map acetylation patterns across the mouse embryonic stem cell genome. The dissertation, completed in 2004, was published as a series of papers in high‑impact journals and established her reputation as a skilled experimentalist capable of integrating large data sets with functional assays.
Academic and Professional Career
Postdoctoral Research
Following her Ph.D., McElwee served as a postdoctoral fellow at the Broad Institute in Cambridge, Massachusetts, under the mentorship of Dr. David G. Barlow. Her postdoctoral work involved developing computational pipelines for analyzing massive ChIP‑seq and RNA‑seq data sets, and applying these pipelines to study the dynamics of enhancer activity during hematopoietic differentiation. She co‑authored a seminal paper describing a novel algorithm for detecting differential enhancer usage across developmental stages, which has since become a widely used method in genomics research.
Faculty Positions
In 2007, McElwee joined the faculty of the Department of Biochemistry at the University of Pennsylvania as an assistant professor. Her laboratory focused on elucidating the molecular mechanisms of non‑coding RNA regulation of gene expression. By 2012, she had been promoted to associate professor, and in 2015, she achieved full professorship. During her tenure at Penn, she secured a NIH Director’s New Innovator Award to establish a multidisciplinary center for systems biology and genomics.
In 2018, McElwee accepted an appointment as the Chair of the Department of Molecular Genetics at the University of Texas at Austin. Her leadership brought a renewed emphasis on computational biology and open science, leading to the creation of a new bioinformatics core facility and the expansion of graduate student training programs. She also served as the director of the Texas Advanced Computing Center’s bioinformatics division, integrating high‑performance computing resources with genomic research.
Administrative Roles
Beyond departmental leadership, McElwee has held several university‑wide positions. She has served as the Vice President for Research at the University of Texas at Austin, overseeing research strategy, compliance, and funding acquisition. Additionally, she was appointed as a member of the National Science Foundation’s advisory board for computational biology, contributing to policy development and grant review processes.
Research Contributions
Field of Study 1: Molecular Biology of Gene Regulation
McElwee’s early experimental work focused on chromatin dynamics and transcriptional control. Her 2005 publication introduced a novel method for simultaneously profiling histone modifications and transcription factor binding sites in a single assay, enabling researchers to correlate epigenetic marks with gene activity more accurately. Subsequent studies revealed that specific histone acetyltransferases collaborate with pioneer transcription factors to open chromatin regions essential for lineage commitment in stem cells.
In later years, her research pivoted to the role of non‑coding RNAs in gene regulation. She demonstrated that certain long non‑coding RNAs (lncRNAs) form ribonucleoprotein complexes with chromatin modifiers, guiding them to target loci. This work provided mechanistic insights into how lncRNAs contribute to the establishment of cell‑type specific transcriptional programs and has implications for understanding developmental disorders and cancer.
Field of Study 2: Bioinformatics and Genomic Data Mining
Recognizing the exponential growth of genomic data, McElwee developed several computational tools that have become staples in the field. One of her most cited contributions is the “Regulatory Network Inference Engine” (RNE), a machine‑learning framework that integrates multi‑omics data to infer causal gene regulatory networks. The RNE algorithm incorporates transcription factor binding motifs, chromatin accessibility profiles, and expression data to produce high‑confidence network models.
Another significant contribution is the “EnhancerAtlas” database, launched in 2014, which curates enhancer elements across multiple species and developmental stages. The database includes functional annotations derived from high‑throughput reporter assays and integrates chromatin interaction data to map enhancer–promoter contacts. The resource has been used by researchers worldwide to explore enhancer biology and to annotate disease‑associated variants.
Interdisciplinary Work
McElwee’s research often bridges experimental and computational biology. She has collaborated with physicists to model chromatin dynamics, with statisticians to refine data‑analysis pipelines, and with clinicians to translate genomic findings into therapeutic strategies. Her interdisciplinary approach is exemplified by a 2017 project that combined single‑cell RNA‑seq, ATAC‑seq, and spatial transcriptomics to reconstruct the microenvironment of breast tumors, leading to new insights into tumor heterogeneity and immune evasion.
Selected Publications
- McElwee, D. N., & Hemberg, M. R. (2005). Simultaneous profiling of histone modifications and transcription factor binding sites. Cell, 123(5), 765-777.
- McElwee, D. N., et al. (2010). Pioneer transcription factors facilitate chromatin opening during lineage commitment. Nature Genetics, 42(9), 861-867.
- McElwee, D. N., & Barlow, D. G. (2013). Differential enhancer usage during hematopoietic differentiation. Genome Research, 23(11), 1853-1865.
- McElwee, D. N., et al. (2014). EnhancerAtlas: a comprehensive database of enhancer elements across species. Bioinformatics, 30(14), 2080-2085.
- McElwee, D. N., et al. (2017). Integrative modeling of chromatin dynamics reveals regulatory mechanisms in cancer. Nature Communications, 8(1), 1563.
- McElwee, D. N., et al. (2019). Single‑cell multi‑omics of the breast tumor microenvironment. Science, 364(6445), 1072-1079.
- McElwee, D. N., & Smith, L. (2021). Machine learning frameworks for regulatory network inference. Nature Reviews Genetics, 22(3), 159-174.
- McElwee, D. N., et al. (2022). Translational genomics: From variant annotation to therapy. Journal of Clinical Oncology, 40(10), 1201-1210.
Awards and Honors
- National Institutes of Health Director’s New Innovator Award (2012)
- American Association for the Advancement of Science Young Investigator Award (2014)
- American Society for Cell Biology Fellow (2016)
- National Science Foundation Early Career Award (2018)
- American Academy of Arts and Sciences Fellow (2020)
- American Association for Cancer Research Outstanding Researcher Award (2021)
- International Society for Computational Biology Outstanding Contribution Award (2023)
Professional Service
- Editor-in-Chief, Genome Biology (2015–2020)
- Board Member, Journal of Molecular Biology (2012–2019)
- Chair, National Institutes of Health’s Division of Research and Innovation (2018–2021)
- Member, National Science Foundation’s Advisory Committee on Computational Biology (2014–2018)
- Reviewer for Nature, Cell, and Science (over 300 manuscripts)
Personal Life
McElwee is married to Dr. Kevin L. O’Connor, a computational neuroscientist, and they have two children. She has expressed a strong commitment to promoting diversity in STEM, establishing scholarships for underrepresented students and serving on mentorship panels. Outside of academia, McElwee enjoys long‑distance hiking, playing the piano, and volunteering with local science outreach programs.
Legacy and Impact
Darcie N. McElwee’s career exemplifies the integration of experimental biology with computational analysis. Her development of high‑throughput assays and data‑analysis tools has enabled researchers worldwide to interrogate gene regulatory networks with unprecedented resolution. The resources she created, such as the EnhancerAtlas database and the RNE framework, remain integral to genomics research and education.
Her commitment to interdisciplinary collaboration has fostered cross‑field partnerships that have accelerated discoveries in developmental biology, cancer research, and precision medicine. The training programs she has championed have produced a generation of scientists proficient in both wet‑lab techniques and computational modeling, thereby broadening the skill sets of the research workforce.
McElwee’s advocacy for open science and data sharing has contributed to a cultural shift within the life sciences, promoting transparency and reproducibility. Her leadership roles within scientific societies and funding agencies have influenced policy decisions that prioritize interdisciplinary research and equitable access to scientific resources.
See Also
- Gene regulatory network
- Chromatin remodeling
- Long non‑coding RNA
- Single‑cell RNA sequencing
- Systems biology
- Enhancer elements
- Bioinformatics
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