Christina Theodoris, MD, PhD
Assistant Professor
Pediatrics
School of Medicine
Our lab leverages cutting-edge machine learning and experimental genomics to map the gene regulatory networks disrupted in cardiovascular disease and discover network-correcting therapeutics.
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We develop machine learning models that leverage the unprecedented volume of transcriptomic and epigenomic data now available to gain a fundamental understanding of network dynamics that can be democratized to a vast array of downstream applications. Investigating the consequences of network rewiring that occurs in disease states uncovers the key mechanisms that coordinate gene transcription to ensure normal development and tissue maintenance. Furthermore, mapping the network dysregulation driving disease allows targeting normalization of central elements to treat the core disease mechanism rather than merely managing symptoms. We apply an innovative network-based framework for therapeutic discovery to cardiovascular disease to accelerate development of much-needed treatments for patients as well as to advance our fundamental understanding of the regulatory circuitry governing human development and disease.
Education & Training
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- postdoc Computational Biology Broad Institute of MIT and Harvard; Dept. of Data Science, Dana-Farber Cancer Institute 09/2022
- residency Pediatrics-Medical Genetics Residency Boston Children's Hospital 06/2022
- MD, PhD Developmental and Stem Cell Biology University of California, San Francisco 06/2017
- BS Biology California Institute of Technology 06/2009
Websites
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- Gladstone profile (gladstone.org)
- Lab website (theodorislab.gladstone.org)
Publications (11)
Top publication keywords:
BiologyCalcinosisNitrilesThiazolesHeart Valve DiseasesCRISPR-Cas SystemsAortic Valve StenosisTelomereHeart Septal DefectsHaploinsufficiencyReceptor, Notch1Machine LearningTelomere HomeostasisAortic ValveGene Regulatory Networks
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Interpretable model of CRISPR-Cas9 enzymatic reactions.
Nature computational science 2023 Wen DJ, Theodoris CV -
Race, Ethnicity, and Ancestry in Clinical Pathways: A Framework for Evaluation.
Pediatrics 2023 Rosen RH, Epee-Bounya A, Curran D, Chung S, Hoffmann R, Lee LK, Marcus C, Mateo CM, Miller JE, Nereim C, Silberholz E, Shah SN, Theodoris CV, Wardell H, Winn AS, Toomey S, Finkelstein JA, Ward VL, … -
Transfer learning enables predictions in network biology.
Nature 2023 Theodoris CV, Xiao L, Chopra A, Chaffin MD, Al Sayed ZR, Hill MC, Mantineo H, Brydon EM, Zeng Z, Liu XS, Ellinor PT -
MIRA: joint regulatory modeling of multimodal expression and chromatin accessibility in single cells.
Nature methods 2022 Lynch AW, Theodoris CV, Long HW, Brown M, Liu XS, Meyer CA -
Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease.
Science (New York, N.Y.) 2020 Theodoris CV, Zhou P, Liu L, Zhang Y, Nishino T, Huang Y, Kostina A, Ranade SS, Gifford CA, Uspenskiy V, Malashicheva A, Ding S, Srivastava D
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Long telomeres protect against age-dependent cardiac disease caused by NOTCH1 haploinsufficiency.
The Journal of clinical investigation 2017 Theodoris CV, Mourkioti F, Huang Y, Ranade SS, Liu L, Blau HM, Srivastava D -
The ACVR1 R206H mutation found in fibrodysplasia ossificans progressiva increases human induced pluripotent stem cell-derived endothelial cell formation and collagen production through BMP-mediated SMAD1/5/8 signaling.
Stem cell research & therapy 2016 Barruet E, Morales BM, Lwin W, White MP, Theodoris CV, Kim H, Urrutia A, Wong SA, Srivastava D, Hsiao EC -
NOTCH1 regulates matrix gla protein and calcification gene networks in human valve endothelium.
Journal of molecular and cellular cardiology 2015 White MP, Theodoris CV, Liu L, Collins WJ, Blue KW, Lee JH, Meng X, Robbins RC, Ivey KN, Srivastava D -
Human disease modeling reveals integrated transcriptional and epigenetic mechanisms of NOTCH1 haploinsufficiency.
Cell 2015 Theodoris CV, Li M, White MP, Liu L, He D, Pollard KS, Bruneau BG, Srivastava D -
A spatially dynamic cohort of regulatory genes in the endomesodermal gene network of the sea urchin embryo.
Developmental biology 2007 Smith J, Kraemer E, Liu H, Theodoris C, Davidson E -
A gene regulatory network subcircuit drives a dynamic pattern of gene expression.
Science (New York, N.Y.) 2007 Smith J, Theodoris C, Davidson EH