Christina Theodoris, MD, PhD

Asst Professor in Residence

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. 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.


Interpretable model of CRISPR-Cas9 enzymatic reactions.

Nature computational science

Wen DJ, Theodoris CV

Race, Ethnicity, and Ancestry in Clinical Pathways: A Framework for Evaluation.


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, Starmer A, BOSTON CHILDREN’S HOSPITAL RACE, ETHNICITY, AND ANCESTRY IN CLINICAL PATHWAYS WORKING GROUP

Transfer learning enables predictions in network biology.


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

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.)

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

Long telomeres protect against age-dependent cardiac disease caused by NOTCH1 haploinsufficiency.

The Journal of clinical investigation

Theodoris CV, Mourkioti F, Huang Y, Ranade SS, Liu L, Blau HM, Srivastava D

NOTCH1 regulates matrix gla protein and calcification gene networks in human valve endothelium.

Journal of molecular and cellular cardiology

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.


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

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.)

Smith J, Theodoris C, Davidson EH