Christina Theodoris, MD, PhD

Asst Professor in Residence
Pediatrics
Research Description: 

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.

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Human Genetics
Research Summary: 
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.

Websites

Featured Publications: 

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, Malaschicheva 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

Human disease modeling reveals integrated transcriptional and epigenetic mechanisms of NOTCH1 haploinsufficiency.

Cell

Theodoris CV, Li M, White MP, Liu L, He D, Pollard KS, Bruneau BG, Srivastava D

A gene regulatory network subcircuit drives a dynamic pattern of gene expression.

Science (New York, N.Y.)

Smith J, Theodoris C, Davidson EH