MC² Research Program Research Overview



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The MC² team will enhance CAVATICA, a data analysis and sharing platform developed by D3b, to enable open access to pediatric genomic data and establish a first-of-its-kind multi-omics data dynamic modeling infrastructure.

The program also serves as a conduit for internal and external partnerships related to mitochondrial and precision medicine, supporting work with the Center for Precision Medicine for High-Risk Pediatric Cancer and the Developmental Therapeutics Program to benefit a wide range of future studies across CHOP.

MC2 is developing strong preliminary data to support future federal funding and novel therapeutic leads with commercial development potential to facilitate the translation to precision therapies for pediatric patients with mitochondrial disease and cancer.

Drs. Falk and Resnick are deeply grateful to Patricia and David Holveck, whose generosity and support made the launch of MC2 possible.

Learn how MC2 Research Program scientists are identifying mechanistic targets for therapeutic intervention and evaluating potential therapeutic efficacy of mitochondrial and metabolic function in the context of osteosarcoma.

The MC2 research program aims to create high integrity multi-omics data generation routes and integrated modeling platforms to enable discovery of complex cellular strategies for survival, growth, stress response, function, and response to therapies that are discrepant between primary mitochondrial disease and pediatric cancer cells.

Developing and implementing informatics platforms in the CAVATICA environment will support multi-dimensional data integrity and access, integration, and computational modeling of diverse types of existing and newly captured high-dimensional data in human mitochondrial disease cells and pediatric cancers, with an initial focus on osteosarcoma.

Innovative analyses are underway to apply deep cell immunophenotyping to evaluate complementary cellular signaling, immune, cell death, and biochemical pathway alterations that indicate novel mechanistic targets for therapeutic intervention.

Researchers are developing novel approaches to characterize immune system and cell death alterations across major biochemical categories of (genetic based) mitochondrial disease patient cells and osteosarcoma tumor cells. Their methods include:

  • Applying deep cell phenotyping flow cytometry methodology
  • Evaluating comparative transcriptional profiles using RNAseq and methylation analysis
  • Applying unbiased proteomics profiles to simultaneously quantify thousands of cellular proteins
  • Using targeted and unbiased metabolomics approaches to profile biochemical pathway responses with liquid chromatography tandem mass spectrometry analysis.

MC2 investigators will evaluate the therapeutic effects of novel mitochondrial oxidative phosphorylation inhibition strategies in small animal models of cancer. They will establish novel human osteosarcoma xenograft models in zebrafish to determine whether genetic-based mitochondrial dysfunction or pharmacologic inhibition of mitochondria, as well as broader metabolic function(s), has therapeutic efficacy for osteosarcoma.

Ongoing work will focus on functional validation of the therapeutic efficacy of targeting key points of variance as well as evaluation of therapeutic effects at the multi-omics level. Biopharma and academic partnerships are actively pursued to accelerate the preclinical stage development of therapies for osteosarcoma, and advance lead compounds to clinical trial readiness.