Bringing model systems closer to the clinic
Goal of the clonal redesign lab is to change a tumor’s environment so as to favor certain tumor subclones over others. We will redesign a tumor’s fitness landscape, rather than directly the clones themselves. Why then clonal redesign? Because by redesigning the environment, adaptation of clones to the new environment is implicit. Anticipating and preparing for this adaptation is at the core of our lab.
WELCOME TO OUR PERSONALIZED ONCOLOGY PLATFORM
We combine computational biology, mathematical modeling and pharmacology to up our odds in the race against tumor evolution.
Our research program runs on two parallel tracks, the first complementing and supporting the second. The first track aims to improve consilience among clone perspectives: developing methods to quantify the clonal composition of a tumor from different perspectives, such as their genome, transcriptome, or appearance, and integrating those methods with each other. In short, the first track characterizes clones. The second track uses these clone characteristics to make treatment predictions.
Jordan Albrecht started her internship, to quantify cell features from live cell imaging and link them, by phenotype, to single cell RNA sequencing. Welcome Jordan!
John Kyei joins the CRD lab as postdoctoral fellow in mathematical modeling. John brings experience in data-driven modeling of dynamical systems and operator theory, which he will use to model the spatio-temporal evolution of tumor cells in resource-sparse environments. Welcome John!
Tommy’s first, first-author paper was published today, Mathematical Modeling of Clonal Interference by Density-Dependent Selection in Heterogeneous Cancer Cell Lines!
CRD lab was awarded the NCI's R21 from the ITCR to develop the software tool CLONEID! CLONEID simplifies collaborations between computational and experimental biologists. Without CLONEID, coordinating experimental data with mathematical modelling often takes weeks per experiment. CLONEID’s workflow can take years of cell imaging data and move it seamlessly into deep learning algorithms and mathematical models. Potential applications include evolutionary steering, lineage tracing, multi-omics, identification of mycoplasma contamination and distinction of dead from live cells.
Modeling mis-segregations is hard because of the sheer number of possible karyotypes. More than 70 quintillions (considering 8 states/chr)! We derived a deterministic framework for modeling mis-segregations. Published today in Plos Comp Bio.
IMO X Winners!
CRD lab was awarded the NCI's R37, dedicated to quantify the cost to benefit ratio of high ploidy and explain inter-tumoral differences in DNA content. Collaboration with many brilliant minds at Moffitt, including Ana Gomes, Sandy Anderson, Xiaoqing Yu, and Andriy Marusyk. At least 5 and up to 7 years of non-competitive funding! Let the journey begin!
CRD lab was selected to receive the 2022 Evolutionary Therapy award to evaluate aneuploidy as biomarker of cell fate. Exciting collaboration with Dr. Ana Gomes!
Our R03 grant was awarded to integrate live-cell imaging with single-cell sequencing and learn how cells adapt to new environments.
Wonderful international collaborations with Laura Heiser (OHSU), Zaid Siddiqui (UPMC) and Saeed Alahmari.
Richard Beck joins the CRD lab as postdoctoral fellow in computational biology. Richard brings strong skills in quantitative biology as well as math. modeling, which he will combine to develop data driven mathematical models. Welcome Richard!
Pallavi Singh and Navami Jain started their summer internships, working on feature selection to integrate imaging and single-cell sequencing data. Welcome Pallavi & Navami!
Welcome Andrew Schultz to our lab! Andrew will run our cell culture lab while also crunching numbers to find expression signatures of O2 and PO4 availability in the microenvironment.
What cost do cells with a higher DNA content pay for the robustness benefit it provides? Mathonco, RNASeq and microenvironment profiling join forces to find out! Thrilled to share our first paper from the clonal redesign lab.
Tremendously excited to welcome Thomas Veith as the 1st PhD student in the clonal redesign lab! Thomas is a PhD candidate studying Integrated Mathematical Oncology. He will embark on understanding how in-vitro cellular heterogeneity emerges and is maintained.
Welcome to Bradley Fox into the lab! Bradley is part of the off-campus program IMO is organizing for Dartmouth College students. Bradley's work explores the hypothesis that different timings of splitting and passaging a cell line will benefit different co-existing clones.
The Pathway to Independence Award (K99/R00) is funding us