On Friday we said farewell to Xiaojun, who is moving on from the MacLean lab to join a team of cancer immunologists at AstraZeneca. We wish you all the best Xiaojun!
Adam and Jonathan attended ECMTB / SMB 2026 in Graz, Austria. Jonathan presented his recent work on control of early hematopoietic stem cell fate decisions. In his new model of stem cell exit-from-quiescence a two-gene circuit permits up to four coexisting stable steady states (tetrastability), including two intermediate states. Thus predicting that stem-to-multipotent differentiation proceeds through a series of fine-scale transitions rather than a single commitment event. Read the preprint here.
In a new preprint led by Jonathan and Anupam, we have developed a model of the Mecom—Cdk6 toggle switch, predicted to control early hematopoietic stem cell fate decisions as stem cells exit from quiescence and differentiate into a multipotent progenitor state. This two-gene circuit permits up to four coexisting stable steady states (tetrastability), including two intermediate states. Thus, we predict that stem-to-multipotent differentiation proceeds through a series of fine-scale transitions rather than a single commitment event. More broadly, analysis of this toggle simple two-gene circuit with complicated dynamics allowed us to address a deeper question that regarding that is fundamentally dynamical rather than molecular: how does the structure of such a small gene regulatory network determine the geometry of the landscape on which cell fate decisions are made, thereby controlling the paths that connect cell states. Read the preprint here.
The lab attended the 15th annual Southern California Systems Biology conference, held this year at UCLA. Jonathan presented a lightning talk on his recent results on stem cell catastrophes (mathematically speaking, not pertaining to the PhD journey) and most of the lab presented posters. Adam held to co-organize the event and chaired an afternoon session of reprogramming biology. With 20 speakers, 64 posters, and close to 200 participants, the SoCal systems biology community is strong!
iLR: iterative logistic regression, is a novel method for the inference of genes marking for subtle effects in single-cell RNA-sequencing data. Yingtong led the development of iLR, which uses Pareto front optimization to find optimal gene sets which are small yet accurately classify subtle effects. In collaboration with the Evanthia Roussos Torres lab at USC Keck, iLR was used to identify myeloid cell differentiation pathways as a target of entinostat, an epigenetic modulator.
popInfer: a novel method for the inference of gene regulatory networks governing dynamic cell state transitions is published now in iScience. popInfer learns cell type-specific networks governing dynamic transitions by learning a joint regression model using both RNA-seq and ATAC-seq signals from the same single cells. Applied to a multiomic dataset on hematopoietic stem cell aging, popInfer discovered a mutual inhibition network between Mecom and Cdk6 that controlled stem cell quiescence.
Adam attended the mathematical oncology 2025 conference #mathonco25 in St. Petersburg, FL, for three days at the cutting edge of mathematical & computational research in oncology centered around the theme of “Evolutionary therapy” on the beach. Adam presented a didactic talk on “Non-genetic paths of tumor escape” based on our recent work into the logic of gene regulatory networks and its impact on EMT and metastasis.
Our new preprint led by Jesse with input from Xiaojun and the Roussos Torres lab is out now: Beyond RECIST: mathematical modeling and Bayesian inference reveal the importance of immune parameters in metastatic breast cancer.
In which we present a modeling+inference framework to extrapolate beyond small, heterogeneous phase 1 cohorts and personalize tumor-immune models of response to triple combination therapy. We discover that control only of the immune suppressive parameters and not of the cytotoxic parameters is necessary to explain response. Read the paper here.
Today on the mathematical oncology blog (a great resource to follow), Jesse has written a blog post highlighting the findings of our recent preprint on cancer systems immunology. Integrating theory and modeling with preclinical and clinical data enabled discovery of how combination therapy acts on intricate tumor-immune networks to mediate tumor response. Read the blog post here.
The Society for Mathematical Biology (SMB) held its annual meeting in Edmonton, where Xiaojun presented on methods for model discovery from noisy biological data (read the paper),
and Adam presented on our recent cancer systems immunology work leading to the discovery of mechanisms driving response to combination therapy (read the preprint) plus new work inferring patient- and site-specific tumor-immune dynamics to inform clinical decision making from RECIST data. Thanks to the hosts, the SMB community is strong!