Decoding Cancer Biology Through Genomics and Computation

Changde Cheng

I am a computational biologist and geneticist investigating the molecular mechanisms driving cancer progression and therapeutic resistance. My lab integrates genomic technologies with computational methods to understand the pattern and process of cancer biology at single-cell resolution.

With a background spanning computational genomics, evolutionary biology, and cancer research, I bring unique interdisciplinary perspectives to tackle complex biomedical challenges. We are committed to translating genomic insights into clinical applications that improve patient outcomes.

Stem Cell Biology Program
Division of Hematology and Oncology
Institute for Cancer Outcomes and Survivorship
Department of Biomedical Informatics and Data Science
O’Neal Comprehensive Cancer Center
Department of Medicine, Heersink School of Medicine
University of Alabama at Birmingham, USA

Wallace Tumor Institute 520A.
1824 6th Ave S Birmingham, Alabama 35233.

Email: ccheng [at] uabmc [dot] edu


Current Research

Our lab integrates genomics, computational biology, and cancer research to explore the molecular mechanisms of cancer progression and therapeutic resistance. We employ advanced single-cell and spatial genomic approaches to dissect tumor complexity through single-cell transcriptomics, spatial genomics, and multi-modal analyses integrating genomic, epigenomic, and proteomic data. Our current research investigates epigenetic regulation of gene expression and clonal dynamics in hematopoietic stem cells, with a particular focus on understanding how epigenetic modifications drive cellular differentiation and potential malignant transformation.


Measure of Rescue: Wherein Resistance to Remedy is Accounted

In our recent Blood publication (with friends, led by Dr. Rui Lu, Lu Lab at UAB), we introduced the “rescue index” - a metric that measures how gene expression returns to normal levels in resistant leukemia cells.

Type I and Type II menin targets

Barplot of Rescue Index

This index quantifies resistance on a scale from 0 (no rescue) to 1 (complete rescue), revealing that genes co-bound by both menin and H2AK119ub (Type II targets) show significantly higher rescue values than those bound only by menin (Type I). The rescue index demonstrated that loss of PRC1.1 enables noncanonical menin targets like MYC to escape suppression despite treatment.

Rescue Index

Plot showing Type I and Type II menin targets

This quantitative approach identified a critical balance between activating and repressive epigenetic marks that determines treatment response and highlighted venetoclax as an effective strategy against PRC1.1-deficient leukemia cells.

Rescue index comparison between Type I and Type II menin targets through RNAseq analysis

Plot showing higher rescue index values in Type II menin targets

Epigenetic regulation of non-canonical menin targets modulates menin inhibitor response in acute myeloid leukemia
Xinyue Zhou, Lixia Zhang, Sajesan Aryal, Virginia Veasey, Amanda Tajik, Cecilia Restelli, Steven Moreira, Pengcheng Zhang, Yanfeng Zhang, Kristin Hope, Yang Zhou, Changde Cheng, Ravi Bhatia, and Rui Lu.
Blood 2024 Nov 7; 144 (19): 2018–2032.

Also read this commentary on our work

Back to Top


Tempests in the Blood: When Sex Guide the Fates of Clones

One main focus is on the complex dynamics of clonal evolution in hematopoietic stem cells, exploring how genetic and epigenetic mechanisms shape cellular lineage development and contribute to disease progression.

Our recent collaboration (with friends, led by Drs. Smita Bhatia nd Ravi Bhatia) in the Journal of Clinical Oncology documents how evolutionary forces operate differently based on biological sex. In blood cell production after cancer treatment, mutations emerge in 37.2% of patients. These mutations appear at nearly identical rates in males (35.8%) and females (39.6%), affecting the same genes including DNMT3A, PPM1D, TET2, and TP53.

Study Design for CH Detection and Sex-Based Therapy-Related Myeloid Neoplasms Incidence

The temporal trajectories of clones diverge dramatically. In males, mutated clones expand and evolve, leading to therapy-related blood cancers in 12.4% of cases. In females, similar mutations rarely achieve dominance, with only 3.6% progressing to malignancy.

Mutations persist, expand, or disappear during disease progression, associated with specific chromosomal abnormalities across biological groups.

This suggests differential selection: mutants or clones face distinct evolutionary pressures in male versus female physiological environments, creating different fitness landscapes despite identical genetic starting points. Biological context shapes evolutionary outcomes in cancer development.

Sex-based differences in risk for therapy-related myeloid neoplasms
Melissa A Richard\(^{\ast}\), Chengcheng Yan\(^{\ast}\), Yanjun Chen, Christopher J Gibson, Rashi Kalra, Alysia Bosworth, David K Crossman, Purnima Singh, Lindsey Hageman, Jianbo He, Saro H Armenian, Julie Vose, Daniel J Weisdorf, Benjamin L Ebert, Yutaka Yasui, Changde Cheng, Stephen J Forman , Smita Bhatia\(^{\dagger}\), Ravi Bhatia\(^{\dagger}\)
Journal of Clinical Oncology 2024 Nov 1; Vol. 42, No 31.

Also read this editorials on our work

Back to Top