Dr. Changde Cheng

Assistant Professor
Stem Cell Biology | Cancer Outcomes and Survivorship | Biomedical Informatics and Data Science
University of Alabama at Birmingham

Before joining UAB, I developed methods for single-cell genomics in cancer research at the Computational Biology Department at St. Jude Children’s Research Hospital.

During my postdoc, I worked with Mark Kirkpatrick and David Houle, studying sexual antagonistic selection, the evolution of sexual differentiation, and aging.

Prior to that, I completed my Ph.D. at the University of Notre Dame, under the guidance of Nora Besansky, where I researched speciation, chromosomal evolution, ecological genomics, and evolutionary genomics.

Before pursuing my Ph.D., I worked with Charles Taylor at UCLA on evolutionary genetics, though my interests were drawn toward artificial life research.

Research Focus

Therapy Design and Engineering

We design and engineer combination therapies by mapping epistasis, inferring causal control, and optimizing interventions with mechanism-informed AI, translating molecular and cellular insights into therapeutic strategies.

Research Highlights

Sex Differences and Disease

Males and females share almost the same genome, yet they often differ in appearance, physiology, and disease risk. I study why those differences arise and how they matter for health, tracing how sex-biased selection and sexual antagonism shape genomic architecture over evolutionary timescales and yield consequences in contemporary medicine.

My work focuses on four linked themes. First, I ask which forces leave the deeper imprint on genomes and traits: sexually concordant selection, which pushes both sexes in the same direction, or sexually discordant selection, which benefits one sex while harming the other.

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Second, I investigate why sex chromosomes become focal points of conflict, testing whether chromosomal inversions (stretches of DNA flipped end-to-end) act as recombination suppressors that preserve advantageous, sex-specific allele combinations.

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Third, I examine how environmental plasticity modulates sex-biased gene expression and shifts the intersexual correlation of expression, allowing organisms to navigate the tug-of-war between male-optimal and female-optimal states.

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Finally, I study how aging alters these dynamics as purifying selection weakens, potentially amplifying sex differences in late-onset disease, including cancer.

These ideas motivate my current analyses of clonal evolution in hematopoietic stem cells after cancer therapy. Many patients develop clonal hematopoiesis, in which mutations arise and a subset of stem-cell clones expands. In our cohort, clonal hematopoiesis occurs in 37.2% of patients, with similar incidence in males (35.8%) and females (39.6%), and recurrently involves the same genes in both sexes, including DNMT3A, PPM1D, TET2, and TP53. The subsequent trajectories diverge: in males, mutated clones expand more often and progress to therapy-related blood cancers in 12.4% of cases, whereas progression in females is 3.6%.

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

These patterns suggest that selection on clones is sex-conditioned. Comparable genetic starting points can yield different outcomes because the surrounding biology—hormonal milieu, immune surveillance, stromal niches, and epigenetic states—reshapes fitness landscapes in sex-specific ways. My model aims to identify which components shift a clone from benign passenger to malignant driver, and how those components change with age.

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Sexual dimorphism/antagonism is not a theoretical curiosity confined to sex chromosomes but a living force that shapes disease. By connecting evolutionary principles to measurable cellular mechanisms, we seek to improve risk prediction, refine surveillance, and design therapies that remain effective within the sex-specific and age-dependent constraints imposed by evolution.