The Wang Lab

Project 1: 

Early evolution and spatial architecture of rare melanoma subtypes 

Acral and mucosal melanomas are biologically distinct from cutaneous melanomas, exhibiting unique patterns of early evolution, spatial heterogeneity, and genomic complexity. A striking feature of these rare melanoma subtypes is the frequent presence of complex genomic aberrations, which we termed “hailstorms”, which often amplifies multiple oncogenes, such as TERT, CCND1, GAB2, CDK4 and CRKL, at very early stages of tumorigenesis (Wang et al, Nature Communications, 2024). Notably, such alterations can be detected in morphologically normal-appearing melanocytes, or “field cells,” which clonally expand across large areas of skin before visible tumor formation. We also found that early clonal divergence is common in acral melanoma, with highly distinct subclones coexisting within the primary tumor. To dissect the basis of this early evolution and clonal heterogeneity, we are applying an integrated approach that combines multi-regional sequencing with spatial transcriptomics approaches. Through this work, we aim to gain new insights into the earliest steps of melanoma development. 

Project 2: 

The genomic and evolutionary differences of melanoma and other cancers across populations 

Understanding how the cancer genomic landscape varies across populations is critical for developing tailored therapeutic strategies. In melanoma, mutational processes such as UV-induced DNA damage are well characterized in Caucasian patients. However, alternative mechanisms may play larger roles in other populations, where environmental exposures and underlying genomic contexts differ. To address this, we are investigating the genetic differences of cutaneous melanomas in patients from non-Caucasian backgrounds. This work seeks to comprehensively characterize genomic alterations in cutaneous melanoma from diverse patient populations, with the long-term goal of generating a genomic framework that better reflects patient diversity and supports efforts to address disparities in outcomes. Beyond melanoma, we are broadly interested in applying these approaches to other cancer types to uncover shared and distinct evolutionary principles. 

Project 3: 

Other directions in cancer genomics 

We are also broadly interested in applying computational approaches to study cancer genomics. One area of interest is investigating how repetitive DNA elements, such as microsatellites, telomeric repeats, and rDNA arrays, are maintained or destabilized during cancer progression, and how their disruption contributes to genome-wide instability, tumor evolution, and therapeutic vulnerability. To address this, we combine analyses of public datasets with newly generated short- and long-read whole-genome sequencing data, enabling a comprehensive assessment of repeat element dynamics in cancer.