Shan Zha, MD, PhD (left)
James A Wolff Professor of Pediatrics, Pathology and Cell Biology and of Microbiology and Immunology
Department of Pediatrics, Gastroenterology
Program: Cancer Genomics and Epigenomics (CGE)
Title: "Too Much or Too Little PAR: Understanding the PARP–PARG Axis in Cancer Therapy"
Description: PARP1/2 inhibitors (PARPi) have transformed the treatment of BRCA1/2-deficient cancers, yet their clinical potential is constrained by hematological toxicity and acquired resistance. Emerging strategies—including PARP1-selective inhibitors and targeting PARG, the enzyme that removes poly(ADP-ribose) (PAR)—offer new opportunities to refine this therapeutic axis. Using integrated genetic, cellular, and pharmacological approaches, we define the mechanisms underlying PARPi-induced hematopoietic toxicity in vivo and identify key vulnerabilities associated with PARG inhibition. These findings reveal PAR metabolism as a tunable node in cancer therapy and highlight the importance of achieving the right balance—neither too little nor too much PAR—for optimal therapeutic outcome. Dr. Zha is the principal investigator of three NCI R01 grants focused on PARP1, PARP2, and their regulatory pathways, organized three Cold Spring Harbor Laboratory meetings on PARP and PAR Biology (2024, 2026, and 2028). She has published 13 peer-reviewed manuscripts on DNA damage–induced PARylation over the past four years and is also the author of an invited review on PARP–PARG inhibition in Nature Cancer (scheduled for publication in 2026).
Akanksha Thawani, PhD (right)
Assistant Professor of Biochemistry and Molecular Biophysics
Department of Biochemistry & Molecular Biophyscs
Program: Cancer Genomics and Epigenomics (CGE)
Title: "Genetic Architects: Structural Mechanisms of Retrotransposon Spread in Our Genomes"
Description: Dr. Thawani’s research focuses on understanding how mobile genetic elements shape our genomes and its defenses. Retrotransposons make up a family of mobile elements that copy-and-paste themselves and dominate the genomes of multicellular eukaryotes. Despite their abundance, the mechanisms that drive retrotransposon spread have remained a mystery due to challenges in purification and biochemical characterization. Dr. Thawani will present her efforts to unravel the molecular and structural basis of human LINE-1 retrotransposon spread, the gene responsible for an astonishing one-third of the human genome.
Retrotransposons hold the key to developing programmable transgene insertion technologies that do not rely on donor DNA, offering a new and safer approach for gene therapy. Dr. Thawani will further present recent cryo-EM structures that allow us to understand how site-specific retrotransposons from vertebrate species mobilize and describe ongoing efforts to engineer vertebrate retrotransposons for transgene insertion technology.
Join Zoom Meeting
https://columbiacuimc.zoom.us/j/98062087107?pwd=ODN1TFwbtR23dO0Pk7Bq73td7fG91L.1
Meeting ID: 980 6208 7107
Passcode: 267022
