Three UT Southwestern Medical Center faculty members, including two from the Harold C. Simmons Comprehensive Cancer Center, will present at the American Association for Cancer Research’s Annual Meeting on the growth of breast and ovarian cancers, STING signaling, and compartmentalization in gene activation.

W. Lee Kraus, Ph.D., Director of the Cecil H. and Ida Green Center for Reproductive Biology Sciences and Professor of Obstetrics and Gynecology, and Pharmacology at UT Southwestern, will show that naturally occurring mutations in histone proteins, called oncohistones, control the growth of breast and ovarian cancers by blocking functional sites of ADP-ribosylation. In the noncancerous state, the chemical modification of the histones through ADP-ribosylation stimulates cellular pathways that control cell growth. In the cancerous state, the oncohistone mutations block ADP-ribosylation leading to uncontrolled cell growth. This work suggests that using PARP inhibitors for certain cancers harboring oncohistone mutations may actually be detrimental. Dr. Kraus, who, has worked extensively on PARP inhibitor research, serves as Assistant Director for Basic Research at UTSW’s Simmons Cancer Center and Chief of the Division of Basic Reproductive Biology Research in the Department of Obstetrics and Gynecology.

Nan Yan, Ph.D., Associate Professor of Immunology and Microbiology at UT Southwestern, will discuss mechanisms of innate immune STING signaling, current STING cancer drug designs and challenges, and his recent publication in the journal Immunity on IFN-dependent and independent activities of STING in cancer. Dr. Yan, a member of the Simmons Cancer Center, will also discuss unpublished work on the STING trafficking mechanism and how it can be harnessed for a new mode of STING activation in cancer.

Ben Sabari, Ph.D., Assistant Professor of Molecular Biology and Obstetrics and Gynecology at UT Southwestern, will present on his recent piece in the journal Developmental Cell. He will speak about how activating the right gene at the right time and place is essential for development and is often dysregulated in cancer. Emerging evidence suggests that this process is regulated by dynamic compartmentalization of the gene-control machinery, RNA polymerase II and its co-factors, within biomolecular condensates. The processes that lead to condensate formation represent a new regulatory axis in normal and disease cell states. In his education session, Dr. Sabari will review the current understanding of how condensate formation is coupled to gene regulation and the potential implications for cancer biology. Dr. Sabari, a Cancer Prevention and Research Institute of Texas Scholar, holds a faculty appointment in Cecil H. and Ida Green Center for Reproductive Biology Sciences.

Drs. Kraus and Yan are members of the Cellular Networks in Cancer Program at the Simmons Cancer Center.